Sample records for keq ha-1 yr-1

  1. Generation of recombinant pandemic H1N1 influenza virus with the HA cleavable by bromelain and identification of the residues influencing HA bromelain cleavage.

    PubMed

    Wang, Weijia; Suguitan, Amorsolo L; Zengel, James; Chen, Zhongying; Jin, Hong

    2012-01-20

    The proteolytic enzyme bromelain has been traditionally used to cleave the hemagglutinin (HA) protein at the C-terminus of the HA2 region to release the HA proteins from influenza virions. The bromelain cleaved HA (BHA) has been routinely used as an antigen to generate antiserum that is essential for influenza vaccine product release. The HA of the 2009 pandemic H1N1 influenza A/California/7/2009 (CA09) virus could not be cleaved efficiently by bromelain. To ensure timely delivery of BHA for antiserum production, we generated a chimeric virus that contained the HA1 region from CA09 and the HA2 region from the seasonal H1N1 A/South Dakota/6/2007 (SD07) virus that is cleavable by bromelain. The BHA from this chimeric virus was antigenically identical to CA09 and induced high levels of HA-specific antibodies and protected ferrets from wild-type H1N1 CA09 virus challenge. To determine the molecular basis of inefficient cleavage of CA09 HA by bromelain, the amino acids that differed between the HA2 of CA09 and SD07 were introduced into recombinant CA09 virus to assess their effect on bromelain cleavage. The D373N or E374G substitution in the HA2 stalk region of CA09 HA enabled efficient cleavage of CA09 HA by bromelain. Sequence analysis of the pandemic H1N1-like viruses isolated from 2010 revealed emergence of the E374K change. We found that K374 enabled the HA to be cleaved by bromelain and confirmed that the 374 residue is critical for HA bromelain cleavage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Minor histocompatibility antigen HA-1 and HA-2 polymorphisms in Taiwan: frequency and application in hematopoietic stem cell transplantation.

    PubMed

    Lio, Hoi-Yan; Tang, Jih-Luh; Wu, Jui; Wu, Shang-Ju; Lin, Chun-Ying; Yang, Ya-Chien

    2010-09-01

    Minor histocompatibility antigens influence the occurrence of graft-vs.-host disease and graft-vs.-leukemia effects after hematopoietic stem cell transplantation (HSCT). We determined the population frequencies of HA-1 and HA-2 alleles in Taiwan and exploited their potential applications in allogeneic HSCT. HA-1 and HA-2 were genotyped using polymerase chain reaction and restriction fragment length polymorphism in healthy controls (221 for HA-1 and 306 for HA-2) and HLA-matched donor-recipient sibling pairs with HSCT (92 for HA-1 and 38 for HA-2). The association of genetic polymorphisms with HSCT outcome was evaluated by univariate and multivariate analyses. The allele frequencies in controls were 35.3% and 64.7% for HA-1(H) and HA-1(R), and 89.0% and 11.0% for HA-2(V) and HA-2(M), respectively. HA-1 disparity was denoted in 16.3% of HLA-matched donor-recipient sibling pairs, while it was not associated with HSCT outcome. HA-2 disparity was not observed in the donor-recipient pairs studied. The possibilities of using HA-1 and HA-2 variabilities as molecular markers for hematopoietic chimerism after HSCT were 39.2% and 18.4%, respectively. Our data provide the information on allele and genotype frequencies of HA-1 and HA-2 in a Taiwanese population, and suggest that prospective genomic typing for HA-1 and HA-2 alleles of the donor and recipient could be a useful approach for molecular identification of hematopoietic chimerism after HSCT, rather than prognosis of clinical outcome.

  3. Promotion of PDT efficacy by HA14-1

    NASA Astrophysics Data System (ADS)

    Kessel, David; Price, Michael; Haagenson, Kelly

    2008-02-01

    Photodynamic therapy (PDT) can target the members of the Bcl-2 family that protect cells from the initiation of apoptosis, a well-known death pathway. We examined the ability of HA14-1, a non-peptidic Bcl-2/Bcl-xL antagonist, to promote the efficacy of PDT. The photosensitizer was the porphycene CPO that causes photodamage to Bcl-2 located in the endoplasmic reticulum. Using low PDT doses together with LD5-20 concentrations of HA14-1, we found a marked synergistic effect. These results indicate that such an effect occurs when PDT is coupled with pharmacologic suppression of Bcl-2 function. HA14-1 is an unstable compound that decomposes in aqueous solution. This resulted in a rapid (~60 sec) burst of fluorescence that closely mimicked the properties of many fluorescent probes, but was traced to an effect produced when HA14-1 contacts serum proteins. Other Bcl-2 antagonists that do not produce any intrinsic fluorescence also promoted PDT efficacy. Moreover, briefly storing HA14-1 in aqueous medium until the fluorescent burst is over does not inhibit a subsequent synergistic promotion of PDT efficacy. We conclude that Bcl-2 antagonists can promote the efficacy of low-dose PDT in a manner unrelated to ROS production. The most likely explanation is an enhanced loss of anti-apoptotic Bcl-2 family function such that a threshold for initiation of apoptosis is crossed.

  4. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients.

    PubMed

    Caglioti, Claudia; Selleri, Marina; Rozera, Gabriella; Giombini, Emanuela; Zaccaro, Paola; Valli, Maria Beatrice; Capobianchi, Maria Rosaria

    2016-01-01

    In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8-42.3) X 10-4 vs 30.6 (27.4-33.6) X 10-4 substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients.

  5. Monitoring bound HA1(H1N1) and HA1(H5N1) on freely suspended graphene over plasmonic platforms with infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Banerjee, Amrita; Chakraborty, Sumit; Altan-Bonnet, Nihal; Grebel, Haim

    2013-09-01

    Infrared (IR) spectroscopy provides fingerprinting of the energy and orientation of molecular bonds. The IR signals are generally weak and require amplification. Here we present a new plasmonic platform, made of freely suspended graphene, which was coating periodic metal structures. Only monolayer thick films were needed for a fast signal recording. We demonstrated unique IR absorption signals of bound proteins: these were the hemagglutinin area (HA1) of swine influenza (H1N1) and the avian influenza (H5N1) viruses bound to their respective tri-saccharides ligand receptors. The simplicity and sensitivity of such approach may find applications in fast monitoring of binding events.

  6. Antigenicity of the 2015-2016 seasonal H1N1 human influenza virus HA and NA proteins.

    PubMed

    Clark, Amelia M; DeDiego, Marta L; Anderson, Christopher S; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S; Sangster, Mark Y; Topham, David J

    2017-01-01

    Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015-2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015-2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2-4 fold lower for the 2015-2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of

  7. Aerobic exercise training conserves insulin sensitivity for 1 yr following weight loss in overweight women.

    PubMed

    Fisher, Gordon; Hunter, Gary R; Gower, Barbara A

    2012-02-01

    The objectives of this study were to 1) identify the independent effects of exercise (aerobic or resistance training) and weight loss on whole body insulin sensitivity and 2) determine if aerobic or resistance training would be more successful for maintaining improved whole body insulin sensitivity 1 yr following weight loss. Subjects were 97 healthy, premenopausal women, body mass index (BMI) 27-30 kg/m(2). Following randomized assignment to one of three groups, diet only, diet + aerobic, or diet + resistance training until a BMI <25 kg/m(2) was achieved, body composition, fat distribution, and whole body insulin sensitivity were determined at baseline, in the weight reduced state, and at 1-yr follow up. The whole body insulin sensitivity index (S(I)) was determined using a frequently sampled intravenous glucose tolerance test. Results of repeated-measures ANOVA indicated a significant improvement in S(I) following weight loss. However, there were no group or group×time interactions. At 1-yr follow up, there were no significant time or group interactions for S(I;) however, there was a significant group×time interaction for S(I). Post hoc analysis revealed that women in the aerobic training group showed a significant increased S(I) from weight reduced to 1-yr follow up (P < 0.05), which was independent of intra-abdominal adipose tissue and %fat. No significant differences in S(I) from weight reduced to 1-yr follow up were observed for diet only or diet + resistance groups. Additionally, multiple linear regression analysis revealed that change in whole body insulin sensitivity from baseline to 1-yr follow up was independently associated with the change in Vo(2max) from baseline to 1-yr follow up (P < 0.05). These results suggest that long-term aerobic exercise training may conserve improvements in S(I) following weight loss and that maintaining cardiovascular fitness following weight loss may be important for maintaining improvements in S(I).

  8. Characterization of Three Novel Fatty Acid- and Retinoid-Binding Protein Genes (Ha-far-1, Ha-far-2 and Hf-far-1) from the Cereal Cyst Nematodes Heterodera avenae and H. filipjevi

    PubMed Central

    Peng, Huan; Luo, Shujie; Huang, Wenkun; Cui, Jiangkuan; Li, Xin; Kong, Lingan; Jiang, Daohong; Chitwood, David J.; Peng, Deliang

    2016-01-01

    Heterodera avenae and H. filipjevi are major parasites of wheat, reducing production worldwide. Both are sedentary endoparasitic nematodes, and their development and parasitism depend strongly on nutrients obtained from hosts. Secreted fatty acid- and retinol-binding (FAR) proteins are nematode-specific lipid carrier proteins used for nutrient acquisition as well as suppression of plant defenses. In this study, we obtained three novel FAR genes Ha-far-1 (KU877266), Ha-far-2 (KU877267), Hf-far-1 (KU877268). Ha-far-1 and Ha-far-2 were cloned from H. avenae, encoding proteins of 191 and 280 amino acids with molecular masses about 17 and 30 kDa, respectively and sequence identity of 28%. Protein Blast in NCBI revealed that Ha-FAR-1 sequence is 78% similar to the Gp-FAR-1 protein from Globodera pallida, while Ha-FAR-2 is 30% similar to Rs-FAR-1 from Radopholus similis. Only one FAR protein Hf-FAR-1was identified in H. filipjevi; it had 96% sequence identity to Ha-FAR-1. The three proteins are alpha-helix-rich and contain the conserved domain of Gp-FAR-1, but Ha-FAR-2 had a remarkable peptide at the C-terminus which was random-coil-rich. Both Ha-FAR-1 and Hf-FAR-1 had casein kinase II phosphorylation sites, while Ha-FAR-2 had predicted N-glycosylation sites. Phylogenetic analysis showed that the three proteins clustered together, though Ha-FAR-1 and Hf-FAR-1 adjoined each other in a plant-parasitic nematode branch, but Ha-FAR-2 was distinct from the other proteins in the group. Fluorescence-based ligand binding analysis showed the three FAR proteins bound to a fluorescent fatty acid derivative and retinol and with dissociation constants similar to FARs from other species, though Ha-FAR-2 binding ability was weaker than that of the two others. In situ hybridization detected mRNAs of Ha-far-1 and Ha-far-2 in the hypodermis. The qRT-PCR results showed that the Ha-far-1and Ha-far-2 were expressed in all developmental stages; Ha-far-1 expressed 70 times more than Ha-far-2 in

  9. Characterization of Three Novel Fatty Acid- and Retinoid-Binding Protein Genes (Ha-far-1, Ha-far-2 and Hf-far-1) from the Cereal Cyst Nematodes Heterodera avenae and H. filipjevi.

    PubMed

    Qiao, Fen; Luo, Lilian; Peng, Huan; Luo, Shujie; Huang, Wenkun; Cui, Jiangkuan; Li, Xin; Kong, Lingan; Jiang, Daohong; Chitwood, David J; Peng, Deliang

    2016-01-01

    Heterodera avenae and H. filipjevi are major parasites of wheat, reducing production worldwide. Both are sedentary endoparasitic nematodes, and their development and parasitism depend strongly on nutrients obtained from hosts. Secreted fatty acid- and retinol-binding (FAR) proteins are nematode-specific lipid carrier proteins used for nutrient acquisition as well as suppression of plant defenses. In this study, we obtained three novel FAR genes Ha-far-1 (KU877266), Ha-far-2 (KU877267), Hf-far-1 (KU877268). Ha-far-1 and Ha-far-2 were cloned from H. avenae, encoding proteins of 191 and 280 amino acids with molecular masses about 17 and 30 kDa, respectively and sequence identity of 28%. Protein Blast in NCBI revealed that Ha-FAR-1 sequence is 78% similar to the Gp-FAR-1 protein from Globodera pallida, while Ha-FAR-2 is 30% similar to Rs-FAR-1 from Radopholus similis. Only one FAR protein Hf-FAR-1was identified in H. filipjevi; it had 96% sequence identity to Ha-FAR-1. The three proteins are alpha-helix-rich and contain the conserved domain of Gp-FAR-1, but Ha-FAR-2 had a remarkable peptide at the C-terminus which was random-coil-rich. Both Ha-FAR-1 and Hf-FAR-1 had casein kinase II phosphorylation sites, while Ha-FAR-2 had predicted N-glycosylation sites. Phylogenetic analysis showed that the three proteins clustered together, though Ha-FAR-1 and Hf-FAR-1 adjoined each other in a plant-parasitic nematode branch, but Ha-FAR-2 was distinct from the other proteins in the group. Fluorescence-based ligand binding analysis showed the three FAR proteins bound to a fluorescent fatty acid derivative and retinol and with dissociation constants similar to FARs from other species, though Ha-FAR-2 binding ability was weaker than that of the two others. In situ hybridization detected mRNAs of Ha-far-1 and Ha-far-2 in the hypodermis. The qRT-PCR results showed that the Ha-far-1and Ha-far-2 were expressed in all developmental stages; Ha-far-1 expressed 70 times more than Ha-far-2 in

  10. Homology modeling study toward identifying structural properties in the HA2 B-loop that would influence the HA1 receptor-binding site.

    PubMed

    Cueno, Marni E; Imai, Kenichi; Shimizu, Kazufumi; Ochiai, Kuniyasu

    2013-07-01

    Influenza hemagglutinin (HA) consists of a fibrous globular stem (HA2) inserted into the viral membrane supporting a globular head (HA1). HA1 receptor-binding has been hypothesized to be structurally correlated to the HA2 B-loop, however, this was never fully understood. Here, we elucidated the structural relationship between the HA2 B-loop and the HA1 receptor-binding site (RBS). Throughout this study, we analyzed 2486 H1N1 HA homology models obtained from human, swine and avian strains during 1976-2012. Quality of all homology models were verified before further analyses. We established that amino acid residue 882 is putatively strain-conserved and differs in the human (K882), swine (H882) and avian (N882) strains. Moreover, we observed that the amino acid at residue 882 and, similarly, its orientation has the potential to influence the HA1 RBS diameter measurements which we hypothesize may consequentially affect influenza H1N1 viral infectivity, immune escape, transmissibility, and evolution. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Chemical Denudation and Cation Depletion in a Semi-Arid Catchment of the Long-Term Agroecological Research Observatory

    NASA Astrophysics Data System (ADS)

    Shaljian, M.; Keller, C. K.; Jones, K. B.; Brooks, E. S.; Huggins, D. R.

    2016-12-01

    The Long-Term Agroecosystem Research (LTAR) network of the USDA is a nationwide observatory and decadal-timescale field-experimental study of sustainable food production. The LTAR thus supports investigation of hydroecological and biogeochemical processes that could affect agricultural sustainability over the course of the 21st century. Mineral-derived nutrient cations are essential to fertility, and acidification of soils due to chemical fertilization may result in unsustainable chemical denudation of the soil exchange pool. Mineral weathering also contributes to base cation denudation. This study investigated base cation losses for one year in drainage from a semi-arid, rain-fed catchment at the Cook Agronomy Farm (CAF) LTAR site in southeastern Washington. We measured flows, analyzed drainage samples and estimated hydrologic effluxes of base cations from the catchment. The total dissolved base cation denudation rate at CAF-LTAR is about 40 kg ha-1 yr-1, which is comparable to other catchments on silicate terranes. The 2.1keq ha-1 yr-1 of denuded cationic charge is dominated by Ca2+ (61%) and Mg2+ (35%). Principal counter-ions are HCO3- (43%), NO3- (38%) and SO42- (16%), suggesting that both H2CO3 and HNO3 are important acids. Comparing 2008 soil pH and base saturation at CAF-LTAR to a nearby native prairie site, we preliminarily estimate a loss of 120 keq ha-1 of base cations from the upper 1.5m of the soil exchangeable cation pool. Dividing this depletion by the estimated denudation flux returns 60 years, which is approximately the interval of chemically intensive agriculture here. This may suggest that the source of exported base cations in drainage is primarily cation exchange rather than mineral weathering. The LTAR observatory will support ongoing monitoring and experimentation necessary to better understand base cation depletion and how it interacts with agroecological changes over the next several decades.

  12. Antigenicity of the 2015–2016 seasonal H1N1 human influenza virus HA and NA proteins

    PubMed Central

    Anderson, Christopher S.; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S.; Sangster, Mark Y.; Topham, David J.

    2017-01-01

    Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015–2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015–2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2–4 fold lower for the 2015–2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of

  13. Novel antigenic shift in HA sequences of H1N1 viruses detected by big data analysis.

    PubMed

    Zhang, Ruiying; Xu, Chongfeng; Duan, Ziyuan

    2017-07-01

    The influenza virus H1N1 has been prevalent all over the world for nearly a century. Many studies on its evolutionary history, substitution rate and antigenicity-associated sites have been done with small datasets. To have a complete view, we analysed 3171 full-length HA sequences from human H1N1 viruses sampled from 1918 to 2016, and discovered a new clade has formed with sequences isolated in Iran. Based on genetic distance calculations, we revealed an uneven evolutionary rate among sequences isolated in different years. We also found that the HA1 fragment of the new clade is like that of viruses that existed in the 1930s, while the HA2 fragment is closely associated with strains isolated after the 2009 pandemic. This new, "mixed" HA sequence indicates a cryptic antigenic shift event occurred, and it should draw more attention to the new clade identified from sequences from Iran. Copyright © 2017. Published by Elsevier B.V.

  14. Oral vaccine of Lactococcus lactis harbouring pandemic H1N1 2009 haemagglutinin1 and nisP anchor fusion protein elevates anti-HA1 sIgA levels in mice.

    PubMed

    Joan, Stella Siaw Xiu; Pui-Fong, Jee; Song, Adelene Ai-Lian; Chang, Li-Yen; Yusoff, Khatijah; AbuBakar, Sazaly; Rahim, Raha Abdul

    2016-05-01

    An oral lactococcal-based vaccine which haboured the haemagglutinin1 (HA1) antigen fused to nisP anchor protein for the purpose of surface displaying the HA1 antigen was developed against H1N1 virus. Recombinant L. lactis strains expressed HA1-nisP fusion proteins when induced with nisin, as confirmed through western blotting. However, immunofluorescense did not detect any surface-displayed proteins, suggesting that the protein was either unsuccessfully translocated or improperly displayed. Despite this, oral administration of recombinant L. lactis strains to BALB/c mice revealed that significant levels of anti-HA1 sIgA antibodies were detected in mice fecal suspension samples of mice group NZ9000 (pNZ:HN) when compared to the negative control NZ9000 (pNZ8048) group. Specific anti-HA1 sIgA antibodies were locally produced and live recombinant lactococcal vaccine was able to elicit humoral response of BALB/c mice despite unsuccessful surface display of the HA1 epitope.

  15. Molecular aspects of zygotic embryogenesis in sunflower (Helianthus annuus L.): correlation of positive histone marks with HaWUS expression and putative link HaWUS/HaL1L.

    PubMed

    Salvini, Mariangela; Fambrini, Marco; Giorgetti, Lucia; Pugliesi, Claudio

    2016-01-01

    The link HaWUS/ HaL1L , the opposite transcriptional behavior, and the decrease/increase in positive histone marks bond to both genes suggest an inhibitory effect of WUS on HaL1L in sunflower zygotic embryos. In Arabidopsis, a group of transcription factors implicated in the earliest events of embryogenesis is the WUSCHEL-RELATED HOMEOBOX (WOX) protein family including WUSCHEL (WUS) and other 14 WOX protein, some of which contain a conserved WUS-box domain in addition to the homeodomain. WUS transcripts appear very early in embryogenesis, at the 16-cell embryo stage, but gradually become restricted to the center of the developing shoot apical meristem (SAM) primordium and continues to be expressed in cells of the niche/organizing center of SAM and floral meristems to maintain stem cell population. Moreover, WUS has decisive roles in the embryonic program presumably promoting the vegetative-to-embryonic transition and/or maintaining the identity of the embryonic stem cells. However, data on the direct interaction between WUS and key genes for seed development (as LEC1 and L1L) are not collected. The novelty of this report consists in the characterization of Helianthus annuus WUS (HaWUS) gene and in its analysis regarding the pattern of the methylated lysine 4 (K4) of the Histone H3 and of the acetylated histone H3 during the zygotic embryo development. Also, a parallel investigation was performed for HaL1L gene since two copies of the WUS-binding site (WUSATA), previously identified on HaL1L nucleotide sequence, were able to be bound by the HaWUS recombinant protein suggesting a not described effect of HaWUS on HaL1L transcription.

  16. Biomedical potential of chitosan/HA and chitosan/β-1,3-glucan/HA biomaterials as scaffolds for bone regeneration--A comparative study.

    PubMed

    Przekora, Agata; Palka, Krzysztof; Ginalska, Grazyna

    2016-01-01

    The aim of this work was to compare biomedical potential of chitosan/hydroxyapatite (chit/HA) and novel chitosan/β-1,3-glucan/hydroxyapatite (chit/glu/HA) materials as scaffolds for bone regeneration via characterization of their biocompatibility, porosity, mechanical properties, and water uptake behaviour. Biocompatibility of the scaffolds was assessed in direct-contact with the materials using normal human foetal osteoblast cell line. Cytotoxicity and osteoblast proliferation rate were evaluated. Porosity was assessed using computed microtomography analysis and mechanical properties were determined by compression testing. Obtained results demonstrated that chit/HA scaffold possessed significantly better mechanical properties (compressive strength: 1.23 MPa, Young's modulus: 0.46 MPa) than chit/glu/HA material (compressive strength: 0.26 MPa, Young's modulus: 0.25 MPa). However, addition of bacterial β-1,3-glucan to the chit/HA scaffold improved its flexibility and porosity. Moreover, chit/glu/HA scaffold revealed significantly higher water uptake capability (52.6% after 24h of soaking) compared to the chit/HA (30.7%) and thus can serve as a very good drug delivery carrier. Chit/glu/HA scaffold was also more favourable to osteoblast survival (near 100% viability after 24-h culture), proliferation, and spreading compared to the chit/HA (63% viability). The chit/glu/HA possesses better biomedical potential than chit/HA scaffold. Nevertheless, poor mechanical properties of the chit/glu/HA limit its application to non-load bearing implantation area. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Spatial distribution and seasonal variations of atmospheric sulfur deposition over Northern China

    NASA Astrophysics Data System (ADS)

    Pan, Y. P.; Wang, Y. S.; Tang, G. Q.; Wu, D.

    2012-09-01

    of acidifying deposition on the receiving environment, we calculated the deposition of "potential acidity" that takes into account the microbial transformation of ammonium to nitrate in the ecosystems, resulting in the release of hydrogen ions. The estimated total "acid equivalents" deposition of S and nitrogen (N) fell within the range of 4.2-11.6 keq ha-1 yr-1, with a ten-site, 3-yr mean of 8.4 keq ha-1 yr-1. This value is significantly higher than that of other regions in the world and exceeds the critical loads for natural ecosystems in Northern China, thus prompting concerns regarding ecological impacts. The contribution of S to total acid deposition was comparable to that of N at most of sites; however, the importance of S on acidification risks was more pronounced in the industrial sites, highlighting that further SO2 abatement from industrial emissions is still needed. Taking these findings and our previous studies together, a multi-pollutant perspective and joint mitigate strategies to abate SO2 and NH3 simultaneously in the target areas are recommended to protect the natural ecosystems from excess acid deposition caused by anthropogenic emissions.

  18. AmeriFlux US-Ha1 Harvard Forest EMS Tower (HFR1)

    DOE Data Explorer

    Munger, J. William [Harvard University

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site US-Ha1 Harvard Forest EMS Tower (HFR1). Site Description - The Harvard Forest tower is on land owned by Harvard University. The site is designated as an LTER site. Most of the surrounding area was cleared for agrigulture during European settlement in 1600-1700. The site has been regrowing since before 1900 (based on tree ring chronologies) and is now predominantly red oak and red maple, with patches of mature hemlock stand and individual white pine. Overstory trees were uprooted by hurricane in 1938. Climate measurements have been made at Harvard Forest since 1964.

  19. THE SOLAR NEIGHBORHOOD. XXV. DISCOVERY OF NEW PROPER MOTION STARS WITH 0.''40 yr{sup -1} > {mu} {>=} 0.''18 yr{sup -1} BETWEEN DECLINATIONS -47{sup 0} AND 00{sup 0}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boyd, Mark R.; Winters, Jennifer G.; Henry, Todd J.

    2011-07-15

    We present 2817 new southern proper motion systems with 0.''40 yr{sup -1} > {mu} {>=} 0.''18 yr{sup -1} and declination between -47{sup 0} and 00{sup 0}. This is a continuation of the SuperCOSMOS-RECONS (SCR) proper motion searches of the southern sky. We use the same photometric relations as previous searches to provide distance estimates based on the assumption that the objects are single main-sequence stars. We find 79 new red dwarf systems predicted to be within 25 pc, including a few new components of previously known systems. Two systems-SCR 1731-2452 at 9.5 pc and SCR 1746-3214 at 9.9 pc-are anticipatedmore » to be within 10 pc. We also find 23 new white dwarf (WD) candidates with distance estimates of 15-66 pc, as well as 360 new red subdwarf candidates. With this search, we complete the SCR sweep of the southern sky for stars with {mu} {>=} 0.''18 yr{sup -1} and R{sub 59F} {<=} 16.5, resulting in a total of 5042 objects in 4724 previously unreported proper motion systems. Here we provide selected comprehensive lists from our SCR proper motion search to date, including 152 red dwarf systems estimated to be within 25 pc (9 within 10 pc), 46 WDs (10 within 25 pc), and 598 subdwarf candidates. The results of this search suggest that there are more nearby systems to be found at fainter magnitudes and lower proper motion limits than those probed so far.« less

  20. Plasma 1-carbon metabolites and academic achievement in 15-yr-old adolescents

    PubMed Central

    Nilsson, Torbjörn K.; Hurtig-Wennlöf, Anita; Sjöström, Michael; Herrmann, Wolfgang; Obeid, Rima; Owen, Jennifer R.; Zeisel, Steven

    2015-01-01

    Academic achievement in adolescents is correlated with 1-carbon metabolism (1-CM), as folate intake is positively related and total plasma homocysteine (tHcy) negatively related to academic success. Because another 1-CM nutrient, choline is essential for fetal neurocognitive development, we hypothesized that choline and betaine could also be positively related to academic achievement in adolescents. In a sample of 15-yr-old children (n = 324), we measured plasma concentrations of homocysteine, choline, and betaine and genotyped them for 2 polymorphisms with effects on 1-CM, methylenetetrahydrofolate reductase (MTHFR) 677C>T, rs1801133, and phosphatidylethanolamine N-methyltransferase (PEMT), rs12325817 (G>C). The sum of school grades in 17 major subjects was used as an outcome measure for academic achievement. Lifestyle and family socioeconomic status (SES) data were obtained from questionnaires. Plasma choline was significantly and positively associated with academic achievement independent of SES factors (paternal education and income, maternal education and income, smoking, school) and of folate intake (P = 0.009, R2 = 0.285). With the addition of the PEMT rs12325817 polymorphism, the association value was only marginally changed. Plasma betaine concentration, tHcy, and the MTHFR 677C>T polymorphism did not affect academic achievement in any tested model involving choline. Dietary intake of choline is marginal in many adolescents and may be a public health concern.—Nilsson, T. K., Hurtig-Wennlöf, A., Sjöström, M., Herrmann, W., Obeid, R., Owen, J. R., Zeisel, S. Plasma 1-carbon metabolites and academic achievement in 15-yr-old adolescents. PMID:26728177

  1. Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition

    PubMed Central

    Nicholls, Sarah; Piper, Karen P.; Mohammed, Fiyaz; Dafforn, Timothy R.; Tenzer, Stefan; Salim, Mahboob; Mahendra, Premini; Craddock, Charles; van Endert, Peter; Schild, Hansjörg; Cobbold, Mark; Engelhard, Victor H.; Moss, Paul A. H.; Willcox, Benjamin E.

    2009-01-01

    T cell recognition of minor histocompatibility antigens (mHags) underlies allogeneic immune responses that mediate graft-versus-host disease and the graft-versus-leukemia effect following stem cell transplantation. Many mHags derive from single amino acid polymorphisms in MHC-restricted epitopes, but our understanding of the molecular mechanisms governing mHag immunogenicity and recognition is incomplete. Here we examined antigenic presentation and T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (HA-1H versus HA-1R) in the HMHA1 gene. The HA-1H peptide is restricted by HLA-A2 and is immunogenic in HA-1R/R into HA-1H transplants, while HA-1R has been suggested to be a “null allele” in terms of T cell reactivity. We found that proteasomal cleavage and TAP transport of the 2 peptides is similar and that both variants can bind to MHC. However, the His>Arg change substantially decreases the stability and affinity of HLA-A2 association, consistent with the reduced immunogenicity of the HA-1R variant. To understand these findings, we determined the structure of an HLA-A2-HA-1H complex to 1.3Å resolution. Whereas His-3 is accommodated comfortably in the D pocket, incorporation of the lengthy Arg-3 is predicted to require local conformational changes. Moreover, a soluble TCR generated from HA-1H-specific T-cells bound HA-1H peptide with moderate affinity but failed to bind HA-1R, indicating complete discrimination of HA-1 variants at the level of TCR/MHC interaction. Our results define the molecular mechanisms governing immunogenicity of HA-1, and highlight how single amino acid polymorphisms in mHags can critically affect both MHC association and TCR recognition. PMID:19234124

  2. Performance evaluation of the Arkray Adams HA-8160 HbA1c analyser.

    PubMed

    Thevarajah, T Malathi; Nani, Nordin; Chew, Y Y

    2008-12-01

    HbA1c measurement is currently routinely used to predict long term outcome of diabetes, thus playing a fundamental role in the management of diabetes. The relationship between HbA1c value and long term diabetic complications has been established by a randomised control Diabetes Control and Complications Trial (DCCT) which used high performance liquid chromatography (HPLC) as a reference method for HbA1c assay. To ensure that HbA1c results from a variety HbA1c assay methods are similar to the DCCT values, the American Diabetes Association (ADA) recommended that all laboratories should use methods certified by the National Glycohemoglobin Standardization Programme (NGSP) with interassay coefficient variation (CV) of < 5% (ideally < 3%). The International Federation of Clinical Chemistry (IFCC) working group on HbA1c standardisation has set a CV < 2.5% as a criteria for its reference laboratories. To evaluate the performance of Arkray Adams HA-8160 HbA1c analyser which uses a cation exchange HPLC method and its correlation to HbA1c assay on Cobas Integra 800 which is an immunoturbidimetric method. For the imprecision study, patient samples and control material of two levels were analysed on HA-8160 analyser 20 times in a single run (within-run imprecision) and twice a day on five consecutive days (between-run imprecision). For the recovery study, two samples each with high and low values were selected and mixed in ratios of 1:3, 1:1 and 3:1, and were analysed by HA-8160. Sixty samples were analysed by both Cobas Integra 800 and HA-8160 for method comparison study. Ten uraemic samples and ten thalassaemic samples were assayed on Cobas Integra 800 and HA 8160 for interference study. Within-run CVs were 0.6% and 0.7% for medium and high value samples respectively, 0.6% and 0.7% for low and high level controls respectively. Between-run CVs were 0.5% and 0.4% for medium and high value samples respectively, 0.5% and 0.6% for low and high level controls respectively. The

  3. Structural-based designed modular capsomere comprising HA1 for low-cost poultry influenza vaccination.

    PubMed

    Waneesorn, Jarurin; Wibowo, Nani; Bingham, John; Middelberg, Anton P J; Lua, Linda H L

    2018-05-24

    Highly pathogenic avian influenza (HPAI) viruses cause a severe and lethal infection in domestic birds. The increasing number of HPAI outbreaks has demonstrated the lack of capabilities to control the rapid spread of avian influenza. Poultry vaccination has been shown to not only reduce the virus spread in animals but also reduce the virus transmission to humans, preventing potential pandemic development. However, existing vaccine technologies cannot respond to a new virus outbreak rapidly and at a cost and scale that is commercially viable for poultry vaccination. Here, we developed modular capsomere, subunits of virus-like particle, as a low-cost poultry influenza vaccine. Modified murine polyomavirus (MuPyV) VP1 capsomere was used to present structural-based influenza Hemagglutinin (HA1) antigen. Six constructs of modular capsomeres presenting three truncated versions of HA1 and two constructs of modular capsomeres presenting non-modified HA1 have been generated. These modular capsomeres were successfully produced in stable forms using Escherichia coli, without the need for protein refolding. Based on ELISA, this adjuvanted modular capsomere (CaptHA1-3C) induced strong antibody response (almost 10 5 endpoint titre) when administered into chickens, similar to titres obtained in the group administered with insect cell-based HA1 proteins. Chickens that received adjuvanted CaptHA1-3C followed by challenge with HPAI virus were fully protected. The results presented here indicate that this platform for bacterially-produced modular capsomere could potentially translate into a rapid-response and low-cost vaccine manufacturing technology suitable for poultry vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Structure of novel rat major histocompatibility complex class II genes RT1.Ha and Hb

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arimura, Yutaka; Tang, Wei Ran; Koda, Toshiaki

    1995-03-01

    We have cloned the novel rat MHC class II genes, RT1.Ha and Hb, which are homologous to human HLA-DPA and DPB. RT1.Hb is a pseudogene, whereas RT1.Ha is apparently intact and may have transcriptional potential. In addition, with an RT1.Ha probe, we detecteda single Southern hybridization band in the genome of the mouse. This finding may aford an opportunity to analyze the HLA-DPA homologue in the mouse genome. 18 refs., 4 figs., 1 tab.

  5. Sequence diversity within the HA-1 gene as detected by melting temperature assay without oligonucleotide probes

    PubMed Central

    Graziano, Claudio; Giorgi, Massimo; Malentacchi, Cecilia; Mattiuz, Pier Luigi; Porfirio, Berardino

    2005-01-01

    Background The minor histocompatibility antigens (mHags) are self-peptides derived from common cellular proteins and presented by MHC class I and II molecules. Disparities in mHags are a potential risk for the development of graft-versus-host disease (GvHD) in the recipients of bone marrow from HLA-identical donors. Two alleles have been identified in the mHag HA-1. The correlation between mismatches of the mHag HA-1 and GvHD has been suggested and methods to facilitate large-scale testing were afterwards developed. Methods We used sequence specific primer (SSP) PCR and direct sequencing to detect HA-1 gene polymorphisms in a sample of 131 unrelated Italian subjects. We then set up a novel melting temperature (Tm) assay that may help identification of HA-1 alleles without oligonucleotide probes. Results We report the frequencies of HA-1 alleles in the Italian population and the presence of an intronic 5 base-pair deletion associated with the immunogeneic allele HA-1H. We also detected novel variable sites with respect to the consensus sequence of HA-1 locus. Even though recombination/gene conversion events are documented, there is considerable linkage disequilibrium in the data. The gametic associations between HA-1R/H alleles and the intronic 5-bp ins/del polymorphism prompted us to try the Tm analysis with SYBR® Green I. We show that the addition of dimethylsulfoxide (DMSO) during the assay yields distinct patterns when amplicons from HA-1H homozygotes, HA-1R homozygotes, and heterozygotes are analysed. Conclusion The possibility to use SYBR® Green I to detect Tm differences between allelic variants is attractive but requires great caution. We succeeded in allele discrimination of the HA-1 locus using a relatively short (101 bp) amplicon, only in the presence of DMSO. We believe that, at least in certain assets, Tm assays may benefit by the addition of DMSO or other agents affecting DNA strand conformation and stability. PMID:16202172

  6. Characterization of Monoclonal Antibodies against HA Protein of H1N1 Swine Influenza Virus and Protective Efficacy against H1 Viruses in Mice.

    PubMed

    Liu, Yun; Li, Hongtao; Xue, Yujia; Zhao, Shuang; Li, Chenxi; Qu, Liandong; Zhang, Yun; Liu, Ming

    2017-08-08

    H1N1 swine influenza viruses (SIV) are prevalent in pigs globally, and occasionally emerge in humans, which raises concern about their pandemic threats. To stimulate hemagglutination (HA) of A/Swine/Guangdong/LM/2004 (H1N1) (SW/GD/04) antibody response, eukaryotic expression plasmid pCI-neo-HA was constructed and used as an immunogen to prepare monoclonal antibodies (mAbs). Five mAbs (designed 8C4, 8C6, 9D6, 8A4, and 8B1) against HA protein were obtained and characterized. Western blot showed that the 70 kDa HA protein could be detected by all mAbs in MDCK cells infected with SW/GD/04. Three mAbs-8C4, 8C6, and 9D6-have hemagglutination inhibition (HI) and neutralization test (NT) activities, and 8C6 induces the highest HI and NT titers. The protection efficacy of 8C6 was investigated in BALB/c mice challenged with homologous or heterologous strains of the H1 subtype SIV. The results indicate that mAb 8C6 protected the mice from viral infections, especially the homologous strain, which was clearly demonstrated by the body weight changes and reduction of viral load. Thus, our findings document for the first time that mAb 8C6 might be of potential therapeutic value for H1 subtype SIV infection.

  7. MiR-30e suppresses proliferation of hepatoma cells via targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feng, Guoxing; Shi, Hui; Li, Jiong

    Aberrant microRNA expression has been shown to be characteristic of many cancers. It has been reported that the expression levels of miR-30e are decreased in liver cancer tissues. However, the role of miR-30e in hepatocellular carcinoma remains poorly understood. In the present study, we investigated the significance of miR-30e in hepatocarcinogenesis. Bioinformatics analysis reveals a putative target site of miR-30e in the 3′-untranslated region (3′UTR) of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA. Moreover, luciferase reporter gene assays verified that miR-30e directly targeted 3′UTR of P4HA1 mRNA. Then, we demonstrated that miR-30e was able to reduce the expression of P4HA1 atmore » the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blot analysis. Enforced expression of miR-30e suppressed proliferation of HepG2 cells by 5-ethynyl-2-deoxyuridine (EdU) assay and reduced colony formation of these cells by colony formation analysis. Conversely, anti-miR-30e enhanced the proliferation of hepatoma cells in vitro. Interestingly, the ectopic expression of P4HA1 could efficiently rescue the inhibition of cell proliferation mediated by miR-30e in HepG2 cells. Meanwhile, silencing of P4HA1 abolished the anti-miR-30e-induced proliferation of cells. Clinically, quantitative real-time PCR showed that miR-30e was down-regulated in liver tumor tissues relative to their peritumor tissues. The expression levels of miR-30e were negatively correlated to those of P4HA1 mRNA in clinical liver tumor tissues. Thus, we conclude that miR-30e suppresses proliferation of hepatoma cells through targeting P4HA1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • P4HA1 is a novel target gene of miR-30e. • P4HA1 is increased in clinical HCC tissues. • MiR-30e is negatively correlated with P4HA1 in clinical HCC tissues. • MiR-30e suppresses the proliferation of HCC cells

  8. New High Proper Motion Stars from the Digitized Sky Survey. II. Northern Stars with 0.5" yr-1 < μ < 2.0" yr-1 at High Galactic Latitudes

    NASA Astrophysics Data System (ADS)

    Lépine, Sébastien; Shara, Michael M.; Rich, R. Michael

    2003-08-01

    In a continuation of our systematic search for high proper motion stars in the Digitized Sky Survey, we have completed the analysis of northern sky fields at Galactic latitudes above 25°. With the help of our SUPERBLINK software, a powerful automated blink comparator developed by us, we have identified 1146 stars in the magnitude range 8yr-1<μ<2.000"yr-1. These include 1080 stars previously listed in Luyten's proper-motion catalogs (the Luyten Half-Second catalog and the New Luyten Two-Tenths catalog), nine stars not previously listed in the Luyten catalogs but reported elsewhere in the literature (including one previously reported by our team), and 57 new objects reported here for the first time. This paper includes a list of positions, proper motions, magnitudes, and finder charts for all the new high proper motion stars. Combined with our previous study of low Galactic latitude fields (see Paper I), our survey now covers over 98% of the northern sky. We conclude that the Luyten catalogs were ~=90% complete in the northern sky for stars with 0.5"<μ<2.0" down to magnitude r=19. We discuss the incompleteness of the old Luyten proper-motion survey and estimate completeness limits for our new survey. Based on data mining of the Digitized Sky Survey, developed and operated by the Catalogs and Surveys Branch of the Space Telescope Science Institute, Baltimore.

  9. Characterizing climate-change impacts on the 1.5-yr flood flow in selected basins across the United States: a probabilistic approach

    USGS Publications Warehouse

    Walker, John F.; Hay, Lauren E.; Markstrom, Steven L.; Dettinger, Michael D.

    2011-01-01

    The U.S. Geological Survey Precipitation-Runoff Modeling System (PRMS) model was applied to basins in 14 different hydroclimatic regions to determine the sensitivity and variability of the freshwater resources of the United States in the face of current climate-change projections. Rather than attempting to choose a most likely scenario from the results of the Intergovernmental Panel on Climate Change, an ensemble of climate simulations from five models under three emissions scenarios each was used to drive the basin models. Climate-change scenarios were generated for PRMS by modifying historical precipitation and temperature inputs; mean monthly climate change was derived by calculating changes in mean climates from current to various future decades in the ensemble of climate projections. Empirical orthogonal functions (EOFs) were fitted to the PRMS model output driven by the ensemble of climate projections and provided a basis for randomly (but representatively) generating realizations of hydrologic response to future climates. For each realization, the 1.5-yr flood was calculated to represent a flow important for sediment transport and channel geomorphology. The empirical probability density function (pdf) of the 1.5-yr flood was estimated using the results across the realizations for each basin. Of the 14 basins studied, 9 showed clear temporal shifts in the pdfs of the 1.5-yr flood projected into the twenty-first century. In the western United States, where the annual peak discharges are heavily influenced by snowmelt, three basins show at least a 10% increase in the 1.5-yr flood in the twenty-first century; the remaining two basins demonstrate increases in the 1.5-yr flood, but the temporal shifts in the pdfs and the percent changes are not as distinct. Four basins in the eastern Rockies/central United States show at least a 10% decrease in the 1.5-yr flood; the remaining two basins demonstrate decreases in the 1.5-yr flood, but the temporal shifts in the pdfs

  10. Registration of an oilseed sunflower germplasm HA-DM1 resistant to sunflower downy mildew

    USDA-ARS?s Scientific Manuscript database

    HA-DM1 (Reg. No.xxx, PI 674793) sunflower (Helianthus annuus L.) germplasm was developed and released cooperatively by the USDA-ARS, Sunflower and Plant Biology Research Unit and the North Dakota Agricultural Experiment Station in 2015. HA-DM1 is a BC2F4 derived oilseed maintainer line from the cros...

  11. Trypanosoma cruzi H+-ATPase 1 (TcHA1) and 2 (TcHA2) genes complement yeast mutants defective in H+ pumps and encode plasma membrane P-type H+-ATPases with different enzymatic properties.

    PubMed

    Luo, Shuhong; Scott, David A; Docampo, Roberto

    2002-11-15

    Previous studies in Trypanosoma cruzi have shown that intracellular pH homeostasis requires ATP and is affected by H(+)-ATPase inhibitors, indicating a major role for ATP-driven proton pumps in intracellular pH control. In the present study, we report the cloning and sequencing of a pair of genes linked in tandem (TcHA1 and TcHA2) in T. cruzi which encode proteins with homology to fungal and plant P-type proton-pumping ATPases. The genes are expressed at the mRNA level in different developmental stages of T. cruzi: TcHA1 is expressed maximally in epimastigotes, whereas TcHA2 is expressed predominantly in trypomastigotes. The proteins predicted from the nucleotide sequence of the genes have 875 and 917 amino acids and molecular masses of 96.3 and 101.2 kDa, respectively. Full-length TcHA1 and an N-terminal truncated version of TcHA2 complemented a Saccharomyces cerevisiae strain deficient in P-type H(+)-ATPase activity, the proteins localized to the yeast plasma membrane, and ATP-driven proton pumping could be detected in proteoliposomes reconstituted from plasma membrane purified from transfected yeast. The reconstituted proton transport activity was reduced by inhibitors of P-type H(+)-ATPases. C-terminal truncation did not affect complementation of mutant yeast, suggesting the lack of C-terminal autoinhibitory domains in these proteins. ATPase activity in plasma membrane from TcHA1- and (N-terminal truncated) TcHA2-transfected yeast was inhibited to different extents by vanadate, whereas the latter yeast strain was more resistant to extremes of pH, suggesting that the native proteins may serve different functions at different stages in the T. cruzi life cycle.

  12. Phylogenetic and nucleotide sequence analysis of influenza A (H1N1) HA and NA genes of strains isolated from Saudi Arabia.

    PubMed

    Al-Qahtani, Ahmed Ali; Mubin, Muhammad; Dela Cruz, Damian M; Althawadi, Sahar Isa; Ul Rehman, Muhammad Shah Nawaz; Bohol, Marie Fe F; Al-Ahdal, Mohammed N

    2017-01-30

    In early 2009, a novel influenza A (H1N1) virus appeared in Mexico and rapidly disseminated worldwide. Little is known about the phylogeny and evolutionary dynamics of the H1N1 strain found in Saudi Arabia. Nucleotide sequencing and bioinformatics analyses were used to study molecular variation between the virus isolates. In this report, 72 hemagglutinin (HA) and 45 neuraminidase (NA) H1N1 virus gene sequences, isolated in 2009 from various regions of Saudi Arabia, were analyzed. Genetic characterization indicated that viruses from two different clades, 6 and 7, were circulating in the region, with clade 7, the most widely circulating H1N1 clade globally in 2009, being predominant. Sequence analysis of the HA and NA genes revealed a high degree of sequence identity with the corresponding genes from viruses circulating in the South East Asia region and with the A/California/7/2009 strain. New mutations in the HA gene of pandemic H1N1 (pH1N1) viruses, that could alter viral fitness, were identified. Relaxed-clock and Bayesian Skyline Plot analyses, based on the isolates used in this study and closely related globally representative strains, indicated marginally higher substitution rates than the type strain (5.14×10-3 and 4.18×10-3 substitutions/nucleotide/year in the HA and NA genes, respectively). The Saudi isolates were antigenically homogeneous and closely related to the prototype vaccine strain A/California/7/2009. The antigenic site of the HA gene had acquired novel mutations in some isolates, making continued monitoring of these viruses vital for the identification of potentially highly virulent and drug resistant variants.

  13. Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.

    PubMed

    Nakamura, Toshio; Tonozuka, Takashi; Ide, Azusa; Yuzawa, Takayuki; Oguma, Keiji; Nishikawa, Atsushi

    2008-02-22

    Clostridium botulinum type C 16S progenitor toxin contains a hemagglutinin (HA) subcomponent, designated HA1, which appears to play an important role in the effective internalization of the toxin in gastrointestinal epithelial cells and in creating a broad specificity for the oligosaccharide structure that corresponds to various targets. In this study, using the recombinant protein fused to glutathione S-transferase, we investigated the binding specificity of the HA1 subcomponent to sugars and estimated the binding sites of HA1 based on X-ray crystallography and soaking experiments using various sugars. N-Acetylneuraminic acid, N-acetylgalactosamine, and galactose effectively inhibited the binding that occurs between glutathione S-transferase-HA1 and mucins, whereas N-acetylglucosamine and glucose did not inhibit it. The crystal structures of HA1 complex with N-acetylneuraminic acid, N-acetylgalactosamine, and galactose were also determined. There are two sugar-binding sites, sites I and II. Site I corresponds to the electron densities noted for all sugars and is located at the C-terminal beta-trefoil domain, while site II corresponds to the electron densities noted only for galactose. An aromatic amino acid residue, Trp176, at site I has a stacking interaction with the hexose ring of the sugars. On the other hand, there is no aromatic residue at site II; thus, the interaction with galactose seems to be poor. The double mutant W176A at site I and D271F at site II has no avidity for N-acetylneuraminic acid but has avidity for galactose. In this report, the binding specificity of botulinum C16S toxin HA1 to various sugars is demonstrated based on its structural features.

  14. Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-ras(val12)-transformed cells.

    PubMed

    Stanhill, A; Levin, V; Hendel, A; Shachar, I; Kazanov, D; Arber, N; Kaminski, N; Engelberg, D

    2006-03-09

    Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Ras(val12) induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Ras(val12) induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12) induction of HSE-mediated transcription was dramatically reduced in HSF1-/- cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/- cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha-ras(Val12) is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.

  15. Molecular mapping and marker development for the Triticum dicoccoides-derived stripe rust resistance gene YrSM139-1B in bread wheat cv. Shaanmai 139.

    PubMed

    Zhang, Hong; Zhang, Lu; Wang, Changyou; Wang, Yajuan; Zhou, Xinli; Lv, Shikai; Liu, Xinlun; Kang, Zhensheng; Ji, Wanquan

    2016-02-01

    YrSM139-1B maybe a new gene for effective resistance to stripe rust and useful flanking markers for marker-assisted selection were developed. Stripe rust, caused by Puccinia striiformis f. sp. tritici, is an important foliar disease of wheat. Two dominant stripe rust resistant genes YrSM139-1B and YrSM139-2D were pyramided in bread wheat cultivar Shaanmai 139; one from wild emmer and the other from Thinopyrum intermedium. Three near-isogenic F7:8 line pairs (contrasting RILs), N122-1013R/S, N122-185R/S, and N122-1812R/S, independently derived from different F2 plants and differing at the YrSM139-1B locus were generated from the cross Shaanmai 139 × Hu 901-19 through marker-assisted selection. A large F2:3 population from cross N122-1013R × N122-1013S tested for stripe rust response and subjected to analysis with markers in the 1BS10-0.5 bin region using SSR expressed sequence tags (EST) and site-specific sequence markers developed from the 90 K Illumina iSelect SNP array. Five EST-STS markers and four allele-specific PCR markers were mapped to the YrSM139-1B region. The 30.5 cM genetic map for YrSM139-1B consisted of nine markers, two of which were closer to YrSM139-1B than Xgwm273, which was used in producing the contrasting RIL pairs. Race response data and allelism tests showed that YrSM139-1B is different from Yr10, Yr15, and Yr24/26/CH42.

  16. An Influenza HA and M2e Based Vaccine Delivered by a Novel Attenuated Salmonella Mutant Protects Mice against Homologous H1N1 Infection.

    PubMed

    Hajam, Irshad A; Lee, John H

    2017-01-01

    Attenuated Salmonella strains constitute a promising technology for the development of a more efficient multivalent protein based vaccines. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the H1N1 hemagglutinin (HA) and the conserved extracellular domain of the matrix protein 2 (M2e). We demonstrated that the constructed Salmonella strain exhibited efficient HA and M2e protein expressions and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we showed that the mice vaccinated with a Salmonella strain expressing HA and M2e protein antigens, respectively, induced significant production of HA and M2e-specific serum IgG1 and IgG2a responses, and of anti-HA interferon-γ producing T cells. Furthermore, immunization with Salmonella-HA-M2e-based vaccine via different routes provided protection in 66.66% orally, 100% intramuscularly, and 100% intraperitoneally immunized mice against the homologous H1N1 virus while none of the animals survived treated with either the PBS or the Salmonella carrying empty expression vector. Ex vivo stimulated dendritic cells (DCs) with heat killed Salmonella expressing HA demonstrated that DCs play an important role in the elicitation of HA-specific humoral immune responses in mice. In summary, Salmonella -HA-M2e-based vaccine elicits efficient antigen-specific humoral and cellular immune responses, and provides significant immune protection against a highly pathogenic H1N1 influenza virus.

  17. Silencing of HaAce1 gene by host-delivered artificial microRNA disrupts growth and development of Helicoverpa armigera.

    PubMed

    Saini, Ravi Prakash; Raman, Venkat; Dhandapani, Gurusamy; Malhotra, Era Vaidya; Sreevathsa, Rohini; Kumar, Polumetla Ananda; Sharma, Tilak R; Pattanayak, Debasis

    2018-01-01

    The polyphagous insect-pest, Helicoverpa armigera, is a serious threat to a number of economically important crops. Chemical application and/or cultivation of Bt transgenic crops are the two strategies available now for insect-pest management. However, environmental pollution and long-term sustainability are major concerns against these two options. RNAi is now considered as a promising technology to complement Bt to tackle insect-pests menace. In this study, we report host-delivered silencing of HaAce1 gene, encoding the predominant isoform of H. armigera acetylcholinesterase, by an artificial microRNA, HaAce1-amiR1. Arabidopsis pre-miRNA164b was modified by replacing miR164b/miR164b* sequences with HaAce1-amiR1/HaAce1-amiR1* sequences. The recombinant HaAce1-preamiRNA1 was put under the control of CaMV 35S promoter and NOS terminator of plant binary vector pBI121, and the resultant vector cassette was used for tobacco transformation. Two transgenic tobacco lines expressing HaAce1-amiR1 was used for detached leaf insect feeding bioassays. Larval mortality of 25% and adult deformity of 20% were observed in transgenic treated insect group over that control tobacco treated insect group. The reduction in the steady-state level of HaAce1 mRNA was 70-80% in the defective adults compared to control. Our results demonstrate promise for host-delivered amiRNA-mediated silencing of HaAce1 gene for H. armigera management.

  18. Word Criticality Analysis. MOS:71L. Skill Levels 1 & 2.

    DTIC Science & Technology

    1981-09-01

    I| AC CORD ANCE .. . TRW o I ACCaliN TABIL ITY f, - " - I AC RNOWL EOGEO oTAN 80 • I AC WUN YN . . . . .. . . . . . . . . . . . ..M. / blJ I.. so...REMOV ING 2,2 7,t _ I REPeAT IJ, 1 32,1 2 RUED’if% 2S,1 13,1 8.2 7,1 2,1 ? m kEQ1JF $ TED 13, 1 2 SE0FII STING, 1 Fill 2 REVAEf 11 1 *’ 2 ROuTrIt ) 2,2 2

  19. Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women.

    PubMed

    Linscheid, C; Heitmann, E; Singh, P; Wickstrom, E; Qiu, L; Hodes, H; Nauser, T; Petroff, M G

    2015-08-01

    Maternal T-cells reactive towards paternally inherited fetal minor histocompatibility antigens are expanded during pregnancy. Placental trophoblast cells express at least four fetal antigens, including human minor histocompatibility antigen 1 (HA-1). We investigated oxygen as a potential regulator of HA-1 and whether HA-1 expression is altered in preeclamptic placentas. Expression and regulation of HA-1 mRNA and protein were examined by qRT-PCR and immunohistochemistry, using first, second, and third trimester placentas, first trimester placental explant cultures, and term purified cytotrophoblast cells. Low oxygen conditions were achieved by varying ambient oxygen, and were mimicked using cobalt chloride. HA-1 mRNA and protein expression levels were evaluated in preeclamptic and control placentas. HA-1 protein expression was higher in the syncytiotrophoblast of first trimester as compared to second trimester and term placentas (P<0.01). HA-1 mRNA was increased in cobalt chloride-treated placental explants and purified cytotrophoblast cells (P = 0.04 and P<0.01, respectively) and in purified cytotrophoblast cells cultured under 2% as compared to 8% and 21% oxygen (P<0.01). HA-1 mRNA expression in preeclamptic vs. control placentas was increased 3.3-fold (P = 0.015). HA-1 protein expression was increased in syncytial nuclear aggregates and the syncytiotrophoblast of preeclamptic vs. control placentas (P = 0.02 and 0.03, respectively). Placental HA-1 expression is regulated by oxygen and is increased in the syncytial nuclear aggregates and syncytiotrophoblast of preeclamptic as compared to control placentas. Increased HA-1 expression, combined with increased preeclamptic syncytiotrophoblast deportation, provides a novel potential mechanism for exposure of the maternal immune system to increased fetal antigenic load during preeclampsia. Published by Elsevier Ltd.

  20. HA222 polymorphism in Influenza A(H1N1) 2009 isolates from Intensive Care Units and ambulatory patients during three influenza seasons.

    PubMed

    Corcioli, F; Arvia, R; Pierucci, F; Clausi, V; Bonizzoli, M; Peris, A; Azzi, A

    2014-02-13

    Amino acid substitutions which can affect the receptor binding specificity of the influenza virus, like the substitution of aspartic acid with glycine in position 222 of the haemagglutinin (HA) of influenza virus A(H1N1) 2009, have been associated with increased viral pathogenicity and increased tropism for the lower respiratory tract. In this paper, the polymorphic site 222 and the site 223 of the HA1 polypeptide of H1N1 2009 viruses were analyzed in order to better clarify the role of these substitutions in H1N1 2009 virus virulence. Viral strains included in this study were collected in Tuscany during 3 different influenza seasons from patients with severe as well as with mild forms of influenza caused by A(H1N1) 2009 virus. In addition, the oseltamivir resistance of the H1N1 2009 strains circulating during the same seasons was monitored with the aim to evaluate whether these changes in the HA and in neuraminidase (NA) tend to be linked and to influence each other. Altogether, the results indicate that in severe forms of influenza viral population is more variable than in mild influenza, as regards the site 222. The frequency of such substitutions varied among the three seasons, it was highest in the season 2010-2011 and very low in the season 2012-2013. However these differences were not significant. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years.

    PubMed

    Almansour, Iman; Chen, Huaiqing; Wang, Shixia; Lu, Shan

    2013-10-01

    In the past three decades, ten H1 subtype influenza vaccines have been recommended for global seasonal flu vaccination. Some of them were used only for one year before being replaced by another H1 flu vaccine while others may be used for up to seven years. While the selection of a new seasonal flu vaccine was based on the escape of a new emerging virus that was not effectively protected by the existing flu formulation, there is limited information on the magnitude and breadth of cross reactivity among H1 subtype virus circulation over a long period. In the current study, HA-expressing DNA vaccines were constructed to express individual HA antigens from H1 subtype vaccines used in the past 30 y. Rabbits naïve to HA antibody responses were immunized with these HA DNA vaccines and the cross reactivity of these sera against HA antigen and related H1 viruses in the same period was studied. Our data indicate that the level of cross reactivity was different for different viral isolates and the key mutations responsible for the cross reactivity may involve only a limited number of residues. Our results provide useful information for the development of improved seasonal vaccines than can achieve broad protection against viruses within the same H1 subtype.

  2. Enhanced humoural and cellular immune responses to influenza H7N9 antigen HA1-2 fused with flagellin in chickens.

    PubMed

    Song, Li; Xiong, Dan; Hu, Maozhi; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2017-06-21

    Sudden increases in the number of human A (H7N9) cases reported during December and January have been observed in previous years. Most reported infection cases are due to prior exposure to live poultry or potentially contaminated environments. Low pathogenicity of influenza A (H7N9) virus in avian species complicates timely discovery of infected birds. Therefore, there is a pressing need to develop safe and effective anti-H7N9 vaccines for poultry to reduce the risk of human infection and prevent the emergence of novel mutated strains. In addition to a good antigen, an effective vaccine also requires an appropriate adjuvant to enhance its immunogenicity. Previously, we generated an H7N9 influenza recombinant subunit vaccine (HA1-2-fliC), in which haemagglutinin globular head domain (HA1-2) was fused with flagellin (fliC), a potent TLR5 ligand, and demonstrated that HA1-2-fliC elicited effective HA1-2-specific immune responses in mice. In this study, we determined flagellin-induced expression profiles of cytokines and chemokines in different types of avian immune cells in vitro and ex vivo. We found that flagellin significantly increased the expression levels of CXCL inflammatory chemokines (CXCLi1 and CXCLi2) and CCL chemokines (MIP-1β and MCP-3) in avian macrophage HD11 cells. In addition, HA1-2-fliC induced significant upregulation of cytokines (IL-1β, IL-6, IL-18 and IFN-γ) and chemokines (CXCLi1, CXCLi2 and MIP-1β) in ex vivo splenic lymphocytes and peripheral blood mononuclear cells (PBMCs), suggesting that flagellin promoted immune responses of avian cells in vitro. We also evaluated specific humoural and cellular immune responses induced by HA1-2-fliC and found that chickens immunised intramuscularly with HA1-2-fliC showed significantly higher HA1-2-specific immunoglobulin (Ig)G titers in serum. Furthermore, HA1-2-fliC potentiated cellular immune responses, as reflected by an increase in CD4 + and CD8 + T cells and proliferation of PBMCs. Significantly

  3. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    PubMed

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P < 0.01) than those of the control groups. Complete protection of guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  4. Green synthesis of nanosilver particles by Aspergillus terreus HA1N and Penicillium expansum HA2N and its antifungal activity against mycotoxigenic fungi.

    PubMed

    Ammar, H A M; El-Desouky, T A

    2016-07-01

    The aim of this study was to synthesize silver nanoparticles (AgNPs) by an eco-friendly and low-cost method using the fungi Aspergillus terreus HA1N and Penicillium expansum HA2N as an alternative to chemical procedures mostly requiring drastic experimental conditions emitting toxic chemical byproducts. Also, this study has been extended to evaluate the effect of AgNPs on the growth of some mycotoxigenic fungi and ochratoxin A (OTA) produced by Aspergillus ochraceus. The AgNPs have been characterized by UV-Visible Spectrophotometer, Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR) and Transmission Electron Microscope (TEM). The TEM analysis has revealed that the size of AgNPs ranged between 14 and 25 nm in the case of P. expansum and 10-18 nm in the case of A. terreus. The antifungal activity of AgNP colloids has indicated that the highest inhibition zone was detected with AgNPs synthesized by A. terreus HA1N against all tested fungi. The highest inhibition zone was detected with Aspergillus niger at concentrations 3 and 6 μg of AgNP solution (7·56 ± 0·38 and 11·3 ± 1·8 mm, respectively) while, A. ochraceus showed the maximum inhibition zone (16·33 ± 0·96 mm) at the concentration 9 μg of AgNPs synthesized by A. terreus. The results have also indicated that the AgNPs synthesized by A. terreus and P. expansum at the concentration 220 μg/100 ml media gave the highest reduction of OTA, where the percentages of reduction were 58·87 and 52·18% respectively. The smallest size AgNPs synthesized by A. terreus HA1N are better in their antifungal activity against all tested mycotoxigenic fungi than the largest one synthesized by P. expansum HA2N. This is the first study focused on using AgNPs in control of OTA production. © 2016 The Society for Applied Microbiology.

  5. Construction and cellular immune response induction of HA-based alphavirus replicon vaccines against human-avian influenza (H5N1).

    PubMed

    Yang, Shi-gui; Wo, Jian-er; Li, Min-wei; Mi, Fen-fang; Yu, Cheng-bo; Lv, Guo-liang; Cao, Hong-Cui; Lu, Hai-feng; Wang, Bao-hong; Zhu, Hanping; Li, Lan-Juan

    2009-12-09

    Several approaches are being taken worldwide to develop vaccines against H5N1 viruses; most of them, however, pose both practical and immunological challenges. One potential strategy for improving the immunogenicity of vaccines involves the use of alphavirus replicons and VP22, a herpes simplex type 1 (HSV-1) protein. In this study, we analysed the antigenic peptides and homogeneity of the HA sequences (human isolates of the H5N1 subtype, from 1997 to 2003) and explored a novel alphavirus replicon system of VP22 fused with HA, to assess whether the immunogenicity of an HA-based replicon vaccine could be induced and augmented via fusion with VP22. Further, replicon particles expressing VP22, and enhanced green fluorescent protein (EGFP) were individually used as controls. Cellular immune responses in mice immunised with replicons were evaluated by identifying specific intracellular cytokine production with flow cytometry (FCM). Animal-based experimentation indicated that both the IL-4 expression of CD4(+) T cells and the IFN-gamma expression of CD8(+) T cells were significantly increased in mice immunised with VPR-HA and VPR-VP22/HA. A dose titration effect vis-à-vis both IL-4 expression and IFN-gamma expression were observed in VPR-HA- and VPR-VP22/HA-vaccinated mice. Our results revealed that both VPR-VP22/HA and VPR-HA replicon particles presented a promising approach for developing vaccines against human-avian influenza, and VP22 could enhance the immunogenicity of the HA antigens to which it is fused.

  6. 7 CFR Appendix A to Subpart E of... - Form FmHA 49-1, Application for Loan and Guarantee

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Form FmHA 49-1, Application for Loan and Guarantee A Appendix A to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued... Industrial Loan Program Pt. 1980, Subpt. E, App. A Appendix A to Subpart E of Part 1980—Form FmHA 49-1...

  7. 7 CFR Appendix A to Subpart E of... - Form FmHA 49-1, Application for Loan and Guarantee

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false Form FmHA 49-1, Application for Loan and Guarantee A Appendix A to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued... Industrial Loan Program Pt. 1980, Subpt. E, App. A Appendix A to Subpart E of Part 1980—Form FmHA 49-1...

  8. Nitrogen cycling in ombrotrophic peat bogs in the Czech Republic: Is microbial N-fixation occurring at atmospheric depositions of reactive N higher than 10 kg/ha/yr?

    NASA Astrophysics Data System (ADS)

    Novak, Martin; Jackova, Ivana; Cejkova, Bohuslava; Buzek, Frantisek; Curik, Jan; Stepanova, Marketa; Prechova, Eva; Veselovsky, Frantisek; Komarek, Arnost

    2017-04-01

    Biogeochemical cycling of carbon (C) and nitrogen (N) in peat bogs are coupled. Whereas at low pollution levels, reactive nitrogen (Nr, mainly nitrate- and ammonium-N) inputs may positively affect C storage, high Nr deposition may have a detrimental effect on C storage. We have previously reported N isotope systematics at two ombrotrophic peat bogs in the Czech Republic, receiving medium levels of Nr of about 10 kg/ha/yr via atmospheric deposition. Nitrogen of living Sphagnum was systematically heavier than N of the atmospheric input (p < 0.001), and close to the N isotope signature of atmospheric N2 (del15N-N2 of 0.0 per mil). We argued that even at medium Nr pollution, such as that in the Czech Republic, the amount of Nr in rainfall becomes minute toward the end of major precipitation events, possible triggering off microbial N-fixation. This process may be responsible for the del15N shift in Sphagnum from negative values of atmospheric deposition to the zero value of N2. In 2016, we conducted a laboratory study in which living Sphagnum from sites receiving annually slightly over 10 kg Nr/ha/yr via atmospheric deposition was incubated in an atmosphere enriched in 15N-N2. At the end of the incubation, we detected a 1 to 3 per mil increase in del15N of Sphagnum. Rinsing Sphagnum capitula in deionized water prior to the 15N-N2 incubation has led to a slight further increase in del15N of Sphagnum. Also in 2016, we monitored del15N of atmospheric deposition at three medium Nr-polluted peat bogs. Open-area precipitation had the following mean del 15N values: Uhlirska -6.1 per mil (NH4) and -6.2 per mil (NO3); Brumiste -1.7 per mil (NH4) and -3.4 per mil (NO3); Male Mechove Jezirko -3.3 per mil (NH4) and -3.9 per mil (NO3). At all sites, atmospheric Nr deposition was made up by NO3-N and NH4-N in a roughly 1.1 ratio. We found that N of winter-time deposition became isotopically extremely light (less than -10.0 per mil). During the growing season, del15N of total

  9. Caveolin-1 down-regulation is required for Wnt5a-Frizzled 2 signalling in Ha-RasV12 -induced cell transformation.

    PubMed

    Lin, Hsiu-Kuan; Lin, Hsi-Hui; Chiou, Yu-Wei; Wu, Ching-Lung; Chiu, Wen-Tai; Tang, Ming-Jer

    2018-05-01

    Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-Ras V12 gene) transformation by Ha-Ras V12 . Cav1 overexpression abrogates the Ha-Ras V12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells. Nanoparticle tracking analysis showed that Ha-Ras V12 -inducing MK4 cells increased exosome-like microvesicles release compared with their normal counterparts. The cellular and mechanical transformation activities of MK4+I-CM were abolished after heat treatment and exosome depletion and were copied by exosomes derived from MK4+I-CM (MK4+I-EXs). Wnt5a, a downstream product of Ha-Ras V12 , was markedly secreted by MK4+I-CM and MK4+I-EXs. Suppression of Wnt5a expression and secretion using the porcupine inhibitor C59 or Wnt5a siRNA inhibited the Ha-Ras V12 - and MK4+I-CM-induced transformation of MK4 cells and MDCK/shCav1 cells, respectively. Cav1 down-regulation, either by Ha-Ras V12 or targeted shRNA, increased frizzled-2 (Fzd2) protein levels without affecting its mRNA levels, suggesting a novel role of Cav1 in negatively regulating Fzd2 expression. Additionally, silencing Cav1 facilitated the internalization of MK4+I-EXs in MDCK cells. These data suggest that Cav1-dependent repression of Fzd2 and exosome uptake is potentially relevant to its antitransformation activity, which hinders the activation of Ha-Ras V12 -Wnt5a-Stat3 pathway. Altogether, these results suggest that both decreasing Cav1 and increasing exosomal Wnt5a must be implemented during Ha-Ras V12 -driven cell transformation. © 2018 The Authors

  10. Three dehalogenases and physiological restraints in the biodegradation of haloalkanes by Arthrobacter sp. strain HA1.

    PubMed Central

    Scholtz, R; Messi, F; Leisinger, T; Cook, A M

    1988-01-01

    Arthrobacter sp. strain HA1 utilizes 18 C2-to-C8 1-haloalkanes for growth and synthesizes an inducible 1-bromoalkane debrominase of unknown physiological function (R. Scholtz, T. Leisinger, F. Suter, and A.M. Cook, J. Bacteriol. 169:5016-5021, 1987) in addition to an inducible 1-chlorohexane halidohydrolase which dehalogenates some 50 substrates, including alpha, omega-dihaloalkanes. alpha, omega-Dihaloalkanes were utilized by cultures of strain HA1 under certain conditions only. C9 and C8 homologs prevented growth. At suitable concentrations, C7-to-C5 homologs could serve as sole sources of carbon and energy for growth. C4 and C3 homologs could be utilized only in the presence of a second substrate (e.g., butanol), and the C2 homolog was not degraded. Kinetics of growth and substrate utilization indicated that cells of strain HA1 growing in butanol-salts medium could be used to test whether compounds induced the 1-chlorohexane halidohydrolase. No gratuitous induction of synthesis of the enzyme was observed. Many enzyme substrates (e.g., bromobenzene) did not induce synthesis of the enzyme, though the enzyme sequence to degrade the product (phenol) was present. Some inducers (e.g., bromomethane) were enzyme substrates but not growth substrates. In an attempt to find a physiological role for the 1-bromoalkane debrominase, we observed that several long-chain haloaliphatic compounds (greater than C9; e.g., 1-bromohexadecane and 1-chlorohexadecane) were utilized for growth and that induced cells could dehalogenate several 1-haloalkanes (at least C4 to C16). The dehalogenation of the long-chain compounds could not be assayed in the cell extract, so we presume that a third haloalkane dehalogenase was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3223767

  11. Possible role of PAPR-1 in protecting human HaCaT cells against cytotoxicity of SiO2 nanoparticles.

    PubMed

    Gong, Chunmei; Yang, Linqing; Zhou, Jichang; Guo, Xiang; Zhuang, Zhixiong

    2017-10-05

    Nano-SiO 2 materials play a significant role in the engineered nanomaterials (ENMs) field. The ease of their production as well as their relatively low cost has promoted the wide use of these products in many fields. Nano-SiO 2 exposure is known to cause severe DNA damage; however, the underlying mechanisms remain poorly understood. In a previous study, we found that nano-SiO 2 exposure regulate the expression of the poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal DNA repair gene, in human HaCaT cells. Here, we employed lentivirus-mediated RNA interference (RNAi) to knock down PAPR-1 expression in HaCaT cells and explored the potential role of PARP-1 in nano-SiO 2 induced cytotoxicity. We found that nano-SiO 2 treatment of HaCaT cells causes decreased cell viability, increased apoptosis and DNA damage. Nano-SiO 2 -treated HaCaT cells were also found to have slightly changed cell cycle distribution. Lentivirus-mediated PAPR-1 knockdown partially aggravated cytotoxicity and increased apoptosis induced by nano-SiO 2 treatment. Nano-SiO 2 had significant toxicity to human HaCaT cells and causes DNA damage. PAPR-1 knock-down cell line appears more sensitive to nano-SiO 2 than the control cells in DNA damage. The results suggest that PAPR-1 is involved in protecting cells from damage caused by nano-SiO 2 . Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Genetic diversity of HA1 domain of heammaglutinin gene of influenza A(H1N1)pdm09 in Tunisia

    PubMed Central

    2013-01-01

    We present major results concerning isolation and determination of the nucleotide sequence of hemagglutinin (HA1) of the pandemic (H1N1)pdm09 influenza viruses found in Tunisia. Amino acid analysis revealed minor amino acid changes in the antigenic or receptor-binding domains. We found mutations that were also present in 1918 pandemic virus, which includes S183P in 4 and S185T mutation in 19 of 27 viruses analyzed from 2011, while none of the 2009 viruses carried these mutations. Also two specific amino acid differences into N-glycosylation sites (N288T and N276H) were detected. The phylogenetic analysis revealed that the majority of the Tunisian isolates clustered with clade A/St. Petersburg/27/2011 viruses characterized by D97N and S185T mutations. However it also reveals a trend of 2010 strains to accumulate amino acid variation and form new phylogenetic clade with three specific amino acid substitutions: V47I, E172K and K308E. PMID:23679923

  13. PACE-90 water and solute transport calculations for 0.01, 0.1, and 0. 5 mm/yr infiltration into Yucca Mountain; Yucca Mountain Site Characterization Project

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dykhuizen, R.C.; Eaton, R.R.; Hopkins, P.L.

    1991-12-01

    Numerical results are presented for the Performance Assessment Calculational Exercise (PACE-90). One- and two-dimensional water and solute transport are presented for steady infiltration into Yucca Mountain. Evenly distributed infiltration rates of 0.01, 0.1, and 0.5 mm/yr were considered. The calculations of solute transport show that significant amounts of radionuclides can reach the water table over 100,000 yr at the 0.5 mm/yr rate. For time periods less than 10,000 yr or infiltrations less than 0.1 mm/yr very little solute reaches the water table. The numerical simulations clearly demonstrate that multi-dimensional effects can result in significant decreases in the travel time ofmore » solute through the modeled domain. Dual continuum effects are shown to be negligible for the low steady state fluxes considered. However, material heterogeneities may cause local amplification of the flux level in multi-dimensional flows. These higher flux levels may then require modeling of a dual continuum porous medium.« less

  14. Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively.

    PubMed

    Zhang, Shishuo; Wang, Ruifang; Su, Huijuan; Wang, Biaoxiong; Sizhu, Suolang; Lei, Zhixin; Jin, Meilin; Chen, Huanchun; Cao, Jiyue; Zhou, Hongbo

    2017-04-03

    The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays. The messenger RNA (mRNA) levels of viral HA and NS were significantly suppressed when newborn pig trachea (NPTr) cells respectively overexpressed ssc-miR-204 and ssc-miR-4331 and were infected with SIV-H1N1/2009, whereas the suppression effect could be restored when respectively decreasing endogenous ssc-miR-204 and ssc-miR-4331 with inhibitors. Because of the importance of viral HA and NS in the life cycle of influenza A virus, ssc-miR-204 and ssc-miR-4331 exhibited an inhibition effect on SIV-H1N1/2009 replication. The antiviral effect was sequence-specific of SIV-H1N1/2009, for the target sites in HA and NS of H5N1 or H9N2 influenza A virus were not conserved. Furthermore, SIV-H1N1/2009 infection reversely downregulated the expression of ssc-miR-204 and ssc-miR-4331, which might facilitate the virus replication in the host. In summary, this work will provide us some important clues for controlling the prevalence of SIV-H1N1/2009 in pig populations.

  15. Prevention of influenza virus shedding and protection from lethal H1N1 challenge using a consensus 2009 H1N1 HA and NA adenovirus vector vaccine

    PubMed Central

    Jones, Frank R.; Gabitzsch, Elizabeth S.; Xu, Younong; Balint, Joseph P.; Borisevich, Viktoriya; Smith, Jennifer; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Salazar, Magda; Paessler, Slobodan

    2013-01-01

    Vaccines against emerging pathogens such as the 2009 H1N1 pandemic virus can benefit from current technologies such as rapid genomic sequencing to construct the most biologically relevant vaccine. A novel platform (Ad5 [E1-, E2b-]) has been utilized to induce immune responses to various antigenic targets. We employed this vector platform to express hemagglutinin (HA) and neuraminidase (NA) genes from 2009 H1N1 pandemic viruses. Inserts were consensuses sequences designed from viral isolate sequences and the vaccine was rapidly constructed and produced. Vaccination induced H1N1 immune responses in mice, which afforded protection from lethal virus challenge. In ferrets, vaccination protected from disease development and significantly reduced viral titers in nasal washes. H1N1 cell mediated immunity as well as antibody induction correlated with the prevention of disease symptoms and reduction of virus replication. The Ad5 [E1-, E2b-] should be evaluated for the rapid development of effective vaccines against infectious diseases. PMID:21821082

  16. Neuroprotection and lifespan extension in Ppt1−/− mice by NtBuHA: therapeutic implications for INCL

    PubMed Central

    Sarkar, Chinmoy; Chandra, Goutam; Peng, Shyiong; Zhang, Zhongjian; Liu, Aiyi; Mukherjee, Anil B.

    2013-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disease (LSD) that has no effective treatment. It is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1-deficiency impairs the cleavage of thioester linkage in palmitoylated proteins (constituents of ceroid), preventing degradation by lysosomal hydrolases. Consequently, accumulation of lysosomal ceroid leads to INCL. Thioester linkage is cleaved by nucleophilic attack. Hydroxylamine, a potent nucleophilic cellular metabolite, may have therapeutic potential for INCL but its toxicity precludes clinical application. Here we report that a hydroxylamine-derivative, N-(tert-Butyl) hydroxylamine (NtBuHA), is non-toxic, cleaves thioester linkage in palmitoylated proteins and mediates lysosomal ceroid depletion in cultured cells from INCL patients. Importantly, in Ppt1−/− mice, which mimic INCL, NtBuHA crossed the blood-brain-barrier, depleted lysosomal ceroid, suppressed neuronal apoptosis, slowed neurological deterioration and extended lifespan. Our findings provide the proof of concept that thioesterase-mimetic and antioxidant small molecules like NtBuHA are potential drug-targets for thioesterase deficiency diseases like INCL. PMID:24056696

  17. Reassortment between Influenza B Lineages and the Emergence of a Coadapted PB1–PB2–HA Gene Complex

    PubMed Central

    Dudas, Gytis; Bedford, Trevor; Lycett, Samantha; Rambaut, Andrew

    2015-01-01

    Influenza B viruses make a considerable contribution to morbidity attributed to seasonal influenza. Currently circulating influenza B isolates are known to belong to two antigenically distinct lineages referred to as B/Victoria and B/Yamagata. Frequent exchange of genomic segments of these two lineages has been noted in the past, but the observed patterns of reassortment have not been formalized in detail. We investigate interlineage reassortments by comparing phylogenetic trees across genomic segments. Our analyses indicate that of the eight segments of influenza B viruses only segments coding for polymerase basic 1 and 2 (PB1 and PB2) and hemagglutinin (HA) proteins have maintained separate Victoria and Yamagata lineages and that currently circulating strains possess PB1, PB2, and HA segments derived entirely from one or the other lineage; other segments have repeatedly reassorted between lineages thereby reducing genetic diversity. We argue that this difference between segments is due to selection against reassortant viruses with mixed-lineage PB1, PB2, and HA segments. Given sufficient time and continued recruitment to the reassortment-isolated PB1–PB2–HA gene complex, we expect influenza B viruses to eventually undergo sympatric speciation. PMID:25323575

  18. Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

    PubMed

    Liu, Xiaoli; Simpson, Jeremy A; Brunt, Keith R; Ward, Christopher A; Hall, Sean R R; Kinobe, Robert T; Barrette, Valerie; Tse, M Yat; Pang, Stephen C; Pachori, Alok S; Dzau, Victor J; Ogunyankin, Kofo O; Melo, Luis G

    2007-07-01

    We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

  19. Annual cycle of magmatic CO2 in a tree-kill soil at Mammoth Mountain, California: implications for soil acidification

    USGS Publications Warehouse

    McGee, K.A.; Gerlach, T.M.

    1998-01-01

    Time-series sensor data reveal significant short-term and seasonal variations of magmatic CO2 in soil over a 12 month period in 1995-1996 at the largest tree-kill site on Mammoth Mountain, central-eastern California. Short-term variations leading to ground-level soil CO2 concentrations hazardous and lethal to humans were triggered by shallow faulting in the absence of increased seismicity or intrusion, consistent with tapping a reservoir of accumulated CO2, rather than direct magma degassing. Hydrologic processes closely modulated seasonal variations in CO2 concentrations, which rose to 65%-100% in soil gas under winter snowpack and plunged more than 25% in just days as the CO2 dissolved in spring snowmelt. The high efflux of CO2 through the tree-kill soils acts as an open-system CO2 buffer causing infiltration of waters with pH values commonly of < 4.2, acid loading of up to 7 keqH+.ha-1.yr-1, mobilization of toxic Al3+, and long-term decline of soil fertility.

  20. Lateglacial vegetation dynamics in the eastern Baltic region between 14,500 and 11,400 cal yr BP: A complete record since the Bølling (GI-1e) to the Holocene

    NASA Astrophysics Data System (ADS)

    Veski, Siim; Amon, Leeli; Heinsalu, Atko; Reitalu, Triin; Saarse, Leili; Stivrins, Normunds; Vassiljev, Jüri

    2012-04-01

    This paper discusses a complete record of vegetation history since the Bølling (GI-1e) warming (14,500 cal yr BP) up to the Holocene in Latvia. To date, this is the only complete record of such age in the eastern Baltic area and the northernmost area for which Bølling records are present. Combining pollen evidence, pollen accumulation rates (PAR) and plant macrofossil data, we assess the local and regional vegetation development, and we attempt to separate the true Lateglacial vegetation signal by removing the obviously redeposited thermophilous pollen; however, we remove not only their signal, we discuss the possibilities of separating the redeposition signal of the so-called "local Lateglacial trees", pine and birch, by looking at their corrosion and degradation. The results show that the Bølling warming in the eastern Baltic area was a treeless tundra community consisting of the shrubs Betula nana, Dryas octopetala and Salix polaris. The Older Dryas cold spell is clearly recognised as a decline in the total concentration of plant macrofossils and PARs at between 14,200 and 13,500 cal yr BP. At 13,460 cal yr BP, the B. nana macrofossils disappear, and tree birch (Betula sect. Albae) appears, marking the start of tree birch forest. The presence of pine forest is confirmed by a variety of macrofossils, including bark, wood, needles and seeds, since 13,400 cal yr BP, at the same time at which pine stomata are found. The first identified pine stomata finds are associated with a Pinus PAR over 3000 grains cm-2 yr-1 and pine macrofossil finds with a Pinus PAR over 4000 grains cm-2 yr-1. During the warmest period of the GI-1a (Allerød) at 13,000-12,700 cal yr BP, a pine forest with deciduous trees (birch -Betula pendula and aspen -Populus tremula) developed in the study area. The Younger Dryas (GS-1) cooling strongly affected the floral composition in eastern Latvia. The PAR of the tree taxa declined abruptly from a maximum value at 12,700 to below 1000 grains cm-2

  1. UCAC3 PROPER MOTION SURVEY. I. DISCOVERY OF NEW PROPER MOTION STARS IN UCAC3 WITH 0.''40 yr{sup -1} > {mu} {>=} 0.''18 yr{sup -1} BETWEEN DECLINATIONS -90{sup 0} AND -47{sup 0}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Finch, Charlie T.; Zacharias, Norbert; Henry, Todd J., E-mail: finch@usno.navy.mi

    2010-09-15

    This paper presents 442 new proper motion stellar systems in the southern sky between declinations -90{sup 0} and -47{sup 0} with 0.''40 yr{sup -1} > {mu} {>=} 0.''18 yr{sup -1}. These systems constitute a 25.3% increase in new systems for the same region of the sky covered by previous SuperCOSMOS RECONS (SCR) searches that used Schmidt plates as the primary source of discovery. Among the new systems are 25 multiples, plus an additional 7 new common proper motion (CPM) companions to previously known primaries. All stars have been discovered using the third U.S. Naval Observatory (USNO) CCD Astrograph Catalog (UCAC3).more » A comparison of the UCAC3 proper motions to those from the Hipparcos, Tycho-2, Southern Proper Motion (SPM4), and SuperCOSMOS efforts is presented and shows that UCAC3 provides similar values and precision to the first three surveys. The comparison between UCAC3 and SuperCOSMOS indicates that proper motions in R.A. are systematically shifted in the SuperCOSMOS data but are consistent in decl. data, while overall showing a significantly higher scatter. Distance estimates are derived for stars having SuperCOSMOS Sky Survey B{sub J} , R{sub 59F}, and I{sub IVN} plate magnitudes and Two-Micron All Sky Survey infrared photometry. We find 15 systems estimated to be within 25 pc, including UPM 1710-5300 our closest new discovery estimated at 13.5 pc. Such new discoveries suggest that more nearby stars are yet to be found in these slower proper motion regimes, indicating that more work is needed to develop a complete map of the solar neighborhood.« less

  2. Reversible Association of the Hemagglutinin Subcomplex, HA-33/HA-17 Trimer, with the Botulinum Toxin Complex.

    PubMed

    Sagane, Yoshimasa; Mutoh, Shingo; Koizumi, Ryosuke; Suzuki, Tomonori; Miyashita, Shin-Ichiro; Miyata, Keita; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro

    2017-10-01

    Botulinum neurotoxin (BoNT) associates with nontoxic proteins, either a nontoxic nonhemagglutinin (NTNHA) or the complex of NTNHA and hemagglutinin (HA), to form M- or L-toxin complexes (TCs). Single BoNT and NTNHA molecules are associated and form M-TC. A trimer of the 70-kDa HA protein (HA-70) attaches to the M-TC to form M-TC/HA-70. Further, 1-3 arm-like 33- and 17-kDa HA molecules (HA-33/HA-17 trimer), consisting of 1 HA-17 protein and 2 HA-33 proteins, can attach to the M-TC/HA-70 complex, yielding 1-, 2-, and 3-arm L-TC. In this study, the purified 1- and 2-arm L-TCs spontaneously converted into another L-TC species after acquiring the HA-33/HA-17 trimer from other TCs during long-term storage and freezing/thawing. Transmission electron microscopy analysis provided evidence of the formation of detached HA-33/HA-17 trimers in the purified TC preparation. These findings provide evidence of reversible association/dissociation of the M-TC/HA-70 complex with the HA-33/HA-17 trimers, as well as dynamic conversion of the quaternary structure of botulinum TC in culture.

  3. Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts.

    PubMed

    Nagaoka, Aya; Yoshida, Hiroyuki; Nakamura, Sachiko; Morikawa, Tomohiko; Kawabata, Keigo; Kobayashi, Masaki; Sakai, Shingo; Takahashi, Yoshito; Okada, Yasunori; Inoue, Shintaro

    2015-12-25

    Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-β1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly produced HA is dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of the MAPK and/or Smad signaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-β1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-β1 up-regulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-β1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts, TGF-β1 most efficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient down-regulation of HYBID by TGF-β1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Disease progression among 446 children with newly diagnosed type 1 diabetes located in Scandinavia, Europe, and North America during the last 27 yr.

    PubMed

    Max Andersen, Marie Louise; Nielsen, Lotte B; Svensson, Jannet; Pörksen, Sven; Hougaard, Philip; Beam, Craig; Greenbaum, Carla; Becker, Dorothy; Petersen, Jacob S; Hansen, Lars; Mortensen, Henrik B

    2014-08-01

    To clarify whether the rate of decline in stimulated C-peptide (SCP) from 2 to 15 months after diagnosis has changed over an interval of 27 yr. The rate of decline in SCP levels at 1, 2, 3, 6, 9, 12, and 15 months after diagnosis was compared in four paediatric cohorts from Scandinavian and European countries including 446 children with new onset type 1 diabetes (T1D, 1982-2004). Findings were evaluated against 78 children (2004-2009) from the TrialNet studies. The mean rate of decline [%/month (±SEM)] in SCP for a 10-yr-old child was 7.7%/month (±1.5) in the 1982-1985 Cohort, 6.3%/month (±1.7) in the 1995-1998 Cohort, 7.8%/month (±0.7) in the 1999-2000 Cohort, and 10.7%/month (±0.9) in the latest 2004-2005 Cohort (p = 0.05). Including the TrialNet Cohort with a rate of decline in SCP of 10.0%/month (±0.9) the differences between the cohorts are still significant (p = 0.039). The rate of decline in SCP was negatively associated with age (p < 0.0001), insulin antibodies (IA) (p = 0.003), and glutamic acid decarboxylase-65 (GAD65A) (p = 0.03) initially with no statistically significant effect of body mass index (BMI) Z-score at 3 months. Also, at 3 months the time around partial remission, the effect of age on SCP was significantly greater in children ≤5 yr compared with older children (p ≤ 0.0001). During the past 27 yr, initial C-peptide as well as the rate of C-peptide decline seem to have increased. The rate of decline was affected significantly by age, GAD65A, and IA, but not BMI Z-score or initial C-peptide. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1-2 Co-Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens.

    PubMed

    Song, Li; Xiong, Dan; Song, Hongqin; Wu, Lili; Zhang, Meihua; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2017-01-01

    Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine. Mice immunized intranasally with HA1-2-fliC and HA1-2-PEI showed higher HA1-2-specific immunoglobulin (Ig)G and IgA titers in serum, nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation and proliferation and the number of HA1-2-specific interferon (IFN)-γ- and interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and PEI groups; in the latter, there were more cells secreting IL-4 than IFN-γ, suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and PEI induced Th2-biased responses, consistent with the serum antibody isotype pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a chicken model. The results showed that chickens receiving fliC and PEI adjuvant vaccine exhibited robust immune responses leading to a significant reduction in viral loads of throat and cloaca compared to chickens receiving only HA1-2. These findings provide a basis for the development of H7N9 influenza HA1-2 mucosal subunit vaccines.

  6. Cosmological constraints from measurements of type Ia supernovae discovered during the first 1.5 yr of the Pan-STARRS1 survey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rest, A.; Scolnic, D.; Riess, A.

    2014-11-01

    We present griz {sub P1} light curves of 146 spectroscopically confirmed Type Ia supernovae (SNe Ia; 0.03 < z < 0.65) discovered during the first 1.5 yr of the Pan-STARRS1 Medium Deep Survey. The Pan-STARRS1 natural photometric system is determined by a combination of on-site measurements of the instrument response function and observations of spectrophotometric standard stars. We find that the systematic uncertainties in the photometric system are currently 1.2% without accounting for the uncertainty in the Hubble Space Telescope Calspec definition of the AB system. A Hubble diagram is constructed with a subset of 113 out of 146 SNemore » Ia that pass our light curve quality cuts. The cosmological fit to 310 SNe Ia (113 PS1 SNe Ia + 222 light curves from 197 low-z SNe Ia), using only supernovae (SNe) and assuming a constant dark energy equation of state and flatness, yields w=−1.120{sub −0.206}{sup +0.360}(Stat){sub −0.291}{sup +0.269}(Sys). When combined with BAO+CMB(Planck)+H {sub 0}, the analysis yields Ω{sub M}=0.280{sub −0.012}{sup +0.013} and w=−1.166{sub −0.069}{sup +0.072} including all identified systematics. The value of w is inconsistent with the cosmological constant value of –1 at the 2.3σ level. Tension endures after removing either the baryon acoustic oscillation (BAO) or the H {sub 0} constraint, though it is strongest when including the H {sub 0} constraint. If we include WMAP9 cosmic microwave background (CMB) constraints instead of those from Planck, we find w=−1.124{sub −0.065}{sup +0.083}, which diminishes the discord to <2σ. We cannot conclude whether the tension with flat ΛCDM is a feature of dark energy, new physics, or a combination of chance and systematic errors. The full Pan-STARRS1 SN sample with ∼three times as many SNe should provide more conclusive results.« less

  7. Experimental determination of Henry's law constants of difluoromethane (HFC-32) and the salting-out effects in aqueous salt solutions relevant to seawater

    NASA Astrophysics Data System (ADS)

    Kutsuna, Shuzo

    2017-06-01

    Gas-to-water equilibrium coefficients, KeqS (in M atm-1), of difluoromethane (CH2F2), a hydrofluorocarbon refrigerant (HFC-32), in aqueous salt solutions relevant to seawater were determined over a temperature (T) range from 276 to 313 K and a salinity (S) range up to 51 ‰ by means of an inert-gas stripping method. From the van't Hoff equation, the KeqS value in water, which corresponds to the Henry's law constant (KH), at 298 K was determined to be 0.065 M atm-1. The salinity dependence of KeqS (the salting-out effect), ln(KH/KeqS), did not obey the Sechenov equation but was proportional to S0. 5. Overall, the KeqS(T) value was expressed by ln(KeqS(T)) = -49.71 + (77.70 - 0.134 × S0. 5) × (100/T) + 19.14 × ln(T/100). By using this equation in a lower-tropospheric semi-hemisphere (30-90 °S) of the Advanced Global Atmospheric Gases Experiment (AGAGE) 12-box model, we estimated that 1 to 4 % of the atmospheric burden of CH2F2 resided in the ocean mixed layer and that this percentage was at least 4 % in the winter; dissolution of CH2F2 in the ocean may partially influence estimates of CH2F2 emissions from long-term observational data of atmospheric CH2F2 concentrations.

  8. Role of the HaHOG1 MAP Kinase in Response of the Conifer Root and But Rot Pathogen (Heterobasidion annosum) to Osmotic and Oxidative Stress

    PubMed Central

    Raffaello, Tommaso; Keriö, Susanna; Asiegbu, Fred O.

    2012-01-01

    The basidiomycete Heterobasidion annosum (Fr.) Bref. s.l. is a filamentous white rot fungus, considered to be the most economically important pathogen of conifer trees. Despite the severity of the tree infection, very little is known about the molecular and biochemical aspects related to adaptation to abiotic stresses. In this study, the osmotic and oxidative tolerance as well as the role of the HaHOG1 Mitogen Activated Protein Kinase (MAPK) gene were investigated. The transcript levels of the yeast orthologues GPD1, HSP78, STL1, GRE2 and the ATPase pumps ENA1, PMR1, PMC1 known to have an important role in osmotolerance were also quantified under salt osmotic conditions. The HaHOG1 gene was used for a heterologous expression and functional study in the Saccharomyces cerevisiae Δhog1 strain. Moreover, the phosphorylation level of HaHog1p was studied under salt osmotic and oxidative stress. The result showed that H. annosum displayed a decreased growth when exposed to an increased concentration of osmotic and oxidative stressors. GPD1, HSP78, STL1 and GRE2 showed an induction already at 10 min after exposure to salt stress. Among the ATPase pumps studied, PMC1 was highly induced when the fungus was exposed to 0.2 M CaCl2 for 60 min. The heterologous expression of the HaHOG1 sequence in yeast confirmed that the gene is able to restore the osmotolerance and oxidative tolerance in the S. cerevisiae hog1Δ mutant strain. The HaHog1p was strongly phosphorylated in the presence of NaCl, KCl, H2O2 but not in the presence of CaCl2 and MgCl2. The GFP-HaHog1p fusion protein accumulated in the nuclei of the S. cerevisiae hog1Δ cells when exposed to high osmotic conditions but not under oxidative stress. These results provide the first insights about the response of H. annosum to osmotic and oxidative stress and elucidate the role of the HaHOG1 gene in such conditions. PMID:22319614

  9. Changes in aerobic power of men, ages 25-70 yr

    NASA Technical Reports Server (NTRS)

    Jackson, A. S.; Beard, E. F.; Wier, L. T.; Ross, R. M.; Stuteville, J. E.; Blair, S. N.

    1995-01-01

    This study quantified and compared the cross-sectional and longitudinal influence of age, self-report physical activity (SR-PA), and body composition (%fat) on the decline of maximal aerobic power (VO2peak). The cross-sectional sample consisted of 1,499 healthy men ages 25-70 yr. The 156 men of the longitudinal sample were from the same population and examined twice, the mean time between tests was 4.1 (+/- 1.2) yr. Peak oxygen uptake was determined by indirect calorimetry during a maximal treadmill exercise test. The zero-order correlations between VO2peak and %fat (r = -0.62) and SR-PA (r = 0.58) were significantly (P < 0.05) higher that the age correlation (r = -0.45). Linear regression defined the cross-sectional age-related decline in VO2peak at 0.46 ml.kg-1.min-1.yr-1. Multiple regression analysis (R = 0.79) showed that nearly 50% of this cross-sectional decline was due to %fat and SR-PA, adding these lifestyle variables to the multiple regression model reduced the age regression weight to -0.26 ml.kg-1.min-1.yr-1. Statistically controlling for time differences between tests, general linear models analysis showed that longitudinal changes in aerobic power were due to independent changes in %fat and SR-PA, confirming the cross-sectional results.

  10. Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1–2 Co-Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens

    PubMed Central

    Song, Li; Xiong, Dan; Song, Hongqin; Wu, Lili; Zhang, Meihua; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2017-01-01

    Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1–2-fliC fusion protein consisting of the globular head domain (HA1–2; amino acids 62–284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine. Mice immunized intranasally with HA1–2-fliC and HA1–2-PEI showed higher HA1–2-specific immunoglobulin (Ig)G and IgA titers in serum, nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation and proliferation and the number of HA1–2-specific interferon (IFN)-γ- and interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and PEI groups; in the latter, there were more cells secreting IL-4 than IFN-γ, suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and PEI induced Th2-biased responses, consistent with the serum antibody isotype pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a chicken model. The results showed that chickens receiving fliC and PEI adjuvant vaccine exhibited robust immune responses leading to a significant reduction in viral loads of throat and cloaca compared to chickens receiving only HA1–2. These findings provide a basis for the development of H7N9 influenza HA1–2 mucosal subunit vaccines. PMID:28424686

  11. Construction and heterologous expression of a truncated Haemagglutinin (HA) protein from the avian influenza virus H5N1 in Escherichia coli.

    PubMed

    Chee Wei, T; Nurul Wahida, A G; Shaharum, S

    2014-12-01

    Malaysia first reported H5N1 poultry case in 2004 and subsequently outbreak in poultry population in 2007. Here, a recombinant gene encoding of peptide epitopes, consisting fragments of HA1, HA2 and a polybasic cleavage site of H5N1 strain Malaysia, was amplified and cloned into pET-47b(+) bacterial expression vector. DNA sequencing and alignment analysis confirmed that the gene had no alteration and in-frame to the vector. Then, His-tagged truncated HA protein was expressed in Escherichia coli BL21 (DE3) under 1 mM IPTG induction. The protein expression was optimized under a time-course induction study and further purified using Ni-NTA agarose under reducing condition. Migration size of protein was detected at 15 kDa by Western blot using anti-His tag monoclonal antibody and demonstrated no discrepancy compared to its calculated molecular weight.

  12. Modelling soil erosion in a Mediterranean watershed: Comparison between SWAT and AnnAGNPS models.

    PubMed

    Abdelwahab, O M M; Ricci, G F; De Girolamo, A M; Gentile, F

    2018-06-20

    In this study, the simulations generated by two of the most widely used hydrological basin-scale models, the Annualized Agricultural Non-Point Source (AnnAGNPS) and the Soil and Water Assessment Tool (SWAT), were compared in a Mediterranean watershed, the Carapelle (Apulia, Southern Italy). Input data requirements, time and efforts needed for input preparation, strength and weakness points of each model, ease of use and limitations were evaluated in order to give information to users. Models were calibrated and validated at monthly time scale for hydrology and sediment load using a four year period of observations (streamflow and suspended sediment concentrations). In the driest year, the specific sediment load measured at the outlet was 0.89 t ha -1 yr -1 , while the simulated values were 0.83 t ha -1 yr -1 and 1.99 t ha -1 yr -1 for SWAT and AnnAGNPS, respectively. In the wettest year, the specific measured sediment load was 7.45 t ha -1 yr -1 , and the simulated values were 8.27 t ha -1 yr -1 and 6.23 t ha -1 yr -1 for SWAT and AnnAGNPS, respectively. Both models showed from fair to a very good correlation between observed and simulated streamflow and satisfactory for sediment load. Results showed that most of the basin is under moderate (1.4-10 t ha -1 yr -1 ) and high-risk erosion (> 10 t ha -1 yr -1 ). The sediment yield predicted by the SWAT and AnnAGNPS models were compared with estimates of soil erosion simulated by models for Europe (PESERA and RUSLE2015). The average gross erosion estimated by the RUSLE2015 model (12.5 t ha -1 yr -1 ) resulted comparable with the average specific sediment yield estimated by SWAT (8.8 t ha -1 yr -1 ) and AnnAGNPS (5.6 t ha -1 yr -1 ), while it was found that the average soil erosion estimated by PESERA is lower than the other estimates (1.2 t ha -1 yr -1 ). Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Sulforaphane suppresses ultraviolet B-induced inflammation in HaCaT keratinocytes and HR-1 hairless mice.

    PubMed

    Shibata, Akira; Nakagawa, Kiyotaka; Yamanoi, Hiroko; Tsuduki, Tsuyoshi; Sookwong, Phumon; Higuchi, Ohki; Kimura, Fumiko; Miyazawa, Teruo

    2010-08-01

    Ultraviolet B (UVB) irradiation induces skin damage and inflammation. One way to reduce the inflammation is via the use of molecules termed photochemopreventive agents. Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SF), which is found in cruciferous vegetables, is known for its potent physiological properties. This study was designed to evaluate the effect of SF on skin inflammation in vitro and in vivo. In in vitro study using immortalized human keratinocytes (HaCaT), UVB caused marked inflammatory responses [i.e., decrease of HaCaT viability and increase of production of an inflammatory marker interleukin-6 (IL-6)]. SF recovered the cell proliferation and suppressed the IL-6 production. These anti-inflammatory effects of SF were explained by its ability to reduce UVB-induced inflammatory gene expressions [IL-6, IL-1beta and cyclooxgenase-2 (COX-2)]. Because SF seems to have an impact on COX-2 expression, we focused on COX-2 and found that SF reduced UVB-induced COX-2 protein expression. In support of this, PGE(2) released from HaCaT was suppressed by SF. Western blot analysis revealed that SF inhibited p38, ERK and SAPK/JNK activation, indicating that the inhibition of mitogen-activated protein kinases (MAPK) by SF would attenuate the expression of inflammatory mediators (e.g., COX-2), thereby reducing inflammatory responses. Moreover, we conducted skin thickening assay using HR-1 hairless mice and found that UVB-induced skin thickness, COX-2 protein expression and hyperplasia were all suppressed by feeding SF to the mice. These results suggest that SF has a potential use as a compound for protection against UVB-induced skin inflammation. Copyright 2010 Elsevier Inc. All rights reserved.

  14. Reliability of confidence intervals calculated by bootstrap and classical methods using the FIA 1-ha plot design

    Treesearch

    H. T. Schreuder; M. S. Williams

    2000-01-01

    In simulation sampling from forest populations using sample sizes of 20, 40, and 60 plots respectively, confidence intervals based on the bootstrap (accelerated, percentile, and t-distribution based) were calculated and compared with those based on the classical t confidence intervals for mapped populations and subdomains within those populations. A 68.1 ha mapped...

  15. The homologous HD-Zip I transcription factors HaHB1 and AtHB13 confer cold tolerance via the induction of pathogenesis-related and glucanase proteins.

    PubMed

    Cabello, Julieta V; Arce, Agustín L; Chan, Raquel L

    2012-01-01

    Plants deal with cold temperatures via different signal transduction pathways. The HD-Zip I homologous transcription factors HaHB1 from sunflower and AtHB13 from Arabidopsis were identified as playing a key role in such cold response. The expression patterns of both genes were analyzed indicating an up-regulation by low temperatures. When these genes were constitutively expressed in Arabidopsis, the transgenic plants showed similar phenotypes including cell membrane stabilization under freezing treatments and cold tolerance. An exploratory transcriptomic analysis of HaHB1 transgenic plants indicated that several transcripts encoding glucanases and chitinases were induced. Moreover, under freezing conditions some proteins accumulated in HaHB1 plants apoplasts and these extracts exerted antifreeze activity in vitro. Three genes encoding two glucanases and a chitinase were overexpressed in Arabidopsis and these plants were able to tolerate freezing temperatures. All the obtained transgenic plants exhibited cell membrane stabilization after a short freezing treatment. Finally, HaHB1 and AtHB13 were used to transiently transform sunflower and soybean leading to the up-regulation of HaHB1/AtHB13-target homologues thus indicating the conservation of cold response pathways. We propose that HaHB1 and AtHB13 are involved in plant cold tolerance via the induction of proteins able to stabilize cell membranes and inhibit ice growth. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  16. Changes in aerobic power of women, ages 20-64 yr

    NASA Technical Reports Server (NTRS)

    Jackson, A. S.; Wier, L. T.; Ayers, G. W.; Beard, E. F.; Stuteville, J. E.; Blair, S. N.

    1996-01-01

    This study quantified and compared the cross-sectional and longitudinal influence of age, self-report physical activity (SR-PA), and body composition (%fat) on the decline of maximal aerobic power (VO2peak) of women. The cross-sectional sample consisted of 409 healthy women, ages 20-64 yr. The 43 women of the longitudinal sample were from the same population and examined twice, the mean time between tests was 3.7 (+/-2.2) yr. Peak oxygen uptake was determined by indirect calorimetry during a maximal treadmill test. The zero-order correlation of -0.742 between VO2peak and %fat was significantly (P < 0.05) higher then the SR-PA (r = 0.626) and age correlations (r = -0.633). Linear regression defined the cross-sectional age-related decline in VO2peak at 0.537 ml.kg-1.min-1.yr-1. Multiple regression analysis (R = 0.851) showed that adding %fat and SR-PA and their interaction to the regression model reduced the age regression weight of -0.537, to -0.265 ml.kg-1.min-1.yr-1. Statistically controlling for time differences between tests, general linear models analysis showed that longitudinal changes in aerobic power were due to independent changes in %fat and SR-PA, confirming the cross-sectional results. These findings are consistent with men's data from the same lab showing that about 50% of the cross-sectional age-related decline in VO2peak was due to %fat and SR-PA.

  17. Global Sea Ice Coverage from Satellite Data: Annual Cycle and 35-Yr Trends

    NASA Technical Reports Server (NTRS)

    Parkinson, Claire L.

    2014-01-01

    Well-established satellite-derived Arctic and Antarctic sea ice extents are combined to create the global picture of sea ice extents and their changes over the 35-yr period 1979-2013. Results yield a global annual sea ice cycle more in line with the high-amplitude Antarctic annual cycle than the lower-amplitude Arctic annual cycle but trends more in line with the high-magnitude negative Arctic trends than the lower-magnitude positive Antarctic trends. Globally, monthly sea ice extent reaches a minimum in February and a maximum generally in October or November. All 12 months show negative trends over the 35-yr period, with the largest magnitude monthly trend being the September trend, at -68200 +/- 10500 km sq yr(exp -1) (-2.62% +/- 0.40%decade(exp -1)), and the yearly average trend being -35000 +/-5900 km sq yr(exp -1) (-1.47% +/- 0.25%decade(exp -1)).

  18. Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B

    PubMed Central

    Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming

    2016-01-01

    The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin–Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines. PMID:27222326

  19. Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B.

    PubMed

    Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming

    2016-05-25

    The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin-Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines.

  20. Modeling sustainable reuse of nitrogen-laden wastewater by poplar.

    PubMed

    Wang, Yusong; Licht, Louis; Just, Craig

    2016-01-01

    Numerical modeling was used to simulate the leaching of nitrogen (N) to groundwater as a consequence of irrigating food processing wastewater onto grass and poplar under various management scenarios. Under current management practices for a large food processor, a simulated annual N loading of 540 kg ha(-1) yielded 93 kg ha(-1) of N leaching for grass and no N leaching for poplar during the growing season. Increasing the annual growing season N loading to approximately 1,550 kg ha(-1) for poplar only, using "weekly", "daily" and "calculated" irrigation scenarios, yielded N leaching of 17 kg ha(-1), 6 kg ha(-1), and 4 kg ha(-1), respectively. Constraining the simulated irrigation schedule by the current onsite wastewater storage capacity of approximately 757 megaliters (Ml) yielded N leaching of 146 kg ha(-1) yr(-1) while storage capacity scenarios of 3,024 and 4,536 Ml yielded N leaching of 65 and 13 kg ha(-1) yr(-1), respectively, for a loading of 1,550 kg ha(-1) yr(-1). Further constraining the model by the current wastewater storage volume and the available land area (approximately 1,000 hectares) required a "diverse" irrigation schedule that was predicted to leach a weighted average of 13 kg-N ha(-1) yr(-1) when dosed with 1,063 kg-N ha(-1) yr(-1).

  1. Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

    PubMed Central

    Pappas, Claudia; Aguilar, Patricia V.; Basler, Christopher F.; Solórzano, Alicia; Zeng, Hui; Perrone, Lucy A.; Palese, Peter; García-Sastre, Adolfo; Katz, Jacqueline M.; Tumpey, Terrence M.

    2008-01-01

    The 1918 influenza pandemic was exceptionally severe, resulting in the death of up to 50 million people worldwide. Here, we show which virus genes contributed to the replication and virulence of the 1918 influenza virus. Recombinant viruses, in which genes of the 1918 virus were replaced with genes from a contemporary human H1N1 influenza virus, A/Texas/36/91 (Tx/91), were generated. The exchange of most 1918 influenza virus genes with seasonal influenza H1N1 virus genes did not alter the virulence of the 1918 virus; however, substitution of the hemagglutinin (HA), neuraminidase (NA), or polymerase subunit PB1 genes significantly affected the ability of this virus to cause severe disease in mice. The 1918 virus virulence observed in mice correlated with the ability of 1918 recombinant viruses to replicate efficiently in human airway cells. In a second series of experiments, eight 1918 1:7 recombinants were generated, in which each Tx/91 virus gene was individually replaced by a corresponding gene from 1918 virus. Replication capacity of the individual 1:7 reassortant viruses was assessed in mouse lungs and human airway cells. Increased virus titers were observed among 1:7 viruses containing individual 1918 HA, NA, and PB1 genes. In addition, the 1918 PB1:Tx/91 (1:7) virus showed a distinctly larger plaque size phenotype than the small plaque phenotype of the 1918 PA:Tx/91 and 1918 PB2:Tx/91 1:7 reassortants. These results highlight the importance of the 1918 HA, NA, and PB1 genes for optimal virus replication and virulence of this pandemic strain. PMID:18287069

  2. Trichonomas vaginalis metalloproteinase induces apoptosis of SiHa cells through disrupting the Mcl-1/Bim and Bcl-xL/Bim complexes.

    PubMed

    Quan, Juan-Hua; Kang, Byung-Hun; Cha, Guang-Ho; Zhou, Wei; Koh, Young-Bok; Yang, Jung-Bo; Yoo, Heon-Jong; Lee, Min-A; Ryu, Jae-Sook; Noh, Heung-Tae; Kwon, Jaeyul; Lee, Young-Ha

    2014-01-01

    To elucidate the roles of metalloproteinases and the Bcl-2 family of proteins in Trichovaginalis. vaginalis-induced apoptosis in human cervical cancer cells (SiHa cells) and vaginal epithelial cells (MS74 cells), SiHa cells and MS74 cells were incubated with live T. vaginalis, T. vaginalis excretory and secretory products (ESP), and T. vaginalis lysates, either with or without the specific metalloproteinase inhibitor 1,10-phenanthroline (1,10-PT), and examined apoptotic events and Bcl-2 signaling. The live T. vaginalis and the T. vaginalis ESP induced the release of cytochrome c into the cytosol, the activation of caspase-3 and caspase-9, and the cleavage of PARP. Additionally, the live T. vaginalis, but not the T. vaginalis lysate, induced the cleavage of the proapoptotic Bim protein. The live T. vaginalis and the T. vaginalis ESP, but not the T. vaginalis lysate, induced the dose-dependent cleavage of the antiapoptotic Bcl-xL and Mcl-1 proteins and decreased the association levels of Bcl-xL/Bim and Mcl-1/Bim complexes. We performed gelatin zymography and casein-hydrolysis assays on the live T. vaginalis and the T. vaginalis ESP to identify the apoptosis-inducing factor. Both the live T. vaginalis and the ESP contained high levels of metalloproteinases, of which activities were significantly inhibited by 1,10-PT treatment. Furthermore, the 1,10-PT blocked the cleavage of Bcl-xL, Mcl-1, PARP, caspase-3, and caspase-9, as well as the release of cytochrome c into the cytosol, and it significantly increased the association levels of the Bcl-xL/Bim and Mcl-1/Bim protein complexes, returning them to normal levels. Our results demonstrate that T. vaginalis induces mitochondria-dependent apoptosis in SiHa cells through the dissociation of Bcl-xL/Bim and Mcl-1/Bim complexes and that the apoptosis is blocked by the metalloproteinase inhibitor 1,10-PT. These results expand our understanding of the role of metalloproteinases in T. vaginalis-induced apoptosis and the signaling

  3. Acetylcholine receptor gating at extracellular transmembrane domain interface: the "pre-M1" linker.

    PubMed

    Purohit, Prasad; Auerbach, Anthony

    2007-12-01

    Charged residues in the beta10-M1 linker region ("pre-M1") are important in the expression and function of neuromuscular acetylcholine receptors (AChRs). The perturbation of a salt bridge between pre-M1 residue R209 and loop 2 residue E45 has been proposed as being a principle event in the AChR gating conformational "wave." We examined the effects of mutations to all five residues in pre-M1 (positions M207-P211) plus E45 in loop 2 in the mouse alpha(1)-subunit. M207, Q208, and P211 mutants caused small (approximately threefold) changes in the gating equilibrium constant (K(eq)), but the changes for R209, L210, and E45 were larger. Of 19 different side chain substitutions at R209 on the wild-type background, only Q, K, and H generated functional channels, with the largest change in K(eq) (67-fold) from R209Q. Various R209 mutants were functional on different E45 backgrounds: H, Q, and K (E45A), H, A, N, and Q (E45R), and K, A, and N (E45L). Phi values for R209 (on the E45A background), L210, and E45 were 0.74, 0.35, and 0.80, respectively. Phi values for R209 on the wt and three other backgrounds could not be estimated because of scatter. The average coupling energy between 209/45 side chains (six different pairs) was only -0.33 kcal/mol (for both alpha subunits, combined). Pre-M1 residues are important for expression of functional channels and participate in gating, but the relatively modest changes in closed- vs. open-state energy caused mutations, the weak coupling energy between these residues and the functional activity of several unmatched-charge pairs are not consistent with the perturbation of a salt bridge between R209 and E45 playing the principle role in gating.

  4. Mutations that abolish the ability of Ha-Ras to associate with Raf-1.

    PubMed

    Shirouzu, M; Koide, H; Fujita-Yoshigaki, J; Oshio, H; Toyama, Y; Yamasaki, K; Fuhrman, S A; Villafranca, E; Kaziro, Y; Yokoyama, S

    1994-08-01

    Recent studies have revealed that Ras can associate physically with Raf. In the present study, we tested 34 mutants of Ha-Ras carrying substitution(s) in the region of residues 23-71 for their ability to associate with Raf-1. Mouse Ba/F3 cell lysates were incubated with each mutant Ras protein, in either the guanosine 5'-[gamma-thio]triphosphate (GTP gamma S)- or the guanosine 5'-[beta-thio]diphosphate (GDP beta S)-bound form, and the anti-Ras antibody Y13-238. The immunoprecipitates were analysed for the presence of Raf-1 by Western blotting with an anti-Raf-1 antibody. Six mutants of Ras, E31K, P34G, T35S, D38N, D57A and A59T, failed to bind Raf-1. Mutations N26G, V29A, S39A, Y40W, R41A, V44A, V45E, L56A and T58A partially reduced the ability to bind Raf-1. All the other mutants could associate with Raf-1 with nearly the same efficiency as that of wild-type Ras. Thus, the Raf-I-binding ability of Ras appears to be affected by mutations in the N-terminal region, and in particular, by those in and neighboring the effector region (residues 32-40) and in the region (residues 56-59) flanking the N-terminal of Switch II. The abilities to bind Raf-1 and to induce neurite outgrowth of pheochromocytoma (PC) 12 cells correlate to each other for 22 Ras mutants. However, mutation A59T, which does not reduce the neurite-inducing or transforming activities, abolishes the ability to bind Raf-1. In contrast, mutations Y32F, K42A and L53A, which impair the neurite-inducing activity of Ras, have no effect on the Ras.Raf-1 association. Partially reduced Raf-1-binding ability was observed for mutants V29A, S39A, Y40W, R41A, V44A, L56A and T58A, which exhibit full neurite-inducing activity, and also for mutant V45E, which has no activity of neurite induction.

  5. A Gaia-PS1-SDSS (GPS1) Proper Motion Catalog Covering 3/4 of the Sky

    NASA Astrophysics Data System (ADS)

    Tian, Hai-Jun; Gupta, Prashansa; Sesar, Branimir; Rix, Hans-Walter; Martin, Nicolas F.; Liu, Chao; Goldman, Bertrand; Platais, Imants; Kudritzki, Rolf-Peter; Waters, Christopher Z.

    2017-09-01

    We combine Gaia DR1, PS1, Sloan Digital Sky Survey (SDSS), and 2MASS astrometry to measure proper motions for 350 million sources across three-fourths of the sky down to a magnitude of {m}r˜ 20. Using positions of galaxies from PS1, we build a common reference frame for the multi-epoch PS1, single-epoch SDSS and 2MASS data, and calibrate the data in small angular patches to this frame. As the Gaia DR1 excludes resolved galaxy images, we choose a different approach to calibrate its positions to this reference frame: we exploit the fact that the proper motions of stars in these patches are linear. By simultaneously fitting the positions of stars at different epochs of—Gaia DR1, PS1, SDSS, and 2MASS—we construct an extensive catalog of proper motions dubbed GPS1. GPS1 has a characteristic systematic error of less than 0.3 {mas} {{yr}}-1 and a typical precision of 1.5-2.0 {mas} {{yr}}-1. The proper motions have been validated using galaxies, open clusters, distant giant stars, and QSOs. In comparison with other published faint proper motion catalogs, GPS1's systematic error (< 0.3 {mas} {{yr}}-1) should be nearly an order of magnitude better than that of PPMXL and UCAC4 (> 2.0 {mas} {{yr}}-1). Similarly, its precision (˜1.5 {mas} {{yr}}-1) is a four-fold improvement relative to PPMXL and UCAC4 (˜6.0 {mas} {{yr}}-1). For QSOs, the precision of GPS1 is found to be worse (˜2.0-3.0 {mas} {{yr}}-1), possibly due to their particular differential chromatic refraction. The GPS1 catalog will be released online and be available via the VizieR Service and VO Service.

  6. ADCC employing an NK cell line (haNK) expressing the high affinity CD16 allele with avelumab, an anti-PD-L1 antibody.

    PubMed

    Jochems, Caroline; Hodge, James W; Fantini, Massimo; Tsang, Kwong Y; Vandeveer, Amanda J; Gulley, James L; Schlom, Jeffrey

    2017-08-01

    NK-92 cells, and their derivative, designated aNK, were obtained from a patient with non-Hodgkin lymphoma. Prior clinical studies employing adoptively transferred irradiated aNK cells have provided evidence of clinical benefit and an acceptable safety profile. aNK cells have now been engineered to express IL-2 and the high affinity (ha) CD16 allele (designated haNK). Avelumab is a human IgG1 anti-PD-L1 monoclonal antibody, which has shown evidence of clinical activity in a range of human tumors. Prior in vitro studies have shown that avelumab has the ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells when combined with NK cells. In the studies reported here, the ability of avelumab to enhance the lysis of a range of human carcinoma cells by irradiated haNK cells via the ADCC mechanism is demonstrated; this ADCC is shown to be inhibited by anti-CD16 blocking antibody and by concanamycin A, indicating the use of the granzyme/perforin pathway in tumor cell lysis. Studies also show that while NK cells have the ability to lyse aNK or haNK cells, the addition of NK cells to irradiated haNK cells does not inhibit haNK-mediated lysis of human tumor cells, with or without the addition of avelumab. Avelumab-mediated lysis of tumor cells by irradiated haNK cells is also shown to be similar to that of NK cells bearing the V/V Fc receptor high affinity allele. These studies thus provide the rationale for the clinical evaluation of the combined use of avelumab with that of irradiated adoptively transferred haNK cells. © 2017 UICC.

  7. Expression of the hemagglutinin HA1 subunit of the equine influenza virus using a baculovirus expression system.

    PubMed

    Sguazza, Guillermo H; Fuentealba, Nadia A; Tizzano, Marco A; Galosi, Cecilia M; Pecoraro, Marcelo R

    2013-01-01

    Equine influenza virus is a leading cause of respiratory disease in horses worldwide. Disease prevention is by vaccination with inactivated whole virus vaccines. Most current influenza vaccines are generated in embryonated hens' eggs. Virions are harvested from allantoic fluid and chemically inactivated. Although this system has served well over the years, the use of eggs as the substrate for vaccine production has several well-recognized disadvantages (cost, egg supply, waste disposal and yield in eggs). The aim of this study was to evaluate a baculovirus system as a potential method for producing recombinant equine influenza hemagglutinin to be used as a vaccine. The hemagglutinin ectodomain (HA1 subunit) was cloned and expressed using a baculovirus expression vector. The expression was determined by SDS-PAGE and immunoblotting. A high yield, 20μg/ml of viral protein, was obtained from recombinant baculovirus-infected cells. The immune response in BALB/c mice was examined following rHA1 inoculation. Preliminary results show that recombinant hemagglutinin expressed from baculovirus elicits a strong antibody response in mice; therefore it could be used as an antigen for subunit vaccines and diagnostic tests. Copyright © 2013 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.

  8. Angelica archengelica extract induced perturbation of rat skin and tight junctional protein (ZO-1) of HaCaT cells

    PubMed Central

    Kaushal, N.; Naz, S.; Tiwary, AK.

    2011-01-01

    Background and purpose of the study Herbal enhancers compared to the synthetic ones have shown less toxis effects. Coumarins have been shown at concentrations inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ) permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The purpose of this study was to evaluate the influence of ethanolic extract of Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT cells. Methods Transepidermal water loss (TEWL) from the rat skin treated with different concentrations of AA-E was assessed by Tewameter. Scanning and Transmission Electron Microscopy (TEM) on were performed on AA-E treated rat skin portions. The possibility of AA-E influence on the architecture of tight junctions by adverse effect on the cytoplasmic ZO-1 in HaCaT cells was investigated. Finally, the systemic delivery of repaglinide from the optimized transdermal formulation was investigated in rats. Results The permeation of repaglinide across excised rat epidermis was 7-fold higher in the presence of AA-E (5% w/v) as compared to propylene glycol:ethanol (7:3) mixture. The extract was found to perturb the lipid microconstituents in both excised and viable rat skin, although, the effect was less intense in the later. The enhanced permeation of repaglinide across rat epidermis excised after treatment with AA-E (5% w/v) for different periods was in concordance with the high TEWL values of similarly treated viable rat skin. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. Treatment of HaCaT cell line with AA-E (0.16% w/v) for 6 hrs influenced ZO-1 as evidenced by reduced immunofluorescence of anti-TJP1 (ZO-1) antibody in Confocal Laser Scanning Microscopy studies (CLSM) studies. The plasma

  9. Spatial boundary of urban 'acid islands' in southern China.

    PubMed

    Du, E; de Vries, W; Liu, X; Fang, J; Galloway, J N; Jiang, Y

    2015-07-27

    Elevated emissions of sulfur dioxide, nitrogen oxides and ammonia in China have resulted in high levels of sulfur and nitrogen deposition, being contributors to soil acidification, especially in and near large cities. However, knowledge gaps still exist in the way that large cities shape spatial patterns of acid deposition. Here, we assessed the patterns of pH, sulfate, nitrate and ammonium in bulk precipitation and throughfall in southern China's forests by synthesizing data from published literature. Concentrations and fluxes of sulfate, nitrate and ammonium in bulk precipitation and throughfall exhibited a power-law increase with a closer distance to the nearest large cities, and accordingly pH showed a logarithmic decline. Our findings indicate the occurrence of urban 'acid islands' with a critical radius of approximately 70 km in southern China, receiving potential acid loads of more than 2 keq ha(-1) yr(-1). These urban acid islands covered an area of 0.70 million km(2), accounting for nearly 30% of the land area in southern China. Despite a significant capacity to neutralize acids in precipitation, our analysis highlights a substantial contribution of ammonium to potential acid load. Our results suggest a joint control on emissions of multiple acid precursors from urban areas in southern China.

  10. [Promoting effect of cyclin D1 overexpression on proliferation and epithelial mesenchymal transition of cervical squamous cell carcinoma SiHa cells].

    PubMed

    Wang, P; Liu, S; Cheng, B; Wu, X Z; Ding, S S; Xu, L; Liu, Y; Duan, L; Sun, S Z

    2017-03-08

    Objective: To study effects of cyclin D1 overexpression on the proliferation and differentiation of cervical squamous cell carcinoma SiHa cells and to investigate related signaling molecules. Methods: Primers were designed to amplify the full length of cyclin D1 gene and cyclin D1 gene was amplified by PCR for constructing pcDNA3.1 plasmid vector. The construct was then transfected into SiHa cells, and the cells with stable overexpression of cyclin D1 were established, cyclin D1 gene and protein expression were detected by RT-PCR and Western blot, respectively. Cell growth curve was documented by MTT assay. CK7, E-cadherin, vimentin, Snail gene and protein expression in transfected cells were detected by RT-PCR and Western blot. RT-PCR was used to detect the mRNA expression of proliferation and differentiation-related genes like CDK4, CDK2, p21, p27, cyclin E, Rb, E2F, E6/E7 and Ki-67. After synchronization of cells, RT-PCR was used to detect of cyclin D1 and p21 mRNA expression at different time points of the cell cycle. Results: The G-3 cells with cyclin D1 overexpression were successfully established. The growth curve and Ki-67 mRNA expression accelerated in G-3 cells.Vimentin and Snail expression significantly increased at both gene and protein levels, while E-cadherin, CK7 gene and protein expression significantly decreased, indicating epithelial mesenchymal transitionoccurred in G-3 cells.Meanwhile, mRNA expression of cyclin D1, CDK4, CDK2, p21, p27, cyclin E, E2F and Rb increased, while E6/E7 and p16 showed no significant change. The expression trends of p21 and cyclin D1 were almost identical with fluctuation at different time points in the cell cycle. Conclusions: Overexpression of cyclin D1 induced by gene transfection promotes proliferation and epithelial mesenchymal transition in SiHa cells.The process is accompanied by up-regulation of CDK4, CDK2, p21, p27 and cyclin E genes.p21 expression increases synchronously with cyclin D1, suggesting a regulatory

  11. Trichonomas vaginalis Metalloproteinase Induces Apoptosis of SiHa Cells through Disrupting the Mcl-1/Bim and Bcl-xL/Bim Complexes

    PubMed Central

    Zhou, Wei; Koh, Young-Bok; Yang, Jung-Bo; Yoo, Heon-Jong; Lee, Min-A; Ryu, Jae-Sook; Noh, Heung-Tae; Kwon, Jaeyul; Lee, Young-Ha

    2014-01-01

    To elucidate the roles of metalloproteinases and the Bcl-2 family of proteins in Trichovaginalis. vaginalis-induced apoptosis in human cervical cancer cells (SiHa cells) and vaginal epithelial cells (MS74 cells), SiHa cells and MS74 cells were incubated with live T. vaginalis, T. vaginalis excretory and secretory products (ESP), and T. vaginalis lysates, either with or without the specific metalloproteinase inhibitor 1,10-phenanthroline (1,10-PT), and examined apoptotic events and Bcl-2 signaling. The live T. vaginalis and the T. vaginalis ESP induced the release of cytochrome c into the cytosol, the activation of caspase-3 and caspase-9, and the cleavage of PARP. Additionally, the live T. vaginalis, but not the T. vaginalis lysate, induced the cleavage of the proapoptotic Bim protein. The live T. vaginalis and the T. vaginalis ESP, but not the T. vaginalis lysate, induced the dose-dependent cleavage of the antiapoptotic Bcl-xL and Mcl-1 proteins and decreased the association levels of Bcl-xL/Bim and Mcl-1/Bim complexes. We performed gelatin zymography and casein-hydrolysis assays on the live T. vaginalis and the T. vaginalis ESP to identify the apoptosis-inducing factor. Both the live T. vaginalis and the ESP contained high levels of metalloproteinases, of which activities were significantly inhibited by 1,10-PT treatment. Furthermore, the 1,10-PT blocked the cleavage of Bcl-xL, Mcl-1, PARP, caspase-3, and caspase-9, as well as the release of cytochrome c into the cytosol, and it significantly increased the association levels of the Bcl-xL/Bim and Mcl-1/Bim protein complexes, returning them to normal levels. Our results demonstrate that T. vaginalis induces mitochondria-dependent apoptosis in SiHa cells through the dissociation of Bcl-xL/Bim and Mcl-1/Bim complexes and that the apoptosis is blocked by the metalloproteinase inhibitor 1,10-PT. These results expand our understanding of the role of metalloproteinases in T. vaginalis-induced apoptosis and the signaling

  12. Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009–10

    PubMed Central

    Kao, Chuan-Liang; Chan, Ta-Chien; Tsai, Chu-Han; Chu, Kuan-Ying; Chuang, Shu-Fang; Lee, Chang-Chun; Li, Zheng-Rong Tiger; Wu, Ko-Wen; Chang, Luan-Yin; Shen, Yea-Huei; Huang, Li-Min; Lee, Ping-Ing; Yang, ChingLai; Compans, Richard; Rouse, Barry T.; King, Chwan-Chuen

    2012-01-01

    The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas -Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post–peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post–peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at

  13. Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses.

    PubMed

    Carter, Donald M; Darby, Christopher A; Johnson, Scott K; Carlock, Michael A; Kirchenbaum, Greg A; Allen, James D; Vogel, Thorsten U; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold; Ross, Ted M

    2017-12-15

    Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long

  14. Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

    PubMed Central

    Carter, Donald M.; Darby, Christopher A.; Johnson, Scott K.; Carlock, Michael A.; Kirchenbaum, Greg A.; Allen, James D.; Vogel, Thorsten U.; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold

    2017-01-01

    ABSTRACT Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long

  15. Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.

    PubMed

    Huang, Wen-Chung; Dai, Yi-Wen; Peng, Hui-Ling; Kang, Chiao-Wei; Kuo, Chun-Yu; Liou, Chian-Jiun

    2015-07-01

    Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Ozone and fine particle in the western Yangtze River Delta: an overview of 1 yr data at the SORPES station

    NASA Astrophysics Data System (ADS)

    Ding, A. J.; Fu, C. B.; Yang, X. Q.; Sun, J. N.; Zheng, L. F.; Xie, Y. N.; Herrmann, E.; Nie, W.; Petäjä, T.; Kerminen, V.-M.; Kulmala, M.

    2013-06-01

    This work presents an overview of 1 yr measurements of ozone (O3) and fine particular matter (PM2.5) and related trace gases at a recently developed regional background site, the Station for Observing Regional Processes of the Earth System (SORPES), in the western part of the Yangtze River Delta (YRD) in eastern China. Ozone and PM2.5 showed strong seasonal cycles but with contrast patterns: O3 reached a maximum in warm seasons but PM2.5 in cold seasons. Correlation analysis suggests a VOC-sensitive regime for O3 chemistry and a formation of secondary aerosols under conditions of high O3 in summer. Compared with the National Ambient Air Quality Standards in China, our measurements report 15 days of O3 exceedance and 148 days of PM2.5 exceedance during the 1 yr period, suggesting a severe air pollution situation in this region. Case studies for typical O3 and PM2.5 episodes demonstrated that these episodes were generally associated with an air mass transport pathway over the mid-YRD, i.e., along the Nanjing-Shanghai axis with its city clusters, and showed that synoptic weather played an important role in air pollution, especially for O3. Agricultural burning activities caused high PM2.5 and O3 pollution during harvest seasons, especially in June. A calculation of potential source contributions based on Lagrangian dispersion simulations suggests that emissions from the YRD contributed to over 70% of the O3 precursor CO, with a majority from the mid-YRD. North-YRD and the North China Plain are the main contributors to PM2.5 pollution in this region. This work shows an important environmental impact from industrialization and urbanization in the YRD region, and suggests an urgent need for improving air quality in these areas through collaborative control measures among different administrative regions.

  17. Incidence and prevalence of diabetes in children aged <15 yr in Fiji, 2001-2012.

    PubMed

    Ogle, Graham D; Morrison, Melinda K; Silink, Martin; Taito, Rigamoto S

    2016-05-01

    Determine the incidence and prevalence of diabetes in children <15 yr in Fiji. Data on all new cases from 2001 to 2012 was collected from the three paediatric diabetes services through the International Diabetes Federation Life for a Child Program. There was no formal secondary ascertainment source, however the medical community is small and all known cases are believed to be included. Forty-two children aged <15 yr were diagnosed from 2001 to 2012. Twenty-eight were type 1 (66.7%), 13 type 2 (31.0%), and 1 (2.4%) had neonatal diabetes (INS gene mutation). For type 1, the mean ± standard deviation (SD) age of diagnosis was 10.2 ± 2.9 yr, with similar proportions of males and females. Four (14.3%) were native Fijians and 24 (86.7%) were of Indo-Fijian descent (p < 0.001). The mean annual incidence of type 1 in children <15 yr was 0.93/100,000 and prevalence in 2012 was 5.9/100,000. There was no evidence of a rise in incidence, but low numbers would preclude recognition of a small increased rate. For the 13 cases of type 2 diabetes, the mean SD age of diagnosis was 12.2 ± 2.7 yr, 85% were female (p < 0.01), and 85% were of Indo-Fijian descent (p = 0.001). The mean annual incidence of type 2 was 0.43/100,000 and 2012 prevalence was 2.4/100,000. No child with diabetes aged <15 yr died during the 12-yr period. The incidence of type 1 diabetes in Fiji is very low. Furthermore, its occurrence is markedly more frequent in Indo-Fijians than in native Fijians. Type 2 and neonatal diabetes also occur. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Year-round atmospheric wet and dry deposition of nitrogen and phosphorus on water and land surfaces in Nanjing, China.

    PubMed

    Sun, Liying; Li, Bo; Ma, Yuchun; Wang, Jinyang; Xiong, Zhengqin

    2013-06-01

    The dry deposition of ammonium, nitrate, and total phosphorus (TP) to both water (DW) and land (DD) surfaces, along with wet deposition, were simultaneously monitored from March 2009 to February 2011 in Nanjing, China. Results showed that wet deposition of total phosphorus was 1.1 kg phosphorus ha (-1)yr(-1), and inorganic nitrogen was 28.7 kg nitrogen ha (-1)yr(-1), with 43% being ammonium nitrogen. Dry deposition of ammonium, nitrate, and total phosphorus, measured by the DW/DD method, was 7.5/2.2 kg nitrogen ha (-1)yr(-1), 6.3/ 4.9 kg nitrogen ha (-1)yr(-1), and 1.9/0.4 kg phosphorus ha (-1)yr(-1), respectively. Significant differences between the DW and DD methods indicated that both methods should be employed simultaneously when analyzing deposition to aquatic and terrestrial ecosystems in watershed areas. The dry deposition of ammonium, nitrate, and total phosphorus contributed 38%, 28%, and 63%, respectively, to the total deposition in the simulated aquatic ecosystem; this has significance for the field of water eutrophication control.

  19. Fab MAbs specific to HA of influenza virus with H5N1 neutralizing activity selected from immunized chicken phage library.

    PubMed

    Pitaksajjakul, Pannamthip; Lekcharoensuk, Porntippa; Upragarin, Narin; Barbas, Carlos F; Ibrahim, Madiha Salah; Ikuta, Kazuyoshi; Ramasoota, Pongrama

    2010-05-14

    Hemagglutinin protein (HA) was considered to be the primary target for monoclonal antibody production. This protein not only plays an important role in viral infections, but can also be used to differentiate H5N1 virus from other influenza A viruses. Hence, for diagnostic and therapeutic applications, it is important to develop anti-HA monoclonal antibody (MAb) with high sensitivity, specificity, stability, and productivity. Nine unique Fab MAbs were generated from chimeric chicken/human Fab phage display library constructed from cDNA derived from chickens immunized with recombinant hemagglutinin protein constructed from H5N1 avian influenza virus (A/Vietnam/1203/04). The obtained Fab MAbs showed several characteristics for further optimization and development-three clones were highly specific to only H5N1 virus. This finding can be applied to the development of H5N1 diagnostic testing. Another clone showed neutralization activity that inhibited H5N1 influenza virus infection in Madin-Darby canine kidney (MDCK) cells. In addition, one clone showed strong reactivity with several of the influenza A virus subtypes tested. The conversion of this clone to whole IgG is a promising study for a cross-neutralization activity test. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  20. Remapping of the stripe rust resistance gene Yr10 in common wheat.

    PubMed

    Yuan, Cuiling; Wu, Jingzheng; Yan, Baiqiang; Hao, Qunqun; Zhang, Chaozhong; Lyu, Bo; Ni, Fei; Caplan, Allan; Wu, Jiajie; Fu, Daolin

    2018-06-01

    Yr10 is an important gene to control wheat stripe rust, and the search for Yr10 needs to be continued. Wheat stripe rust or yellow rust is a devastating fungal disease caused by Puccinia striiformis f. sp. tritici (Pst). Host disease resistance offers a primary source for controlling wheat stripe rust. The stripe rust resistance gene Yr10 confers the race-specific resistance to most tested Pst races in China including CYR29. Early studies proposed that Yr10 was a nucleotide-binding site, leucine-rich repeat gene archived as GenBank accession AF149112 (hereafter designated the Yr10 candidate gene or Yr10 CG ). In this study, we revealed that 15 Chinese wheat cultivars positive for Yr10 CG are susceptible to CYR29. We then expressed the Yr10 CG cDNA in the common wheat 'Bobwhite'. The Yr10 CG -cDNA positive transgenic plants were also susceptible to CYR29. Thus, it is highly unlikely that Yr10 CG corresponds to the Yr10 resistance gene. Using the Yr10 donor 'Moro' and the Pst-susceptible wheat 'Huixianhong', we generated two F 3 populations that displayed a single Mendelian segregation on the Yr10 gene, and used them to remap the Yr10 gene. Six markers were placed in the Yr10 region, with the Yr10 CG gene now mapping about 1.2-cM proximal to the Yr10 locus and the Xsdauw79 marker is completely linked to the Yr10 locus. Apparently, the Yr10 gene has not yet been identified. Fine mapping and positional cloning of Yr10 is important for gene pyramiding for stripe rust resistance in wheat.

  1. Calculated trends and the atmospheric abundance of 1,1,1,2-tetrafluoroethane, 1,1-dichloro-1-fluoroethane, and 1-chloro-1,1-difluoroethane using automated in-situ gas chromatography-mass spectrometry measurements recorded at Mace Head, Ireland, from October 1994 to March 1997

    NASA Astrophysics Data System (ADS)

    Simmonds, P. G.; O'Doherty, S.; Huang, J.; Prinn, R.; Derwent, R. G.; Ryall, D.; Nickless, G.; Cunnold, D.

    1998-01-01

    The first in-situ measurements by automated gas chromatograph-mass spectrometer are reported for 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1-dichloro-1-fluoroethane, (HCFC-141b), and 1-chloro-1,1-difluoroethane, (HCFC-142b). These compounds are steadily replacing the chlorofluorocarbons (CFCs) as refrigerants, foam-blowing agents, and solvents. The concentrations of all three compounds are shown to be rapidly increasing in the atmosphere, with 134a increasing at a rate of 2.05±0.02 ppt yr-1 over the 30 months of observations. Similarly, 141b and 142b increased at rates of 2.49±0.03 and 1.24±0.02 ppt yr-1, respectively, over the same period. The concentrations recorded at the atmospheric research station at Mace Head, Ireland, on January 1, 1996, the midpoint of the time series, were 3.67 ppt (134a), 7.38 ppt (141b), and 8.78 ppt (142b). From these observations we optimally estimate the HCFC and HFC emissions using a 12-box global model and OH concentrations derived from global 1,1,1-trichloroethane (CCl3CH3) measurements. Comparing two methods of estimating emissions with independent industry estimates shows satisfactory agreement for 134a and 141b, while for 142b, industry estimates are less than half those required to explain our observations.

  2. In vitro testing of calcium phosphate (HA, TCP, and biphasic HA-TCP) whiskers.

    PubMed

    Jalota, Sahil; Bhaduri, Sarit B; Tas, A Cuneyt

    2006-09-01

    Calcium phosphate [single-phase hydroxyapatite (HA, Ca(10)(PO(4))(6)(OH)(2)), single-phase tricalcium phosphate (beta-TCP, Ca(3)(PO(4))(2)), and biphasic HA-TCP] whiskers were formed by using a novel microwave-assisted molten salt mediated process. Aqueous solutions containing NaNO(3), HNO(3), Ca(NO(3))(2) x 4H(2)O, and KH(2)PO(4) (with or without urea) were used as starting reagents. These solutions were irradiated in a household microwave oven for 5 min. As-recovered precursors were then simply stirred in water at room temperature for 1 h to obtain the whiskers of the desired calcium phosphate (CaP) bioceramics. These whiskers were evaluated, respectively, in vitro by (1) soaking those in synthetic body fluid (SBF) solutions at 37 degrees C for one week, and (2) performing cell attachment and total protein assay tests on the neat whiskers by using a mouse osteoblast cell line (7F2). beta-TCP, HA, and HA-TCP biphasic whiskers were all found to possess apatite-inducing ability when soaked in SBF. SBF-soaked whiskers were found to have BET surface areas ranging from 45 to 112 m(2)/g. Although the osteoblast viability and protein concentrations were found to be the highest on the neat HA whiskers, cells were attached and proliferated on all the whiskers.

  3. Comparison of the laryngoscopy views with the size 1 Miller and Macintosh laryngoscope blades lifting the epiglottis or the base of the tongue in infants and children <2 yr of age.

    PubMed

    Passi, Y; Sathyamoorthy, M; Lerman, J; Heard, C; Marino, M

    2014-11-01

    Miller laryngoscope blades are preferred for laryngoscopy in infants and children <2 yr of age. Despite their long history, the laryngeal view with the Miller blade size 1 has never been compared with that with the Macintosh (MAC) blade in children. This prospective, single-blinded, randomized study was designed to compare the laryngeal views with the size 1 Miller and MAC blades in children <2 yr. With IRB approval, 50 ASA I and II children <2 yr undergoing elective surgery were enrolled. After an inhalation induction and neuromuscular block with i.v. rocuronium 0.5 mg kg(-1), two laryngeal views were obtained with a single blade (Miller or MAC) in each child: one lifting the epiglottis and another lifting the tongue base. The best laryngeal views in each blade position were photographed with a SONY(®) Cyber-shot camera and rated by a blinded anaesthesiologist using the percentage of glottic opening scale. The scores with the Miller blade lifting the epiglottis and the MAC blade lifting the tongue base were similar. The scores with the Miller blade lifting the epiglottis and the tongue base were similar. The scores for the MAC blade lifting the tongue base were greater than those lifting the epiglottis (95% confidence interval: 7.6-26.8) (P=0.0004). In infants and children <2 yr of age, optimal laryngeal views may be obtained with either the Miller size 1 blade lifting the epiglottis or with the Miller or MAC blades lifting the tongue base. NCT01717872 at Clinical Trials.gov. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Molecular Dynamics Analysis of Antibody Recognition and Escape by Human H1N1 Influenza Hemagglutinin

    PubMed Central

    Ieong, Pek; Amaro, Rommie E.; Li, Wilfred W.

    2015-01-01

    The antibody immunoglobulin (Ig) 2D1 is effective against the 1918 hemagglutinin (HA) and also known to cross-neutralize the 2009 pandemic H1N1 influenza HA through a similar epitope. However, the detailed mechanism of neutralization remains unclear. We conducted molecular dynamics (MD) simulations to study the interactions between Ig-2D1 and the HAs from the 1918 pandemic flu (A/South Carolina/1/1918, 18HA), the 2009 pandemic flu (A/California/04/2009, 09HA), a 2009 pandemic flu mutant (A/California/04/2009, 09HA_mut), and the 2006 seasonal flu (A/Solomon Islands/3/2006, 06HA). MM-PBSA analyses suggest the approximate free energy of binding (ΔG) between Ig-2D1 and 18HA is −74.4 kcal/mol. In comparison with 18HA, 09HA and 06HA bind Ig-2D1 ∼6 kcal/mol (ΔΔG) weaker, and the 09HA_mut bind Ig-2D1 only half as strong. We also analyzed the contributions of individual epitope residues using the free-energy decomposition method. Two important salt bridges are found between the HAs and Ig-2D1. In 09HA, a serine-to-asparagine mutation coincided with a salt bridge destabilization, hydrogen bond losses, and a water pocket formation between 09HA and Ig-2D1. In 09HA_mut, a lysine-to-glutamic-acid mutation leads to the loss of both salt bridges and destabilizes interactions with Ig-2D1. Even though 06HA has a similar ΔG to 09HA, it is not recognized by Ig-2D1 in vivo. Because 06HA contains two potential glycosylation sites that could mask the epitope, our results suggest that Ig-2D1 may be active against 06HA only in the absence of glycosylation. Overall, our simulation results are in good agreement with observations from biological experiments and offer novel mechanistic insights, to our knowledge, into the immune escape of the influenza virus. PMID:26039171

  5. Evidence of a prolonged drought ca. 4200 yr BP correlated with prehistoric settlement abandonment from the Gueldaman GLD1 Cave, N-Algeria

    NASA Astrophysics Data System (ADS)

    Ruan, J.; Kherbouche, F.; Genty, D.; Blamart, D.; Cheng, H.; Dewilde, F.; Hachi, S.; Edwards, L. R.; Régnier, E.; Michelot, J.-L.

    2015-07-01

    Middle Holocene cultures have been widely studied round the E-Mediterranean basin in the last 30 years and past cultural activities have been commonly linked with regional climate changes. However, in many cases such linkage is equivocal, in part due to existing climatic evidence that has been derived from areas outside the distribution of ancient settlements, leading to uncertainty from complex spatial heterogeneity in both climate and demography. A few high-resolution well-dated paleoclimate records were recently established using speleothems in the Central and E-Mediterranean basin, however, the scarcity of such records in the western part of the Mediterranean prevents us from correlating past climate evolutions across the basin and deciphering climate-culture relation at fine time scales. Here we report the first decadal-resolved Mid-Holocene climate proxy records from the W-Mediterranean basin based on the stable carbon and oxygen isotopes analyses of two U/Th dated stalagmites from the Gueldaman GLD1 Cave in N-Algeria. Comparison of our records with those from Italy and Israel reveals synchronous (multi) centennial dry phases centered at ca. 5600, ca. 5200 and ca. 4200 yr BP across the Mediterranean basin. New calibrated radiocarbon dating constrains reasonably well the age of rich anthropogenic deposits (e.g., faunal remains, pottery, charcoal) excavated inside the cave, which allows the comparison between in situ evidence of human occupation and of climate change. This approach shows that the timing of a prolonged drought at ca. 4400-3800 yr BP blankets the onset of cave abandonment shortly after ca. 4403 cal yr BP, supporting the hypothesis that a climate anomaly may have played a role in this cultural disruption.

  6. Evidence of a prolonged drought ca. 4200 yr BP correlated with prehistoric settlement abandonment from the Gueldaman GLD1 Cave, Northern Algeria

    NASA Astrophysics Data System (ADS)

    Ruan, J.; Kherbouche, F.; Genty, D.; Blamart, D.; Cheng, H.; Dewilde, F.; Hachi, S.; Edwards, R. L.; Régnier, E.; Michelot, J.-L.

    2016-01-01

    Middle Holocene cultures have been widely studied around the Eastern-Mediterranean basin in the last 30 years and past cultural activities have been commonly linked with regional climate changes. However, in many cases such linkage is equivocal, in part due to existing climatic evidence that has been derived from areas outside the distribution of ancient settlements, leading to uncertainty from complex spatial heterogeneity in both climate and demography. A few high-resolution well-dated paleoclimate records were recently established using speleothems in the Central and Eastern-Mediterranean basin, however, the scarcity of such records in the western part of the Mediterranean prevents us from correlating past climate evolutions across the basin and deciphering climate-culture relation at fine timescales. Here we report the first decadal-resolved Mid-Holocene climate proxy records from the Western-Mediterranean basin based on the stable carbon and oxygen isotopes analyses of two U/Th dated stalagmites from the Gueldaman GLD1 Cave in Northern Algeria. Comparison of our records with those from Italy and Israel reveals synchronous (multi) centennial dry phases centered at ca. 5600, ca. 5200 and ca. 4200 yr BP across the Mediterranean basin. New calibrated radiocarbon dating constrains reasonably well the age of rich anthropogenic deposits (e.g., faunal remains, pottery, charcoal) excavated inside the cave, which allows the comparison between in situ evidence of human occupation and of climate change. This approach shows that the timing of a prolonged drought at ca. 4400-3800 yr BP blankets the onset of cave abandonment shortly after ca. 4403 cal yr BP, supporting the hypothesis that a climate anomaly may have played a role in this cultural disruption.

  7. Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry.

    PubMed

    Clements, Mark A; Foster, Nicole C; Maahs, David M; Schatz, Desmond A; Olson, Beth A; Tsalikian, Eva; Lee, Joyce M; Burt-Solorzano, Christine M; Tamborlane, William V; Chen, Vincent; Miller, Kellee M; Beck, Roy W

    2016-08-01

    Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes-related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre-adolescence-to-adolescence and adolescence-to-young adulthood, and the demographic and clinical factors associated with these changes. Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements. HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age-centered HbA1c (p < 0.001). For the 8-18 cohort, insulin pump use, age of onset, and health insurance were significant in predicting individual HbA1c trajectory. Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Soccer increases bone mass in prepubescent boys during growth: a 3-yr longitudinal study.

    PubMed

    Zouch, Mohamed; Zribi, Anis; Alexandre, Christian; Chaari, Hamada; Frere, Delphine; Tabka, Zouhair; Vico, Laurence

    2015-01-01

    The aim of this study was to examine the effect of 3-yr soccer practice on bone acquisition in prepubescent boys. We investigated 65 boys (aged 10-13 yr, Tanner stage I) at baseline, among which only 40 boys (Tanner stages II and III) have continued the 3-yr follow-up: 23 soccer players (F) completed 2-5 h of training plus 1 competition game per week and 17 controls (C). Bone mineral density (BMD, g/cm(2)) and bone mineral content (BMC, g) were measured by dual-energy X-ray absorptiometry at different sites. At baseline, BMD was higher in soccer players than in controls in the whole body and legs. In contrast, there was nonsignificant difference BMD in head, femoral neck, arms, and BMC in all measured sites between groups. At 3-yr follow-up, soccer players were found to have higher BMD and BMC at all sites than controls, except for head BMD and BMC and arms BMC in which the difference was nonsignificant between groups. During the 3-yr follow-up, the soccer players were found to gain significantly more in lumbar spine (31.2% ± 2.9% vs 23.9% ± 2.1%; p < 0.05), femoral neck (24.1% ± 1.8% vs 11.4% ± 1.9%; p < 0.001), whole body (16.5% ± 1.4% vs 11.8% ± 1.5%; p < 0.05), and nondominant arm BMD (18.2% ± 1.4% vs 13.6% ± 1.7%; p < 0.05) as well as lumbar spine (62.5% ± 20.1% vs 39.5% ± 20.1%; p < 0.001), femoral neck, (37.7% ± 14.2% vs 28.9% ± 12.8%; p < 0.05) and nondominant arm BMC (68.6% ± 22.9% vs 50.1% ± 22.4%; p < 0.05) than controls. In contrast, soccer players have less %BMD and %BMC changes in the head than controls. A nonsignificant difference was found in legs, dominant arm, head %BMD and %BMC changes, and whole-body %BMC changes between groups. In summary, we suggest that soccer has an osteogenic effect BMD and BMC in loaded sites in pubertal soccer players. The increased bone mass induced by soccer training in the stressed sites was associated to a decreased skull bone mass after 3 yr of follow-up. Copyright © 2015 The International Society for

  9. Highly stretchable HA/SA hydrogels for tissue engineering.

    PubMed

    Zhu, Chengcheng; Yang, Rui; Hua, Xiaobin; Chen, Hong; Xu, Jumei; Wu, Rile; Cen, Lian

    2018-04-01

    A highly stretchable hyaluronic acid (HA)/sodium alginate (SA) hydrogel was developed in this study based on an interpenetrating polymer network. HA/SA hydrogels were prepared by mixing two polysaccharides followed by covalent crosslinking via epoxy groups on HA molecules and ionic crosslinking via divalent ions on SA chains sequentially. The effect of HA/SA ratio on the pore size and distribution, swelling ratio, elongation and rheological properties as well as protein loading and release properties of HA/SA hydrogels was explored. Moreover, a surface modification method, layer-by-layer (LBL) assembly technique, was applied to modify the hydrogel to evaluate the hydrogel's tenability in varying biological performance. It was then shown that the hydrogels had the pore sizes ranging from 100 to 50 μm. With the increase in SA content of the resulting hydrogels, the pore size, swelling ratio, and storage modulus (G') and loss modulus (G″) of the hydrogel all decreased, whereas the in vitro bulk weight loss was fastened. Moreover, elongation at break (EB) value increased first, reached a peak value and then decreased, that is HA8/SA1 (HA:SA = 8:1) had the highest EB value of 417%. This hydrogel could retain 33.2% of the pre-loaded protein even after 72 h, which could be further attenuated when LBL was used to shell the hydrogel. The growth of fibroblasts on HA8/SA1 hydrogel gave preliminary assessment on its suitability as a cellular carrier, while the LBL modified HA8/SA1 hydrogel also favored the anchoring of keratinocytes, further enhancing its cell carrier role for tissue regeneration, especially skin engineering.

  10. Miscanthus biomass productivity within US croplands and its potential impact on soil organic carbon

    DOE PAGES

    Mishra, Umakant; Torn, Margaret S.; Fingerman, Kevin

    2012-08-10

    Interest in bioenergy crops is increasing due to their potential to reduce greenhouse gas emissions and dependence on fossil fuels. Here, we combined process-based and geospatial models to estimate the potential biomass productivity of miscanthus and its potential impact on soil carbon stocks in the croplands of the continental United States. The optimum (climatic potential) rainfed productivity for field-dried miscanthus biomass ranged from 1 to 23 Mg biomass ha -1 yr -1, with a spatial average of 13 Mg ha -1 yr -1 and a coefficient of variation of 30%. This variation resulted primarily from the spatial heterogeneity of effectivemore » rainfall, growing degree days, temperature, and solar radiation interception. Cultivating miscanthus would result in a soil organic carbon (SOC) sequestration at the rate of 0.16–0.82 Mg C ha -1 yr -1 across the croplands due to cessation of tillage and increased biomass carbon input into the soil system. We identified about 81 million ha of cropland, primarily in the eastern United States, that could sustain economically viable (>10 Mg ha -1 yr -1) production without supplemental irrigation, of which about 14 million ha would reach optimal miscanthus growth. To meet targets of the US Energy Independence and Security Act of 2007 using miscanthus as feedstock, 19 million ha of cropland would be needed (spatial average 13 Mg ha -1 yr -1) or about 16% less than is currently dedicated to US corn-based ethanol production.« less

  11. Renner-Teller quantum dynamics of NH(a(1)Delta) + H reactions on the NH(2) A(2)A(1) and X(2)B(1) coupled surfaces.

    PubMed

    Defazio, P; Gamallo, P; González, M; Petrongolo, C

    2010-09-16

    Four reactions NH(a1Delta) + H′(2S) are investigated by the quantum mechanical real wavepacket method, taking into account nonadiabatic Renner-Teller (RT) and rovibronic Coriolis couplings between the involved states. We consider depletion (d) to N(2D) + H2(X1Sigmag+), exchange (e) to NH′(a1Delta) + H(2S), quenching (q) to NH(X3Sigma-) + H′(2S), and exchange-quenching (eq) to NH′(X3Sigma-) + H(2S). We extend our RT theory to a general AB + C collision using a geometry-dependent but very simple and empirical RT matrix element. Reaction probabilities, cross sections, and rate constants are presented, and RT results are compared with Born-Oppenheimer (BO), experimental, and semiclassical data. The nonadiabatic couplings open two new channels, (q) and (eq), and increase the (d) and (e) reactivity with respect to the BO one, when NH(a1Delta) is rotationally excited. In this case, the quantum cross sections are larger than the semiclassical ones at low collision energies. The calculated rate constants at 300 K are k(d) = 3.06, k(e) = 3.32, k(q) = 1.44, and k(eq) = 1.70 in 10(-11) cm3 s(-1) compared with the measured values k(d) = (3.2 =/- 1.7), k(q + eq) = (1.7 +/- 0.3), and k(total) = (4.8 +/- 1.7). The theoretical depletion rate is thus in good agreement with the experimental value, but the quenching and total rates are overestimated, because the present RT couplings are too large. This discrepancy is probably due to our simple and empirical RT matrix element.

  12. 4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling

    PubMed Central

    Kim, Sang-Cheol; Kang, Jung-Il; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Kim, Young-Heui; Kim, Ki-Ho; Ko, Ji-Hee; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2017-01-01

    4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-β1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-β1-induced cell cycle arrest. PMID:28190316

  13. 4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling.

    PubMed

    Kim, Sang-Cheol; Kang, Jung-Il; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Kim, Young-Heui; Kim, Ki-Ho; Ko, Ji-Hee; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2017-07-01

    4- O -methylhonokiol, a neolignan compound from Magnolia Officinalis , has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4- O -methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4- O -methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4- O -methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4- O -methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4- O -methylhonokiol. 4- O -methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4- O -methylhonokiol could inhibit TGF-β1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4- O -methylhonokiol might have protective action on TGF-β1-induced cell cycle arrest.

  14. [Construction of a recombinant HVT virus expressing the HA gene of avian influenza virus H5N1 via Rde/ET recombination system].

    PubMed

    Lan, Desong; Shi, Xingming; Wang, Yunfeng; Liu, Changjun; Wang, Mei; Cui, Hongyu; Tian, Guobin; Li, Jisong; Tong, Guangzhi

    2009-01-01

    In recent years,manipulation of large herpesvirus genomes has been facilitated by using bacterial artificial chromosome (BAC) vectors. We have previously reported the construction of the BAC clones (HVT BACs) of herpesvirus of turkey (HVT). With these BAC clones in hand,we manipulated the genome of HVT by utilizing Red/ET recombination system, and developed a biologically safe live vaccine based on the HVT BACs. In this two-step approach, we first transformed the plasmid pRedET into the DH10B competent cells that carried the HVT BACs,and added inducer L-arabinose into the cells. We prepared the cells into competent cells and electroporated the linear rpsL-neo counter-selection/selection cassette flanked by the 50 bp long homology arms into the cells. So the functional cassette was inserted into the U(S)2 locus. Only colonies carrying the modified BAC would survive Kanamycin selection on the agar plates. The successful integration of the rpsL-neo cassette was monitored by PCR and Streptomycin selection, for the insertion of rpsL-neo cassette cells will become Streptomycin sensitive. Secondly, in the same way, we replaced the rpsL-neo cassette with the hemagglutinin (HA) gene of (HPAIV) A/Goose/ Guangdong/1/96(H5N1) flanked by the same homology arms. Only colonies which lost the rpsL-neo cassette will grow on Streptomycin containing plates. Finally, we obtained many colonies of which the HA gene of the AIV was inserted into the U(S)2 locus to be modified of HVT. And we reconstituted one recombinant virus from transfecting one of these BAC clones DNA into chick embryo fibroblasts (CEFs). We achieved one rescued recombinant virus which designated as rHVT-HA3. The H5 subtype HA gene expression in this recombinant virus rHVT-HA3 was confirmed by immunofluorescence assay.

  15. Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus

    PubMed Central

    2013-01-01

    Background Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can

  16. Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation.

    PubMed

    Raghavendran, Hanumantha Rao Balaji; Mohan, Saktiswaren; Genasan, Krishnamurithy; Murali, Malliga Raman; Naveen, Sangeetha Vasudevaraj; Talebian, Sepehr; McKean, Robert; Kamarul, Tunku

    2016-03-01

    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Molecular Mapping of Stripe Rust Resistance Gene Yr76 in Winter Club Wheat Cultivar Tyee.

    PubMed

    Xiang, C; Feng, J Y; Wang, M N; Chen, X M; See, D R; Wan, A M; Wang, T

    2016-10-01

    Tyee, one of the wheat cultivars used to differentiate races of Puccinia striiformis f. sp. tritici in the United States, was identified to have a single gene for all-stage resistance, tentatively named YrTye. To map the gene, Tyee was crossed with 'Avocet Susceptible' (AvS). Genetic analysis of the F 1 , F 2 , F 2:3 , and BC 1 progenies confirmed a single dominant gene for resistance to race PSTv-37 that is avirulent to YrTye. A mapping population of 135 F 2 plants was phenotyped with PSTv-37 and the derived F 2:3 lines were tested with races PSTv-37, PSTv-40, and PSTv-79. The F 2 mapping population was genotyped with simple sequence repeat (SSR) markers. A genetic map comprising 13 SSR markers located YrTye in chromosome 3AS flanked distally by SSR marker wmc11 and proximally by wmc532 at 2.6 and 3.4 cM, respectively. Amplification of Chinese Spring 3A deletion lines placed the gene in the distal bin 3AS4-0.45 to 1.00. Because YrTye is different from all formally named Yr genes in chromosomal location, we permanently name the gene Yr76. A near-isogenic line of spring common wheat was developed and selected by testing F 3 lines derived from a AvS*4/Tyee cross with Tyee-avirulent and virulent races and the flanking markers. The specific SSR alleles flanking Yr76 were validated using cultivars and breeding lines with and without the gene, and showed high polymorphisms. The specificity of Yr76 is useful in differentiating P. striiformis f. sp. tritici races, and its tightly linked markers will be useful in developing resistant cultivars when combining the gene with other genes for resistance to stripe rust.

  18. Phosphorus loss from an agricultural watershed as a function of storm size.

    PubMed

    Sharpley, Andrew N; Kleinman, Peter J A; Heathwaite, A Louise; Gburek, William J; Folmar, Gordon J; Schmidt, John P

    2008-01-01

    Phosphorus (P) loss from agricultural watersheds is generally greater in storm rather than base flow. Although fundamental to P-based risk assessment tools, few studies have quantified the effect of storm size on P loss. Thus, the loss of P as a function of flow type (base and storm flow) and size was quantified for a mixed-land use watershed (FD-36; 39.5 ha) from 1997 to 2006. Storm size was ranked by return period (<1, 1-3, 3-5, 5-10, and >10 yr), where increasing return period represents storms with greater peak and total flow. From 1997 to 2006, storm flow accounted for 32% of watershed discharge yet contributed 65% of dissolved reactive P (DP) (107 g ha(-1) yr(-1)) and 80% of total P (TP) exported (515 g ha(-1) yr(-1)). Of 248 storm flows during this period, 93% had a return period of <1 yr, contributing most of the 10-yr flow (6507 m(3) ha(-1); 63%) and export of DP (574 g ha(-1); 54%) and TP (2423 g ha(-1); 47%). Two 10-yr storms contributed 23% of P exported between 1997 and 2006. A significant increase in storm flow DP concentration with storm size (0.09-0.16 mg L(-1)) suggests that P release from soil and/or area of the watershed producing runoff increase with storm size. Thus, implementation of P-based Best Management Practice needs to consider what level of risk management is acceptable.

  19. Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies

    PubMed Central

    Kirchenbaum, Greg A.; Carter, Donald M.

    2015-01-01

    ABSTRACT Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus. IMPORTANCE The influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor-binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses

  20. Calcium depletion in a Southeastern United States forest ecosystem

    USGS Publications Warehouse

    Huntington, T.G.; Hooper, R.P.; Johnson, C.E.; Aulenbach, Brent T.; Cappellato, R.; Blum, A.E.

    2000-01-01

    Forest soil Ca depletion through leaching and vegetation uptake may threaten long-term sustainability of forest productivity in the southeastern USA. This study was conducted to assess Ca pools and fluxes in a representative southern Piedmont forest to determine the soil Ca depletion rate. Soil Ca storage, Ca inputs in atmospheric deposition, and outputs in soil leaching and vegetation uptake were investigated at the Panola Mountain Research Watershed (PMRW) near Atlanta, GA. Average annual outputs of 12.3 kg ha-1 yr-1 in uptake into merchantable wood and 2.71 kg ha-1 yr-1 soil leaching exceeded inputs in atmospheric deposition of 2.24 kg ha-1 yr-1. The annual rate of Ca uptake into merchantable wood exceeds soil leaching losses by a factor of more than five. The potential for primary mineral weathering to provide a substantial amount of Ca inputs is low. Estimates of Ca replenishment through mineral weathering in the surface 1 m of soil and saprolite was estimated to be 0.12 kg ha-1 yr-1. The weathering rate in saprolite and partially weathered bedrock below the surface 1 m is similarly quite low because mineral Ca is largely depleted. The soil Ca depletion rate at PMRW is estimated to be 12.7 kg ha-1 yr-1. At PMRW and similar hardwood-dominated forests in the Piedmont physiographic province, Ca depletion will probably reduce soil reserves to less than the requirement for a merchantable forest stand in ???80 yr. This assessment and comparable analyses at other southeastern USA forest sites suggests that there is a strong potential for a regional problem in forest nutrition in the long term.Forest soil Ca depletion through leaching and vegetation uptake may threaten long-term sustainability of forest productivity in the southeastern USA. This study was conducted to assess Ca pools and fluxes in a representative southern Piedmont forest to determine the soil Ca depletion rate. Soil Ca storage, Ca inputs in atmospheric deposition, and outputs in soil leaching and

  1. The Impact of HA Oligomer Content on Physical, Mechanical, and Biologic Properties of Divinyl Sulfone-Crosslinked HA Hydrogels

    PubMed Central

    Ibrahim, Samir; Kang, Qian K; Ramamurthi, Anand

    2009-01-01

    In recent studies, we showed that exogenous hyaluronic acid oligomers (HA-o) stimulate functional endothelialization, though native long-chain HA is more bioinert and possibly more biocompatible. Thus, in this study, hydrogels containing high molecular weight (HMW) HA (1×106 Da) and HA oligomer mixtures (HA-o: 0.75–10 kDa) were created by crosslinking with divinyl sulfone (DVS). The incorporation of HA oligomers was found to compromise the physical and mechanical properties of the gels (rheology, apparent crosslinking density, swelling ratio, degradation) and to very mildly enhance inflammatory cell recruitment in vivo; increasing the DVS crosslinker content within the gels in general, had the opposite effect, though the relatively high concentration of DVS within these gels (necessary to create a solid gel) also stimulated a mild sub-cutaneous inflammatory response in vivo and VCAM-1 expression by ECs cultured atop; ICAM-expression levels remained very low irrespective extent of DVS crosslinking or HA-o content. The greatest EC attachment and proliferation (MTT assay) was observed on gels that contained the highest amount of HA-o. The study shows that the beneficial EC response to HA oligomers and biocompatibility of HA is mostly unaltered by their chemical derivatization and crosslinking into a hydrogel. However, the study also demonstrates that the relatively high concentrations of DVS, necessary to create solid gels, compromises their biocompatibility. Moreover, the poor mechanics of even these heavily crosslinked gels, in the context of vascular implantation, necessitates the investigation of other, more appropriate crosslinking agents. Alternately, the outcomes of this study may be used to guide an approach based on chemical immobilization and controlled surface-presentation of both bioactive HA oligomers and more biocompatible HMW HAon synthetic or tissue engineered grafts already in use, without the use of a crosslinker, so that improved, predictable

  2. Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian 'avian-like' H1N1 swine viruses in mice.

    PubMed

    Castrucci, Maria R; Facchini, Marzia; Di Mario, Giuseppina; Garulli, Bruno; Sciaraffia, Ester; Meola, Monica; Fabiani, Concetta; De Marco, Maria A; Cordioli, Paolo; Siccardi, Antonio; Kawaoka, Yoshihiro; Donatelli, Isabella

    2014-05-01

    To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian "avian-like" (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs. Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice. Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study. Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses. Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge. Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans. © 2013 The Authors Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  3. Increasing Base Cations in Streams: Another Legacy of Deicing Salts?

    NASA Astrophysics Data System (ADS)

    Helton, A. M.; Barclay, J. R.; Bellucci, C.; Rittenhouse, C.

    2017-12-01

    Elevated use of deicing salts directly increases sodium chloride inputs to watersheds. Sodium can accumulate in soils over time and has the potential to leach other cations (e.g., calcium, magnesium, and potassium) from the soil through cation exchange. We hypothesize that increased use of deicing salts results in a legacy of soils depleted in non-sodium base cations with loss of cations to receiving waters. The goal of this project is to quantify temporal trends in base cations and chloride in streams and rivers across the United States. We used Weighted Regressions on Time, Discharge, and Season (WRTDS) to analyze trends in base cations. Our preliminary analysis of 10 rivers in Connecticut with chemical periods of record ranging from 24 - 64 years (median = 55 years), shows that the flux of base cations is increasing in all sites (25 - 366 103 meq ha-1 yr-1 yr-1), driven largely by increases in sodium (23 - 222 103 meq ha-1 yr-1 yr-1), the dominant cation in 7 of the sites. Chloride is also increasing at all sites (26 - 261 103 meq ha-1 yr-1 yr-1), which, in combination with salt use trends, suggests a road salt source for the increased sodium. Non-sodium cations are also increasing in 9 of the sites (8 - 54 103 meq ha-1 yr-1 yr-1), though they are not directly added with most deicing salts. We will compare these trends to other long-term sites across the United States, and quantify relationships between cation trends and land cover, road density, and snowfall.

  4. Yields in high density, short rotation intensive culture (SRIC)—plantations of Eucalyptus and Other Hardwood Species

    Treesearch

    R.M. Sachs; C.B. Low

    1983-01-01

    Initial high density (17,200 trees ha-1, 6961 trees a-1) plantations of Eucalyptus grandis yielded up to 22 oven dry tons (ODT) ha-l yr-I (10 ta-1 yr-1) on an approximate 6 month rotation. Border effects could not be eliminated from the small sized plots used...

  5. Purification and characteristics of an inducible by polycyclic aromatic hydrocarbons NADP(+)-dependent naphthalenediol dehydrogenase (NDD) in Mucor circinelloides YR-1.

    PubMed

    Camacho-Morales, Reyna Lucero; Zazueta-Novoa, Vanesa; Casillas, Juana Lizbeth González; Ballesteros, Elizabeth Aranda; Bote, Juan Antonio Ocampo; Zazueta-Sandoval, Roberto

    2014-05-01

    We detected NADP(+)-dependent dihydrodiol dehydrogenase (DD) activity in a cell-free extract from Mucor circinelloides YR-1, after high-speed centrifugation. We analyzed the enzymatic activity in the cytosolic fraction by zymograms, as described previously, and eight different DD activity bands were revealed. Five constitutive DD activities (DD1-5) were present when glucose was used as carbon source and three inducible activities (NDD, PDD1 and PDD2) when aromatic hydrocarbon compounds were used. NDD activity was induced all of the aromatic hydrocarbon compounds. The highest DD activity inducer was naphthalene and the lowest was pyrene. One of the enzymes showed higher activity with cis-naphthalene-diol rather than with trans-nahthalenediol as a substrate. We purified this particular enzyme to homogeneity and found that it had an isoelectric point of 4.6. The molecular weight for the native protein was 197.4kDa and 49.03±0.5kDa for the monomer that conforms it, suggesting a homotetrameric structure for the complete enzyme. Polyclonal antibodies were raised against it and obtained. NDD activity was almost totally inhibited when antibodies were used at low concentrations, and in native immunoblots only one band, which corresponds to the activity band detected in the zymograms, could be detected. In denaturing PAGE immunoblots only one band was detected. This band corresponds to the purified protein band of 49kDa detected in SDS-PAGE gels. The other two inducible enzymes PDD1 and PDD2 were present only when phenanthrene was used as sole carbon source in the culture media. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. The hemagglutinin structure of an avian H1N1 influenza A virus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Tianwei; Wang, Gengyan; Li, Anzhang

    2009-09-15

    The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptormore » binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.« less

  7. Nitrous oxide emission inventory of German forest soils

    NASA Astrophysics Data System (ADS)

    Schulte-Bisping, Hubert; Brumme, Rainer; Priesack, Eckart

    2003-02-01

    Annual fluxes of N2O trace gas emissions were assessed after stratifying German forest soils into Seasonal Emission Pattern (SEP) and Background Emission Pattern (BEP). Broad-leaved forests with soil pH(KCl) ≤ 3.3 were assigned to have SEP, broad-leaved forests with soil pH(KCl) > 3.3 and all needle-leaved forests to have BEP. BEPs were estimated by a relationship between annual N2O emissions and carbon content of the O-horizon. SEPs were primarily controlled by temperature and moisture and simulated by the model Expert-N after calibration to a 9-year record of N2O measurements. Analysis with different climate and soil properties indicated that the model reacts highly sensitive to changes in soil temperature, soil moisture, and soil texture. A geographic information system (ARC/INFO) was used for a spatial resolution of 1 km × 1 km grid where land cover, dominant soil units, and hygro climate classes were combined. The mean annual N2O emission flux from German forest soils was estimated as 0.32 kg ha-1 yr-1. Broad-leaved forests with SEP had the highest emissions (2.05 kg ha-1 yr-1) followed by mixed forests (0.38 kg ha-1 yr-1), broad-leaved forests (0.37 kg ha-1 yr-1), and needle-leaved forests with BEP (0.17 kg ha-1 yr-1). The annual N2O emission from German forest soils was calculated as 3.26 Gg N2O-N yr-1. Although needle-leaved trees cover about 57% of the entire forest area in Germany, their contribution is low (0.96 Gg N2O-N yr-1). Broad-leaved forests cover about 22% of the forest area but have 55% higher emissions (1.49 Gg N2O-N yr-1) than needle-leaved. Mixed forests cover 21% of the area and contribute 0.81 Gg N2O-N yr-1. Compared to the total N2O emissions in Germany of 170 Gg N yr-1, forest soils contribute only 1.9%. However, there are some uncertainties in this emission inventory, which are intensely discussed.

  8. Seasonal Patterns of Dry Deposition at a High-Elevation Site in the Colorado Rocky Mountains

    NASA Astrophysics Data System (ADS)

    Oldani, Kaley M.; Mladenov, Natalie; Williams, Mark W.; Campbell, Cari M.; Lipson, David A.

    2017-10-01

    In the Colorado Rocky Mountains, high-elevation barren soils are deficient in carbon (C) and phosphorus (P) and enriched in nitrogen (N). The seasonal variability of dry deposition and its contributions to alpine elemental budgets is critical to understanding how dry deposition influences biogeochemical cycling in high-elevation environments. In this 2 year study, we evaluated dry and wet deposition inputs to the Niwot Ridge Long Term Ecological Research (NWT LTER) site in the Colorado Rocky Mountains. The total organic C flux in wet + dry (including soluble and particulate C) deposition was >30 kg C ha-1 yr-1 and represents a substantial input for this C-limited environment. Our side-by-side comparison of dry deposition collectors with and without marble insert indicated that the insert improved retention of dry deposition by 28%. Annual average dry deposition fluxes of water-soluble organic carbon (4.25 kg C ha-1 yr-1) and other water-soluble constituents, including ammonium (0.16 kg NH4+ha-1 yr-1), nitrate (1.99 kg NO3- ha-1 yr-1), phosphate (0.08 kg PO43- ha-1 yr-1), and sulfate (1.20 kg SO42- ha-1 yr-1), were comparable to those in wet deposition, with highest values measured in the summer. Backward trajectory analyses implicate air masses passing through the arid west and Four Corners, USA, as dominant source areas for dry deposition, especially in spring months. Synchronous temporal patterns of deposition observed at the NWT LTER site and a distant Rocky Mountain National Park Clean Air Status and Trends Network site indicate that seasonal dry deposition patterns are regional phenomena with important implications for the larger Rocky Mountain region.

  9. The legacy of forest harvest and burning on ecosystem carbon storage in the northern midwest, USA

    NASA Astrophysics Data System (ADS)

    Gough, C. M.; Vogel, C. S.; Harrold, K. H.; George, K. D.; Curtis, P. S.

    2005-12-01

    Over 90 % of the forested area in the upper Great Lakes region was harvested by the early 20th century. In many cases, harvests were followed by uncontrolled burns, similar to current patterns of disturbance in many developing countries. While afforestation in the northern midwest has resulted in increased regional carbon (C) storage, the rate of C storage by forests will depend on the severity of prior disturbance and consequent changes in site quality. We were interested in how long the legacy of poor management practices from the early 20th century would be reflected in forest C storage rates. We investigated C cycling and storage following disturbance in mixed deciduous forests of northern lower Michigan, USA. Study plots ranged in age from 6 to 68 yrs and were created following experimental clear-cut harvesting and fire disturbance. Annual C storage was estimated biometrically from measurements of wood, leaf, fine root, and woody debris mass, mass losses to herbivory, soil carbon content, and soil respiration. Maximum annual carbon storage, or net ecosystem production (NEP), in the disturbed stands was 50 % lower than that of adjacent, undisturbed forest. This decrease was caused by a reduction in site quality following disturbance. However, during regrowth the cut and burned forest rapidly became a net C sink, storing 0.86 Mg C ha-1 yr-1 after six yrs. Carbon storage reached a peak of 1.00 Mg C ha-1 yr-1 after 50 yrs and declined to 0.57 Mg C ha-1 yr-1 after 68 yrs. Above- and below-ground net primary production (NPP) averaged 42 and 59 % of total NPP, respectively, with fine root litter production accounting for 57 % of total NPP. Soil heterotrophic respiration was high, ranging from 4.55 Mg C ha-1 yr-1 in the 6-yr-old stand to 5.74 Mg C ha-1 yr-1 in the 50-yr-old stand. Soil C and coarse woody debris pools exhibited a U-shaped trend over time following disturbance. Mineral soil and coarse woody debris pools lost C at a combined annual rate of 1.10 Mg C ha-1

  10. Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

    PubMed

    Valkenburg, Sophie A; Mallajosyula, V Vamsee Aditya; Li, Olive T W; Chin, Alex W H; Carnell, George; Temperton, Nigel; Varadarajan, Raghavan; Poon, Leo L M

    2016-03-07

    Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.

  11. Changes in plant functional groups, litter quality, and soil carbon and nitrogen mineralization with sheep grazing in an Inner Mongolian Grassland

    USGS Publications Warehouse

    Barger, N.N.; Ojima, D.S.; Belnap, J.; Shiping, W.; Yanfen, W.; Chen, Z.

    2004-01-01

    This study reports on changes in plant functional group composition, litter quality, and soil C and N mineralization dynamics from a 9-year sheep grazing study in Inner Mongolia. Addressed are these questions: 1) How does increasing grazing intensity affect plant community composition? 2) How does increasing grazing intensity alter soil C and N mineralization dynamics? 3) Do changes in soil C and N mineralization dynamics relate to changes in plant community composition via inputs of the quality or quantity of litter? Grazing plots were set up near the Inner Mongolia Grassland Ecosystem Research Station (IMGERS) with 5 grazing intensities: 1.3, 2.7, 4.0, 5.3, and 6.7 sheep ha -1??yr-1. Plant cover was lower with increasing grazing intensity, which was primarily due to a dramatic decline in grasses, Carex duriuscula, and Artemisia frigida. Changes in litter mass and percentage organic C resulted in lower total C in the litter layer at 4.0 and 5.3 sheep ha-1??yr-1 compared with 2.7 sheep ha -1??yr-1. Total litter N was lower at 5.3 sheep ha-1??yr-1 compared with 2.7 sheep ha -1??yr-1. Litter C:N ratios, an index of litter quality, were significantly lower at 4.0 sheep ha-1??yr -1 relative to 1.3 and 5.3 sheep ha-1??yr -1. Cumulative C mineralized after 16 days decreased with increasing grazing intensity. In contrast, net N mineralization (NH4+ + NO3-) after a 12-day incubation increased with increasing grazing intensity. Changes in C and N mineralization resulted in a narrowing of CO2-C:net Nminratios with increasing grazing intensity. Grazing explained 31% of the variability in the ratio of CO 2-C:net Nmin. The ratio of CO2-C:net N min was positively correlated with litter mass. Furthermore, there was a positive correlation between litter mass and A. frigida cover. Results suggest that as grazing intensity increases, microbes become more C limited resulting in decreased microbial growth and demand for N.

  12. Comprehensive description of the carbon cycle of an ancient temperate broadleaved woodland

    NASA Astrophysics Data System (ADS)

    Fenn, K.; Malhi, Y.; Morecroft, M.; Lloyd, C.; Thomas, M.

    2010-05-01

    There exist very few comprehensive descriptions of the productivity and carbon cycling of forest ecosystems. Here we present a description of the components of annual Net Primary Productivity (NPP), Gross Primary Productivity (GPP), autotrophic and heterotrophic respiration, and ecosystem respiration (RECO) for a temperate mixed deciduous woodland at Wytham Woods in southern Britain, calculated using "bottom-up" biometric and chamber measurements (leaf and wood production and soil and stem respiration). These are compared with estimates of these parameters from eddy-covariance measurements made at the same site. NPP was estimated as 7.0±0.8 Mg C ha-1 yr-1, and GPP as 20.3+1.0 Mg C ha-1 yr-1, a value which closely matched to eddy covariance-derived GPP value of 21.1 Mg C ha-1 yr-1. Annual RECO was calculated as 18.9±1.7 Mg C ha-1 yr-1, close to the eddy covariance value of 19.8 Mg C ha-1 yr-1; the seasonal cycle of biometric and eddy covariance RECO estimates also closely matched. The consistency between eddy covariance and biometric measurements substantially strengthens the confidence we attach to each as alternative indicators of site carbon dynamics, and permits an integrated perspective of the ecosystem carbon cycle. 37% of NPP was allocated below ground, and the ecosystem carbon use efficiency (CUE, = NPP/GPP) calculated to be 0.35±0.05, lower than reported for many temperate broadleaved sites.

  13. H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

    PubMed

    Russier, Marion; Yang, Guohua; Marinova-Petkova, Atanaska; Vogel, Peter; Kaplan, Bryan S; Webby, Richard J; Russell, Charles J

    2017-03-01

    A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5) and human and ferret (pH ≤5.5) species. Using an early 2009 pandemic H1N1 (pH1N1) virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5), HA1-Y17H (pH 6.0), and HA2-R106K (pH 5.3). All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0) acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like) HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses.

  14. H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets

    PubMed Central

    Yang, Guohua; Marinova-Petkova, Atanaska; Kaplan, Bryan S.; Webby, Richard J.

    2017-01-01

    A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5) and human and ferret (pH ≤5.5) species. Using an early 2009 pandemic H1N1 (pH1N1) virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5), HA1-Y17H (pH 6.0), and HA2-R106K (pH 5.3). All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0) acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like) HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses. PMID:28282440

  15. Plasma flows in the heliosheath along the Voyager 1 and 2 trajectories due to effects of the 11 yr solar cycle

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Provornikova, E.; Opher, M.; Izmodenov, V. V.

    We investigate the role of the 11 yr solar cycle variations in the solar wind (SW) parameters on the flows in the heliosheath using a new three-dimensional time-dependent model of the interaction between the SW and the interstellar medium. For boundary conditions in the model we use realistic time and the latitudinal dependence of the SW parameters obtained from SOHO/SWAN and interplanetary scintillation data for the last two solar cycles (1990-2011). This data set generally agrees with the in situ Ulysses measurements from 1991 to 2009. For the first ∼30 AU of the heliosheath the time-dependent model predicts constant radialmore » flow speeds at Voyager 2 (V2), which is consistent with observations and different from the steady models that show a radial speed decrease of 30%. The model shows that V2 was immersed in SW with speeds of 500-550 km s{sup –1} upstream of the termination shock before 2009 and in wind with upstream speeds of 450-500 km s{sup –1} after 2009. The model also predicts that the radial velocity along the Voyager 1 (V1) trajectory is constant across the heliosheath, contrary to observations. This difference in observations implies that additional effects may be responsible for the different flows at V1 and V2. The model predicts meridional flows (VN) higher than those observed because of the strong bluntness of the heliosphere shape in the N direction in the model. The modeled tangential velocity component (VT) at V2 is smaller than observed. Both VN and VT essentially depend on the shape of the heliopause.« less

  16. HA-1 T TCR T Cell Immunotherapy for the Treating of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

    ClinicalTrials.gov

    2018-04-30

    HLA-A*0201 HA-1 Positive Cells Present; Minimal Residual Disease; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Undifferentiated Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  17. Identification of different hemagglutinin isoforms of influenza A virus H1N1.

    PubMed

    Wu, Hanzhi; Sun, Ningning; Song, Wenjun; Zhu, Lin; Chen, Honglin; Cai, Zongwei

    2018-06-01

    Influenza A viruses (IAVs) still threaten human health and life. The process of virus infection involves a series of biological regulations, such as signal transduction that may be closely linked with the function of glycoproteins. However, the number and level of glycoproteins is low compared with other proteins in the whole protein pool. Viruses obtained from chicken embryos were purified by sucrose gradient centrifugation. PNGase F enzyme was then used to remove the glycan modification, followed by two-dimensional electrophoresis (2DE) to separate the hemagglutinin1 (HA1) glycoprotein. In-gel digestion was used to obtain peptides that were detected by MALDI-TOF mass spectrometry. Remarkably, we found 5 isoforms of HA1 with the same molecular weight but different isoelectric points. Furthermore, HA1 treatment with PNGase F enzyme changed all but one protein spot from 2DE, indicating that the different HA1 isoforms in 2DE were a result of different glycosylation modifications. The difference in isoelectric point of these HA1 was caused by glycan modification. This method provides a new approach for the study of glycosylation of the proteome for viruses or any other organisms. This article is protected by copyright. All rights reserved.

  18. Evaluation of Liposome, Heat-Killed Mycobacterium w, and Alum Adjuvants in the Protection Offered by Different Combinations of Recombinant HA, NP proteins, and M2e Against Homologous H5N1 Virus.

    PubMed

    Ingle, Nilesh B; Virkar, Rashmi G; Agnihotri, Kalpana; Sharma, Kapil S; Lole, Kavita S; Arankalle, Vidya A

    2016-10-01

    Continued evolution of highly pathogenic H5N1 viruses causing high mortality in humans obviates need for broadly cross-reactive vaccines. For this, hemagglutinin (HA) inducing specific protective antibodies, highly conserved nucleoprotein (NP), and ectodomain of matrix (M2e) protein, either singly or in combination, were evaluated in BALB/c mice. Recombinant HA and NP (baculovirus system) and M2e (synthetic peptide) and 3 adjuvants, that is, liposomes, Mw (heat killed Mycobacterium w), and alum were utilized for the homologous virus challenge. Additional immunogens included liposome-encapsulated HA/NP proteins and corresponding DNAs. Mice groups received two doses of respective formulations given at 3-week intervals and challenged intranasally with 100LD50 of H5N1 virus strain. Dynamics of weight loss, lung viral load, titres of IgG-anti-HA, NP, and M2e antibodies (ELISA), and IgG-subtype analysis was done. Two doses of all the formulations led to 100% seroconversion against the immunogens evaluated (100% seroconversion after the first dose in majority). Antibody titres against the components were dependent on the adjuvant and combination. HA-driven Th2 response with all the adjuvants, balanced Th1/Th2 response to NP protein, and Th2-bias with alum were noted. Low anti-M2e antibody titres did not allow subtype analysis. On challenge, complete protection was observed with Mw-HA, alum-HA+NP, Lipo-HA+NP+M2e, alum-HA+NP+M2e, and HA-DP formulations with 12-fold, 8-fold, 720-fold, 17-fold, and no reduction, respectively, in lung viral load. In conclusion, the results identify several adjuvant-immunogen combinations conferring 100% protection in mice that need further evaluation in higher animals.

  19. Chloride and sodium uptake potential over an entire rotation of Populus irrigated with landfill leachate.

    PubMed

    Zalesny, Jill A; Zalesny, Ronald S

    2009-07-01

    There is a need for information about the response of Populus genotypes to repeated application of high-salinity water and nutrient sources throughout an entire rotation. We have combined establishment biomass and uptake data with mid- and full-rotation growth data to project potential chloride (Cl-) and sodium (Na+) uptake for 2- to 11-year-old Populus in the north central United States. Our objectives were to identify potential levels of uptake as the trees developed and stages of plantation development that are conducive to variable application rates of high-salinity irrigation. The projected cumulative uptake of Cl- and Na+ during mid-rotation plantation development was stable 2 to 3 years after planting but increased steadily from year 3 to 6. Year six cumulative uptake ranged from 22 to 175 kg Cl- ha(-1) and 8 to 74 kg Na+ ha(-1), while annual uptake ranged from 8 to 54 kg Cl- ha(-1) yr(-1) and 3 to 23 kg Na+ ha(-1) yr(-1). Full-rotation uptake was greatest from 4 to 9 years (Cl-) and 4 to 8 years (Na+), with maximum levels of Cl- (32 kg ha(-1) yr(-1)) and Na+ (13 kg ha(-1) yr(-1)) occurring in year six. The relative uptake potential of Cl- and Na+ at peak accumulation (year six) was 2.7 times greater than at the end of the rotation.

  20. Water turnover in 458 American adults 40-79 yr of age.

    PubMed

    Raman, Aarthi; Schoeller, Dale A; Subar, Amy F; Troiano, Richard P; Schatzkin, Arthur; Harris, Tamara; Bauer, Douglas; Bingham, Shiela A; Everhart, James E; Newman, Anne B; Tylavsky, Frances A

    2004-02-01

    Despite recent interest in water intake, few data are available on water metabolism in adults. To determine the average and range of usual water intake, urine output, and total body water, we administered 2H oxide to 458 noninstitutionalized 40- to 79-yr-old adults living in temperate climates. Urine was collected in a subset of individuals (n = 280) to measure 24-h urine production using p-aminobenzoic acid to ensure complete collection. Preformed water intake was calculated from isotopic turnover and corrected for metabolic water and insensible water absorption from humidity. Preformed water intake, which is water from beverages and food moisture, averaged 3.0 l/day in men (range: 1.4-7.7 l/day) and 2.5 l/day in women (range: 1.2-4.6 l/day). Preformed water intake was lower in 70- to 79 (2.8 l/day)- than in 40- to 49-yr-old men and was lower in 70- to 79 (2.3 l/day)- than in 40- to 49- and 50- to 59-yr-old women. Urine production averaged 2.2 l/day in men (range: 0.6-4.9 l/day) and 2.2 l/day in women (0.9-6.0 l/day). There were no age-related differences in results in women, but 60- to 69-yr-old men had significantly higher urine output than 40- to 49- and 50- to 59-yr-old men. Only the 70- to 79-yr-old group included sufficient blacks for a racial analysis. Blacks in this age group showed significantly lower preformed water intake than did whites. Whites had significantly higher water turnover rates than blacks as well. Multivariate regression indicated that age, weight, height, and body mass index explained <12% of the gender-specific variance in water input or urine output, yet repeat measures indicated that within-individual coefficient of variation was 8% for preformed water intake (n = 22) and 9% for 24-h urine production (n = 222). These results demonstrate that water turnover is highly variable among individuals and that little of the variance is explained by anthropometric parameters.

  1. HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

    PubMed

    Cox, Freek; Kwaks, Ted; Brandenburg, Boerries; Koldijk, Martin H; Klaren, Vincent; Smal, Bastiaan; Korse, Hans J W M; Geelen, Eric; Tettero, Lisanne; Zuijdgeest, David; Stoop, Esther J M; Saeland, Eirikur; Vogels, Ronald; Friesen, Robert H E; Koudstaal, Wouter; Goudsmit, Jaap

    2016-01-01

    Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the in vivo protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies. We used a panel of anti-stem and anti-head influenza A and B monoclonal antibodies with identical human IgG1 Fc domains and investigated their ability to mediate ADCC-associated FcγRIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate FcγRIIIa activation. However, the FcγRIIIa activation was inhibited when a mutant HA, unable to bind sialic acids, was used. Antibodies which block sialic acid receptor interactions of HA interfered with FcγRIIIa activation. The inhibition of FcγRIIIa activation by HA head-binding and sialic acid receptor-blocking antibodies was confirmed in plasma samples of H5N1 vaccinated human subjects. Together, these results suggest that in addition to Fc-FcγR binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.

  2. Influence of insertion site of the avian influenza virus haemagglutinin (HA) gene within the Newcastle disease virus genome on HA expression.

    PubMed

    Ramp, Kristina; Skiba, Martin; Karger, Axel; Mettenleiter, Thomas C; Römer-Oberdörfer, Angela

    2011-02-01

    Members of the order Mononegavirales express their genes in a transcription gradient from 3' to 5'. To assess how this impacts on expression of a foreign transgene, the haemagglutinin (HA) of highly pathogenic avian influenza virus (HPAIV) A/chicken/Vietnam/P41/05 (subtype H5N1) was inserted between the phosphoprotein (P) and matrix protein (M), M and fusion protein (F), or F and haemagglutinin-neuraminidase protein (HN) genes of attenuated Newcastle disease virus (NDV) Clone 30. In addition, the gene encoding the neuraminidase of HPAIV A/duck/Vietnam/TG24-01/05 (subtype H5N1) was inserted into the NDV genome either alone or in combination with the HA gene. All recombinants replicated well in embryonated chicken eggs. The expression levels of HA-specific mRNA and protein were quantified by Northern blot analysis and mass spectrometry, with good correlation. HA expression levels differed only moderately and were highest in the recombinant carrying the HA insertion between the F and HN genes of NDV.

  3. Test of bioengineering structures in large eroded marly gullies (1 to 3 ha) in a mountainous and Mediterranean climate: resistance of the structures and survival of willow cuttings (Southern Alps, France)

    NASA Astrophysics Data System (ADS)

    Rey, Freddy; Labonne, Sophie; Dangla, Laure; Lavandier, Géraud

    2014-05-01

    In the Southern French Alps under a mountainous and Mediterranean climate, bioengineering structures installed in gully bottoms of highly weathered marly catchments aim at trapping a part of the eroded materials in order to reduce suspended sediment in the water system. They are made of brush layers and brush mats of cuttings on deadwood microdams. Purple and white Willows (Salix purpurea and S. incana) are used as they proved their efficiency to survive in such environment and efficiently trap marly sediment, but only in gullies with surface area less than 1 ha. Extrapolating their use to larger gullies could allow increasing the impact of such operations for reduction of sediment yield at the scale of large catchments. To this view, bioengineering structures have been built in spring and autumn 2010 in large eroded marly gullies with surface areas between 1 and 3 ha, in the Roubines and Fontaugier catchments (Southern Alps, France). 165 bioengineering structures (150 in spring and 15 in autumn) were built in 10 experimental gullies. After 3 observation years for each modality (2010 to 2012, and 2011 to 2013, respectively), the results revealed that 2/3 of the structures well resisted to damages due to concentrated flows. However, they were generally filled of sediment very rapidly, thus killing a large number of cuttings, particularly in the brush mats in gullies with surface area comprised between 2 and 3 ha. Therefore it has been proved that cuttings survival is possible in gullies with surface area less than 3 ha. In the French Southern Alps, bioengineering strategies have been improved by adding gullies of 1 to 3 ha in restoration plans. For gullies with surface area superior to 2 ha, it is recommended to first install the brush layers, and 1 to 2 years later the brush mats.

  4. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP.

    PubMed

    Yeom, Miji; Lee, HansongI; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

    2018-03-23

    Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

  5. Perfluorinated Surfactant Chain-Length Effects on Sonochemical Kinetics

    NASA Astrophysics Data System (ADS)

    Campbell, Tammy Y.; Vecitis, Chad D.; Mader, Brian T.; Hoffmann, Michael R.

    2009-08-01

    The sonochemical degradation kinetics of the aqueous perfluorochemicals (PFCs) perfluorobutanoate (PFBA), perfluorobutanesulfonate (PFBS), perfluorohexanoate (PFHA), and perfluorohexanesulfonate (PFHS) have been investigated. Surface tension measurements were used to evaluate chain-length effects on equilibrium air-water interface partitioning. The PFC air-water interface partitioning coefficients, KeqPF, and maximum surface concentrations, ΓmaxPF, were determined from the surface pressure equation of state for PFBA, PFBS, PFHA, and PFHS. Relative KeqPF values were dependent upon chain length KeqPFHS ≅ 2.1KeqPFHA ≅ 3.9KeqPFBS ≅ 5.0KeqPFBA, whereas relative ΓmaxPF values had minimal chain length dependence ΓmaxPFHS ≅ ΓmaxPFHA ≅ ΓmaxPFBS ≅ 2.2ΓmaxPFBA. The rates of sonolytic degradation were determined over a range of frequencies from 202 to 1060 kHz at dilute (<1 μM) initial PFC concentrations and are compared to previously reported results for their C8 analogs: perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA). Under all conditions, the time-dependent PFC sonolytic degradation was observed to follow pseudo-first-order kinetics, i.e., below kinetic saturation, suggesting bubble-water interface populations were significantly below the adsorption maximum. The PFHX (where X = A or S) sonolysis rate constant was observed to peak at an ultrasonic frequency of 358 kHz, similar to that for PFOX. In contrast, the PFBX degradation rate constants had an apparent maximum at 610 kHz. Degradation rates observed for PFHX are similar to previously determined PFOX rates, kapp,358PFOX ≅ kapp,358PFHX. PFOX is sonolytically pyrolyzed at the transiently cavitating bubble-water interface, suggesting that rates should be proportional to equilibrium interfacial partitioning. However, relative equilibrium air-water interfacial partitioning predicts that KeqPFOX ≅ 5KeqPFHX. This suggests that at dilute PFC concentrations, adsorption to the bubble

  6. Ethanolic Extract of Agaricus blazei Fermentation Product Inhibits the Growth and Invasion of Human Hepatoma HA22T/VGH and SK-Hep-1 Cells

    PubMed Central

    Tung, Yen-Chen; Su, Zheng-Yuan; Kuo, Min-Liang; Sheen, Lee-Yan

    2012-01-01

    Hepatoma is a leading cause of death in the world. SK-Hep-1 and HA22T/VGH cells are poorly differentiated human hepatocellular carcinoma cell lines with invasive and migratory abilities. Agaricus blazei (AB) is a mushroom with many biological effects and active ingredients, and the ethanolic extract of AB fermentation product (AB-pE) was demonstrated to inhibit the growth of hepatoma Hep3B and HepG2 cells in our previous study. In this study, we further investigated the anticancer and anti-invasive abctivities of the AB-pE. Results showed that the AB-pE inhibited the growth of SK-Hep1 and HA22T/VGH cells (with IC50 values of 26.8 and 28.7 μg/mL, respectively) and led cells toward apoptosis after 48 h of treatment. Activation of caspase-3 by AB-pE (12.5~200 μg/mL) in a dose-dependent manner was observed in both cell lines using fluorescence microscopy and flow cytometry. The apoptosis triggered by the AB-pE was regulated by the increased expression of Bax, the activation of caspase-3, caspase-9, and PARP, and the decreased expression of Bcl-2. Additionally, the AB-pE showed the potential ability to inhibit invasion of SK-Hep1 and HA22T/VGH cells according to the results of a Matrigel invasion assay. Our results suggested that the AB-pE may be a further developed for its potential against hepatoma due to its antiproliferative (via apoptosis) and anti-invasive activities in hepatoma cells. PMID:24716127

  7. Crop production and economic loss due to wind erosion in hot arid ecosystem of India

    NASA Astrophysics Data System (ADS)

    Santra, Priyabrata; Moharana, P. C.; Kumar, Mahesh; Soni, M. L.; Pandey, C. B.; Chaudhari, S. K.; Sikka, A. K.

    2017-10-01

    Wind erosion is a severe land degradation process in hot arid western India and affects the agricultural production system. It affects crop yield directly by damaging the crops through abrasion, burial, dust deposition etc. and indirectly by reducing soil fertility. In this study, an attempt was made to quantify the indirect impact of wind erosion process on crop production loss and associated economic loss in hot arid ecosystem of India. It has been observed that soil loss due to wind erosion varies from minimum 1.3 t ha-1 to maximum 83.3 t ha-1 as per the severity. Yield loss due to wind erosion was found maximum for groundnut (Arachis hypogea) (5-331 kg ha-1 yr-1), whereas minimum for moth bean (Vigna aconitifolia) (1-93 kg ha-1 yr-1). For pearl millet (Pennisetum glaucum), which covers a major portion of arable lands in western Rajasthan, the yield loss was found 3-195 kg ha-1 yr-1. Economic loss was found higher for groundnut and clusterbean (Cyamopsis tetragonoloba) than rest crops, which are about

  8. Analytical evaluation of the ADAMS™ A1c HA 8180 thalassemia mode high-pressure liquid chromatography analyser for the measurement of HbA2 and HbF.

    PubMed

    Urrechaga, E

    2016-12-01

    ADAMS ™ A1cHA-8180T is a HPLC system; within 3.5 min, it quantifies HbF, HbA 2 , and HbA 0 and flags abnormal peaks. We evaluate its analytical performance for routine estimation of HbA 2 and HbF, and critical tests were performed for identifying β-thalassemia carriers. Trueness imprecision, carry over, linearity, and effect of anemia were evaluated according to ICLH, ICLS, or manufacture's guidelines. Comparison (ADAMS ™ A1c HA-8160T) was performed by running 400 samples from healthy subjects, 30 alpha and 80 beta carriers (range: 1.9-5.7 %). Trueness - HbA 2 2.7 %, bias 0.81 %; HbA 2 5.8 %, bias 0.38 %. HbA 2 4.0% is not affected by Hb in the range 221-40 g/L. Carry over was negligible. Within run: normal control - CV 1.5 %, high control - CV 0.9 %.Within laboratory: normal control - total CV% 1.59%; high control - 0.92 %. Linearity - y = 1.034x - 0.17, R 2  = 0.998 (range: 2.8-4.8%).Method comparison - y = 0.93x + 0.22, R 2  = 0.997. HbF imprecision CVs between 0.66 and 1.24% and trueness between 0 and 2.8%. Linearity - y = 1.088x - 0.27, R 2  = 0.999 (0.1-5.7%). ADAMS ™ A1c HA-8180T provides a rapid and reliable separation of HbA 2 . The measurement is accurate and reproducible, which is needed because of the slight difference between normal and pathological values. The gap in HbA 2 values between normal subjects and β-thalassemia carriers makes this an appropriate method for rapid screening for carriers. © 2016 John Wiley & Sons Ltd.

  9. Influence of carbonate ion in the crystallization medium on the formation and chemical composition of CaHA-SrHA solid solutions

    NASA Astrophysics Data System (ADS)

    Nikolaev, Anton; Kuz'mina, Maria; Frank-Kamenetskaya, Olga; Zorina, Maina

    2015-06-01

    The study of the influence of carbonate ions in a solution to Sr-distribution in system «solution-crystal» and to ion substitutions and the non-stoichiometry of formed CaHA-SrHA solid solutions was carried out. The CaHA-SrHA solid solutions were synthesized by precipitation from aqueous solutions with the atomic C/P ratio equal to 0, 0.05 and 0.1 at T = 90 °C. Resulting precipitates were studied using various methods including X-ray powder diffraction, infrared spectroscopy and different chemical analyses. The results of the study have shown that in the range of values of (Ca + Sr)/P in the water solution from 40% to 85%, the presence of carbonate ions (C/P = 0.05-0.1) promotes the incorporation of strontium in the apatite. Crystalline apatite solid solutions formed from water solutions of such composition are more defective compared to apatites that are mainly calcium or strontium. They are characterized by a smaller size coherence scattering domain length along [0 0 1] direction and a greater number of carbonate ions, water molecules and vacancies at the Ca-sites.

  10. Nutrient exports from watersheds with varying septic system densities in the North Carolina Piedmont.

    PubMed

    Iverson, G; Humphrey, C P; O'Driscoll, M A; Sanderford, C; Jernigan, J; Serozi, B

    2018-04-01

    Septic systems (SSs) have been shown to be a significant source of nitrogen and phosphorus to nutrient-sensitive coastal surface and groundwaters. However, few published studies have quantified the effects of SSs on nutrient inputs to water supply watersheds in the Piedmont region of the USA. This region consists of rolling hills at the surface underlain by clayey soils. There are nearly 1 million SSs in this region, which accounts for approximately 50% of all SSs in North Carolina. The goal of this study was to determine if significant differences in nutrient concentrations and exports exist between Piedmont watersheds with different densities of SSs. Water quality was assessed in watersheds with SSs (n = 11) and a sewer and a forested watershed, which were designated as controls. Stream flow and environmental readings were recorded and water samples were collected from the watersheds from January 2015-December 2016. Additional samples were collected from sand filter watersheds in April 2015-March 2016 to compare to septic and control watersheds. Samples were analyzed for total dissolved nitrogen (TDN) and orthophosphate (PO 4 -P). Results indicated that watersheds served by a high-density (HD) of SSs (4.9 kg-N yr -1 ha -1 ; 0.2 kg-P yr -1 ha -1 ) exported more than double the median masses of TDN and PO 4 -P, respectively, relative to low-density (1.0 kg-N yr -1 ha -1 ; <0.1 kg-P yr -1 ha -1 ) and control watersheds (1.4 kg-N yr -1 ha -1 ; <0.1 kg-P yr -1 ha -1 ) during baseflow. Isotopic analysis indicated that wastewater was the most likely source of nitrate-N in HD watersheds. In all other watersheds, isotopic results suggested non-wastewater sources as the dominant nitrate-N provider. These findings indicated that SS density was a significant factor in the delivery of septic-derived nutrients to these nutrient-sensitive, water supply watersheds of the North Carolina Piedmont. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Antibodies induced by the HA2 glycopolypeptide of influenza virus haemagglutinin improve recovery from influenza A virus infection.

    PubMed

    Gocník, M; Fislová, T; Mucha, V; Sládková, T; Russ, G; Kostolansky, F; Varecková, E

    2008-04-01

    The haemagglutinin (HA) of influenza A virus consists of two glycopolypeptides designated HA1 and HA2. Antibodies recognizing HA1 inhibit virus haemagglutination, neutralize virus infectivity and provide good protection against infection, but do not cross-react with the HA of other subtypes. Little is known regarding the biological activities of antibodies against HA2. To study the role of antibodies directed against HA2 during influenza virus infection, two vaccinia virus recombinants (rVVs) were used expressing chimeric molecules of HA, in which HA1 and HA2 were derived from different HA subtypes. The KG-11 recombinant expressed HA1 from A/PR/8/34 (H1N1) virus and HA2 from A/NT/60 (H3N2) virus, whilst KG-12 recombinant expressed HA1 from A/NT/60 virus and HA2 from A/PR/8/34 virus. Immunization of BALB/c mice with rVV expressing HA2 of the HA subtype homologous to the challenge virus [A/PR/8/34 (H1N1) or A/Mississippi/1/85 (H3N2)] did not prevent virus infection, but nevertheless resulted in an increase in mice survival and faster elimination of virus from the lungs. Passive immunization with antibodies purified from mice immunized with rVVs confirmed that antibodies against HA2 were responsible for the described effect on virus infection. Based on the facts that HA2 is a rather conserved part of the HA and that antibodies against HA2, as shown here, may moderate virus infection, future vaccine design should deal with the problem of how to increase the HA2 antibody response.

  12. HA117 endows HL60 cells with a stem-like signature by inhibiting the degradation of DNMT1 via its ability to down-regulate expression of the GGL domain of RGS6

    PubMed Central

    Li, Shuangshuang; Wu, Huan; Wang, Yi; Li, Xiaoqing; Guo, Yuxia; Liang, Shaoyan

    2017-01-01

    All-trans retinoic acid (ATRA) induces complete remission in almost all patients with acute promyelocytic leukemia (APL) via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segment, HA117. In this study, we demonstrate that ATRA induces multi-drug-resistant subpopulations of HL60 cells with a putative stem-like signature by up-regulating the expression of the new gene segment HA117. Western blot analysis and quantitative real-time PCR demonstrated that HA117 causes alternative splicing of regulator of G-protein signaling 6 (RGS6) and down-regulation of the expression of the GGL domain of RGS6, which plays an important role in DNA methyltransferase 1 (DNMT1) degradation. Moreover, DNMT1 expression was increased in multi-drug resistance HL60/ATRA cells. Knockdown of HA117 restored expression of the GGL domain and blocked DNMT1 expression. Moreover, resistant cells displayed a putative stem-like signature with increased expression of cancer steam cell markers CD133 and CD123. The stem cell marker, Nanog, was significantly up-regulated. In conclusion, our study shows that HA117 potentially promotes the stem-like signature of the HL60/ATRA cell line by inhibiting by the ubiquitination and degradation of DNMT1 and by down-regulating the expression of the GGL domain of RGS6. These results throw light on the cellular events associated with the ATRA-induced multi-drug resistance phenotype in acute leukemia. PMID:28665981

  13. Pre-Existing Immunity with High Neutralizing Activity to 2009 Pandemic H1N1 Influenza Virus in Shanghai Population

    PubMed Central

    Chen, Zhihui; Tang, Ziwei; Xu, Qingqiang; Wang, Yue; Zhao, Ping; Qi, Zhongtian

    2013-01-01

    Pre-existing immunity is an important factor countering the pandemic potential of an emerging influenza virus strain. Thus, studying of pre-existing immunity to the 2009 pandemic H1N1 virus (2009 H1N1) will advance our understanding of the pathogenesis and epidemiology of this emerging pathogen. In the present study, sera were collected from 486 individuals in a hospital in Shanghai, China, before the 2009 H1N1 influenza pandemic. The serum anti-hemagglutinins (HA) antibody, hemagglutination inhibition (HI) antibody and neutralizing antibody against the 2009 H1N1 were assayed. Among this population, 84.2%, 14.61% and 26.5% subjects possessed anti-HA antibody, HI antibody and neutralizing antibody, respectively. Although neutralizing antibody only existed in those sera with detectable anti-HA antibody, there was no obvious correlation between the titers of anti-HA and neutralizing antibody. However, the titers of anti-HA and neutralizing antibody against seasonal H1N1 virus were highly correlated. In the same population, there was no correlation between titers of neutralizing antibody against 2009 H1N1 and seasonal H1N1. DNA immunization performed on mice demonstrated that antibodies to the HA of 2009 pandemic and seasonal H1N1 influenza viruses were strain-specific and had no cross-neutralizing activity. In addition, the predicted conserved epitope in the HA of 2009 H1N1 and recently circulating seasonal H1N1 virus, GLFGAIAGFIE, was not an immunologically valid B-cell epitope. The data in this report are valuable for advancing our understanding of 2009 H1N1 influenza virus infection. PMID:23527030

  14. [Restriction polymorphism of the proto-oncogene c-Ha-ras-1 in patients with multiple primary malignant neoplasms and non-small-cell lung cancer].

    PubMed

    Gaspar'ian, A V; Sel'chuk, V Iu; Iakubovskaia, M G; Zborovskaia, I B; Tatosian, A G

    1997-01-01

    Restriction fragment length polymorphism in the human c-Ha-ras-1 locus, associated with a minisatellite sequence, was examined in 45 multiple primary cancer (MPC) patients, 56 patients with squamous cell lung cancer (SCLC), 21 patients with lung adenocarcinoma (LAC), and 53 individuals having no oncopathology. Southern analysis of cellular DNA revealed the presence of 4 common alleles (with collective allele frequency close to 94% in the control group) and a set of rare alleles. Allele a3, (2.1 kb in size under MspI/HpaII digestion) was shown to be more frequent in the MPC than in the control group. The same tendency was observed in the patients with highly differentiated cell lung cancer. An increased frequency of the a4 allele (2.5 kb under MspI/HpaII digestion) was observed in the patients with adenocarcinomas as well as in the patients with metastases and low levels of tumor tissue differentiation. The elevated frequencies of a3 in the MPC group and of a4 in the LAC patients did not correlate with increased risk of the cancers mentioned above but was associated with type of tumor progression. Previously, it was reported that the mini-satellite sequence within the c-Ha-ras-1 locus possesses enhancer activity. Our data indirectly confirm the hypothesis that the efficiency of minisatellite modulator activity is associated with fragment size.

  15. Drought-induced mortality patterns and rapid biomass recovery in a terra firme forest in the Colombian Amazon.

    PubMed

    Zuleta, Daniel; Duque, Alvaro; Cardenas, Dairon; Muller-Landau, Helene C; Davies, Stuart J

    2017-10-01

    Extreme climatic events affecting the Amazon region are expected to become more frequent under ongoing climate change. In this study, we assessed the responses to the 2010 drought of over 14,000 trees ≥10 cm dbh in a 25 ha lowland forest plot in the Colombian Amazon and how these responses varied among topographically defined habitats, with tree size, and with species wood density. Tree mortality was significantly higher during the 2010-2013 period immediately after the drought than in 2007-2010. The post-drought increase in mortality was stronger for trees located in valleys (+243%) than for those located on slopes (+67%) and ridges (+57%). Tree-based generalized linear mixed models showed a significant negative effect of species wood density on mortality and no effect of tree size. Despite the elevated post-drought mortality, aboveground biomass increased from 2007 to 2013 by 1.62 Mg ha -1  yr -1 (95% CI 0.80-2.43 Mg ha -1  yr -1 ). Biomass change varied among habitats, with no significant increase on the slopes (1.05, 95% CI -0.76 to 2.85 Mg ha -1  yr -1 ), a significant increase in the valleys (1.33, 95% CI 0.37-2.34 Mg ha -1  yr -1 ), and a strong increase on the ridges (2.79, 95% CI 1.20-4.21 Mg ha -1  yr -1 ). These results indicate a high carbon resilience of this forest to the 2010 drought due to habitat-associated and interspecific heterogeneity in responses including directional changes in functional composition driven by enhanced performance of drought-tolerant species that inhabit the drier ridges. © 2017 by the Ecological Society of America.

  16. Atmospheric deposition as a source of carbon and nutrients to an alpine catchment of the Colorado Rocky Mountains

    NASA Astrophysics Data System (ADS)

    Mladenov, N.; Williams, M. W.; Schmidt, S. K.; Cawley, K.

    2012-08-01

    illustrated that wet deposition (9.9 kg C ha-1 yr-1) and dry deposition (6.9 kg C ha-1 yr-1) were a combined input of approximately 17 kg C ha-1 yr-1, which could be as high as 24 kg C ha-1 yr-1 in high dust years. This atmospheric C input approached the C input from microbial autotrophic production in barren soils. Atmospheric wet and dry deposition also contributed 4.3 kg N ha-1 yr-1, 0.15 kg P ha-1 yr-1, and 2.7 kg Ca2+ ha-1 yr-1 to this alpine catchment.

  17. Mitigating effects of ex situ application of rice straw on CH4 and N2O emissions from paddy-upland coexisting system

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Wu, Xiaohong; Chen, Anlei; Xie, Xiaoli; Wang, Yunqiu; Yin, Chunmei

    2016-11-01

    The in situ application of rice straw enhances CH4 emissions by a large margin. The ex situ application of rice straw in uplands, however, may mitigate total global warming potential (GWP) of CH4 and N2O emissions from paddy-upland coexisting systems. To evaluate the efficiency of this practice, two field trials were conducted in rice-rice-fallow and maize-rape cropping systems, respectively. Year-round measurements of CH4 and N2O emissions were conducted to evaluate the system-scaled GWP. The results showed that CH4 accounted for more than 98% of GWP in paddy. Straw removal from paddy decreased 44.7% (302.1 kg ha-1 yr-1) of CH4 emissions and 51.2% (0.31 kg ha-1 yr-1) of N2O emissions, thus decreased 44.8% (7693 kg CO2-eqv ha-1 yr-1) of annual GWP. N2O accounted for almost 100% of GWP in upland. Straw application in upland had insignificant effects on CH4 and N2O emissions, which increased GWP only by 91 kg CO2-eqv ha-1 yr-1. So, the transfer of straw from paddy to upland could decrease GWP by 7602 kg CO2-eqv ha-1 yr-1. Moreover, straw retention during late rice season contributed to 88.2% of annual GWP increment. It is recommended to transfer early rice straw to upland considering GWP mitigation, nutrient recycling and labor cost.

  18. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

    PubMed

    Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

    2013-08-28

    Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

  19. Resistance training predicts 6-yr body composition change in postmenopausal women.

    PubMed

    Bea, Jennifer W; Cussler, Ellen C; Going, Scott B; Blew, Robert M; Metcalfe, Lauve L; Lohman, Timothy G

    2010-07-01

    The aim of this study was to examine the association of exercise frequency (ExFreq) and volume (total weight lifted by military press and squats (SQ)) with change in body composition among postmenopausal women participating in a progressive resistance training study. Previously, sedentary women (n = 122, age = 56.3 +/- 4.3 yr) were followed for 6 yr. At 6 yr, there were women who had been randomly assigned to resistance training at baseline (n = 65) controls that were permitted to cross over to the exercise program at 1 yr (n = 32) and 25 true controls. Exercisers and crossovers directed to perform eight core exercises for two sets of eight repetitions at 70%-80% of one-repetition maximum, three times weekly, plus progressive weight bearing, stretching, and balance. Body weight and fat were measured at baseline and annually using anthropometry and dual-energy x-ray absorptiometry. Average change in body weight and total body fat were 0.83 +/- 5.39 and 0.64 +/- 4.95 kg at 6 yr, respectively. In multiple linear regression, ExFreq, military press, and SQ were significantly inversely associated with change in body weight (standardized beta coefficient (SBC) = -0.22 to -0.28, P < 0.01), fat (SBC = -0.25 to -0.33, P < 0.01), and trunk fat (SBC = -0.20 to -0.31, P < 0.03) after adjusting for age, years on hormone therapy, change in lean soft tissue, baseline body composition, and baseline habitual exercise. The lowest tertile of SQ (equivalent to 2.5% attendance) demonstrated significant gain in weight, fat, and trunk fat over 6 yr (P < 0.004), whereas the highest tertile SQ (equivalent to 64% attendance) was able to maintain their weight, total, and regional fat. We conclude that resistance training is a viable long-term method to prevent weight gain and deleterious changes in body composition in postmenopausal women.

  20. Evaluation of N environmental risks on Andosols from an intensive dairy farming watershed using DNDC.

    PubMed

    Deng, Meihua; Bellingrath-Kimura, Sonoko D; Zeng, Lin; Hojito, Masayuki; Zhang, Tianzhu; Yoh, Muneoki

    2015-04-15

    Manure nitrogen (N) in the livestock sector has become a key driver of environmental change. The denitrification-decomposition (DNDC) model was used to evaluate N pollution strengths on Andosols with intensive dairy manure application in Upper Naka River Watershed, Japan. The calibrated model was capable of predicting Andosol N flows because the simulated soil mineral N content, soil nitrogen oxide (N2O) fluxes, denitrification rate, and crop N uptake matched the patterns and magnitudes of the field observations from a wide range of soil textures, as well as manure management and cropping systems. The simulations showed that current intensive manure application systems caused low crop N use efficiency and a large amount of NO3(-)-N leaching and N2O emission. The crop N use efficiency was 27%-42% and 37%-55% of input N for uplands and paddy rice, respectively. The uplands showed much more serious N environmental pollution risks with N leaching 123-362 kg N ha(-1) yr(-1) and N2O emissions 6.53-11.8 kg N ha(-1) yr(-1) than that in the lowland paddy rice with N leaching 17.4-103 kg N ha(-1) yr(-1) and N2O emissions 0.59-2.77 kg N ha(-1) yr(-1). Forage rice/barley crop systems have high N cleaning capability due to the greater crop N uptake which reached to 304 kg N ha(-1) yr(-1). High precipitation stimulated more NO3(-)-N leaching. Sandy soil also showed higher N leaching and was unsuitable for paddy rice. Slurry application stimulated more N2O emission than compost manure. To mitigate the current high N pollution, the critical N application rate was recommended to be approximately 380, 470, 640, and 390 kg N ha(-1) yr(-1) for loam sand planted with maize/grass, loam soil with maize/grass, forage rice/barley, and rice/fallow with winter manure application, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Molecular Characterization and Phylogenetic Analysis of the Hemagglutinin 1 Protein of Human Influenza A Virus Subtype H1N1 Circulating in Kenya During 2007-2008

    DTIC Science & Technology

    2012-01-01

    10.1093/infdis/jis586 S46 • JID 2012:206 (Suppl 1) • Bulimo et al by guest on N ovem ber 20, 2012 http://jid.oxfordjournals.org/ D ow nloaded from Report...immunogenic sites at which immune -driven natural selection happens, the N-terminal (HA1) domain of the HA protein contains the maximum concentration of...antibodies to neutralize the virus. Because the human immune response to viral infection is incompletely cross-protective, amino acid variants of the HA1

  2. Altered expression of hyaluronan, HAS1-2, and HYAL1-2 in oral lichen planus.

    PubMed

    Siponen, Maria; Kullaa, Arja; Nieminen, Pentti; Salo, Tuula; Pasonen-Seppänen, Sanna

    2015-07-01

    Oral lichen planus (OLP) is an immune-mediated mucosal disease of unclear etiology and of unresolved pathogenesis. Hyaluronan (HA) is an extracellular matrix glycosaminoglycan involved in inflammation and tumor progression. However, its presence in OLP has not been reported. We therefore aimed to study the immunohistochemical expression of HA, its receptor CD44, hyaluronan synthases (HAS1-3), and hyaluronidases (HYAL1-2) in OLP. The presence of HA, CD44, HAS1-3, and HYAL1-2 was studied by immunohistochemical methods in 55 OLP and 23 control oral mucosal specimens (CTR). The localization, intensity, and differences of the epithelial expression between OLP and CTRs were analyzed. HA and CD44 were found on cell membranes in the epithelial basal and intermediate layers in CTR and OLP specimens. The HA staining intensity was stronger in the basal layer of the epithelium in OLP than in CTRs (P < 0.001). HAS1 (P = 0.001) and HAS2 (P < 0.001) showed stronger staining in the basal and weaker staining in the superficial (P < 0.001) epithelial layers in OLP than in CTRs. The immunostaining of HAS3 was low in both OLP and CTRs. Positive HYAL1 and HYAL2 staining were mainly found in the basal and intermediate epithelial layers, and their intensities were significantly increased in OLP, except HYAL 2 in the intermediate epithelial layer. HA, HAS1-2, and HYAL1-2 have altered expression in OLP compared to CTRs and may therefore have a role in OLP pathogenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Energy balances of bioenergy crops (Miscanthus, maize, rapeseed) and their CO2-mitigation potential on a regional farm scale

    NASA Astrophysics Data System (ADS)

    Felten, D.; Emmerling, C.

    2012-04-01

    Increasing cultivation of energy crops in agriculture reveals the progressive substitution of fossil fuels, such as crude oil or brown coal. For the future development of renewable resources, the efficiency of different cropping systems will be crucial, as energy crops differ in terms of the energy needed for crop cultivation and refinement and the respective energy yield, e.g. per area. Here, balancing is certainly the most suitable method for the assessment of cropping system efficiency, contrasting energy inputs with energy outputs and the related CO2 emissions with potential CO2 credits due to substitution of fossil fuels, respectively. The aim of the present study was to calculate both energy and CO2 balances for rapeseed and maize, representing the recently most often cultivated energy crops in Germany, on a regional farm scale. Furthermore, special emphasis was made on perennial Miscanthus x giganteus, which is commonly used as a solid fuel for combustion. This C4-grass is of increasing interest due to its high yield potential accompanied by low requirements for soil tillage, weed control, and fertilization as well as long cultivation periods up to 25 years. In contrast to more general approaches, balances were calculated with local data from commercial farms. The site-specific consumption of diesel fuel was calculated using an online-based calculator, developed by the German Association for Technology and Structures in Agriculture (KTBL). By balancing each of the aforementioned cropping systems, our research focused on (i) the quantification of energy gains and CO2 savings due to fossil fuel substitution and (ii) the assessment of energy efficiency, expressed as the ratio of energy output to input. The energy input was highest for maize sites (33.8 GJ ha-1 yr-1), followed by rapeseed (18.2 GJ ha-1 yr-1), and Miscanthus (1.1 GJ ha-1 yr-1); corresponding energy yields were 129.5 GJ ha-1 yr-1 (maize), 83.6 GJ ha-1 yr-1 (rapeseed), and 259.7 GJ ha-1 yr-1

  4. Effects of increased deposition of atmospheric nitrogen on an upland moor: leaching of N species and soil solution chemistry.

    PubMed

    Pilkington, M G; Caporn, S J M; Carroll, J A; Cresswell, N; Lee, J A; Ashenden, T W; Brittain, S A; Reynolds, B; Emmett, B A

    2005-05-01

    This study was designed to investigate the leaching response of an upland moorland to long-term (10 yr) ammonium nitrate additions of 40, 80 and 120 kg N ha(-1) yr(-1) and to relate this response to other indications of potential system damage, such as acidification and cation displacement. Results showed increases in nitrate leaching only in response to high rates of N input, in excess of 96 and 136 kg total N input ha(-1) yr(-1) for the organic Oh horizon and mineral Eag horizon, respectively. Individual N additions did not alter ammonium leaching from either horizon and ammonium was completely retained by the mineral horizon. Leaching of dissolved organic nitrogen (DON) from the Oh horizon was increased by the addition of 40 kg N ha(-1) yr(-1), but in spite of increases, retention of total dissolved nitrogen reached a maximum of 92% and 95% of 80 kg added N ha(-1) yr(-1) in the Oh and Eag horizons, respectively. Calcium concentrations and calcium/aluminium ratios were decreased in the Eag horizon solution with significant acidification mainly in the Oh horizon leachate. Nitrate leaching is currently regarded as an early indication of N saturation in forest systems. Litter C:N ratios were significantly lowered but values remained above a threshold predicted to increase leaching of N in forests.

  5. A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice

    USDA-ARS?s Scientific Manuscript database

    The HA protein of the 2009 pandemic H1N1viruses (14 H1N1pdm) is antigenically closely related to the HA of classical North American swine H1N1 influenza viruses (cH1N1). Since 1998, through reassortment and incorporation of HA genes from human H3N2 and H1N1 influenza viruses, swine influenza strains...

  6. Effect of Water-Glass Coating on HA and HA-TCP Samples for MSCs Adhesion, Proliferation, and Differentiation.

    PubMed

    Bajpai, Indu; Kim, Duk Yeon; Kyong-Jin, Jung; Song, In-Hwan; Kim, Sukyoung

    2016-01-01

    Ca-P and silicon based materials have become very popular as bone tissue engineering materials. In this study, water-glass (also known as sodium silicate glass) was coated on sintered hydroxyapatite (HA) and HA-TCP (TCP stands for tricalcium phosphate) samples and subsequently heat-treated at 600°C for 2 hrs. X-rays diffraction showed the presence of β- and α-TCP phases along with HA in the HA-TCP samples. Samples without coating, with water-glass coating, and heat-treated after water-glass coating were used to observe the adhesion and proliferation response of bone marrow derived-mesenchymal stem cells (MSCs). Cell culture was carried out for 4 hrs, 1 day, and 7 days. Interestingly, all samples showed similar response for cell adhesion and proliferation up to 7-day culture but fibronectin, E-cadherin, and osteogenic differentiation related genes (osteocalcin and osteopontin) were significantly induced in heat-treated water-glass coated HA-TCP samples. A water-glass coating on Ca-P samples was not found to influence the cell proliferation response significantly but activated some extracellular matrix genes and induced osteogenic differentiation in the MSCs.

  7. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma.

    PubMed

    Moreira Carboni, Simone de Sales Costa; Rodrigues Lima, Nathália Alves; Pinheiro, Nanci Mendes; Tavares-Murta, Beatriz Martins; Crema, Virgínia Oliveira

    2015-10-01

    Oral squamous cell carcinoma (OSCC) is the most malignant lesion occurring in the head and neck. The Rho-kinases (ROCKs), effectors of Rho proteins, are involved in actin cytoskeletal organization, cell migration, and maintenance cortex. The HA-1077 inhibits the ROCKs. This study aimed to evaluate the effect of treatment with HA-1077 on cell motility in SCC-4 cells, a cell line originating from human OSCC. F-actin of SCC-4 cells treated or not with HA-1077 (1, 50 and 100 μmol/l), and also HA-1077 50 μmol/l and/or inhibitors Y-27632 30 μmol/l was stained with rhodamine-conjugated phalloidin and analyzed by confocal microscopy. Approximately 1×10 cells/well, control and treated with HA-1077 (25, 50, and 100 μmol/l) were added to the migration plate assay. In addition, 1×10 cells/well, control and treated with HA-1077 50 μmol/l, were tested by invasion assays (plate coated with Matrigel). The inhibition of ROCKs with HA-1077 and/or Y-27632 leads to morphological changes, affecting the organization of the actin. The inhibitory effect of HA-1077 (P<0.0001) was dose dependent as the number of cells migrated at 100 μmol/l was statistically different: 25 μmol/l (P<0.0001) and 50 μmol/l (P<0.01). The number of cells treated with HA-1077 50 μmol/l decreased compared with control cells that invaded through Matrigel (P<0.0001). This study shows an inhibitory effect of HA-1077 on cell migration and invasion, suggesting that the use of HA-1077 can be a potential therapy for OSCC.

  8. Responses of soil hydrolase kinetics to nitrogen and phosphorus additions in Chinese fir plantations of subtropical China

    NASA Astrophysics Data System (ADS)

    Zhang, X.; Zhang, C.; Yang, Y.; Wang, H.; Chen, F.; Fu, X.; Fang, X.; Sun, X.

    2016-12-01

    Nitrogen (N) deposition and low soil phosphorus (P) content aggravate the P limitation in subtropical forest soils. However, the responses of soil organic matter related hydrolyase kinetics to N and P additions in subtropical plantations are still not clear. We tested the hypothesis that P application can improve the potential maximum activities of soil carbon (C) and N related hydrolayase but substrate demand (Km) may tradeoff the catalytic efficiency of the enzymes. Thirty 20m×20m plots were established in November 2011 and six different treatments were randomly distributed with five replicates in the Chinese fir plantations in subtropical China. The ongoing treatments are control (CK, no N and P application), low N addition (N1:50 kg N ha-1 yr-1), high N addition (N2: 100 kg N ha-1 yr-1), P addition (P: 50 kg P ha-1 yr-1), low N andP addition (N1P: 50 kg N ha-1 yr-1 and 50 kg P ha-1 yr-1) and high N and P addition (N2P: 100 kg N ha-1yr-1and 50 kg P ha-1 yr-1). Soil enzyme kinetic parameters for b-1,4-glucosidase (βG), β-1,4-N-acetylglucosaminidase (NAG), and acid phosphatase (aP) were measured in November 2015. The substrate affinities (Km) of βG and NAG were not affected by N or /and P additions. However, the substrate affinities of aP were decreased by N additions (N1, N2) with higher Km values than the other treatments. N additions (N1, N2) or higher N combined P additions (N2P) increased Vmax and catalytic efficiencies for βG, while with P addition treatments (N1P, N2P, and P) decreased Vmax and catalytic efficiencies for aP. The effects of N combined P treatments (N1P and N2P) on kinetic parameters (Vmax, Km) and catalytic efficiencies for AP were similar to P treatment, indicating that P had stronger effects on organic phosphorus hydrolysis than N in the research site. The N additions (N1 and N2) did not affect the catalytic efficiencies for NAG despite of their positive responses to Vmax for NAG compared with CK. The catalytic efficiencies of aP and

  9. Eddy covariance and biometric measurements show that a savanna ecosystem in Southwest China is a carbon sink

    NASA Astrophysics Data System (ADS)

    Fei, Xuehai; Jin, Yanqiang; Zhang, Yiping; Sha, Liqing; Liu, Yuntong; Song, Qinghai; Zhou, Wenjun; Liang, Naishen; Yu, Guirui; Zhang, Leiming; Zhou, Ruiwu; Li, Jing; Zhang, Shubin; Li, Peiguang

    2017-02-01

    Savanna ecosystems play a crucial role in the global carbon cycle. However, there is a gap in our understanding of carbon fluxes in the savanna ecosystems of Southeast Asia. In this study, the eddy covariance technique (EC) and the biometric-based method (BM) were used to determine carbon exchange in a savanna ecosystem in Southwest China. The BM-based net ecosystem production (NEP) was 0.96 tC ha-1 yr-1. The EC-based estimates of the average annual gross primary productivity (GPP), ecosystem respiration (Reco), and net ecosystem carbon exchange (NEE) were 6.84, 5.54, and -1.30 tC ha-1 yr-1, respectively, from May 2013 to December 2015, indicating that this savanna ecosystem acted as an appreciable carbon sink. The ecosystem was more efficient during the wet season than the dry season, so that it represented a small carbon sink of 0.16 tC ha-1 yr-1 in the dry season and a considerable carbon sink of 1.14 tC ha-1 yr-1 in the wet season. However, it is noteworthy that the carbon sink capacity may decline in the future under rising temperatures and decreasing rainfall. Consequently, further studies should assess how environmental factors and climate change will influence carbon-water fluxes.

  10. The Muon Collider as a $H/A$ factory

    DOE PAGES

    Eichten, Estia; Martin, Adam; Univ. of Notre Dame, IN

    2013-11-22

    We show that a muon collider is ideally suited for the study of heavy H/A scalars, cousins of the Higgs boson found in two-Higgs doublet models and required in supersymmetric models. The key aspects of H/A are: (1) they are narrow, yet have a width-to-mass ratio far larger than the expected muon collider beam-energy resolution, and (2) the larger muon Yukawa allows efficient s-channel production. We study in detail a representative Natural Supersymmetry model which has a 1.5 Tev H/A withmore » $$m_H$$- $$m_A$$ = 10 Gev. The large event rates at resonant peak allow the determination of the individual H and A resonance parameters (including CP) and the decays into electroweakinos provides a wealth of information unavailable to any other present or planned collider.« less

  11. Global and regional emissions estimates of 1,1-difluoroethane (HFC-152a, CH3CHF2) from in situ and air archive observations

    NASA Astrophysics Data System (ADS)

    Simmonds, P. G.; Rigby, M.; Manning, A. J.; Lunt, M. F.; O'Doherty, S.; McCulloch, A.; Fraser, P. J.; Henne, S.; Vollmer, M. K.; Mühle, J.; Weiss, R. F.; Salameh, P. K.; Young, D.; Reimann, S.; Wenger, A.; Arnold, T.; Harth, C. M.; Krummel, P. B.; Steele, L. P.; Dunse, B. L.; Miller, B. R.; Lunder, C. R.; Hermansen, O.; Schmidbauer, N.; Saito, T.; Yokouchi, Y.; Park, S.; Li, S.; Yao, B.; Zhou, L. X.; Arduini, J.; Maione, M.; Wang, R. H. J.; Ivy, D.; Prinn, R. G.

    2016-01-01

    High frequency, in situ observations from 11 globally distributed sites for the period 1994-2014 and archived air measurements dating from 1978 onward have been used to determine the global growth rate of 1,1-difluoroethane (HFC-152a, CH3CHF2). These observations have been combined with a range of atmospheric transport models to derive global emission estimates in a top-down approach. HFC-152a is a greenhouse gas with a short atmospheric lifetime of about 1.5 years. Since it does not contain chlorine or bromine, HFC-152a makes no direct contribution to the destruction of stratospheric ozone and is therefore used as a substitute for the ozone depleting chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs). The concentration of HFC-152a has grown substantially since the first direct measurements in 1994, reaching a maximum annual global growth rate of 0.84 ± 0.05 ppt yr-1 in 2006, implying a substantial increase in emissions up to 2006. However, since 2007, the annual rate of growth has slowed to 0.38 ± 0.04 ppt yr-1 in 2010 with a further decline to an annual average rate of growth in 2013-2014 of -0.06 ± 0.05 ppt yr-1. The annual average Northern Hemisphere (NH) mole fraction in 1994 was 1.2 ppt rising to an annual average mole fraction of 10.1 ppt in 2014. Average annual mole fractions in the Southern Hemisphere (SH) in 1998 and 2014 were 0.84 and 4.5 ppt, respectively. We estimate global emissions of HFC-152a have risen from 7.3 ± 5.6 Gg yr-1 in 1994 to a maximum of 54.4 ± 17.1 Gg yr-1 in 2011, declining to 52.5 ± 20.1 Gg yr-1 in 2014 or 7.2 ± 2.8 Tg-CO2 eq yr-1. Analysis of mole fraction enhancements above regional background atmospheric levels suggests substantial emissions from North America, Asia, and Europe. Global HFC emissions (so called "bottom up" emissions) reported by the United Nations Framework Convention on Climate Change (UNFCCC) are based on cumulative national emission data reported to the UNFCCC, which in turn are based on

  12. Development and characterization of a panel of cross-reactive monoclonal antibodies generated using H1N1 influenza virus.

    PubMed

    Guo, Chun-yan; Tang, Yi-gui; Qi, Zong-li; Liu, Yang; Zhao, Xiang-rong; Huo, Xue-ping; Li, Yan; Feng, Qing; Zhao, Peng-hua; Wang, Xin; Li, Yuan; Wang, Hai-fang; Hu, Jun; Zhang, Xin-jian

    2015-08-01

    To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. 40 yr phase-out for conventional coal? If only!

    NASA Astrophysics Data System (ADS)

    Socolow, Robert

    2012-03-01

    Myhrvold and Caldeira worked out the climate consequences of various ways in which the world's current fleet of coal power plants could evolve into something different [1]. They imagined one-fortieth of the world's coal plants being closed down each year for 40 years. Two limiting cases are (1) nothing is built to take the place of this power, because efficiency gains have made them unnecessary, and (2) coal plants exactly like those now running take their place. Since coal power is the most carbon-intensive form of power, all other options fall between these limits. They looked at six single-technology alternatives: taking over from coal as we know it are coal with carbon dioxide capture and storage, natural gas, nuclear power and three forms of intermittent renewables (presented as baseload options). Moreover, whatever the alternative, it remains in place unchanged from year 40 through year 100. Results are presented as 100 yr trajectories for the increment in the average global surface temperature due only to this power production. For the coal-for-coal scenario, the surface temperature increase is about 0.13 °C in 40 yr and 0.31 °C in 100 yr. For the efficiency-for-coal scenario, the rise is 0.07 °C in 40 yr and 0.06 °C in 100 yr. Clearly, temperature rise is approximately proportional to emissions and these are self-consistent answers. For example, after 40 yr efficiency-for-coal has brought approximately half the temperature rise of coal-for-coal, and there have been exactly half the emissions. The efficiency-for-coal trajectory falls ever so slightly between years 40 and 100, because once CO2 enters the atmosphere it lingers. As for the absolute magnitude of the coal-to-coal trajectory, today's global coal power production (8300 TWh in 2008) is almost exactly what would be produced from one thousand one-gigawatt coal plants running flat out (8760 TWh), which is the coal power production assumed by Myhrvold and Caldeira. From table S1 of their

  14. Simultaneous detection of assembly and disassembly of multivalent HA tag and anti-HA antibody in single in-capillary assay.

    PubMed

    Wang, Jianhao; Qin, Yuqin; Qin, Haifang; Liu, Li; Ding, Shumin; Teng, Yiwan; Ji, Junling; Qiu, Lin; Jiang, Pengju

    2016-08-01

    Herein, we have developed an in-capillary assay for simultaneous detection of the assembly and disassembly of the multivalent HA tag peptide and antibody. HA tag with hexahistidine at C terminus (YPYDVPDYAG4 H6 , termed YPYDH6 ) was conjugated with quantum dots (QDs) by metal-affinity force to form a multivalent HA tag (QD-YPYDH6 ). QD-YPYDH6 and monoclonal anti-HA antibody (anti-HA) were sequentially injected into the capillary. They were mixed and assembled inside the capillary. The reaction products were online discriminated and detected by fluorescence coupled capillary electrophoresis (CE-FL). For the in-capillary assay, the binding efficiency of the multivalent HA tag and antibody on was influenced by the molar ratio and injection time. Such novel assay could even give out the self-assembly kinetic constant of QDs and YPYDH6 as KD of 34.1 μM with n (binding cooperativeness) of 2.2 by Hill equation. More importantly, the simultaneous detection of the assembly and imidazole (Im) induced disassembly of the QD-YPYDH6 -anti-HA complex was achieved in a single in-capillary assay. Our study demonstrated a new method for the online detection of antigen-antibody interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Factors controlling CO2 exchange on timescales from hourly to decadal at Harvard Forest

    Treesearch

    Shawn Urbanski; C. Barford; S. Wofsy; C. Kucharik; E. Pyle; J. Budney; K. McKain; D. Fitzjarrald; M. Czikowsky; J. W. Munger

    2007-01-01

    We analyzed 13 years (1992-2004) of CO2 flux data, biometry, and meteorology from a mixed deciduous forest in central Massachusetts. Annual net uptake of CO2 ranged from 1.0 to 4.7 Mg-C ha-1yr-1, with an average of 2.5 Mg-C ha-1yr-1. Uptake rates increased systematically, nearly doubling over the period despite forest age of 75–110 years; there were...

  16. Responses of soil hydrolytic enzymes, ammonia-oxidizing bacteria and archaea to nitrogen applications in a temperate grassland in Inner Mongolia.

    PubMed

    Zhang, Xinyu; Tang, Yuqian; Shi, Yao; He, Nianpeng; Wen, Xuefa; Yu, Qiang; Zheng, Chunyu; Sun, Xiaomin; Qiu, Weiwen

    2016-09-06

    We used a seven-year urea gradient applied field experiment to investigate the effects of nitrogen (N) applications on soil N hydrolytic enzyme activity and ammonia-oxidizing microbial abundance in a typical steppe ecosystem in Inner Mongolia. The results showed that N additions inhibited the soil N-related hydrolytic enzyme activities, especially in 392 kg N ha(-1 )yr(-1) treatment. As N additions increased, the amoA gene copy ratios of ammonia-oxidizing archaea (AOA) to ammonia-oxidizing bacteria (AOB) decreased from 1.13 to 0.65. Pearson correlation analysis showed that the AOA gene copies were negatively related with NH4(+)-N content. However, the AOB gene copies were positively correlated with NO3(-)-N content. Moderate N application rates (56-224 kg N ha(-1 )yr(-1)) accompanied by P additions are beneficial to maintaining the abundance of AOB, as opposed to the inhibition of highest N application rate (392 kg N ha(-1 )yr(-1)) on the abundance of AOB. This study suggests that the abundance of AOB and AOA would not decrease unless N applications exceed 224 kg N ha(-1 )yr(-1) in temperate grasslands in Inner Mongolia.

  17. Fisetin inhibits TNF-α-induced inflammatory action and hydrogen peroxide-induced oxidative damage in human keratinocyte HaCaT cells through PI3K/AKT/Nrf-2-mediated heme oxygenase-1 expression.

    PubMed

    Seo, Seung-Hee; Jeong, Gil-Saeng

    2015-12-01

    Oxidative skin damage and skin inflammation play key roles in the pathogenesis of skin-related diseases. Fisetin is a naturally occurring flavonoid abundantly found in several vegetables and fruits. Fisetin has been shown to exert various positive biological effects, such as anti-cancer, anti-proliferative, neuroprotective and anti-oxidative effects. In this study, we investigate the skin protective effects and anti-inflammatory properties of fisetin in hydrogen peroxide- and TNF-α-challenged human keratinocyte HaCaT cells. When HaCaT cells were treated with non-cytotoxic concentrations of fisetin (1-20μM), heme oxygenase (HO)-1 mRNA and protein expression increased in a dose-dependent manner. Furthermore, fisetin dose-dependently increased cell viability and reduced ROS production in hydrogen peroxide-treated HaCaT cells. Fisetin also inhibited the production of NO, PGE2 IL-1β, IL-6, expression of iNOS and COX-2, and activation of NF-κB in HaCaT cells treated with TNF-α. Fisetin induced Nrf2 translocation to the nuclei. HO-1 siRNA transient transfection reversed the effects of fisetin on cytoprotection, ROS reduction, NO, PGE2, IL-1β, IL-6, and TNF-α production, and NF-κB DNA-binding activity. Moreover, fisetin increased Akt phosphorylation and a PI3K pathway inhibitor (LY294002) abolished fisetin-induced cytoprotection and NO inhibition. Taken together, these results provide evidence for a beneficial role of fisetin in skin therapy. Copyright © 2015. Published by Elsevier B.V.

  18. Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses

    PubMed Central

    Carter, Donald M.; Darby, Christopher A.; Lefoley, Bradford C.; Crevar, Corey J.; Alefantis, Timothy; Oomen, Raymond; Anderson, Stephen F.; Strugnell, Tod; Cortés-Garcia, Guadalupe; Vogel, Thorsten U.; Parrington, Mark; Kleanthous, Harold

    2016-01-01

    ABSTRACT One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. IMPORTANCE Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head

  19. Addition of glycosylation to influenza A virus hemagglutinin modulates antibody-mediated recognition of H1N1 2009 pandemic viruses.

    PubMed

    Job, Emma R; Deng, Yi-Mo; Barfod, Kenneth K; Tate, Michelle D; Caldwell, Natalie; Reddiex, Scott; Maurer-Stroh, Sebastian; Brooks, Andrew G; Reading, Patrick C

    2013-03-01

    Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the viral hemagglutinin (HA). Glycans on the head of HA promote virus survival by shielding antigenic sites, but highly glycosylated seasonal IAV are inactivated by soluble lectins of the innate immune system. In 2009, human strains of pandemic H1N1 [A(H1N1)pdm] expressed a single glycosylation site (Asn(104)) on the head of HA. Since then, variants with additional glycosylation sites have been detected, and the location of these sites has been distinct to those of recent seasonal H1N1 strains. We have compared wild-type and reverse-engineered A(H1N1)pdm IAV with differing potential glycosylation sites on HA for sensitivity to collectins and to neutralizing Abs. Addition of a glycan (Asn(136)) to A(H1N1)pdm HA was associated with resistance to neutralizing Abs but did not increase sensitivity to collectins. Moreover, variants expressing Asn(136) showed enhanced growth in A(H1N1)pdm-vaccinated mice, consistent with evasion of Ab-mediated immunity in vivo. Thus, a fine balance exists regarding the optimal pattern of HA glycosylation to facilitate evasion of Ab-mediated immunity while maintaining resistance to lectin-mediated defenses of the innate immune system.

  20. A Mathematical Model of Neutral Lipid Content in terms of Initial Nitrogen Concentration and Validation in Coelastrum sp. HA-1 and Application in Chlorella sorokiniana

    PubMed Central

    Zhao, Yue; Liu, Zhiyong; Liu, Chenfeng; Hu, Zhipeng

    2017-01-01

    Microalgae are considered to be a potential major biomass feedstock for biofuel due to their high lipid content. However, no correlation equations as a function of initial nitrogen concentration for lipid accumulation have been developed for simplicity to predict lipid production and optimize the lipid production process. In this study, a lipid accumulation model was developed with simple parameters based on the assumption protein synthesis shift to lipid synthesis by a linear function of nitrogen quota. The model predictions fitted well for the growth, lipid content, and nitrogen consumption of Coelastrum sp. HA-1 under various initial nitrogen concentrations. Then the model was applied successfully in Chlorella sorokiniana to predict the lipid content with different light intensities. The quantitative relationship between initial nitrogen concentrations and the final lipid content with sensitivity analysis of the model were also discussed. Based on the model results, the conversion efficiency from protein synthesis to lipid synthesis is higher and higher in microalgae metabolism process as nitrogen decreases; however, the carbohydrate composition content remains basically unchanged neither in HA-1 nor in C. sorokiniana. PMID:28194424

  1. Global and regional emissions estimates of 1,1-difluoroethane (HFC-152a, CH3CHF2) from in situ and air archive observations

    NASA Astrophysics Data System (ADS)

    Simmonds, P. G.; Rigby, M.; Manning, A. J.; Lunt, M. F.; O'Doherty, S.; Young, D.; McCulloch, A.; Fraser, P. J.; Henne, S.; Vollmer, M. K.; Reimann, S.; Wenger, A.; Mühle, J.; Harth, C. M.; Salameh, P. K.; Arnold, T.; Weiss, R. F.; Krummel, P. B.; Steele, L. P.; Dunse, B. L.; Miller, B. R.; Lunder, C. R.; Hermansen, O.; Schmidbauer, N.; Saito, T.; Yokouchi, Y.; Park, S.; Li, S.; Yao, B.; Zhou, L. X.; Arduini, J.; Maione, M.; Wang, R. H. J.; Prinn, R. G.

    2015-08-01

    High frequency, ground-based, in situ measurements from eleven globally-distributed sites covering 1994-2014, combined with measurements of archived air samples dating from 1978 onward and atmospheric transport models, have been used to estimate the growth of 1,1-difluoroethane (HFC-152a, CH3CHF2) mole fractions in the atmosphere and the global emissions required to derive the observed growth. HFC-152a is a significant greenhouse gas but since it does not contain chlorine or bromine, HFC-152a makes no direct contribution to the destruction of stratospheric ozone and is therefore used as a substitute for the ozone depleting chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs). HFC-152a has exhibited substantial atmospheric growth since the first measurements reaching a maximum annualised global growth rate of 0.81 ± 0.05 ppt yr-1 in 2006, implying a substantial increase in emissions up to 2006. However, since 2007, the annualised rate of growth has slowed to 0.38 ± 0.04 ppt yr-1 in 2010 with a further decline to an average rate of change in 2013-2014 of -0.06 ± 0.05 ppt yr-1. The average Northern Hemisphere (NH) mixing ratio in 1994 was 1.2 ppt rising to a mixing ratio of 10.2 ppt in December 2014. Average annual mixing ratios in the Southern Hemisphere (SH) in 1994 and 2014 were 0.34 and 4.4 ppt, respectively. We estimate global emissions of HFC-152a have risen from 7.3 ± 5.6 Gg yr-1 in 1994 to a maximum of 54.4 ± 17.1 Gg yr-1 in 2011, declining to 52.5 ± 20.1 Gg yr-1 in 2014 or 7.2 ± 2.8 Tg-CO2 eq yr-1. Analysis of mixing ratio enhancements above regional background atmospheric levels suggests substantial emissions from North America, Asia and Europe. Global HFC emissions (so called "bottom up" emissions) reported by the United Nations Framework Convention on Climate Change (UNFCCC) are based on cumulative national emission data reported to the UNFCCC, which in turn are based on national consumption data. There appears to be a significant

  2. Investigation of boundary conditions for biomimetic HA deposition on titanium oxide surfaces.

    PubMed

    Lindgren, M; Astrand, M; Wiklund, U; Engqvist, H

    2009-07-01

    To improve the clinical outcome of metal implants, i.e. earlier loading and reduction of the incidence of revision surgery, better bone bonding ability is wanted. One method to achieve this is to change the surface chemistry to give a surface that facilitates bone bonding in vivo, i.e. a bioactive surface. Crystalline titanium oxide has recently been proven to be bioactive in vitro and is an interesting option to the more common hydroxylapatite (HA) coatings on implants. A materials possible in vitro bioactivity is tested through soaking in simulated body fluid and studies of possible HA formation on the surface. For bioactive materials, the formed HA layer can also be used as a coating. The aim of the current paper is to investigate some boundary conditions for HA formation on crystalline titanium oxide surfaces regarding influence from coating thickness, soaking time and soaking temperature. The influence from soaking time and temperature on the HA growth were investigated on oxidised Ti samples, (24 h at 800 degrees C) resulting in a rutile surface structure. The oxidised samples were tested at three temperatures (4, 37 and 65 degrees C) and four times (1 h, 1 day, 1 week and 4 weeks). The influence from titanium coating thickness on the HA growth was investigated via depositing thin films of crystalline titanium dioxide on Ti plates using a reactive magnetron sputtering process. Four different PVD runs with coating thicknesses between 19 and 74 nm were tested. The soaking temperature had an effect on the HA formation and growth on both rutile surfaces and native oxide on Ti substrates. Higher temperatures lead to easier formation of HA. It was even possible, at 65 degrees C, to grow HA on native titanium oxide from soaking in PBS. The coating quality was better for HA formed at 65 degrees C compared to 37 degrees C. All PVD-coatings showed HA growth after 1 week in PBS at 37 degrees C, thus even very thin coatings of crystalline titanium oxide coatings are

  3. A pan-European quantitative assessment of soil loss by wind

    NASA Astrophysics Data System (ADS)

    Borrelli, Pasqualle; Lugato, Emanuele; Panagos, Panos

    2016-04-01

    Soil erosion by wind is a serious environmental problem often low perceived but resulting in severe soil degradation forms. On the long-term a considerable part of topsoil - rich in nutrient and organic matters - could be removed compromising the agricultural productivity and inducing an increased use of fertilizers. Field scale studies and observations proven that wind erosion is a serious problem in many European sites. The state-of-the-art suggests a scenario where wind erosion locally affects the temperate climate areas of the northern European countries, as well as the semi-arid areas of the Mediterranean region. However, observations, field measurements and modelling assessments are extremely limited and unequally distributed across Europe. It implies a lack of knowledge about where and when wind erosion occurs, limiting policy actions aimed at mitigating land degradation. To gain a better understanding about soil degradation process, the Soil Resource Assessment working group of the Joint Research Centre carried out the first pan-European assessments of wind-erodible fraction of soil (EF) (Geoderma, 232, 471-478, 2014) and land susceptibility to wind erosion (Land Degradation & Development, DOI: 10.1002/ldr.2318). Today's challenge is to integrate the insights archived by these pan-European assessments, local experiments and field-scale models into a new generation of regional-scale wind erosion models. A GIS version of the Revised Wind Erosion Equation (RWEQ) was developed with the aim to i) move a step forward into the aforementioned challenges, and ii) evaluate the soil loss potential due to wind erosion in the agricoltural land of the EU. The model scheme was designed to describe daily soil loss potential, combining spatiotemporal conditions of soil erodibility, crust factor, soil moisture content, vegetation coverage and wind erosivity at 1 km2 resolution. The average soil loss predicted by GIS-RWEQ in the EU arable land ranges from 0 to 39.9 Mg ha-1 yr

  4. Responses of soil enzyme activity and microbial community compositions to nitrogen addition in bulk and microaggregate soil in the temperate steppe of Inner Mongolia

    NASA Astrophysics Data System (ADS)

    Shi, Yao; Sheng, Lianxi; Wang, Zhongqiang; Zhang, Xinyu; He, Nianpeng; Yu, Qiang

    2016-10-01

    In order to explore the responses of soil enzyme activities and microbial community compositions to long-term nitrogen (N) addition in both bulk soil and microaggregate of chestnut soil, we conducted a 7-year urea addition experiment with N treatments at 6 levels (0, 56, 112, 224, 392 and 560 kg N ha-1 yr-1) in a temperate steppe of Inner Mongolia in China. Soil properties and the activities of four enzymes involved in carbon (C), nitrogen (N) and phosphorus (P) cycling were measured in both bulk soil and microaggregate, and phospholipid fatty acids (PLFAs) were measured in bulk soil. The results indicated that: 1) in bulk soil, N addition significantly decreased β-1,4-glucosidase (BG) and leucine aminopeptidase (LAP) activities at the treatment amounts of 224, 392 and 560 kg N ha-1 yr-1, and obviously suppressed β-1,4-N-acetylglucosaminidase (NAG) activity at the treatment amount of 560 kg N ha-1 yr-1. N addition enhanced total PLFAs (totPLFAs) and bacterial PLFAs (bacPLFAs) at the treatment amounts of 392 and 560 kg N ha-1 yr-1, respectively, but fungal PLFAs showed no response to N addition. The activities of BG, NAG and LAP were positively correlated with soil pH, but negatively correlated with the concentration of NH 4 + -N; 2) in microaggregate (53-250 μm), the activities of BG, NAG and AP showed no response to increased addition of N, but the significantly decreased LAP activity was observed at the treatment amount of 392 kg N ha-1 yr-1. These results suggested that enzyme activities were more sensitive to N addition than PLFA biomarkers in soil, and LAP activity in microaggregate may be a good indicator for evaluating N cycle response to long-term N addition.

  5. Maintaining vigorous activity attenuates 7-yr weight gain in 8340 runners.

    PubMed

    Williams, Paul T

    2007-05-01

    Body weight generally increases with aging in Western societies. Although training studies show that exercise produces acute weight loss, it is unclear whether the long-term maintenance of vigorous exercise attenuates the trajectory of age-related weight gain. Specifically, prior studies have not tested whether the maintenance of physical activity, in the absence of any change in activity, prevents weight gain. Prospective study of 6119 male and 2221 female runners whose running distances changed < 5 km x wk(-1) between baseline and follow-up surveys 7 yr later. On average, men who maintained modest (0-23 km x wk(-1)), intermediate (24-47 km x wk(-1)), or prolonged running distances (> or = 48 km x wk(-1)) all gained weight through age 64; however, those who maintained > or = 48 km x wk(-1) had one half the average annual weight gain of those who maintained < 24 km x wk(-1). For example, between the ages of 35 and 44 in men and 30 and 39 yr in women, those who maintained < 24 km x wk(-1) gained, on average, 2.1 and 2.9 kg more per decade than those averaging > 48 km x wk(-1). Age-related weight gain, and its attenuation by maintained exercise, were both greater in younger than in older men. Men's gains in waist circumference with age, and its attenuation by maintaining running, were the same in older and younger men. Regardless of age, women increased their body weight, waist circumference, and hip circumference over time, and these measurements were attenuated in proportion to their maintained running distance. In both sexes, running disproportionately prevented more extreme increases in weight. As they aged, men and women gained less weight in proportion to their levels of sustained vigorous activity. This long-term beneficial effect is in addition to the acute weight loss that occurs with increased activity.

  6. Carbon stocks and fluxes in managed peatlands in northern Borneo

    NASA Astrophysics Data System (ADS)

    Arn Teh, Yit; Manning, Frances; Cook, Sarah; Zin Zawawi, Norliyana; Sii, Longwin; Hill, Timothy; Page, Susan; Whelan, Mick; Evans, Chris; Gauci, Vincent; Chocholek, Melanie; Khoon Kho, Lip

    2017-04-01

    Oil palm is the largest agricultural crop in the tropics and accounts for 13 % of current tropical land area. Patterns of land-atmosphere exchange from oil palm ecosystems therefore have potentially important implications for regional and global C budgets due to the large scale of land conversion. This is particularly true for oil palm plantations on peat because of the large C stocks held by tropical peat soils that are potential sensitivity to human disturbance. Here we report preliminary findings on C stocks and fluxes from a long-term, multi-scale project in Sarawak, Malaysia that aims to quantify the impacts of oil palm conversion on C and greenhouse gas fluxes from oil palm recently established on peat. Land-atmosphere fluxes were determined using a combination of top-down and bottom-up methods (eddy covariance, canopy/stem and soil flux measurements, net primary productivity). Fluvial fluxes were determined by quantifying rates of dissolved and particulate organic C export. Ecosystem C dynamics were determined using the intensive C plot method, which quantified all major C stocks and fluxes, including plant and soil stocks, leaf litterfall, aboveground biomass production, root production, stem/canopy respiration, root-rhizosphere respiration, and heterotrophic soil respiration. Preliminary analysis indicates that vegetative aboveground biomass in these 7 year old plantations was 8.9-11.9 Mg C ha-1, or approximately one-quarter of adjacent secondary forest. Belowground biomass was 5.6-6.5 Mg C ha-1; on par with secondary forests. Soil C stocks in the 0-30 cm depth was 233.1-240.8 Mg C ha-1, or 32-36% greater than soil C stocks in secondary forests at the same depth (176.8 Mg C ha-1). Estimates of vegetative aboveground and belowground net primary productivity were 1.3-1.7 Mg C ha-1 yr-1 and 0.8-0.9 Mg C ha-1 yr-1, respectively. Fruit brunch production was approximately 67 Mg C ha-1over 7 yearsor 9.6 Mg C ha-1 yr-1. Total soil respiration rates were 18 Mg C ha

  7. A comparison of cellulosic fuel yields and separated soil-surface CO2 fluxes in maize and prairie biofuel cropping systems

    NASA Astrophysics Data System (ADS)

    Nichols, Virginia A.

    It has been suggested that strategic incorporation of perennial vegetation into agricultural landscapes could provide ecosystem services while maintaining agricultural productivity. To evaluate potential use of prairie as a Midwestern cellulosic feedstock, we investigated theoretical cellulosic fuel yields, as well as soil-surface carbon dioxide emissions of prairie-based biofuel systems as compared to maize-based systems on fertile soils in Boone County, IA, USA. Investigated systems were: a maize-soybean rotation grown for grain only, continuous maize grown for grain and stover both with and without a winter rye cover crop, and a 31-species reconstructed prairie grown with and without spring nitrogen fertilization for fall-harvested biomass. From 2009-2013, the highest producing system was N-fertilized prairie, averaging 10.4 Mg ha -1 yr-1 above-ground biomass with average harvest removals of 7.8 Mg ha-1 yr-1. The unfertilized prairie produced 7.4 Mg ha-1 yr-1, averaging harvests of 5.3 Mg ha-1 yr-1. Lowest cellulosic biomass harvests were realized from continuous maize systems, averaging 3.5 Mg ha -1 yr-1 when grown with, and 3.7 Mg ha-1 yr-1 when grown without a winter rye cover crop, respectively. Un-fertilized prairie biomass and maize stover had equivalent dietary conversion ratios at 330 g ethanol kg-1 dry biomass, but N-fertilized prairie was lower at 315. Over four years prairie systems averaged 1287 L cellulosic ethanol ha-1 yr-1 more than maize systems, with fertilization increasing prairie ethanol production by 865 L ha-1 yr-1. Harvested biomass accounted for >90% of ethanol yield variation. A major hurdle in carbon cycling studies is the separation of the soil-surface CO2 flux into its respective components. From 2012-2013 we used a shading method to separate soil-surface CO2 resulting from oxidation of soil organic matter and CO2 derived from live-root activity in three systems: unfertilized prairie, N-fertilized prairie, and continuous maize

  8. SRWC bioenergy productivity and economic feasibility on marginal lands.

    PubMed

    Ghezehei, Solomon B; Shifflett, Shawn D; Hazel, Dennis W; Nichols, Elizabeth Guthrie

    2015-09-01

    Evolving bioenergy markets necessitate consideration of marginal lands for woody biomass production worldwide particularly the southeastern U.S., a prominent wood pellet exporter to Europe. Growing short rotation woody crops (SRWCs) on marginal lands minimizes concerns about using croplands for bioenergy production and reinforces sustainability of wood supply to existing and growing global biomass markets. We estimated mean annual aboveground green biomass increments (MAIs) and assessed economic feasibility of various operationally established (0.5 ha-109 ha) SRWC stands on lands used to mitigate environmental liabilities of municipal wastewater, livestock wastewater and sludge, and subsurface contamination by petroleum and pesticides. MAIs (Mg ha(-1) yr(-1)) had no consistent relationship with stand density or age. Non-irrigated Populus, Plantanus occidentalis L. and Pinus taeda L. stands produced 2.4-12.4 Mg ha(-1) yr(-1). Older, irrigated Taxodium distchum L., Fraxinus pennsylvanica L., and coppiced P. occidentalis stands had higher MAIs (10.6-21.3 Mg ha(-1) yr(-1)) than irrigated Liquidambar styraciflua L. and non-coppiced, irrigated P. occidentalis (8-18 Mg ha(-1) yr(-1)). Natural hardwood MAIs at 20-60 years were less than hardwood and P. taeda productivities at 5-20 years. Unlike weed control, irrigation and coppicing improved managed hardwood productivity. Rotation length affected economic outcomes although the returns were poor due to high establishment and maintenance costs, low productivities and low current stumpage values, which are expected to quickly change with development of robust global markets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Factors affecting receipt of a medical card in a cohort of colorectal cancer patients, 2002-2006.

    PubMed

    McDevitt, J; Sharp, L; MacDonald, D; Dwane, F; Comber, H

    2013-04-01

    The criteria for allocation of medical cards to colorectal cancer patients < 70 were explored. All invasive colorectal cancers diagnosed during 2002-2006 (n = 4,762) were abstracted and linked to the PCRS master file to determine medical card status. Determinants of medical card possession before diagnosis were; age 65-69yr vs. 15-54 yr (OR = 3.95 (95% CI); 3.20-4.88), other status vs. married (OR = 1.89; 1.61-2.23), most vs. least deprived (OR = 3.65; 2.89-4.61), smoker vs. non-smoker (OR = 1.98; 1.64-2.37), ED population density (< 1/ha vs. > 15/ha; OR = 1.47; 1.20-1.80). Determinants of medical card possession after diagnosis were; age 65-69 yr vs. 15-54 yr (OR = 0.77; 0.62-0.96), most vs. least deprived (OR = 2.15; 1.72-2.70), stage IV vs. 1: OR = 2.49; 1.85-3.36), chemotherapy (OR = 2.30; 1.87-2.83), radiotherapy (OR = 1.40; 1.13-1.72), ED population density (< 1/ha vs. > 15/ha; OR = 1.47; 1.19-1.82), HSE South vs. DNML (OR = 1.76; 1.40-2.21). Medical card possession among colorectal cancer patients was determined by greater age and deprivation before diagnosis; and younger age, greater deprivation, advanced stage and treatments warranted by extent of disease after diagnosis. Low population density of ED of residence also predicted card receipt.

  10. Mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors sensitize reduced glucocorticoid response mediated by TNFalpha in human epidermal keratinocytes (HaCaT).

    PubMed

    Onda, Kenji; Nagashima, Masahiro; Kawakubo, Yo; Inoue, Shota; Hirano, Toshihiko; Oka, Kitaro

    2006-12-08

    Glucocorticoids (GCs) are essential drugs administered topically or systematically for the treatment of autoimmune skin diseases such as pemphigus. However, a certain proportion of patients does not respond well to GCs. Although studies on the relationship between cytokines and GC insensitivity in local tissues have attracted attention recently, little is known about the underlying mechanism(s) for GC insensitivity in epidermal keratinocytes. Here, we report that tumor necrosis factor (TNF) alpha reduces GC-induced transactivation of endogenous genes as well as a reporter plasmid which contains GC responsive element (GRE) in human epidermal keratinocyte cells (HaCaT). The GC insensitivity by TNFalpha was not accompanied by changes in mRNA expressions of GR isoforms (alpha or beta). However, we observed that mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors (PD98059 and U0126) significantly sensitized the GC-induced transactivation of anti-inflammatory genes (glucocorticoid-induced leucine zipper (GILZ) and mitogen-activated protein kinase phosphatase (MKP)-1) and FK506 binding protein (FKBP) 51 gene in the presence of TNFalpha. Additionally, we observed that TNFalpha reduced prednisolone (PSL)-dependent nuclear translocation of GR, which was restored by pre-treatment of MEK-1 inhibitors. This is the first study demonstrating a role of the MEK-1/ERK cascade in TNFalpha-mediated GC insensitivity. Our data suggest that overexpression of TNFalpha leads to topical GC insensitivity by reducing GR nuclear translocation in keratinocytes, and our findings also suggest that inhibiting the MEK-1/ERK cascade may offer a therapeutic potential for increasing GC efficacy in epidermis where sufficient inflammatory suppression is required.

  11. Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals.

    PubMed

    Kelly, Deborah; Burt, Kimberley; Missaghi, Bayan; Barrett, Lisa; Keynan, Yoav; Fowke, Keith; Grant, Michael

    2012-08-31

    Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied. Assess vaccine-related effects on CD4(+) T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic. A single dose of Arepanrix™ split vaccine including 3.75 μg A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1-5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4(+) T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals. Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4(+) T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4(+) T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4(+) T cell numbers, which was greater amongst responders. We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals

  12. Wet deposition and sources of inorganic nitrogen in the Three Gorges Reservoir Region, China.

    PubMed

    Wang, Huanbo; Shi, Guangming; Tian, Mi; Chen, Yang; Qiao, Baoqing; Zhang, Liuyi; Yang, Fumo; Zhang, Leiming; Luo, Qiong

    2018-02-01

    Precipitation samples were collected at five rural and one urban sites in the Three Gorges Reservoir Region (TGR), China from March 2014 to February 2016. The inorganic reactive nitrogen (Nr) contents were analysed to investigate their wet deposition flux, budget, and sources in the area. Annual Nr wet deposition varied from 7.1 to 23.4 kg N ha -1 yr -1 over the six sites during the two-year study campaign. The six-site average Nr wet deposition flux was 17.1 and 11.7 kg N ha -1 yr -1 in 2014 and 2015, respectively, with 71% from NH 4 + and 29% from NO 3 - . Dry deposition flux was estimated using the inferential method, which combined the measured ambient concentrations and modelled dry deposition velocities. The total (dry + wet) Nr deposition fluxes were estimated to be 21.4 kg N ha -1 yr -1 in 2014 and 16.0 kg N ha -1 yr -1 in 2015 at rural sites, and 31.4 and 25.3 kg N ha -1 yr -1 at the urban site. Annual average volume weighted mean (VWM) concentrations in precipitation at all the six sites differed little for NO 3 - but up to a factor of 2.0 for NH 4 + with the highest value at the urban site. Industrial emissions, agricultural emissions, soil dust, and biomass burning were identified as potential sources of the major inorganic ions in precipitation using factor analysis and correlation analysis. Conditional probability function (CPF) analysis indicated that the urban site was predominantly affected by industrial emissions from a power plant, cement manufactory, and salt chemical facility located ∼13 km southeast of the sampling site. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  13. Soil losses in rural watersheds with environmental land use conflicts.

    PubMed

    Pacheco, F A L; Varandas, S G P; Sanches Fernandes, L F; Valle Junior, R F

    2014-07-01

    Soil losses were calculated in a rural watershed where environmental land use conflicts developed in the course of a progressive invasion of forest and pasture/forest lands by agriculture, especially vineyards. The hydrographic basin is located in the Douro region where the famous Port wine is produced (northern Portugal) and the soil losses were estimated by the Universal Soil Loss Equation (USLE) in combination with a Geographic Information System (GIS). Environmental land use conflicts were set up on the basis of land use and land capability maps, coded as follows: 1-agriculture, 2-pasture, 3-pasture/forest, and 4-forest. The difference between the codes of capability and use defines a conflict class, where a negative or nil value means no conflict and a positive i value means class i conflict. The reliability of soil loss estimates was tested by a check of these values against the frequency of stone wall instabilities in vineyard terraces, with good results. Using the USLE, the average soil loss (A) was estimated in A=12.2 t·ha(-1yr(-1) and potential erosion risk areas were found to occupy 28.3% of the basin, defined where soil losses are larger than soil loss tolerances. Soil losses in no conflict regions (11.2 t·ha(-1yr(-1)) were significantly different from those in class 2 (6.8 t·ha(-1yr(-1)) and class 3 regions (21.3 t·ha(-1yr(-1)) that in total occupy 2.62 km(2) (14.3% of the basin). When simulating a scenario of no conflict across the entire basin, whereby land use in class 2 conflict regions is set up to permanent pastures and in class 3 conflict regions to pine forests, it was concluded that A=0.95 t·ha(-1yr(-1) (class 2) or A=9.8 t·ha(-1yr(-1) (class 3), which correspond to drops of 86% and 54% in soil loss relative to the actual values. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Energy Use and Carbon Dioxide Emissions from Cropland Production in the United States, 1990-2004

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    West, Tristram O.; Brandt, Craig C; Marland, Gregg

    2009-01-01

    Changes in cropland production and management influence energy consumption and emissions of CO2 from fossil-fuel combustion. A method was developed to calculate on-site and off-site energy and CO2 emissions for cropping practices in the US at the county scale. Energy consumption and emissions occur on-site from the operation of farm machinery and occur off-site from the manufacture and transport of cropland production inputs, such as fertilizers, pesticides, and agricultural lime. Estimates of fossil-fuel consumption and associated CO2 emissions for cropping practices enable (a) the monitoring of energy and emissions with changes in land management, and (b) the calculation and balancingmore » of regional and national carbon budgets. Results indicate on-site energy use and total energy use (i.e., the sum of on-site and off-site) on US croplands in 2004 ranged from 1.6-7.9 GJ ha-1 yr-1 and from 5.5-20.5 GJ ha-1 yr-1, respectively. On-site and total CO2 emissions in 2004 ranged from 23-176 kg C ha-1 yr-1 and from 91-365 kg C ha-1 yr-1, respectively. During the period of this analysis (1990-2004), national total energy consumption for crop production ranged from 1204-1297 PJ yr-1 (Petajoule = 1 1015 Joule) with associated total fossil CO2 emissions ranging from 22.0-23.2 Tg C yr-1 (Teragram = 1 1012 gram). The annual proportion of on-site CO2 to total CO2 emissions changed depending on the diversity of crops planted. Adoption of reduced tillage practices in the US from 1990 to 2004 resulted in a net emissions reduction of 2.4 Tg C.« less

  15. THE RELATIONSHIP BETWEEN MOTOR COMPETENCE AND PHYSICAL FITNESS IS WEAKER IN THE 15-16 YR. ADOLESCENT AGE GROUP THAN IN YOUNGER AGE GROUPS (4-5 YR. AND 11-12 YR.).

    PubMed

    Haga, Monika; Gísladóttír, Thórdís; Sigmundsson, Hermundur

    2015-12-01

    Developing motor competence and physical fitness can affect the maintenance of a sufficient level of physical activity in children and adolescents. This study assesses the relationship between motor competence and physical fitness from childhood through early adolescence. A cross-sectional sample of 194 participants from 4 to 16 years old were divided into three groups; 4-6 yr. (n=42, M age=5.2, SD 0.6), 11-12 yr. (n=58, M age=12.4, SD=0.3), and 15-16 yr. (n=94, M age=15.9, SD=0.4). To assess motor competence, each child completed the Movement Assessment Battery for Children (MABC). To measure physical fitness, three tasks (strength, speed, and endurance) were selected from the Test of Physical Fitness (TPF). To analyze the significance of the difference between the correlation coefficient in the three age groups (samples) (4-6, 11-12, and 15-16 yr.), Fischer r-to-z transformation was used. The correlation (Pearson's) between motor competence and physical fitness in the age groups was statistically higher for the youngest age groups (4-6 and 11-12 yr.) and the adolescent group (age 15-16). The differences between the two youngest age groups were not statistically significant. The results demonstrate that the correlation between motor competence and physical fitness decreases with age.

  16. The value of coastal wetlands for hurricane protection.

    PubMed

    Costanza, Robert; Pérez-Maqueo, Octavio; Martinez, M Luisa; Sutton, Paul; Anderson, Sharolyn J; Mulder, Kenneth

    2008-06-01

    Coastal wetlands reduce the damaging effects of hurricanes on coastal communities. A regression model using 34 major US hurricanes since 1980 with the natural log of damage per unit gross domestic product in the hurricane swath as the dependent variable and the natural logs of wind speed and wetland area in the swath as the independent variables was highly significant and explained 60% of the variation in relative damages. A loss of 1 ha of wetland in the model corresponded to an average USD 33,000 (median = USD 5000) increase in storm damage from specific storms. Using this relationship, and taking into account the annual probability of hits by hurricanes of varying intensities, we mapped the annual value of coastal wetlands by 1 km x 1 km pixel and by state. The annual value ranged from USD 250 to USD 51,000 ha(-1) yr(-1), with a mean of USD 8240 ha(-1) yr(-1) (median = USD 3230 ha(-1) yr(-1)) significantly larger than previous estimates. Coastal wetlands in the US were estimated to currently provide USD 23.2 billion yr(-1) in storm protection services. Coastal wetlands function as valuable, selfmaintaining "horizontal levees" for storm protection, and also provide a host of other ecosystem services that vertical levees do not. Their restoration and preservation is an extremely cost-effective strategy for society.

  17. Nitrogen solutes in an Adirondack forested watershed: Importance of dissolved organic nitrogen

    USGS Publications Warehouse

    McHale, M.R.; Mitchell, M.J.; McDonnell, Jeffery J.; Cirmo, C.P.

    2000-01-01

    Nitrogen (N) dynamics were evaluated from 1 June 1995 through 31 May 1996 within the Arbutus Lake watershed in the Adirondack Mountains of New York State, U.S.A. At the Arbutus Lake outlet dissolved organic nitrogen (DON), NO3/- and NH4/+ contributed 61%, 33%, and 6% respectively, to the total dissolved nitrogen (TDN) flux (259 mol ha-1 yr-1). At the lake inlet DON, NO3/-, and NH4/+ constituted 36%, 61%, and 3% respectively, of TDN flux (349 mol ha-1 yr-1). Differences between the factors that control DON, NO3/-, and NH4+ stream water concentrations were evaluated using two methods for estimating annual N flux at the lake inlet. Using biweekly sampling NO3/- and NH4/+ flux was 10 and 4 mol ha-1 yr-1 respectively, less than flux estimates using biweekly plus storm and snowmelt sampling. DON flux was 18 mol ha-1 yr-1 greater using only biweekly sampling. These differences are probably not of ecological significance relative to the total flux of N from the watershed (349 mol ha-1 yr-1). Dissolved organic N concentrations were positively related to discharge during both the dormant (R2 = 0.31; P<0.01) and growing season (R2= 0.09; P<0.01). There was no significant relationship between NO3/- concentration and discharge during the dormant season, but a significant negative relationship was found during the growing season (R2 = 0.29; P<0.01). Biotic controls in the growing season appeared to have had a larger impact on stream water NO3- concentrations than on DON concentrations. Arbutus Lake had a major impact on stream water N concentrations of the four landscape positions sampled, suggesting the need to quantify within lake processes to interpret N solute losses and patterns in watershed-lake systems.

  18. Influenza Virus Vaccines: Lessons from the 2009 H1N1 pandemic

    PubMed Central

    Broadbent, Andrew J.; Subbarao, Kanta

    2011-01-01

    Reflecting on the 2009 H1N1 pandemic, we summarize lessons regarding influenza vaccines that can be applied in the future. The two major challenges to vaccination during the 2009 H1N1 pandemic were timing and availability of vaccine. Vaccines were, however, well-tolerated and immunogenic, with inactivated vaccines containing 15μg of HA generally inducing antibody titers ≥1:40 in adults within 2 weeks of the administration of a single dose. Moreover, the use of oil-in-water adjuvants in Europe permitted dose- reduction, with vaccines containing as little as 3.75 or 7.5μg HA being immunogenic. Case-control studies demonstrated that monovalent 2009 H1N1 vaccines were effective in preventing infection with the 2009 H1N1 virus, but preliminary data suggests that it is important for individuals to be re-immunized annually. PMID:22125588

  19. Aptamers that bind to the hemagglutinin of the recent pandemic influenza virus H1N1 and efficiently inhibit agglutination.

    PubMed

    Gopinath, Subash C B; Kumar, Penmetcha K R

    2013-11-01

    Influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for typing influenza A viruses. In this study we have selected RNA aptamers (D-12 and D-26) that specifically target the HA protein of the recent pandemic influenza virus pdmH1N1 (A/California/07/2009). Among the selected aptamers the D-26 aptamer showed higher affinity for the HA of pdmH1N1 and was able to distinguish HA derived from other sub-types of influenza A viruses. The affinity of the D-26 aptamer was further improved upon incorporation of 2'-fluoropyrimidines to a level of 67 fM. Furthermore, the high affinity D-12 and D-26 aptamers were tested for their ability to interfere with HA-glycan interactions using a chicken red blood cell (RBC) agglutination assay. At a concentration of 200 nM the D-26 aptamer completely abolished the agglutination of RBCs, whereas D-12 only did so at 400 nM. These studies suggest that the selected aptamer D-26 not only has a higher affinity and specificity for the HA of pdmH1N1 but also has a better ability to efficiently interfere with HA-glycan interactions compared with the D-12 aptamer. The D-26 aptamer warrants further study regarding its application in developing topical virucidal products against the pdmH1N1 virus and also in surveillance of the pdmH1N1 influenza virus. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Litter and nutrient flows in tropical upland forest flooded by a hydropower plant in the Amazonian basin.

    PubMed

    Pereira, Guilherme Henrique A; Jordão, Henos Carlos K; Silva, Vanessa Francieli V; Pereira, Marcos Gervasio

    2016-12-01

    Extensive areas in the Brazilian Amazon have been flooded for the construction of hydroelectric dams. However, the water regime of these areas affects the dynamics of igarapés (streams) in adjacent terra firme (upland forests). When the reservoirs are filled, the water levels of streams rise above the normal levels and upland bank forests are flooded. We investigated how this flooding affects the litterfall and nutrient input in the upland forests upstream of a hydroelectric dam reservoir in the Central Amazonia. When the reservoir was filled, the forests were flooded and produced more than twice the litter (8.80Mg·ha -1 yr -1 ), with three times more leaves (6.36Mg·ha -1 yr -1 ) than when they were not flooded (4.20 and 1.92Mg·ha -1 yr -1 , respectively). During flooding, the decomposition rate was four times lower in flooded forests (0.328g·g -1 yr -1 ) than in control forests (1.460g·g -1 yr -1 ). Despite this, the flooding did not favor litter or nutrient accumulation. Therefore, dam construction changes the organic matter and nutrient cycling in upland Amazon rainforests. This may influence the important role that they play in organic matter dynamics and could have consequences for the regional carbon balance and, ultimately, global climate. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Immune efficacy of an adenoviral vector-based swine influenza vaccine against antigenically distinct H1N1 strains in mice.

    PubMed

    Wu, Yunpu; Yang, Dawei; Xu, Bangfeng; Liang, Wenhua; Sui, Jinyu; Chen, Yan; Yang, Huanliang; Chen, Hualan; Wei, Ping; Qiao, Chuanling

    2017-11-01

    Avian-like H1N1 swine influenza viruses are prevalent in pigs and have occasionally crossed the species barrier and infected humans, which highlights the importance of preventing swine influenza. Human adenovirus serotype 5 (Ad5) has been tested in human influenza vaccine clinical trials and has exhibited a reliable safety profile. Here, we generated a replication-defective, recombinant adenovirus (designated as rAd5-avH1HA) expressing the hemagglutinin gene of an avian-like H1N1 virus (A/swine/Zhejiang/199/2013, ZJ/199/13). Using a BALB/c mouse model, we showed that a two-dose intramuscular administration of recombinant rAd5-avH1HA induced high levels of hemagglutination inhibition antibodies and prevented homologous and heterologous H1N1 virus-induced weight loss, as well as viral replication in the nasal turbinates and lungs of mice. Furthermore, a prime-boost immunization strategy trial with a recombinant plasmid (designated as pCAGGS-HA) followed by rAd5-avH1HA vaccine provided effective protection against homologous and heterologous H1N1 virus infection in mice. These results indicate that rAd5-avH1HA is an efficacious genetically engineered vaccine candidate against H1N1 swine influenza. Future studies should examine its immune efficacy in pigs. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Highly sensitive detection and discrimination of LR and YR microcystins based on protein phosphatases and an artificial neural network.

    PubMed

    Covaci, O I; Sassolas, A; Alonso, G A; Muñoz, R; Radu, G L; Bucur, B; Marty, J-L

    2012-08-01

    The inhibition characteristics of three different protein phosphatases by three microcystin (MC) variants--LR, YR, and RR--were studied. The corresponding K (I) for each enzyme-MC couple was calculated. The toxicity of MC varies in the following order: MC-LR > MC-YR > MC-RR. The sensitivity of the enzymes increased in the following order: mutant PP2A < mutant PP1 < natural PP2A. The best limit of detection obtained was 21.2 pM MC-LR using the most sensible enzyme. Methanol, ethanol, and acetonitrile up to 2 % (v/v) may be used in inhibition measurements. An artificial neural network (ANN) was used to discriminate two MC variants--LR and YR--using the differences in inhibition percentages measured with mutant PP1 and natural PP2A. The ANN is able to analyze mixtures with concentrations ranging from 8 to 98 pM MC-LR and 31 to 373 pM MC-YR.

  3. Growth of historical Sitka spruce plantations at Unalaska Bay, Alaska.

    Treesearch

    J. Alden; D. Bruce

    1989-01-01

    Sitka spruce (Picea sitchensis (Bong.) Carr.) grew an estimated 37 cubic feet of stemwood per acre per year (2.6 m3·ha-1·yr-1) in remnant World War II plantations on Amaknak Island and 38 cubic feet of stemwood per acre per year (2.7 m3·ha-1·yr-1) in an early 19th century grove on Expedition Island, 520 miles (837 km) southwest of natural tree...

  4. H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion.

    PubMed

    Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter; Matrosovich, Mikhail

    2016-02-01

    The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T492S, N722D, R752K, and S1132F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in the HA, which decreased

  5. H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion

    PubMed Central

    Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter

    2015-01-01

    ABSTRACT The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions—T492S, N722D, R752K, and S1132F—were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. IMPORTANCE Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in

  6. Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States.

    PubMed

    Vincent, Amy L; Ma, Wenjun; Lager, Kelly M; Gramer, Marie R; Richt, Juergen A; Janke, Bruce H

    2009-10-01

    H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.

  7. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin

    PubMed Central

    Wilson, Jason R.; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O.; Katz, Jacqueline M.; York, Ian A.

    2016-01-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72–130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Importance Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely-related viruses. In spite of this limited range of protection, recent findings indicate individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help put bounds on the

  8. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin.

    PubMed

    Wilson, Jason R; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O; Katz, Jacqueline M; York, Ian A

    2014-06-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72-130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help to define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely related viruses. In spite of this limited range of protection, recent findings indicate that individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help to put bounds on the

  9. Phylogeography of influenza A H5N1 clade 2.2.1.1 in Egypt

    PubMed Central

    2013-01-01

    Background Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt. We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin. Results Phylogeography models of hemagglutinin (HA) and neuraminidase (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is weak based on Kullback–Leibler values of 0.09 for HA and 0.01 for NA. Association Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05), indicating that dispersion of H5N1 in Egypt was geographically structured. In addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes had the strongest statistical support. Conclusion We found that the majority of routes with strong statistical support were in the heavily populated Delta region. In particular, the Al Qalyubiyah governorate appears to represent a popular location for virus transition as it represented a large portion of branches in both trees. However, there remains uncertainty about virus dispersion to and from this location and thus more research needs to be conducted in order to examine this. Phylogeography can highlight the drivers of H5N1 emergence and spread. This knowledge can be used to target public health efforts to reduce morbidity and mortality. For Egypt, future work should focus on using data about vaccination and live bird markets in phylogeography models to study their impact on H5N1 diffusion within the country. PMID:24325606

  10. Biomass and carbon dynamics of a tropical mountain rain forest in China.

    PubMed

    Chen, DeXiang; Li, YiDe; Liu, HePing; Xu, Han; Xiao, WenFa; Luo, TuShou; Zhou, Zhang; Lin, MingXian

    2010-07-01

    Biometric inventories for 25 years, from 1983 to 2005, indicated that the Jianfengling tropical mountain rain forest in Hainan, China, was either a source or a modest sink of carbon. Overall, this forest was a small carbon sink with an accumulation rate of (0.56+/-0.22) Mg C ha(-1)yr(-1), integrated from the long-term measurement data of two plots (P9201 and P8302). These findings were similar to those for African and American rain forests ((0.62+/-0.23) Mg C ha(-1)yr(-1)). The carbon density varied between (201.43+/-29.38) Mg C ha(-1) and (229.16+/-39.2) Mg C ha(-1), and averaged (214.17+/-32.42) Mg C ha(-1) for plot P9201. Plot P8302, however, varied between (223.95+/-45.92) Mg C ha(-1) and (254.85+/-48.86) Mg C ha(-1), and averaged (243.35+/-47.64) Mg C ha(-1). Quadratic relationships were found between the strength of carbon sequestration and heavy rainstorms and dry months. Precipitation and evapotranspiration are two major factors controlling carbon sequestration in the tropical mountain rain forest.

  11. Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence in a European-wide population-based cohort.

    PubMed

    Höie, Ole; Wolters, Frank; Riis, Lene; Aamodt, Geir; Solberg, Camilla; Bernklev, Tomm; Odes, Selwyn; Mouzas, Iannis A; Beltrami, Marina; Langholz, Ebbe; Stockbrügger, Reinhold; Vatn, Morten; Moum, Bjorn

    2007-08-01

    Cumulative 10-yr relapse rates in ulcerative colitis (UC) of 70% to almost 100% have been reported in regional studies. The aim of this study was to determine the relapse rate in UC in a European population-based cohort 10 yr after diagnosis and to identify factors that may influence the risk of relapse. From 1991 to 1993, 771 patients with UC from seven European countries and Israel were prospectively included in a population-based inception cohort and followed for 10 yr. A relapse was defined as an increase in UC-related symptoms leading to changes in medical treatment or surgery. The cumulative relapse rate, time to first relapse, and number of relapses in the follow-up period were recorded and possible causative factors were investigated. The cumulative relapse rate of patients with at least one relapse was 0.67 (95% CI 0.63-0.71). The time to first relapse showed a greater hazard ratio (HR) (1.2, CI 1.0-1.5) for women and for patients with a high level of education (1.4, CI 1.1-1.8). The number of relapses decreased with age, and current smokers had a lower relapse rate (0.8, CI 0.6-0.9) than nonsmokers. The relapse rate in women was 1.2 (CI 1.1-1.3) times higher than in men. An inverse relation was found between the time to the first relapse and the total number of relapses. In 67% of patients, there was at least one relapse. Smoking status, level of education, and possibly female gender were found to influence the risk of relapse.

  12. Physical activity patterns measured by accelerometry in 6- to 10-yr-old children.

    PubMed

    Nyberg, Gisela A; Nordenfelt, Anja M; Ekelund, Ulf; Marcus, Claude

    2009-10-01

    To examine differences in patterns of objectively measured physical activity (PA) among weekdays and weekend days and across different time blocks during the day in relation to age and gender. This knowledge is important when planning preventive initiatives aimed at increasing levels of PA in children. This is a cross-sectional analysis in 653 girls and 640 boys (6-10 yr) measured during 1 wk with accelerometry. Periods of the day were divided into school time (8:00 a.m. to 1:30 p.m.), after school care time (1:30-4:00 p.m.), and evening time (4:00-9:00 p.m.). Multivariate ANOVA was used to analyze mean PA. Mean daily PA differed significantly across age groups (6-10 yr) in both boys and girls (P < 0.001). Mean (SE) daily PA was significantly lower during weekends compared with weekdays in all age groups (girls 782 (6.7) vs 681 (7.7) counts per min (CPM), P < 0.001; boys 853 (7.1) vs 729 (8.0) CPM, P < 0.001). This decline was similar across low, medium, and highly active children. Mean PA was highest during after school care time on weekdays (girls 879 (9.8) and boys 990 (10.0) CPM) compared with all other periods. The difference in mean PA between boys and girls was highest during school time (P < 0.001) and after school care time (P < 0.001). The decline in PA in children may start already at the age of 6 yr. The school setting may be an important arena for targeting activity levels in girls because the difference in PA levels between girls and boys is most pronounced during school time. In both girls and boys, PA levels are disproportionally low during weekends and might be important targets for interventions aimed to increase PA.

  13. Observations of 1,1-difluoroethane (HFC-152a) at AGAGE and SOGE monitoring stations in 1994-2004 and derived global and regional emission estimates

    NASA Astrophysics Data System (ADS)

    Greally, B. R.; Manning, A. J.; Reimann, S.; McCulloch, A.; Huang, J.; Dunse, B. L.; Simmonds, P. G.; Prinn, R. G.; Fraser, P. J.; Cunnold, D. M.; O'Doherty, S.; Porter, L. W.; Stemmler, K.; Vollmer, M. K.; Lunder, C. R.; Schmidbauer, N.; Hermansen, O.; Arduini, J.; Salameh, P. K.; Krummel, P. B.; Wang, R. H. J.; Folini, D.; Weiss, R. F.; Maione, M.; Nickless, G.; Stordal, F.; Derwent, R. G.

    2007-03-01

    Ground-based in situ measurements of 1,1-difluoroethane (HFC-152a, CH3CHF2) which is regulated under the Kyoto Protocol are reported under the auspices of the AGAGE (Advanced Global Atmospheric Gases Experiment) and SOGE (System of Observation of halogenated Greenhouse gases in Europe) programs. Observations of HFC-152a at five locations (four European and one Australian) over a 10 year period were recorded. The annual average growth rate of HFC-152a in the midlatitude Northern Hemisphere has risen from 0.11 ppt/yr to 0.6 ppt/yr from 1994 to 2004. The Southern Hemisphere annual average growth rate has risen from 0.09 ppt/yr to 0.4 ppt/yr from 1998 to 2004. The 2004 average mixing ratio for HFC-152a was 5.0 ppt and 1.8 ppt in the Northern and Southern hemispheres, respectively. The annual cycle observed for this species in both hemispheres is approximately consistent with measured annual cycles at the same locations in other gases which are destroyed by OH. Yearly global emissions of HFC-152a from 1994 to 2004 are derived using the global mean HFC-152a observations and a 12-box 2-D model. The global emission of HFC-152a has risen from 7 Kt/yr to 28 Kt/yr from 1995 to 2004. On the basis of observations of above-baseline elevations in the HFC-152a record and a consumption model, regional emission estimates for Europe and Australia are calculated, indicating accelerating emissions from Europe since 2000. The overall European emission in 2004 ranges from 1.5 to 4.0 Kt/year, 5-15% of global emissions for 1,1-difluoroethane, while the Australian contribution is negligible at 5-10 tonnes/year, <0.05% of global emissions.

  14. Greenhouse gas exchange in West African savanna ecosystems - how important are emissions from termite mounds?

    NASA Astrophysics Data System (ADS)

    Brümmer, C.; Brüggemann, N.

    2012-04-01

    Savannas cover large areas of the Earth's surface and play an important role in global carbon and nitrogen cycling. In this study, we present the soil-atmosphere exchange of N2O, CH4, and CO2 during two field campaigns throughout the growing seasons 2005 and 2006 at a natural savanna site that was not subject to human disturbances except for annual burning, and four agricultural sites planted with sorghum (n=2), cotton and peanut in Burkina Faso. The annual N2O emission of the nature reserve site amounted to 0.52 kg N2O-N ha-1 yr-1 in 2005 and to 0.67 kg N2O-N ha-1 yr-1 in 2006, whereas the calculated average annual N2O release of the crop sites was only 0.19 and 0.20 kg N2O-N ha-1 yr-1 in 2005 and 2006, respectively. As a result of a temporal up-scaling approach, a lower bound of annual N2O release could be given for two fertilized sorghum plots, that is, 0.83 kg N2O-N ha-1 yr-1 for a highly fertilized plot and 0.44 kg N2O-N ha-1 yr-1 for a moderately fertilized plot. During the rainy season both CH4 uptake in the range of up to 20 μg CH4-C m-2 h-1 as well as CH4 emission up to 300 μg CH4-C m-2 h-1 were observed at the nature reserve site, which was on average a CH4 source of 87.4 and 30.8 μg CH4-C m-2 h-1 in 2005 and 2006, respectively. All crop sites were on average weak CH4 sinks without significant seasonal variation. Uptake rates ranged between 2.5 and 8.7 μg CH4-C m-2 h-1. Occasionally very low net CH4 emission was observed after heavy rainfall events. Mean annual CH4 rates could be estimated to 2.48 kg CH4-C ha-1 yr-1 and -0.68 kg CH4-C ha-1 yr-1 for the nature reserve site and the crop sites, respectively. Trace gas emissions from termite (Cubitermes fungifaber) mounds that were almost exclusively found at the nature reserve were one order of magnitude higher for N2O and CO2, and two orders of magnitude higher for CH4 than soil emissions of the respective trace gas. Termite N2O, CH4 and CO2 release at the nature reserve contributed only 3.2%, 8.1% and

  15. Design and synthesis of 1-(benzothiazol-5-yl)-1H-1,2,4-triazol-5-ones as protoporphyrinogen oxidase inhibitors.

    PubMed

    Zuo, Yang; Yang, Sheng-Gang; Luo, Yan-Ping; Tan, Ying; Hao, Ge-Fei; Wu, Qiong-You; Xi, Zhen; Yang, Guang-Fu

    2013-06-01

    Protoporphyrinogen oxidase (PPO, E.C. 1.3.3.4) is the action target for several structurally diverse herbicides. A series of novel 4-(difluoromethyl)-1-(6-halo-2-substituted-benzothiazol-5-yl)-3-methyl-1H-1,2,4-triazol-5(4H)-ones 2a-z were designed and synthesized via the ring-closure of two ortho-substituents. The in vitro bioassay results indicated that the 26 newly synthesized compounds exhibited good PPO inhibition effects with K(i) values ranging from 0.06 to 17.79 μM. Compound 2e, ethyl 2-{[5-(4-(difluoromethyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluorobenzo-thiazol-2-yl]thio}acetate, was the most potent inhibitor with K(i) value of 0.06 μM against mtPPO, comparable to (K(i)=0.03 μM) sulfentrazone. Further green house assays showed that compound 2f (K(i)=0.24 μM, mtPPO), ethyl 2-{[5-(4-(difluoromethyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluorobenzothiazol-2-yl]thio}propanoate, showed the most promising post-emergence herbicidal activity with broad spectrum even at concentrations as low as 37.5 gai/ha. Soybean exhibited tolerance to compound 2f at the dosages of 150 gai/ha, whereas they are susceptible to sulfentrazone even at 75 gai/ha. Thus, compound 2f might be a potential candidate as a new herbicide for soybean fields. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors sensitize reduced glucocorticoid response mediated by TNF{alpha} in human epidermal keratinocytes (HaCaT)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Onda, Kenji; Nagashima, Masahiro; Kawakubo, Yo

    2006-12-08

    Glucocorticoids (GCs) are essential drugs administered topically or systematically for the treatment of autoimmune skin diseases such as pemphigus. However, a certain proportion of patients does not respond well to GCs. Although studies on the relationship between cytokines and GC insensitivity in local tissues have attracted attention recently, little is known about the underlying mechanism(s) for GC insensitivity in epidermal keratinocytes. Here, we report that tumor necrosis factor (TNF) {alpha} reduces GC-induced transactivation of endogenous genes as well as a reporter plasmid which contains GC responsive element (GRE) in human epidermal keratinocyte cells (HaCaT). The GC insensitivity by TNF{alpha} wasmore » not accompanied by changes in mRNA expressions of GR isoforms ({alpha} or {beta}). However, we observed that mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors (PD98059 and U0126) significantly sensitized the GC-induced transactivation of anti-inflammatory genes (glucocorticoid-induced leucine zipper (GILZ) and mitogen-activated protein kinase phosphatase (MKP)-1) and FK506 binding protein (FKBP) 51 gene in the presence of TNF{alpha}. Additionally, we observed that TNF{alpha} reduced prednisolone (PSL)-dependent nuclear translocation of GR, which was restored by pre-treatment of MEK-1 inhibitors. This is the first study demonstrating a role of the MEK-1/ERK cascade in TNF{alpha}-mediated GC insensitivity. Our data suggest that overexpression of TNF{alpha} leads to topical GC insensitivity by reducing GR nuclear translocation in keratinocytes, and our findings also suggest that inhibiting the MEK-1/ERK cascade may offer a therapeutic potential for increasing GC efficacy in epidermis where sufficient inflammatory suppression is required.« less

  17. Production and characterization of soluble human TNFRI-Fc and human HO-1(HMOX1) transgenic pigs by using the F2A peptide.

    PubMed

    Park, Sol Ji; Cho, Bumrae; Koo, Ok Jae; Kim, Hwajung; Kang, Jung Taek; Hurh, Sunghoon; Kim, Su Jin; Yeom, Hye Jung; Moon, Joonho; Lee, Eun Mi; Choi, Ji Yei; Hong, Ju Ho; Jang, Goo; Hwang, Joing-Ik; Yang, Jaeseok; Lee, Byeong Chun; Ahn, Curie

    2014-06-01

    Generation of transgenic pigs for xenotransplantation is one of the most promising technologies for resolving organ shortages. Human heme oxygenase-1 (hHO-1/HMOX1) can protect transplanted organs by its strong anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Soluble human TNFRI-Fc (shTNFRI-Fc) can inhibit the binding of human TNF-α (hTNF-α) to TNF receptors on porcine cells, and thereby, prevent hTNF-α-mediated inflammation and apoptosis. Herein, we successfully generated shTNFRI-Fc-F2A-HA-hHO-1 transgenic (TG) pigs expressing both shTNFRI-Fc and hemagglutinin-tagged-human heme oxygenase-1 (HA-hHO-1) by using an F2A self-cleaving peptide. shTNFRI-Fc and HA-hHO-1 transgenes containing the F2A peptide were constructed under the control of the CAG promoter. Transgene insertion and copy number in the genome of transgenic pigs was confirmed by polymerase chain reaction (PCR) and Southern blot analysis. Expressions of shTNFRI-Fc and HA-hHO-1 in TG pigs were confirmed using PCR, RT-PCR, western blot, ELISA, and immunohistochemistry. shTNFRI-Fc and HA-hHO-1 were expressed in various organs, including the heart, lung, and spleen. ELISA assays detected shTNFRI-Fc in the sera of TG pigs. For functional analysis, fibroblasts isolated from a shTNFRI-Fc-F2A-HA-hHO-1 TG pig (i.e., #14; 1 × 10(5) cells) were cultured with hTNF-α (20 ng/mL) and cycloheximide (10 μg/mL). The viability of shTNFRI-Fc-F2A-HA-hHO-1 TG pig fibroblasts was significantly higher than that of the wild type (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 24 h, 31.6 ± 3.2 vs. 60.4 ± 8.3 %, respectively; p < 0.05). Caspase-3/-7 activity of the shTNFRI-Fc-F2A-HA-hHO-1 TG pig fibroblasts was lower than that of the wild type pig fibroblasts (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 12 h, 812,452 ± 113,078 RLU vs. 88,240 ± 10,438 RLU, respectively; p < 0.05). These results show that shTNFRI-Fc and HA-hHO-1 TG pigs generated by the F2A self-cleaving peptide express both sh

  18. Robot-assisted Partial Nephrectomy: 5-yr Oncological Outcomes at a Single European Tertiary Cancer Center.

    PubMed

    Vartolomei, Mihai Dorin; Matei, Deliu Victor; Renne, Giuseppe; Tringali, Valeria Maria; Crisan, Nicolae; Musi, Gennaro; Mistretta, Francesco Alessandro; Russo, Andrea; Cozzi, Gabriele; Cordima, Giovani; Luzzago, Stefano; Cioffi, Antonio; Di Trapani, Ettore; Catellani, Michele; Delor, Maurizio; Bottero, Danilo; Imbimbo, Ciro; Mirone, Vincenzo; Ferro, Matteo; de Cobelli, Ottavio

    2017-10-27

    Nowadays, there is a debate about which surgical treatment should be best for clinical T1 renal tumors. If the oncological outcomes are considered, there are many open and laparoscopic series published. As far as robotic series are concerned, only a few of them report 5-yr oncological outcomes. The aim of this study was to analyze robot-assisted partial nephrectomy (RAPN) midterm oncological outcomes achieved in a tertiary robotic reference center. Between April 2009 and September 2013, 123 consecutive patients with clinical T1-stage renal masses underwent RAPN in our tertiary cancer center. Inclusion criteria were as follows: pathologically confirmed renal cell carcinomas (RCCs) and follow-up for >12 mo. Eighteen patients were excluded due to follow-up of <12 mo and 15 due to benign final pathology. Median follow-up was 59 mo (interquartile range 44-73 mo). Patients were followed according to guideline recommendations and institutional protocol. Outcomes were measured by time to disease progression, overall survival, or time to cancer-specific death. Kaplan-Meier method was used to estimate survival; log-rank tests were applied for pair-wise comparison of survival. From the 90 patients included, 66 (73.3%) had T1a, 12 (13.3%) T1b, three (3.3%) T2a, and nine (10%) T3a tumors. Predominant histological type was clear cell carcinoma: 67 (74.5%). Fuhrmann grade 1 and 2 was found in 73.3% of all malignant tumors. Two patients (2.2%) had positive surgical margins, and complication rate was 17.8%. Relapse rate was 7.7%, including two cases (2.2%) of local recurrences and five (5.5%) distant metastasis. Five-year disease-free survival was 90.9%, 5-yr cancer-specific survival was 97.5%, and 5-yr overall survival was 95.1%. Midterm oncological outcomes after RAPN for localized RCCs (predominantly T1a tumors of low anatomic complexity) were shown to be good, adding significant evidence to support the oncological efficacy and safety of RAPN for the treatment of this type of

  19. Twins in spirit - episode I: comparative preclinical evaluation of [(68)Ga]DOTATATE and [(68)Ga]HA-DOTATATE.

    PubMed

    Schottelius, Margret; Šimeček, Jakub; Hoffmann, Frauke; Willibald, Marina; Schwaiger, Markus; Wester, Hans-Jürgen

    2015-01-01

    Recently, an intra-patient comparison demonstrated that the somatostatin (sst) ligand [(68)Ga]HA-DOTATATE ([(68)Ga]DOTA-3-iodo-Tyr(3)-octreotate) provides PET images comparable to or superior to those obtained with [(68)Ga]DOTATATE. To provide a comprehensive basis for nevertheless observed slight differences in tracer biodistribution and dosimetry, the characteristics of [(68)Ga]HA-DOTATATE were investigated in a detailed preclinical study. Affinities of (nat)Ga-HA-DOTATATE and (nat)Ga-DOTATATE to sst1-5 were determined using membrane preparations and [(125)I]SST-28 as radioligand. Internalization into AR42J cells was studied in dual-tracer studies with [(125)I]TOC as internal reference. Biodistribution was investigated using AR42J tumor-bearing CD1 mice, and specificity of tracer uptake was confirmed in competition studies by coinjection of 0.8 mg TOC/kg. Sst2 affinities (IC50) of [(nat)Ga]HA-DOTATATE (1.4 ± 0.8 nM, logP: -3.16) and [(nat)Ga]DOTATATE (1.2 ± 0.6 nM, logP: -3.69) were nearly identical. Both compounds displayed IC50 > 1 μM for sst1,3,4, while sst5 affinity was markedly increased for (nat)Ga-HA-DOTATATE (102 ± 65 nM vs >1 μM for (nat)Ga-DOTATATE). [(nat)Lu]HA-DOTATATE and [(nat)Lu]DOTATATE showed slightly lower, identical sst2 affinities (2.0 ± 1.6 and 2.0 ± 0.8 nM, respectively) and sst3 affinities of 93 ± 1 and 162 ± 16 nM. Internalization of [(68)Ga]HA-DOTATATE was tenfold higher than that of [(125)I]TOC but only sixfold higher for [(68)Ga]DOTATATE and [(177)Lu]HA-DOTATATE. While [(68)Ga]HA-DOTATATE and [(68)Ga]DOTATATE had shown similar target- and non-target uptake in patients, biodistribution studies in mice at 1 h post injection (n = 5) revealed slightly increased non-specific uptake of [(68)Ga]HA-DOTATATE in the blood, liver, and intestines (0.7 ± 0.3, 1.0 ± 0.2, and 4.0 ± 0.7 %iD/g vs 0.3 ± 0.1, 0.5 ± 0.1, and 2.7 ± 0.8 %iD/g for [(68)Ga]DOTATATE). However, sst

  20. New outburst of the symbiotic nova AG Pegasi after 165 yr

    NASA Astrophysics Data System (ADS)

    Skopal, A.; Shugarov, S. Yu.; Sekeráš, M.; Wolf, M.; Tarasova, T. N.; Teyssier, F.; Fujii, M.; Guarro, J.; Garde, O.; Graham, K.; Lester, T.; Bouttard, V.; Lemoult, T.; Sollecchia, U.; Montier, J.; Boyd, D.

    2017-08-01

    Context. AG Peg is known as the slowest symbiotic nova, which experienced its nova-like outburst around 1850. After 165 yr, during June of 2015, it erupted again showing characteristics of the Z And-type outburst. Aims: The primary objective is to determine basic characteristics, the nature and type of the 2015 outburst of AG Peg. Methods: We achieved this aim by modelling the spectral energy distribution using low-resolution spectroscopy (330-750 nm; R = 500-1000), medium-resolution spectroscopy (420-720 nm; R 11 000), and UBVRCIC photometry covering the 2015 outburst with a high cadence. Optical observations were complemented with the archival HST and FUSE spectra from the preceding quiescence. Results: During the outburst, the luminosity of the hot component was in the range of 2-11 × 1037 (d/ 0.8 kpc)2 erg s-1, being in correlation with the light curve (LC) profile. To generate the maximum luminosity by the hydrogen burning, the white dwarf (WD) had to accrete at 3 × 10-7 M⊙ yr-1, which exceeds the stable-burning limit and thus led to blowing optically thick wind from the WD. We determined its mass-loss rate to a few × 10-6 M⊙ yr-1. At the high temperature of the ionising source, 1.5-2.3 × 105 K, the wind converted a fraction of the WD's photospheric radiation into the nebular emission that dominated the optical. A one order of magnitude increase of the emission measure, from a few × 1059 (d/ 0.8 kpc)2 cm-3 during quiescence, to a few × 1060 (d/ 0.8 kpc)2 cm-3 during the outburst, caused a 2 mag brightening in the LC, which is classified as the Z And-type of the outburst. Conclusions: The very high nebular emission and the presence of a disk-like H I region encompassing the WD, as indicated by a significant broadening and high flux of the Raman-scattered O vi 6825 Å line during the outburst, is consistent with the ionisation structure of hot components in symbiotic stars during active phases. Full Table 1 and Table 6 are only available at the CDS are

  1. A Candidate H1N1 Pandemic Influenza Vaccine Elicits Protective Immunity in Mice

    PubMed Central

    Steitz, Julia; Barlow, Peter G.; Hossain, Jaber; Kim, Eun; Okada, Kaori; Kenniston, Tom; Rea, Sheri; Donis, Ruben O.; Gambotto, Andrea

    2010-01-01

    Background In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model. Methods We generated two adenovirus(Ad5)-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA) from the recently emerged swine influenza isolate A/California/04/2009 (H1N1)pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNγ Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus. Conclusions/Significance A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization. PMID:20463955

  2. The association between different molecular weights of hyaluronic acid and CHAD, HIF-1α, COL2A1 expression in chondrocyte cultures

    PubMed Central

    Sirin, Duygu Yasar; Kaplan, Necati; Yilmaz, Ibrahim; Karaarslan, Numan; Ozbek, Hanefi; Akyuva, Yener; Kaya, Yasin Emre; Oznam, Kadir; Akkaya, Nuray; Guler, Olcay; Akkaya, Semih; Mahirogullari, Mahir

    2018-01-01

    The aim of the present study was to investigate the effects of three different formulations of hyaluronic acid (HA): Low molecular weight (MW) Sinovial One®, medium MW Viscoplus® and high MW Durolane®, on chondrocyte proliferation and collagen type II (COL2A1), hypoxia-inducible factor 1α (HIF-1α) and chondroadherin (CHAD) expression in primary chondrocyte cultures. Standard primary chondrocyte cultures were established from osteochondral tissues surgically obtained from 6 patients with gonarthrosis. Cell morphology was evaluated using an inverted light microscope; cell proliferation was determined with a MTT assay and confirmed with acridine orange/propidium iodide staining. Levels of CHAD, COL2A1 and HIF-1α expression were assessed using specific TaqMan gene expression assays. The results demonstrated the positive effect of HA treatment on cell proliferation, which was independent from the MW. COL2A1 expression increased in the medium and high MW HA treated groups. It was observed that HIF-1α expression increased in the high MW treated group alone. CHAD expression increased only in the medium MW HA treated group. Evaluation of gene expression revealed that levels of expression increased as the duration of HA application increased, in the medium and high MW HA treated groups. In terms of increased viability and proliferation, a longer duration of HA application was more effective. Taken together, it may be concluded that the administration of medium and high MW HA may be a successful way of treating diseases affecting chondrocytes in a clinical setting. PMID:29849772

  3. Complementation of Human Papillomavirus Type 16 E6 and E7 by Jagged1-Specific Notch1-Phosphatidylinositol 3-Kinase Signaling Involves Pleiotropic Oncogenic Functions Independent of CBF1;Su(H);Lag-1 Activation†

    PubMed Central

    Veeraraghavalu, Karthikeyan; Subbaiah, Vanitha K.; Srivastava, Sweta; Chakrabarti, Oishee; Syal, Ruchi; Krishna, Sudhir

    2005-01-01

    We have analyzed the induction and role of phosphatidylinositol 3-kinase (PI3K) by Notch signaling in human papillomavirus (HPV)-derived cancers. Jagged1, in contrast to Delta1, is preferentially upregulated in human cervical tumors. Jagged1 and not Delta1 expression sustained in vivo tumors by HPV16 oncogenes in HaCaT cells. Further, Jagged1 expression correlates with the rapid induction of PI3K-mediated epithelial-mesenchymal transition in both HaCaT cells and a human cervical tumor-derived cell line, suggestive of Delta1;Serrate/Jagged;Lag2 ligand-specific roles. Microarray analysis and dominant-negatives reveal that Notch-PI3K oncogenic functions can be independent of CBF1;Su(H);Lag-1 activation and instead relies on Deltex1, an alternative Notch effector. PMID:15919944

  4. How do land use intensity, experimentally increased temperature and water level affect methane and nitrous oxide emissions from a drained fen peatland?

    NASA Astrophysics Data System (ADS)

    Heinichen, Jan; Eickenscheidt, Tim; Drösler, Matthias

    2014-05-01

    Rewetting and extensification of peatlands is widely discussed and practiced to reduce losses of CO2 and N2O from drained peat soils. But rewetting is known to carry the risk of increased CH4 emissions. Up to now it is not completely clear how the predicted temperature increase in the face of climate change will alter the N2O and CH4 exchange of grasslands on drained peatland soils in the temperate zone. Therefore we investigated the effects of land use intensity, increased groundwater level, increased temperature and the combination of warming and increased groundwater level on CH4 and N2O exchange of two grassland sites (intensive and extensive grassland) in a drained fen peatland in southern Germany. We set up a factorial design on both land use types, on each three treatments, warming, increased water table level and the combination of warming and increased water table level as well as a control site were established. Temperature was manipulated with open-top chambers (OTCs) and water level manipulation was performed using a pumping system and sheet pile walls. The intensive grassland was cut three times in the year, the extensive grassland once in autumn 2011. Cattle slurry and mineral fertilizer (CAN) were deployed on the intensive grassland. Fluxes of CH4 and N2O were measured biweekly from December 2010 to January 2012 using opaque static closed chambers. The annual mean groundwater level (GWL) of the sites without water level manipulation was -41.5 cm b. g. and -30 cm b. g. at the water level manipulated sites on the intensive grassland. On the extensive grassland the GWL of the sites without water level manipulation was -32 cm b. g. and -21.5 cm b. g. at the water level manipulated sites. Air temperature in 0.2 m was increased in 2011 by 0.7 ° C at the treatments with OTCs on the intensive grassland and by 1.0 ° C at the treatments with OTCs on the extensive grassland respectively. The annual cumulative CH4 exchange ranged from 8.1 ± 3.8 kg C ha-1 yr-1

  5. Phylodynamics of avian influenza clade 2.2.1 H5N1 viruses in Egypt.

    PubMed

    Arafa, Abdelsatar; El-Masry, Ihab; Kholosy, Shereen; Hassan, Mohammed K; Dauphin, Gwenaelle; Lubroth, Juan; Makonnen, Yilma J

    2016-03-22

    Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are widely distributed within poultry populations in Egypt and have caused multiple human infections. Linking the epidemiological and sequence data is important to understand the transmission, persistence and evolution of the virus. This work describes the phylogenetic dynamics of H5N1 based on molecular characterization of the hemagglutinin (HA) gene of isolates collected from February 2006 to May 2014. Full-length HA sequences of 368 H5N1 viruses were generated and were genetically analysed to study their genetic evolution. They were collected from different poultry species, production sectors, and geographic locations in Egypt. The Bayesian Markov Chain Monte Carlo (BMCMC) method was applied to estimate the evolutionary rates among different virus clusters; additionally, an analysis of selection pressures in the HA gene was performed using the Single Likelihood Ancestor Counting (SLAC) method. The phylogenetic analysis of the H5 gene from 2006-14 indicated the presence of one virus introduction of the classic clade (2.2.1) from which two main subgroups were originated, the variant subgroup which was further subdivided into 2 sub-divisions (2.2.1.1 and 2.2.1.1a) and the endemic subgroup (2.2.1.2). The clade 2.2.1.2 showed a high evolution rate over a period of 6 years (6.9 × 10(-3) sub/site/year) in comparison to the 2.2.1.1a variant cluster (7.2 × 10(-3) over a period of 4 years). Those two clusters are under positive selection as they possess 5 distinct positively selected sites in the HA gene. The mutations at 120, 154, and 162 HA antigenic sites and the other two mutations (129∆, I151T) that occurred from 2009-14 were found to be stable in the 2.2.1.2 clade. Additionally, 13 groups of H5N1 HPAI viruses were identified based on their amino acid sequences at the cleavage site and "EKRRKKR" became the dominant pattern beginning in 2013. Continuous evolution of H5N1 HPAI viruses in Egypt has

  6. Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors

    PubMed Central

    Jayaraman, Akila; Koh, Xiaoying; Li, Jing; Raman, Rahul; Viswanathan, Karthik; Shriver, Zachary; Sasisekharan, Ram

    2012-01-01

    The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn91 in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus. PMID:22642577

  7. Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors.

    PubMed

    Jayaraman, Akila; Koh, Xiaoying; Li, Jing; Raman, Rahul; Viswanathan, Karthik; Shriver, Zachary; Sasisekharan, Ram

    2012-06-15

    The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn(91) in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus.

  8. [Frequency of intron 1 inversion of factor VIII gene in Chinese hemophilia A patients with case report of a female patient with heterozygous intron 1 inversion].

    PubMed

    Yan, Zhen-yu; Liang, Yan; Yan, Mei; Fan, Lian-kai; Xiao, Bai; Hua, Bao-lai; Liu, Jing-zhong; Zhao, Yong-qiang

    2008-10-21

    To investigate the frequency of intron 1 inversion (inv1) in FVIII gene in Chinese hemophilia A (HA) patients and to investigate the mechanism of pathogenesis. Peripheral blood samples were collected from 158 unrelated HA patients, aged 20 (1 - 73), including one female HA patient, aged 5, and several family members of a patient positive in inv1. One-stage method was used to assay the FVIII activity (FVIII:C). Long distance PCR and multiple PCR in duplex reactions were used to screen for the intron 22 inversion (inv22) and inv1 of the FVIII coding gene (F8). The F8 coding sequence was amplified with PCR and sequenced with an automatic sequencer. Two unrelated patients (pedigrees) were detected as inv1 positive with a positive rate of 1.26%. A rare female HA patient with inv1 was also discovered in a positive family (3 HA cases were found in this family and regarded as one case in calculating the total detection rate). The full length of FVIII was sequenced, and no other mutation was detected. There frequency of FVIII inv1 is low in Chinese HA patients compared with other populations. Female HA patients are heterozygous for FVIII inv1 and that may be resulted from nonrandom inactivation of X chromosome.

  9. Long-term impacts of manure amendments on carbon and greenhouse gas dynamics of rangelands.

    PubMed

    Owen, Justine J; Parton, William J; Silver, Whendee L

    2015-12-01

    Livestock manure is applied to rangelands as an organic fertilizer to stimulate forage production, but the long-term impacts of this practice on soil carbon (C) and greenhouse gas (GHG) dynamics are poorly known. We collected soil samples from manured and nonmanured fields on commercial dairies and found that manure amendments increased soil C stocks by 19.0 ± 7.3 Mg C ha(-1) and N stocks by 1.94 ± 0.63 Mg N ha(-1) compared to nonmanured fields (0-20 cm depth). Long-term historical (1700-present) and future (present-2100) impacts of management on soil C and N dynamics, net primary productivity (NPP), and GHG emissions were modeled with DayCent. Modeled total soil C and N stocks increased with the onset of dairying. Nitrous oxide (N2 O) emissions also increased by ~2 kg N2 O-N ha(-1)  yr(-1) . These emissions were proportional to total N additions and offset 75-100% of soil C sequestration. All fields were small net methane (CH4 ) sinks, averaging -4.7 ± 1.2 kg CH4 -C ha(-1)  yr(-1) . Overall, manured fields were net GHG sinks between 1954 and 2011 (-0.74 ± 0.73 Mg CO2 e ha(-1)  yr(-1) , CO2 e are carbon dioxide equivalents), whereas nonmanured fields varied around zero. Future soil C pools stabilized 40-60 years faster in manured fields than nonmanured fields, at which point manured fields were significantly larger sources than nonmanured fields (1.45 ± 0.52 Mg CO2 e ha(-1)  yr(-1) and 0.51 ± 0.60 Mg CO2 e ha(-1)  yr(-1) , respectively). Modeling also revealed a large background loss of soil C from the passive soil pool associated with the shift from perennial to annual grasses, equivalent to 29.4 ± 1.47 Tg CO2 e in California between 1820 and 2011. Manure applications increased NPP and soil C storage, but plant community changes and GHG emissions decreased, and eventually eliminated, the net climate benefit of this practice. © 2015 John Wiley & Sons Ltd.

  10. Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013.

    PubMed

    Nguyen, Hang K L; Nguyen, Phuong T K; Nguyen, Thach C; Hoang, Phuong V M; Le, Thanh T; Vuong, Cuong D; Nguyen, Anh P; Tran, Loan T T; Nguyen, Binh G; Lê, Mai Q

    2015-07-01

    Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31, 2009, and continues to circulate in Vietnam as a seasonal influenza virus. This study has monitored genotypic and phenotypic changes in this group of viruses during 2010-2013 period. We sequenced hemagglutinin (HA) and neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared with vaccine strain A/California/07/09 and other contemporary isolates from neighboring countries. Hemagglutination inhibition (HI) and neuraminidase inhibition (NAI) assays also were performed on these isolates. Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI surveillances in northern Vietnam between 2010 and 2013. The HA and NA phylogenies revealed six and seven groups, respectively. Five isolates (8·2%) had substitutions G155E and N156K in the HA, which were associated with reduced HI titers by antiserum raised against the vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from 2013 had a predicted H275Y substitution in the neuraminidase molecule, which was associated with reduced susceptibility to oseltamivir in a NAI assay. We also identified a D222N change in the HA of a virus isolated from a fatal case in 2013. Significant genotypic and phenotypic changes in A/ H1N1pdm09 influenza viruses were detected by the National Influenza Surveillance System (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to Vietnam and to the region. Sustained NISS and continued virological monitoring of seasonal influenza viruses are required for vaccine policy development in Vietnam. 3. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  11. Implications for Planetary System Formation from Interstellar Object 1I/2017 U1 (‘Oumuamua)

    NASA Astrophysics Data System (ADS)

    Trilling, David E.; Robinson, Tyler; Roegge, Alissa; Chandler, Colin Orion; Smith, Nathan; Loeffler, Mark; Trujillo, Chad; Navarro-Meza, Samuel; Glaspie, Lori M.

    2017-12-01

    The recently discovered minor body 1I/2017 U1 (‘Oumuamua) is the first known object in our solar system that is not bound by the Sun’s gravity. Its hyperbolic orbit (eccentricity greater than unity) strongly suggests that it originated outside our solar system; its red color is consistent with substantial space weathering experienced over a long interstellar journey. We carry out a simple calculation of the probability of detecting such an object. We find that the observed detection rate of 1I-like objects can be satisfied if the average mass of ejected material from nearby stars during the process of planetary formation is ˜20 Earth masses, similar to the expected value for our solar system. The current detection rate of such interstellar interlopers is estimated to be 0.2 yr-1, and the expected number of detections over the past few years is almost exactly one. When the Large Synoptic Survey Telescope begins its wide, fast, deep all-sky survey, the detection rate will increase to 1 yr-1. Those expected detections will provide further constraints on nearby planetary system formation through a better estimate of the number and properties of interstellar objects.

  12. [Construction of porous hydroxyapatite (HA) block loaded with cultured chondrocytes].

    PubMed

    Yan, M; Dang, G

    1999-07-01

    To construct a kind of bone healing enhancing implant with cultured chondrocytes bound to hydroxyapatite (HA). Chondrocytes were obtained from the costicartilage of rat and were cultured on the porous HA blocks, 3 mm x 3 mm x 4 mm size, for three and seven days. Scanning electron micrograph was taken to show whether the cells grew outside and inside the pore of HA block. The cells cultured on tiny glass sheet for 2 days were used to prove where the cells come from by in situ hybridization technique with alpha1 (II) cDNA probe. Scanning electron micrographs showed that the pores of the HA surface and inside of the blocks are filled with cultured cells, especially the longer cultured block. The cells were chondrocytes confirmed by in situ hybridization. The porous HA can be used as cell cultured substrate and chondrocyte can adhere and proliferate inside the porous HA block.

  13. Significance and value of non-traded ecosystem services on farmland.

    PubMed

    Sandhu, Harpinder; Wratten, Steve; Costanza, Robert; Pretty, Jules; Porter, John R; Reganold, John

    2015-01-01

    Background. Ecosystem services (ES) generated within agricultural landscapes, including field boundaries, are vital for the sustainable supply of food and fibre. However, the value of ES in agriculture has not been quantified experimentally and then extrapolated globally. Methods. We quantified the economic value of two key but contrasting ES (biological control of pests and nitrogen mineralisation) provided by non-traded non-crop species in ten organic and ten conventional arable fields in New Zealand using field experiments. The arable crops grown, same for each organic and conventional pair, were peas (Pisum sativum), beans (Phaseolus vulgaris), barley (Hordeum vulgare), and wheat (Triticum aestivum). Organic systems were chosen as comparators not because they are the only forms of sustainable agriculture, but because they are subject to easily understood standards. Results. We found that organic farming systems depended on fewer external inputs and produced outputs of energy and crop dry matter generally less than but sometimes similar to those of their conventional counterparts. The economic values of the two selected ES were greater for the organic systems in all four crops, ranging from US$ 68-200 ha(-1) yr(-1) for biological control of pests and from US$ 110-425 ha(-1)yr(-1) for N mineralisation in the organic systems versus US$ 0 ha(-1)yr(-1) for biological control of pests and from US$ 60-244 ha(-1)yr(-1) for N mineralisation in the conventional systems. The total economic value (including market and non-market components) was significantly greater in organic systems, ranging from US$ 1750-4536 ha(-1)yr(-1), with US$ 1585-2560 ha(-1)yr(-1) in the conventional systems. The non-market component of the economic value in organic fields was also significantly higher than those in conventional fields. Discussion. To illustrate the potential magnitude of these two ES to temperate farming systems and agricultural landscapes elsewhere, we then extrapolate these

  14. Spiral Convection Columns: Improved Estimate Of Apparent Rotation Period(=1333.6 yr) Of Earth's Solid Inner Core

    NASA Astrophysics Data System (ADS)

    McDonald, Keith L.

    1999-11-01

    In 1974, an est. was made of turbulence driven rot. period of Earth's inner core(r=R_ic), neglecting forced precession, nutation and assuming core fluid's turbulent differential rot., (T_1c^o)_α, alone drives inner core and has achieved steady state so that viscous boundary condition, Υ_φ(R_ic,θ)=ɛ Υ = Υ_ic - Υ = Υ_φ(R_ic), is closely achieved.^1 Υ is mantle's const. sidereal angular velocity, Υ_ic is inner core's, and Υ_φ(r,θ) is fluid's appar., about Z-axis. In 1st est.^1 we assumed velocity and magnetic modes T_α,P_α and T_β,P_β are stationary random functions of time and deleted classes of modes in simplifying toroidal component eq. of transformed amplification eq.,^2 evaluated for mode (T_2c^o)_β to compute radial function (T_1c^o)_α thru a single integration with respect to r. In making integration we assumed toroidal and poloidal B-field intensities have same radial dependency thru core fluid, R_ic <= r <= 0.9R_c, whereas toroidal mag. field declines monotonely as rarrow 0, where it vanishes. To correct discrepancy, divide T_2c^o(r)_β by f(r) and multiply dr by f(r) and integrate over R_ic,..., R_c; define f(r)=150 gauss × (r/0.9R_c), 0 <= r <= 0.9Rc and f(r)=1500(1-r/R_c) gauss for 0.9Rc <= r <= R_c. Repeating computations^1 gives, for νm = 0.2 × 10^5 esu, rot. period of τ _φ(R_ic)=1768.77 yr, instead of former 812 yr.^1 However, we adopted later Elsasser's 1956 est. electrical conductivity of core fluid, σ = 3 × 10-6 emu, which yields τ_φ=1333.6 yr, as close lower limit since σ continues to increase with depth below mantle's base, R_c. Adopting 0.03 cm sec-1 for upwelling motions we see that spiral motions result that do not influence lifetimes of polar heat sources at Rc but shorten to near 10^3 yr near equator. B_T-,B_P-field replaces turbulance theory to compute τ _φ. ^1 Keith L McDonald, Bul. Am. Phys. Soc., 19(10), 1148, 1974. ^2 K L McDonald, On The Planetary Dynamo Theory, ESSA Tech. Report ERL 64-ESL 3 (Govt

  15. Sargahydroquinoic acid inhibits TNFα-induced AP-1 and NF-κB signaling in HaCaT cells through PPARα activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeon, Youngsic; Jung, Yujung; Kim, Min Cheol

    2014-08-08

    Highlights: • SHQA increases PPARα/γ transactivation and inhibits MMP-2/-9 expression. • SHQA inhibits TNFα-induced AP-1 and MAPK signaling. • SHQA inhibits TNFα-induced p65 translocation and IκBα phosphorylation. • SHQA inhibits TNFα-induced AP-1 and NF-κB signaling via PPARα. - Abstract: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, their ligands are targets for the treatment of various skin disorders, such as photo-aging and chronological aging of skin. Intensive studies have revealed that PPARα/γ functions in photo-agingmore » and age-related inflammation by regulating matrix metalloproteinases (MMPs) via activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). However, the detailed mechanism of PPARα/γ’s role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPARα/γ ligand significantly decreased Tumor Necrosis Factor-alpha (TNFα)-induced MMP-2/-9 expression by downregulating TNFα-induced transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPARα antagonist) not bisphenol A diglycidyl ether (PPARγ antagonists), reversed the effect on TNFα-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNFα-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NF-κB pathway via PPARα.« less

  16. Biomass, production and woody detritus in an old coast redwood (Sequoia sempervirens) forest

    USGS Publications Warehouse

    Busing, R.T.; Fujimori, T.

    2005-01-01

    We examined aboveground biomass dynamics, aboveground net primary production (ANPP), and woody detritus input in an old Sequoia sempervirens stand over a three-decade period. Our estimates of aboveground biomass ranged from 3300 to 5800 Mg ha-1. Stem biomass estimates ranged from 3000 to 5200 Mg ha-1. Stem biomass declined 7% over the study interval. Biomass dynamics were patchy, with marked declines in recent tree-fall patches <0.05 ha in size. Larger tree-fall patches approaching 0.2 ha in size were observed outside the study plot. Our estimates of ANPP ranged from 6 to 14 Mg ha -1yr-1. Estimates of 7 to 10 Mg ha-1yr -1 were considered to be relatively accurate. Thus, our estimates based on long-term data corroborated the findings of earlier short-term studies. ANPP of old, pure stands of Sequoia was not above average for temperate forests. Even though production was potentially high on a per stem basis, it was moderate at the stand level. We obtained values of 797 m3 ha -1 and 262 Mg ha-1 for coarse woody detritus volume and mass, respectively. Fine woody detritus volume and mass were estimated at 16 m3 ha-1 and 5 Mg ha-1, respectively. Standing dead trees (or snags) comprised 7% of the total coarse detritus volume and 8% of the total mass. Coarse detritus input averaged 5.7 to 6.9 Mg ha -1yr-1. Assuming steady-state input and pool of coarse detritus, we obtained a decay rate constant of 0.022 to 0.026. The old-growth stand of Sequoia studied had extremely high biomass, but ANPP was moderate and the amount of woody detritus was not exceptionally large. Biomass accretion and loss were not rapid in this stand partly because of the slow population dynamics and low canopy turnover rate of Sequoia at the old-growth stage. Nomenclature: Hickman (1993). ?? Springer 2005.

  17. Fate of Cd in Agricultural Soils: A Stable Isotope Approach to Anthropogenic Impact, Soil Formation, and Soil-Plant Cycling.

    PubMed

    Imseng, Martin; Wiggenhauser, Matthias; Keller, Armin; Müller, Michael; Rehkämper, Mark; Murphy, Katy; Kreissig, Katharina; Frossard, Emmanuel; Wilcke, Wolfgang; Bigalke, Moritz

    2018-02-20

    The application of mineral phosphate (P) fertilizers leads to an unintended Cd input into agricultural systems, which might affect soil fertility and quality of crops. The Cd fluxes at three arable sites in Switzerland were determined by a detailed analysis of all inputs (atmospheric deposition, mineral P fertilizers, manure, and weathering) and outputs (seepage water, wheat and barley harvest) during one hydrological year. The most important inputs were mineral P fertilizers (0.49 to 0.57 g Cd ha -1 yr -1 ) and manure (0.20 to 0.91 g Cd ha -1 yr -1 ). Mass balances revealed net Cd losses for cultivation of wheat (-0.01 to -0.49 g Cd ha -1 yr -1 ) but net accumulations for that of barley (+0.18 to +0.71 g Cd ha -1 yr -1 ). To trace Cd sources and redistribution processes in the soils, we used natural variations in the Cd stable isotope compositions. Cadmium in seepage water (δ 114/110 Cd = 0.39 to 0.79‰) and plant harvest (0.27 to 0.94‰) was isotopically heavier than in soil (-0.21 to 0.14‰). Consequently, parent material weathering shifted bulk soil isotope compositions to lighter signals following a Rayleigh fractionation process (ε ≈ 0.16). Furthermore, soil-plant cycling extracted isotopically heavy Cd from the subsoil and moved it to the topsoil. These long-term processes and not anthropogenic inputs determined the Cd distribution in our soils.

  18. Liana infestation impacts tree growth in a lowland tropical moist forest

    NASA Astrophysics Data System (ADS)

    van der Heijden, G. M. F.; Phillips, O. L.

    2009-03-01

    Stand-level estimates of the effect of lianas on tree growth in mature tropical forests are needed to evaluate the functional impact of lianas and their potential to affect the ability of tropical forests to sequester carbon, but these are currently lacking. Using data collected on tree growth rates, local growing conditions and liana competition in five permanent sampling plots in Amazonian Peru, we present the first such estimates of the effect of lianas on above-ground productivity of trees. By constructing a multi-level linear mixed effect model to predict individual tree diameter growth model using individual tree growth conditions, we were able to estimate stand-level above-ground biomass (AGB) increment in the absence of lianas. We show that lianas, mainly by competing above-ground with trees, reduce tree annual above-ground stand-level biomass by ~10%, equivalent to 0.51 Mg dry weight ha-1 yr-1 or 0.25 Mg C ha-1 yr-1. AGB increment of lianas themselves was estimated to be 0.15 Mg dry weight ha-1 yr-1 or 0.07 Mg C ha-1 yr-1, thus only compensating ~29% of the liana-induced reduction in stand-level AGB increment. Increasing liana pressure on tropical forests may therefore not only reduce their carbon storage capacity, by indirectly promoting tree species with low-density wood, but also their rate of carbon uptake, with potential consequences for the rate of increase in atmospheric carbon dioxide.

  19. Effects of five years of frequent N additions, with or without acidity, on the growth and below-ground dynamics of a young Sitka spruce stand growing on an acid peat: implications for sustainability

    NASA Astrophysics Data System (ADS)

    Sheppard, L. J.; Crossley, A.; Harvey, F. J.; Skiba, U.; Coward, P.; Ingleby, K.

    A field manipulation study was established to demonstrate effects of simulated wet N and S deposition on a young (planted 1986) stand of Sitka spruce growing on a predominantly organic soil in an area of low (8-10 kg N ha-1 yr-1) background N deposition in the Scottish borders. From 1996, treatments (six) were applied to the canopies of ten-tree plots in each of four blocks. N was provided as NH4NO3, either with H2SO4 (pH 2.5) at 48 or 96 kg N ha-1 yr-1 inputs or without, at 48 kg N ha-1 yr-1 along with wet (rain water) and dry controls (scaffolding) and a S treatment (Na2SO4). Positive responses (+>20% over 5 years) with respect to stem area increment were measured in response to N inputs, irrespective of whether acid was included. The positive response to N was not dose related and was achieved against falling base cation concentrations in the foliage, particularly with respect to K. The results suggest young trees are able to buffer the low nutrient levels and produce new growth when there is sufficient N. Inputs of 96 kg N ha-1 yr-1, in addition to ambient N inputs, on this site exceeded tree demand resulting in elevated foliar N, N2O losses and measurable soil water N. These excessive N inputs did not reduce stem area growth.

  20. A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

    PubMed

    Dirksen, A; Dijkman, J H; Madsen, F; Stoel, B; Hutchison, D C; Ulrik, C S; Skovgaard, L T; Kok-Jensen, A; Rudolphus, A; Seersholm, N; Vrooman, H A; Reiber, J H; Hansen, N C; Heckscher, T; Viskum, K; Stolk, J

    1999-11-01

    We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

  1. A GIS-based estimation of soil erosion parameters for soil loss potential and erosion hazard in the city of Kinshasa, the Democratic Republic of Congo

    NASA Astrophysics Data System (ADS)

    Tshikeba Kabantu, Martin; Muamba Tshimanga, Raphael; Onema Kileshye, Jean Marie; Gumindoga, Webster; Tshimpampa Beya, Jules

    2018-05-01

    Soil erosion has detrimental impacts on socio economic life, thus increasing poverty. This situation is aggravated by poor planning and lack of infrastructure especially in developing countries. In these countries, efforts to planning are challenged by lack of data. Alternative approaches that use remote sensing and geographical information systems are therefore needed to provide decision makers with the so much needed information for planning purposes. This helps to curb the detrimental impacts of soil erosion, mostly emanating from varied land use conditions. This study was carried out in the city of Kinshasa, the Democratic Republic of Congo with the aim of using alternative sources of data, based on earth observation resources, to determine the spatial distribution of soil loss and erosion hazard in the city of Kinshasa. A combined approach based on remote sensing skills and rational equation of soil erosion estimation was used. Soil erosion factors, including rainfall-runoff erosivity R), soil erodibility (K), slope steepness and length (SL), crop/vegetation and management (C) were calculated for the city of Kinshasa. Results show that soil loss in Kinshasa ranges from 0 to 20 t ha-1 yr-1. Most of the south part of the urban area were prone to erosion. From the total area of Kinshasa (996 500 ha), 25 013 ha (2.3 %) is of very high ( > 15 t ha-1 yr-1) risk of soil erosion. Urban areas consist of 4.3 % of the area with very high ( > 15 t ha-1 yr-1) risk of soil erosion compared to a very high risk of 2.3 % ( > 15 t ha-1 yr-1) in the rural area. The study shows that the soil loss in the study area is mostly driven by slope, elevation, and informal settlements.

  2. Influence of the concentrations of hyaluronic acid on the properties and biocompatibility of Cs-Gel-HA membranes.

    PubMed

    Liu, Haifeng; Yin, Yuji; Yao, Kangde; Ma, Dongrui; Cui, Lei; Cao, Yilin

    2004-08-01

    The object of this study was to investigate the relationship between the concentrations of HA solutions and the physicochemical properties and the biocompatibility of Cs-Gel-HA membranes. The addition of different concentrations of HA not only improved the wettability significantly and extended the degradation time of Cs-Gel-HA membranes, but also changed their mechanical properties. The concentration of HA had a significant influence on the biocompatibility of Cs-Gel-HA membranes. Results demonstrated that it was only the concentrations of HA in a certain range (0.01-0.1%), that could promote the cell adhesion, migration and proliferation, while the concentration of HA was above 0.1% it would either reduce or even inhibit these behaviors.

  3. Relationship Between BMD and Prevalent Vertebral Fractures in Indian Women Older Than 50 Yr.

    PubMed

    Gupta, Yashdeep; Marwaha, Raman K; Kukreja, Subhash; Bhadra, Kuntal; Narang, Archana; Mani, Kalaivani; Mithal, Ambrish; Tandon, Nikhil

    2016-01-01

    The purpose of the study was to study the relationship of morphometric vertebral fractures with bone mineral density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip, and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment. Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  4. Osteogenic properties of PBLG-g-HA/PLLA nanocomposites.

    PubMed

    Liao, Lan; Yang, Shuang; Miron, Richard J; Wei, Junchao; Zhang, Yufeng; Zhang, Meng

    2014-01-01

    New development of biomaterial scaffolds remains a prominent issue for the regeneration of lost or fractured bone. Of these scaffolds, a number of bioactive polymers have been synthesized and fabricated for diverse biological roles. Although recent evidence has demonstrated that composite scaffolds such as HA/PLLA have improved properties when compared to either HA or PLLA alone, recent investigations have demonstrated that the phase compatibility between HA and PLLA layers is weak preventing optimal enhancement of the mechanical properties and making the composites prone to breakdown. In the present study, poly (γ-benzyl-L-glutamate) modified hydroxyapatite/(poly (L-lactic acid)) (PBLG-g-HA/PLLA) composite scaffolds were fabricated with improved phase compatibility and tested for their osteogenic properties in 18 Wistar female rats by analyzing new bone formation in 3 mm bilateral femur defects in vivo. At time points, 2, 4 and 8 weeks post surgery, bone formation was evaluated by µ-CT and histological analysis by comparing 4 treatment groups; 1) blank defect, 2) PLLA, 3) HA/PLLA and 4) PBLG-g-HA/PLLA scaffolds. The in vivo analysis demonstrated that new bone formation was much more prominent in HA/PLLA and PBLG-g-HA/PLLA groups as depicted by µ-CT, H&E staining and immunohistochemistry for collagen I. TRAP staining was also utilized to determine the influence of osteoclast cell number and staining intensity to the various scaffolds. No significant differences in either staining intensity or osteoclast numbers between all treatment modalities was observed, however blank defects did contain a higher number of osteoclast-like cells. The results from the present study illustrate the potential of PBLG-g-HA/PLLA scaffolds for bone tissue engineering applications by demonstrating favorable osteogenic properties.

  5. Stratigraphic evidence of desertification in the west-central Great Plains within the past 1000 yr

    USGS Publications Warehouse

    Madole, R.F.

    1994-01-01

    Stratigraphic and geomorphic relations, archaeological data, and eight radiocarbon ages at five widely scattered localities in northeastern Colorado indicate that eolian sand was mobilized over broad areas within the past 1000 yr. The mobilization began after 1 ka, was episodic, and ended at some as yet undetermined time prior to the latter part of the 19th century. Given that climate-model simulations suggest only slight variation in average surface temperature and annual precipitation in this region during the past 1000 yr, this part of the Great Plains evidently is near the threshold of widespread eolian sand transport under the present climate. -Author

  6. Atmospheric nitrogen deposition budget in a subtropical hydroelectric reservoir (Nam Theun II case study, Lao PDR)

    NASA Astrophysics Data System (ADS)

    Adon, Marcellin; Galy-Lacaux, Corinne; Serça, Dominique; Guerin, Frederic; Guedant, Pierre; Vonghamsao, Axay; Rode, Wanidaporn

    2016-04-01

    With 490 km² at full level of operation, Nam Theun 2 (NT2) is one of the largest hydro-reservoir in South East Asia. NT2 is a trans-basin hydropower project that diverts water from the Nam Theun river (a Mekong tributary) to the Xe Ban Fai river (another Mekong tributary). Atmospheric deposition is an important source of nitrogen (N), and it has been shown that excessive fluxes of N from the atmosphere has resulted in eutrophication of many coastal waters. A large fraction of atmospheric N input is in the form of inorganic N. This study presents an estimation of the atmospheric inorganic nitrogen budget into the NT2 hydroelectric reservoir based on a two-year monitoring (July 2010 to July 2012) including gas concentrations and precipitation. Dry deposition fluxes are calculated from monthly mean surface measurements of NH3, HNO3 and NO2 concentrations (passive samplers) together with simulated deposition velocities, and wet deposition fluxes from NH4+ and NO3- concentrations in single event rain samples (automated rain sampler). Annual rainfall amount was 2500 and 3160 mm for the two years. The average nitrogen deposition flux is estimated at 1.13 kgN.ha-1.yr-1 from dry processes and 5.52 kgN.ha-1.yr-1 from wet ones, i.e., an average annual total nitrogen flux of 6.6 kgN.ha-1.yr-1 deposited into the NT2 reservoir. The wet deposition contributes to 83% of the total N deposition. The nitrogen deposition budget has been also calculated over the rain tropical forest surrounding the reservoir. Due to higher dry deposition velocities above forested ecosystems, gaseous dry deposition flux is estimated at 4.0 kgN.ha-1.yr-1 leading to a total nitrogen deposition about 9.5 kgN.ha-1.yr-1. This result will be compared to nitrogen deposition in the African equatorial forested ecosystems in the framework of the IDAF program (IGAC-DEBITS-AFrica).

  7. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hu, Weibin; Chen, Aizhong; Miao, Yi

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarilymore » targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.« less

  8. Transport features of nano-hydroxylapatite (n-HA) embedded silicone rubber (SR) systems: influence of SR/n-HA interaction, degree of reinforcement and morphology.

    PubMed

    M, Bindu; G, Unnikrishnan

    2017-09-27

    We report the transport characteristics of silicone rubber/nano-hydroxylapatite (SR/n-HA) systems at room temperature with reference to the effects of n-HA loading, morphology and penetrant nature, using toluene, xylene, ethyl acetate and butyl acetate in the liquid phase and methanol, ethanol, 1-propanol, 2-propanol and butanol in the vapour phase as probe molecules. The interaction between the n-HA particles and SR matrix has been confirmed by FTIR analysis. As the n-HA content in the SR matrix increased, the penetrant uptake has been found to decrease. The observations have been correlated with the density and void content of the systems. Scanning electron microscopy images have been found to be complementary to the observed transport features. The reinforcement effect of n-HA particles on the SR matrix has been verified by Kraus equation. Molecular mass between the cross links has been observed to decrease with an increase in n-HA loading. The results have been compared with affine, phantom network, parallel, series and Maxwell models. The transport data have been complemented by observations on biological fluid uptake with urea, d-glucose, KI, saline water, phosphate buffer and artificial urine as the media.

  9. Quantifying above- and belowground biomass carbon loss with forest conversion in tropical lowlands of Sumatra (Indonesia).

    PubMed

    Kotowska, Martyna M; Leuschner, Christoph; Triadiati, Triadiati; Meriem, Selis; Hertel, Dietrich

    2015-10-01

    Natural forests in South-East Asia have been extensively converted into other land-use systems in the past decades and still show high deforestation rates. Historically, lowland forests have been converted into rubber forests, but more recently, the dominant conversion is into oil palm plantations. While it is expected that the large-scale conversion has strong effects on the carbon cycle, detailed studies quantifying carbon pools and total net primary production (NPPtotal ) in above- and belowground tree biomass in land-use systems replacing rainforest (incl. oil palm plantations) are rare so far. We measured above- and belowground carbon pools in tree biomass together with NPPtotal in natural old-growth forests, 'jungle rubber' agroforests under natural tree cover, and rubber and oil palm monocultures in Sumatra. In total, 32 stands (eight plot replicates per land-use system) were studied in two different regions. Total tree biomass in the natural forest (mean: 384 Mg ha(-1) ) was more than two times higher than in jungle rubber stands (147 Mg ha(-1) ) and >four times higher than in monoculture rubber and oil palm plantations (78 and 50 Mg ha(-1) ). NPPtotal was higher in the natural forest (24 Mg ha(-1)  yr(-1) ) than in the rubber systems (20 and 15 Mg ha(-1)  yr(-1) ), but was highest in the oil palm system (33 Mg ha(-1)  yr(-1) ) due to very high fruit production (15-20 Mg ha(-1)  yr(-1) ). NPPtotal was dominated in all systems by aboveground production, but belowground productivity was significantly higher in the natural forest and jungle rubber than in plantations. We conclude that conversion of natural lowland forest into different agricultural systems leads to a strong reduction not only in the biomass carbon pool (up to 166 Mg C ha(-1) ) but also in carbon sequestration as carbon residence time (i.e. biomass-C:NPP-C) was 3-10 times higher in the natural forest than in rubber and oil palm plantations. © 2015 John Wiley & Sons Ltd.

  10. Inputs and losses by surface runoff and subsurface leaching for pastures managed by continuous or rotational stocking.

    PubMed

    Owens, L B; Barker, D J; Loerch, S C; Shipitalo, M J; Bonta, J V; Sulc, R M

    2012-01-01

    Pasture management practices can affect forage quality and production, animal health and production, and surface and groundwater quality. In a 5-yr study conducted at the North Appalachian Experimental Watershed near Coshocton, Ohio, we compared the effects of two contrasting grazing methods on surface and subsurface water quantity and quality. Four pastures, each including a small, instrumented watershed (0.51-1.09 ha) for surface runoff measurements and a developed spring for subsurface flow collection, received 112 kg N ha(-1) yr(-1) and were grazed at similar stocking rates (1.8-1.9 cows ha(-1)). Two pastures were continuously stocked; two were subdivided so that they were grazed with frequent rotational stocking (5-6 times weekly). In the preceding 5 yr, these pastures received 112 kg N ha(-1) yr(-1) after several years of 0 N fertilizer and were grazed with weekly rotational stocking. Surface runoff losses of N were minimal. During these two periods, some years had precipitation up to 50% greater than the long-term average, which increased subsurface flow and NO(3)-N transport. Average annual NO(3)-N transported in subsurface flow from the four watersheds during the two 5-yr periods ranged from 11.3 to 22.7 kg N ha(-1), which was similar to or less than the mineral-N received in precipitation. Flow and transport variations were greater among seasons than among watersheds. Flow-weighted seasonal NO(3)-N concentrations in subsurface flow did not exceed 7 mg L(-1). Variations in NO(3)-N leached from pastures were primarily due to variable precipitation rather than the effects of continuous, weekly rotational, or frequent rotational stocking practices. This suggests that there was no difference among these grazing practices in terms of NO(3)-N leaching. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  11. N2O and CH4-emissions from energy crops - Can the use of organic fertilizers in form of biogas digestate be considered as a real alternative? Results from a three and a half year multi-site field study of energy crops fertilized with biogas digestate in so

    NASA Astrophysics Data System (ADS)

    Heintze, Gawan

    2016-04-01

    N amounts and in a crop rotation system called FFA and FFB with same amounts of applied N but three different forms of N application (mineral N, mineral+organic N, organic N). The annual cumulative N2O exchange rates in maize monoculture showed a clear dependence on the amount of applied organic fertilizer. Average annual cumulative exchange rates ranged from 1.65 ± 0.74 kg N ha-1 yr-1 to 11.03 ± 1.63 kg N ha-1 y-1explainable by a twice as high amount of N compared to the conventional fertilized site. The average annual cumulative CH4 exchange rates in maize monoculture varied between -1.2 ± 0.46 kg C ha-1 yr-1 and 3.75 ± 0.48 kg C ha-1 y-1with measured CH4 fluxes around zero between the fertilizing events, indicating a minor role. For FFA and FFB the average annual cumulative N2O exchange rates ranged from 1.45 ± 0.18 kg N ha-1 yr-1 to 3.5 ± 1.1 kg N ha-1 y-1and 1.37 ± 0.57 kg N ha-1 yr-1 to 1.71 ± 0.29 kg N ha-1 y-1 andshowed lower values to comparable treatments in the maize monoculture especially indicating the different management effects. Determined average annual cumulative CH4 exchange rates ranged from 0.19 ± 0.6 kg C ha-1 yr-1 to 0.21 ± 0.45 kg C ha-1 yr-1and -0.8 ± 0.7 kg C ha-1 y-1 to 1 ± 0.6 kg C ha-1 y-1 and played as well a minor role. Altogether, biogas digestate can be seen as a suitable alternative if the amounts of applied N selected appropriately in combination with a customized management.

  12. The growth of continents and some consequences since 1.5 Ga

    NASA Technical Reports Server (NTRS)

    Howell, David G.

    1988-01-01

    The budget of Earth's oceanic sediment masses was discussed in terms of crustal growth and recycling. Based on estimates of the volume of oceanic sediments and the average age of oceanic crust, a continental denudation rate of 1.65 cu km/yr was computed. This crudely balances estimated crustal production rates of about 1 cu km/yr, but the efficiency of sediment loss via subduction, for example, must be considered. It was argued, on the basis of earthquake focal solutions, imagery of subduction zones, and plate kinematic reconstructions that little, if any, sediment was lost in this way. This yields a present day crustal growth rate of about 1 cu km/yr. The volume of continents to 1.5 Ga ago was discussed, assuming constant continental thickness and freeboard, and a constant hydrosphere volume. It was concluded that ocean ridge length was a factor of about 1.75 greater 1.5 Ga ago, but a major uncertainty is the average spreading rate in the past.

  13. Increasing incidence of type 1 diabetes between 1986 and 2015 in Bauru, Brazil.

    PubMed

    Negrato, Carlos Antonio; Lauris, José Roberto Pereira; Saggioro, Ieso Braz; Corradini, Maria Cristina Morato; Borges, Pricila Rubia; Crês, Maria Cristina; Junior, Aluysio Leal; Guedes, Maria Fatima Soares; Gomes, Marilia Brito

    2017-05-01

    To assess temporal trends in the incidence of type 1 diabetes in Bauru, São Paulo State, Brazil from 1986 to 2015. The yearly incidence of type 1 diabetes (per 100,000/yr) from 1986 to 2015 was determined in children ≤14yr of age, using individual case notification and the capture and recapture method. During thirty years (1986-2015), 302 cases were diagnosed in our population. The overall incidence was of 12.8/100,000 (95% CI: 11.2-14.4), ranging from 2.8/100,000 in 1987 to 25.6/100,000 in 2013 with a 9.1-fold variation. It was non-significantly higher in girls [13.7 (95% CI: 11.4-16.1)] than in boys [12.0 (95% CI: 9.8-14.2)] (p=0.48) and significantly higher in the 5-9yr [14.6 (95% CI: 11.8-17.4)] and 10-14yr [15.8 (95% CI: 12.7-18.8)] age ranges compared to the 0-4yr [8.1 (95% CI: 6.0-10.2)] age range (p<0.001). The majority of diagnoses were made in colder months. The patterns of incidence were very high and high in 80.0% of the study-years. The incidence of type1 diabetes in children ≤14yr has increased in Bauru, Brazil, in the last thirty years, in approximately 3.1% annually, with an absolute crude increase of 2.5-fold. These findings pose Brazil as a country with high incidence of type 1 diabetes. All Brazilian regions should be enrolled in future studies to determine the factors that contribute to the predisposition to type 1 diabetes in our population and to the steep rise in its incidence. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Free water surface wetlands for wastewater treatment in Sweden: nitrogen and phosphorus removal.

    PubMed

    Andersson, J L; Kallner Bastviken, S; Tonderski, K S

    2005-01-01

    In South Sweden, free water surface wetlands have been built to treat wastewater from municipal wastewater treatment plants. Commonly, nitrogen removal has been the prime aim, though a significant removal of tot-P and BOD7 has been observed. In this study, performance data for 3-8 years from four large (20-28 ha) FWS wetlands have been evaluated. Two of them receive effluent from WWTP with only mechanical and chemical treatment. At the other two, the wastewater has also been treated biologically resulting in lower concentrations of BOD7 and NH4+-N. The wetlands performed satisfactorily and removed 0.7-1.5 ton N ha(-1) yr(-1) as an average for the time period investigated, with loads between 1.7 and 6.3 ton N ha(-1)yr(-1). Treatment capacity depended on the pre-treatment of the water, as reflected in the k20-values for N removal (first order area based model). In the wetlands with no biological pre-treatment, the k20-values were 0.61 and 1.1 m month(-1), whereas for the other two they were 1.7 and 2.5 m month(-1). P removal varied between 10 and 41 kg ha(-1) yr(-1), and was related to differences in loads, P speciation and to the internal cycling of P in the wetlands.

  15. The optimal SAM surface functional group for producing a biomimetic HA coating on Ti.

    PubMed

    Liu, D P; Majewski, P; O'Neill, B K; Ngothai, Y; Colby, C B

    2006-06-15

    Commercial interest is growing in biomimetic methods that employ self assembled mono-layers (SAMs) to produce biocompatible HA coatings on Ti-based orthopedic implants. Recently, separate studies have considered HA formation for various SAM surface functional groups. However, these have often neglected to verify crystallinity of the HA coating, which is essential for optimal bioactivity. Furthermore, differing experimental and analytical methods make performance comparisons difficult. This article investigates and evaluates HA formation for four of the most promising surface functional groups: --OH, --SO(3)H, --PO(4)H(2) and --COOH. All of them successfully formed a HA coating at Ca/P ratios between 1.49 and 1.62. However, only the --SO(3)H and --COOH end groups produced a predominantly crystalline HA. Furthermore, the --COOH end group yielded the thickest layer and possessed crystalline characteristics very similar to that of the human bone. The --COOH end group appears to provide the optimal SAM surface interface for nucleation and growth of biomimetic crystalline HA. Intriguingly, this finding may lend support to explanations elsewhere of why human bone sialoprotein is such a potent nucleator of HA and is attributed to the protein's glutamic acid-rich sequences.

  16. Runoff and soil erosion for an undisturbed tropical woodland in the Brazilian Cerrado

    NASA Astrophysics Data System (ADS)

    Oliveira, Paulo Tarso S.; Nearing, Mark; Wendland, Edson

    2015-04-01

    The Brazilian Cerrado is a large and important economic and environmental region that is experiencing major loss of its natural landscapes due to pressures of food and energy production, which has caused large increases in soil erosion. However the magnitude of the soil erosion increases in this region is not well understood, in part because scientific studies of surface runoff and soil erosion are scarce or nonexistent in undisturbed Cerrado vegetation. In this study we measured natural rainfall-driven rates of runoff and soil erosion for an undisturbed tropical woodland classified as "cerrado sensu stricto denso" and bare soil to compute the Universal Soil Loss Equation (USLE) cover and management factor (C-factor) to help evaluate the likely effects of land use change on soil erosion rates. Replicated data on precipitation, runoff, and soil loss on plots (5 x 20 m) under bare soil and cerrado were collected for 55 erosive storms occurring in 2012 and 2013. The measured annual precipitation was 1247.4 mm and 1113.0 mm for 2012 and 2013, resulting in a rainfall erosivity index of 4337.1 MJ mm ha-1 h-1 and 3546.2 MJ mm ha-1 h-1, for each year respectively. The erosive rainfall represented 80concentrated in the wet season, which generally runs from October through March. In the plots on bare soil, the runoff coefficient for individual rainfall events (total runoff divided by total rainfall) ranged from 0.003 to 0.860 with an average value and standard deviation of 0.212 ± 0.187. Moreover, the runoff coefficient found for the bare soil plots (~20infiltration capacity. In forest areas the leaf litter and the more porous soil tend to promote the increase of infiltration and water storage, rather than rapid overland flow. Indeed, runoff coefficients ranged from 0.001 to 0.030 with an average of less than 1under undisturbed cerrado. The soil losses measured under bare soil and cerrado were 15.68 t ha-1yr-1 and 0.24 t ha-1 yr-1 in 2012, and 14.82 t ha-1 yr-1, 0.11 t ha-1

  17. Effects of incorporation of HA/ZrO(2) into glass ionomer cement (GIC).

    PubMed

    Gu, Y W; Yap, A U J; Cheang, P; Khor, K A

    2005-03-01

    Glass ionomer cements (GICs) are a class of bioactive cements that bond directly to bone. In this paper, a new bioactive hydroxyapatite (HA)/zirconia (ZrO(2))-filled GIC composite was developed to improve the biocompatibility and bioactivity of the GICs with the surrounding bone and connective tissues. Nano-sized HA/30 wt% ZrO(2) powders were heat treated at 700 degrees Celsius and 800 degrees Celsius for 3 h to elucidate the influence of the crystallinity of composite powders on the performance of HA/ZrO(2)-GICs. The effects of different volume percentages of HA/ZrO(2) powders (4, 12, 28 and 40 vol%) substituted within GICs were investigated based on their microhardness, compressive strength and diametral tensile strength. The HA/ZrO(2)-GICs composite was soaked in distilled water for 1 day and 1 week before subjecting the samples to mechanical testing. Results showed that the glass and HA/ZrO(2) particles were distributed uniformly in the GIC matrix. The substitution of highly crystalline HA/ZrO(2) improved the mechanical properties of the HA/ZrO(2)-GICs due to the slow resorption rate for highly crystalline powders in distilled water. The mechanical properties of HA/ZrO(2)-GICs increased with increasing soak time due to the continuous formation of aluminium salt bridges, which improved the final strength of the cements. The compositions 4 and 12 vol% HA/ZrO(2)-GICs exhibited superior mechanical properties than the original GICs. The mechanical properties of HA/ZrO(2)-GICs were found to be much better than those of HA-GICs because ZrO(2) has the attributes of high strength, high modulus, and is significantly harder than glass and HA particles. Furthermore, ZrO(2) does not dissolve with increasing soaking time.

  18. High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study

    PubMed Central

    Boos, Christopher J.; Bye, Kyo; Sevier, Luke; Bakker-Dyos, Josh; Woods, David R.; Sullivan, Mark; Quinlan, Tom; Mellor, Adrian

    2018-01-01

    Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Methods: Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200–0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4–12 beats) and long-term (α2, 13–64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6–20 RPE scale. Results: All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO2 and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased (p < 0.05). RPE inversely correlated with SD1/SD2 (r = -0.31; p = 0.002), SampEn (r = -0.22; p = 0.03), HFnu (r = -0.27; p = 0.007) and positively correlated with LF (r = 0.24; p = 0.02), LF/HF (r = 0.24; p = 0.02), α1 (r = 0.32; p = 0.002) and α2 (r = 0.21; p = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS. Conclusion: Non-linear HRV is more sensitive to

  19. High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study.

    PubMed

    Boos, Christopher J; Bye, Kyo; Sevier, Luke; Bakker-Dyos, Josh; Woods, David R; Sullivan, Mark; Quinlan, Tom; Mellor, Adrian

    2018-01-01

    Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Methods: Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200-0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4-12 beats) and long-term (α2, 13-64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6-20 RPE scale. Results: All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO 2 and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased ( p < 0.05). RPE inversely correlated with SD1/SD2 ( r = -0.31; p = 0.002), SampEn ( r = -0.22; p = 0.03), HFnu ( r = -0.27; p = 0.007) and positively correlated with LF ( r = 0.24; p = 0.02), LF/HF ( r = 0.24; p = 0.02), α1 ( r = 0.32; p = 0.002) and α2 ( r = 0.21; p = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS. Conclusion: Non-linear HRV is more sensitive to

  20. Atmospheric deposition and canopy exchange processes in alpine forest ecosystems (northern Italy)

    NASA Astrophysics Data System (ADS)

    Balestrini, Raffaella; Tagliaferri, Antonio

    Throughfall and bulk precipitation chemistry were studied for five years (June 1994-May 1999) at two high elevation forest sites (Val Gerola and Val Masino) which were known to differ in terms of tree health, as assessed by live crown condition. The ion concentration of bulk precipitation samples did not differ significantly between sites, except for Mg 2+, while the throughfall concentrations differed in the measured values of H +, N-NO 3-, Cl -, Na +, K +, DOC and weak organic acids. The results of the application of the canopy exchange model indicated a higher contribution from the dry deposition of N-NO 3-, N-NH 4+ and H + at Val Gerola, where the damage symptoms were more evident. In addition, the canopy leaching of Ca 2+, K + and weak organic acids were 47%, 21% and 27% higher at Val Gerola than at Val Masino. Annual SO 42- deposition fluxes (21.3 kg ha -1 yr -1 at Val Masino and 23.6 kg ha -1 yr -1 at Val Gerola) were similar to those reported for moderately polluted European and U.S. sites. Annual N loads were 13.6 and 13.1 kg ha -1 yr -1 in the bulk input, and 15.0 and 18.0 kg ha -1 yr -1 in throughfall inputs, at Val Masino and Val Gerola, respectively. The contribution of the organic fraction to the total N atmospheric deposition load is significant, constituting 17% of the bulk flux and 40% of the throughfall flux. Measured nitrogen loads exceed the critical nutrient loads by several kg N ha -1 at both stations. In particular the nitrogen throughfall load at Val Gerola was about 3 times higher than the critical values.

  1. Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin.

    PubMed

    Nakamura, Toshio; Kotani, Mao; Tonozuka, Takashi; Ide, Azusa; Oguma, Keiji; Nishikawa, Atsushi

    2009-01-30

    The Clostridium botulinum type C 16S progenitor toxin contains a neurotoxin and several nontoxic components, designated nontoxic nonhemagglutinin (HA), HA1 (HA-33), HA2 (HA-17), HA3a (HA-22-23), and HA3b (HA-53). The HA3b subcomponent seems to play an important role cooperatively with HA1 in the internalization of the toxin by gastrointestinal epithelial cells via binding of these subcomponents to specific oligosaccharides. In this study, we investigated the sugar-binding specificity of the HA3b subcomponent using recombinant protein fused to glutathione S-transferase and determined the three-dimensional structure of the HA3a-HA3b complex based on X-ray crystallography. The crystal structure was determined at a resolution of 2.6 A. HA3b contains three domains, domains I to III, and the structure of domain I resembles HA3a. In crystal packing, three HA3a-HA3b molecules are assembled to form a three-leaved propeller-like structure. The three HA3b domain I and three HA3a alternate, forming a trimer of dimers. In a database search, no proteins with high structural homology to any of the domains (Z score >10) were found. Especially, HA3a and HA3b domain I, mainly composed of beta-sheets, reveal a unique fold. In binding assays, HA3b bound sialic acid with high affinity, but did not bind galactose, N-acetylgalactosamine, or N-acetylglucosamine. The electron density of liganded N-acetylneuraminic acid was determined by crystal soaking. In the sugar-complex structure, the N-acetylneuraminic acid-binding site was located in the cleft formed between domains II and III of HA3b. This report provides the first determination of the three-dimensional structure of the HA3a-HA3b complex and its sialic acid binding site. Our results will provide useful information for elucidating the mechanism of assembly of the C16S toxin and for understanding the interactions with oligosaccharides on epithelial cells and internalization of the botulinum toxin complex.

  2. Effects of land clearing techniques and tillage systems on runoff and soil erosion in a tropical rain forest in Nigeria.

    PubMed

    Ehigiator, O A; Anyata, B U

    2011-11-01

    This work reports runoff and soil loss from each of 14 sub-watersheds in a secondary rain forest in south-western Nigeria. The impact of methods of land clearing and post-clearing management on runoff and soil erosion under the secondary forest is evaluated. These data were acquired eighteen years after the deforestation of primary vegetation during the ' West bank' project of the International Institute for Tropical Agriculture (IITA). These data are presented separately for each season; however, statistical analyses for replicates were not conducted due to differences in their past management. Soil erosion was affected by land clearing and tillage methods. The maximum soil erosion was observed on sub-watersheds that were mechanically cleared with tree-pusher/root-rake attachments and tilled conventionally. A high rate of erosion was observed even when graded-channel terraces were constructed to minimize soil erosion. In general there was much less soil erosion on manually cleared than on mechanically cleared sub-watersheds (2.5 t ha(-1yr(-1) versus 13.8 t ha(-1yr(-1)) and from the application of no-tillage methods than from conventionally plowed areas (6.5 t ha(-1yr(-1) versus 12.1 t ha(-1yr(-1)). The data indicate that tillage methods and appropriate management of soils and crops play an important role in soil and water conservation and in decreasing the rate of decline of soil quality. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Tundra Fires in the Noatak National Preserve, Northwestern Alaska, Since 6000 yr BP

    NASA Astrophysics Data System (ADS)

    Chipman, M. L.; Higuera, P. E.; Allen, J.; Rupp, S.; Hu, F. S.

    2008-12-01

    Over 1.7 million hectares of Alaskan tundra have burned over the past 50 years, including the record-setting Anaktuvuk River fire in 2007. Despite this evidence indicating the flammable nature of these ecosystems under warm and dry conditions, land managers and global change scientists lack critical information concerning long-term relationships among fire, climate and tundra vegetation. This knowledge gap limits the ability to assess the response of the tundra fire regime to ongoing and predicted climate warming and potential feedbacks with Earth systems. We utilize macroscopic charcoal from lake-sediment cores to characterize the frequency component of fire regimes in shrub-dominated and herb-dominated tundra ecosystems in northwestern Alaska over the past 6000 years. Here we present the first long-term records of tundra fire regimes from the Noatak National Preserve, a region encompassing some of the most flammable tundra in the state. Results from three lakes indicate that fire has been a consistent process in the region, with fire return intervals (FRIs) ranging from 70 to 800+ years since 6000 yr BP. FRIs were similar between herb- and shrub-dominated tundra sites before ~2000 yr BP, with a mean FRI of 167 yr (95% CI 145-195) Over the past ~2000 years, however, herb- dominated sites burned more frequently (mean FRI 112 yr [95% CI 80-151]) than shrub-dominated sites (mean FRI 247 yr [95% CI 141-377]). At millennial time scales, shifts in historic FRIs were likely related to regional climate changes and/or associated vegetation changes. These results provide a context for resource management and serve to refine the tundra component of an ecosystem model designed to aid land managers in assessing fuels and fire hazards in the context of climatic change.

  4. Responses of epiphytic lichens to an experimental whole-tree nitrogen-deposition gradient.

    PubMed

    Johansson, Otilia; Nordin, Annika; Olofsson, Johan; Palmqvist, Kristin

    2010-12-01

    Here, we examined the responses of the epiphytic lichens Alectoria sarmentosa and Platismatia glauca to increased atmospheric nitrogen (N) deposition in an old-growth boreal spruce forest, to assess the sensitivity of these species to N and define their critical N load. Nitrogen deposition was simulated by irrigating 15 trees over a 3 yr period with water and isotopically labeled NH(4)NO(3), providing N loads ranging from ambient to 50 kg N ha(-1) yr(-1) . Thallus N concentration increased in both species with increasing N load, and uptake rates of both NH(4)(+) and NO(3)(-) were similar. Photobiont concentration increased linearly with increased N in both species, saturating in A. sarmentosa in the third year at the highest N loads (25 and 50 kg ha(-1) yr(-1)). The simulated N deposition decreased the phosphorus (P) concentration in A. sarmentosa, and increased the N:P ratio in both species. Significant responses in lichen chemistry were detected to inputs of 12.5 kg N ha(-1) yr(-1) or higher, suggesting that resources other than N limit lichens at higher N loads. However, the data also suggest that N saturation may be cumulative over time, even at low N. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

  5. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season.

    PubMed

    Linderman, Susanne L; Chambers, Benjamin S; Zost, Seth J; Parkhouse, Kaela; Li, Yang; Herrmann, Christin; Ellebedy, Ali H; Carter, Donald M; Andrews, Sarah F; Zheng, Nai-Ying; Huang, Min; Huang, Yunping; Strauss, Donna; Shaz, Beth H; Hodinka, Richard L; Reyes-Terán, Gustavo; Ross, Ted M; Wilson, Patrick C; Ahmed, Rafi; Bloom, Jesse D; Hensley, Scott E

    2014-11-04

    Influenza viruses typically cause the most severe disease in children and elderly individuals. However, H1N1 viruses disproportionately affected middle-aged adults during the 2013-2014 influenza season. Although H1N1 viruses recently acquired several mutations in the hemagglutinin (HA) glycoprotein, classic serological tests used by surveillance laboratories indicate that these mutations do not change antigenic properties of the virus. Here, we show that one of these mutations is located in a region of HA targeted by antibodies elicited in many middle-aged adults. We find that over 42% of individuals born between 1965 and 1979 possess antibodies that recognize this region of HA. Our findings offer a possible antigenic explanation of why middle-aged adults were highly susceptible to H1N1 viruses during the 2013-2014 influenza season. Our data further suggest that a drifted H1N1 strain should be included in future influenza vaccines to potentially reduce morbidity and mortality in this age group.

  6. Response of soil respiration and ecosystem carbon budget to vegetation removal in Eucalyptus plantations with contrasting ages.

    PubMed

    Wu, Jianping; Liu, Zhanfeng; Huang, Guomin; Chen, Dima; Zhang, Weixin; Shao, Yuanhu; Wan, Songze; Fu, Shenglei

    2014-09-02

    Reforested plantations have substantial effects on terrestrial carbon cycling due to their large coverage area. Although understory plants are important components of reforested plantations, their effects on ecosystem carbon dynamics remain unclear. This study was designed to investigate the effects of vegetation removal/understory removal and tree girdling on soil respiration and ecosystem carbon dynamics in Eucalyptus plantations of South China with contrasting ages (2 and 24 years old). We conducted a field manipulation experiment from 2008 to 2009. Understory removal reduced soil respiration in both plantations, whereas tree girdling decreased soil respiration only in the 2-year-old plantations. The net ecosystem production was approximately three times greater in the 2-year-old plantations (13.4 t C ha(-1) yr(-1)) than in the 24-year-old plantations (4.2 t C h(-1) yr(-1)). The biomass increase of understory plants was 12.6 t ha(-1) yr(-1) in the 2-year-old plantations and 2.9 t ha(-1) yr(-1) in the 24-year-old plantations, accounting for 33.9% nd 14.1% of the net primary production, respectively. Our findings confirm the ecological importance of understory plants in subtropical plantations based on the 2 years of data. These results also indicate that Eucalyptus plantations in China may be an important carbon sink due to the large plantation area.

  7. Technical details concerning development of a 1200 yr proxy index for global volcanism

    NASA Astrophysics Data System (ADS)

    Crowley, T. J.; Unterman, M. B.

    2013-05-01

    This report describes details of developing a volcano forcing reconstruction (Crowley et al., 2008) for climate models that is based primarily on sulphate records in Antarctic and Greenland ice cores. The chronology of eruptions is considered accurate to within 1 yr for the interval AD 1104-2000 and about 2 yr for AD 800-1103. The reconstruction involves (1) calibration against satellite aerosol optical depth (AOD) estimates of the 1991 Pinatubo/Hudson eruptions; (2) partial validation against independent lunar estimates of AOD and global sulphate emissions; (3) partial assessment of uncertainties in AOD estimates; (4) assessment of possible tropical "false positives" in ice core reconstructions due to simultaneous occurrence of mid/high-latitude eruptions in each hemisphere; (5) identification of a new category of eruptions, termed "unipolar" tropical eruptions, in which the eruption plume penetrates mainly to polar regions in only the hemisphere of its eruption; (6) use of different growth curves for high- and low-latitude eruptions; (7) specification of 2/3 power shortwave scaling for eruptions larger than the 1991 Pinatubo eruption; (8) introduction of an estimate of effective particle size that affects lifetime and scattering properties of stratospheric aerosols; and (9) utilization of bimonthly-resolution electrical conductivity measurements to estimate the eruption date of the 1258/1259 eruption as 1257.7±0.2. The data, and a high-temporal resolution reconstruction for climate models, are available at: 1:::::P1_STUDY_ID:14168"target="_blank">http://hurricane.ncdc.noaa.gov/pls/paleox/f?p=519:1:::::P1_STUDY_ID:14168.

  8. Hybrid Macro-Porous Titanium Ornamented by Degradable 3D Gel/nHA Micro-Scaffolds for Bone Tissue Regeneration

    PubMed Central

    Yin, Bo; Ma, Pei; Chen, Jun; Wang, Hai; Wu, Gui; Li, Bo; Li, Qiang; Huang, Zhifeng; Qiu, Guixing; Wu, Zhihong

    2016-01-01

    Porous titanium is a kind of promising material for bone substitution, while its bio-inert property results in demand of modifications to improve the osteointegration capacity. In this study, gelatin (Gel) and nano-hydroxyapatite (nHA) were used to construct 3D micro-scaffolds in the pores of porous titanium in the ratios of Gel:nHA = 1:0, Gel:nHA = 1:1, and Gel:nHA = 1:3, respectively. Cell attachment and proliferation, and gene and protein expression levels of osteogenic markers were evaluated in MC3T3-E1 cells, followed by bone regeneration assessment in a rabbit radius defect model. All hybrid scaffolds with different composition ratio were found to have significant promotional effects in cell adhesion, proliferation and differentiation, in which the group with Gel:nHA = 1:1 showed the best performance in vitro, as well as the most bone regeneration volume in vivo. This 3D micro-scaffolds modification may be an innovative method for porous titanium ornamentation and shows potential application values in clinic. PMID:27092492

  9. Hybrid Macro-Porous Titanium Ornamented by Degradable 3D Gel/nHA Micro-Scaffolds for Bone Tissue Regeneration.

    PubMed

    Yin, Bo; Ma, Pei; Chen, Jun; Wang, Hai; Wu, Gui; Li, Bo; Li, Qiang; Huang, Zhifeng; Qiu, Guixing; Wu, Zhihong

    2016-04-15

    Porous titanium is a kind of promising material for bone substitution, while its bio-inert property results in demand of modifications to improve the osteointegration capacity. In this study, gelatin (Gel) and nano-hydroxyapatite (nHA) were used to construct 3D micro-scaffolds in the pores of porous titanium in the ratios of Gel:nHA = 1:0, Gel:nHA = 1:1, and Gel:nHA = 1:3, respectively. Cell attachment and proliferation, and gene and protein expression levels of osteogenic markers were evaluated in MC3T3-E1 cells, followed by bone regeneration assessment in a rabbit radius defect model. All hybrid scaffolds with different composition ratio were found to have significant promotional effects in cell adhesion, proliferation and differentiation, in which the group with Gel:nHA = 1:1 showed the best performance in vitro, as well as the most bone regeneration volume in vivo. This 3D micro-scaffolds modification may be an innovative method for porous titanium ornamentation and shows potential application values in clinic.

  10. Multiplex RT-PCR assay for differentiating European swine influenza virus subtypes H1N1, H1N2 and H3N2.

    PubMed

    Chiapponi, Chiara; Moreno, Ana; Barbieri, Ilaria; Merenda, Marianna; Foni, Emanuela

    2012-09-01

    In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2) have been isolated in pigs. Developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. This study describes two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe. The HA PCR was able to identify the lineage (avian or human) of the HA of H1 subtypes. The analytical sensitivity of the test, considered to be unique, was assessed using three reference viruses. The detection limit corresponded to 1×10(-1) TCID(50)/200μl for avian-like H1N1, 1×10(0) TCID(50)/200μl for human-like H1N2 and 1×10(1) TCID(50)/200μl for H3N2 SIV. The multiplex RT-PCR was first carried out on a collection of 70 isolated viruses showing 100% specificity and then on clinical samples, from which viruses had previously been isolated, resulting in an 89% positive specificity of the viral subtype. Finally, the test was able to identify the viral subtype correctly in 56% of influenza A positive samples, from which SIV had not been isolated previously. It was also possible to identify mixed viral infections and the circulation of a reassortant strain before performing genomic studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Nitrogen balance of a boreal Scots pine forest

    NASA Astrophysics Data System (ADS)

    Korhonen, J. F. J.; Pihlatie, M.; Pumpanen, J.; Aaltonen, H.; Hari, P.; Levula, J.; Kieloaho, A.-J.; Nikinmaa, E.; Vesala, T.; Ilvesniemi, H.

    2013-02-01

    The productivity of boreal forests is considered to be limited by low nitrogen (N) availability. Increased atmospheric N deposition has altered the functioning and N cycling of these N-sensitive ecosystems by increasing the availability of reactive nitrogen. The most important components of N pools and fluxes were measured in a boreal Scots pine stand in Hyytiälä, Southern Finland. The measurements at the site allowed direct estimations of nutrient pools in the soil and biomass, inputs from the atmosphere and outputs as drainage flow and gaseous losses from two micro-catchments. N was accumulating in the system, mainly in woody biomass, at a rate of 7 kg N ha-1 yr-1. Nitrogen input as atmospheric deposition was 7.4 kg N ha-1 yr-1. Dry deposition and organic N in wet deposition contributed over half of the inputs in deposition. Total outputs were 0.4 kg N ha-1 yr-1, the most important outputs being N2O emission to the atmosphere and organic N flux in drainage flow. Nitrogen uptake and retranslocation were equally important sources of N for plant growth. Most of the assimilated N originated from decomposition of organic matter, and the fraction of N that could originate directly from deposition was about 30%. In conclusion, atmospheric N deposition fertilizes the site considerably, but there are no signs of N saturation. Further research is needed to estimate soil N2 fluxes (emission and fixation), which may amount up to several kg N ha-1 yr-1.

  12. Liana infestation impacts tree growth in a lowland tropical moist forest

    NASA Astrophysics Data System (ADS)

    van der Heijden, G. M. F.; Phillips, O. L.

    2009-10-01

    Ecosystem-level estimates of the effect of lianas on tree growth in mature tropical forests are needed to evaluate the functional impact of lianas and their potential to affect the ability of tropical forests to sequester carbon, but these are currently lacking. Using data collected on tree growth rates, local growing conditions and liana competition in five permanent sampling plots in Amazonian Peru, we present the first ecosystem-level estimates of the effect of lianas on above-ground productivity of trees. By first constructing a multi-level linear mixed effect model to predict individual-tree diameter growth model using individual-tree growth conditions, we were able to then estimate stand-level above-ground biomass (AGB) increment in the absence of lianas. We show that lianas, mainly by competing above-ground with trees, reduce tree annual above-ground stand-level biomass increment by ~10%, equivalent to 0.51 Mg dry weight ha-1 yr-1 or 0.25 Mg C ha-1 yr-1. AGB increment of lianas themselves was estimated to be 0.15 Mg dry weight ha-1 yr-1 or 0.07 Mg C ha-1 yr-1, thus only compensating ~29% of the liana-induced reduction in ecosystem AGB increment. Increasing liana pressure on tropical forests will therefore not only tend to reduce their carbon storage capacity, by indirectly promoting tree species with low-density wood, but also their rate of carbon uptake, with potential consequences for the rate of increase in atmospheric carbon dioxide.

  13. UTF1, a Putative Marker for Spermatogonial Stem Cells in Stallions

    PubMed Central

    Jung, Heejun; Roser, Janet F.; Yoon, Minjung

    2014-01-01

    Spermatogonial stem cells (SSCs) continuously undergo self-renewal and differentiation to sustain spermatogenesis throughout adulthood in males. In stallions, SSCs may be used for the production of progeny from geldings after cryopreservation and therapy for infertile and subfertile stallions. Undifferentiated cell transcription factor 1 (UTF1) is a putative marker for undifferentiated spermatogonia in humans and rats. The main purposes of this study are to determine the following: 1) changes in the expression pattern of UTF1 at various reproductive stages of stallions, 2) subpopulations of spermatogonia that express UTF1. Testicular samples were collected and categorized based on the age of the horses as follows: pre-pubertal (<1 yr), pubertal (11.5 yr), post-pubertal (2–3 yr), and adult (4–8 yr). Western blot analysis was utilized to determine the cross-activity of the UTF1 antibody to horse testes tissues. Immunohistochemistry was conducted to investigate the UTF1 expression pattern in germ cells at different reproductive stages. Whole mount staining was applied to determine the subpopulation of UTF1-positive spermatogonia. Immunohistological analysis showed that most germ cells in the pre-pubertal and pubertal stages were immunolabeled with UTF1, whereas only a few germ cells in the basal compartment of the seminiferous tubule cross-sections of post-pubertal and adult tissues were UTF1-positive. No staining was observed in the Sertoli or Leydig cells at any reproductive stages. Whole mount staining showed that As, Apr, and chains of 4, 8, 16 Aal spermatogonia were immunolabeled with UTF1 in the post-pubertal stallion tubule. Isolated single germ cells were also immunolabeled with UTF1. In conclusion, UTF1 is expressed in undifferentiated spermatogonia, and its antibody can be used as a putative marker for SSCs in stallions. PMID:25272017

  14. Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

    PubMed Central

    Throsby, Mark; van den Brink, Edward; Jongeneelen, Mandy; Poon, Leo L. M.; Alard, Philippe; Cornelissen, Lisette; Bakker, Arjen; Cox, Freek; van Deventer, Els; Guan, Yi; Cinatl, Jindrich; ter Meulen, Jan; Lasters, Ignace; Carsetti, Rita; Peiris, Malik; de Kruif, John; Goudsmit, Jaap

    2008-01-01

    Background The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. PMID:19079604

  15. Glycosylation on Hemagglutinin Affects the Virulence and Pathogenicity of Pandemic H1N1/2009 Influenza A Virus in Mice

    PubMed Central

    Li, Yongtao; Bradley, Konrad C.; Cao, Jiyue; Chen, Huanchun; Jin, Meilin; Zhou, Hongbo

    2013-01-01

    The two glycosylation sites (Asn142 and Asn177) were observed in the HA of most human seasonal influenza A/H1N1 viruses, while none in pandemic H1N1/2009 influenza A (pH1N1) viruses. We investigated the effect of the two glycosylation sites on viral virulence and pathogenicity in mice using recombinant pH1N1. The H1N1/144 and H1N1/177 mutants which gained potential glycosylation sites Asn142 and Asn177 on HA respectively were generated from A/Mexico/4486/2009(H1N1) by site-directed mutagenesis and reverse genetics, the same as the H1N1/144+177 gained both glycosylation sites Asn142 and Asn177. The biological characteristics and antigenicity of the mutants were compared with wild-type pH1N1. The virulence and pathogenicity of recombinants were also detected in mice. Our results showed that HA antigenicity and viral affinity for receptor may change with introduction of the glycosylation sites. Compared with wild-type pH1N1, the mutant H1N1/177 displayed an equivalent virus titer in chicken embryos and mice, and increased virulence and pathogenicity in mice. The H1N1/144 displayed the highest virus titer in mice lung. However, the H1N1/144+177 displayed the most serious alveolar inflammation and pathogenicity in infected mice. The introduction of the glycosylation sites Asn144 and Asn177 resulted in the enhancement on virulence and pathogenicity of pH1N1 in mice, and was also associated with the change of HA antigenicity and the viral affinity for receptor. PMID:23637827

  16. Genetic diversity of influenza A(H1N1)2009 virus circulating during the season 2010-2011 in Spain.

    PubMed

    Ledesma, Juan; Pozo, Francisco; Reina, Gabriel; Blasco, Miriam; Rodríguez, Guadalupe; Montes, Milagrosa; López-Miragaya, Isabel; Salvador, Carmen; Reina, Jordi; Ortíz de Lejarazu, Raúl; Egido, Pilar; López Barba, José; Delgado, Concepción; Cuevas, María Teresa; Casas, Inmaculada

    2012-01-01

    Genetic diversity of influenza A(H1N1)2009 viruses has been reported since the pandemic virus emerged in April 2009. Different genetic clades have been identified and defined based on amino acid substitutions found in the haemagglutinin (HA) protein sequences. In Spain, circulating influenza viruses are monitored each season by the regional laboratories enrolled in the Spanish Influenza Surveillance System (SISS). The analysis of the HA gene sequence helps to detect the genetic diversity and viral evolution. To perform an analysis of the genetic diversity of influenza A(H1N1)2009 viruses circulating in Spain during the season 2010-2011 based on analysis of the HA sequence gene. Phylogenetic analysis based on the HA1 subunit of the haemagglutinin gene was carried out on 220 influenza A(H1N1)2009 viruses circulating during the season 2010-2011. Six different genetic groups were identified among circulating A(H1N1)2009 viruses, five of them were previously reported during season 2010-2011. A new group, characterized by E172K and K308E changes and a proline at position 83, was observed in 12.27% of the Spanish viruses. Co-circulation of six different genetic groups of influenza A(H1N1)2009 viruses was identified in Spain during the season 2010-2011. Nevertheless, at this stage, none of the groups identified to date have resulted in significant antigenic changes according to data collected by World Health Organization Collaborating Centres for influenza surveillance. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Analysis of insulin pump settings in children and adolescents with type 1 diabetes mellitus.

    PubMed

    Lau, Yu Ning; Korula, Sophy; Chan, Albert K; Heels, Kristine; Krass, Ines; Ambler, Geoffrey

    2016-08-01

    To characterize current insulin pump settings used in young patients with type 1 diabetes mellitus (T1DM) and to assess their relationship to glycemic control. This retrospective study included patients aged <18 yr old with T1DM >1 yr using a Medtronic pump device. Pump data including number of blood glucose (BG) tests per day, basal and bolus insulin parameters, carbohydrate ratio (CR), and insulin sensitivity factors (ISFs) were averaged over 14 d for statistical analyses. Anthropometric data and recent glycosylated hemoglobin A1c (HbA1c) were recorded. A total of 292 patients (144 males and 148 females) were included in the study. Participants had a median age (interquartile range, IQR) of 12.9 yr (10.0-15.1 yr) and pump duration of 2.8 yr (1.5-4.2 yr). No significant differences in median HbA1c (IQR) were observed in preschool [n = 14; HbA1c 7.8% (7.3-8.3%)], prepubertal [n = 105; HbA1c 8.1% (7.7-8.9%)], and adolescent subjects [n = 173; HbA1c 8.4% (7.7-9.0%)]. Adolescents took significantly fewer boluses and BG tests per day compared with younger children (p < 0.05). Age-specific diurnal variation in basal insulin delivery was noted. Additionally, stronger carbohydrate cover and weaker corrections were used in real-life compared with theoretical 500 and 100 rules, respectively. Lower HbA1c was associated with higher number of daily boluses, greater number of BG tests per day, lower average CR/500 rule ratio, and higher average ISF/100 rule ratio adjusted for age (R(2) = 0.22; p < 0.01). Insulin pump therapy requires continuous adjustments and glycemic targets are achieved by a minority. We believe this is the first study in pediatric cohort looking at association between CR and ISF with glycemic control. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Impacts of agricultural management and climate change on future soil organic carbon dynamics in North China Plain.

    PubMed

    Wang, Guocheng; Li, Tingting; Zhang, Wen; Yu, Yongqiang

    2014-01-01

    Dynamics of cropland soil organic carbon (SOC) in response to different management practices and environmental conditions across North China Plain (NCP) were studied using a modeling approach. We identified the key variables driving SOC changes at a high spatial resolution (10 km × 10 km) and long time scale (90 years). The model used future climatic data from the FGOALS model based on four future greenhouse gas (GHG) concentration scenarios. Agricultural practices included different rates of nitrogen (N) fertilization, manure application, and stubble retention. We found that SOC change was significantly influenced by the management practices of stubble retention (linearly positive), manure application (linearly positive) and nitrogen fertilization (nonlinearly positive) - and the edaphic variable of initial SOC content (linearly negative). Temperature had weakly positive effects, while precipitation had negligible impacts on SOC dynamics under current irrigation management. The effects of increased N fertilization on SOC changes were most significant between the rates of 0 and 300 kg ha-1 yr-1. With a moderate rate of manure application (i.e., 2000 kg ha-1 yr-1), stubble retention (i.e., 50%), and an optimal rate of nitrogen fertilization (i.e., 300 kg ha-1 yr-1), more than 60% of the study area showed an increase in SOC, and the average SOC density across NCP was relatively steady during the study period. If the rates of manure application and stubble retention doubled (i.e., manure application rate of 4000 kg ha-1 yr-1 and stubble retention rate of 100%), soils across more than 90% of the study area would act as a net C sink, and the average SOC density kept increasing from 40 Mg ha-1 during 2010s to the current worldwide average of ∼ 55 Mg ha-1 during 2060s. The results can help target agricultural management practices for effectively mitigating climate change through soil C sequestration.

  19. Nitrogen and sulfur input-output budgets in the experimental and reference watersheds, Bear Brook Watershed in Maine (BBWM)

    Treesearch

    J. Kahl; S. Norton; I. Fernandez; L. Rustad; M. Handley

    1999-01-01

    Dry (NH4)2SO4 (1,800 eq-1 ha-1 yr-1) has been applied to the western of two contiguous 10 ha catchments at the Bear Brook Watershed in Maine (BBWM) since November, 1989. The initial rapid and significant response in both S and N in...

  20. The Influenza Virus and the 2009 H1N1 Outbreak

    DTIC Science & Technology

    2016-04-08

    Envelope L’ol • Sequencing Figure 1 Influenza Virus Anatomy -Neuramlnldase (Sialldase) ’ Hemagglutlnln 9 Key laboratory techniques...discover the 2009 H1 N1 influenza virus Phylogenetic Tree Out of the over 400 human H1 ’s USAFSAM sequenced this season no specimen has had less than a...surveillance/vaccine contents • Shot Versus Flu Mist • How does Tamiflu work • Sequencing HA - Culture, HAI, PCR, Serology ••• • t.tt

  1. Modeled nitrous oxide emissions from corn fields in iowa based on county level data.

    PubMed

    Jarecki, Marek K; Hatfield, Jerry L; Barbour, Wiley

    2015-03-01

    The U.S. Corn Belt area has the capacity to generate high nitrous oxide (NO) emissions due to medium to high annual precipitation, medium- to heavy-textured soils rich in organic matter, and high nitrogen (N) application rates. The purpose of this work was to estimate NO emissions from cornfields in Iowa at the county level using the DeNitrification-DeComposition (DNDC) model and to compare the DNDC NO emission estimates with available results from field experiments. All data were acquired for 2007 to 2011. Weather Underground Network and the Iowa State University Iowa Soil Properties and Interpretation Database 7.3 were the data sources for DNDC inputs and for computing county soil parameters. The National Agriculture Statistic Service 5-yr averages for corn yield data were used to establish ex post fertilizer N input at the county level. The DNDC output suggested county-wide NO emissions in Iowa ranged from 2.2 kg NO-N ha yr in south-central to 4.6 to 4.7 kg NO-N ha yr in north-central and eastern Iowa counties. In northern districts, the average direct NO emissions were 3.2, 4.4, and 3.6 kg NO-N ha yr for west, central, and east, respectively. In central districts, average NO emissions were 3.5, 3.9, and 3.4 kg NO-N ha yr for west, central, and east, respectively. For southern districts, NO emissions were 3.5, 2.6, and 3.1 kg NO-N ha yr for west, central, and east, respectively. Direct NO emissions estimated by the DNDC model were 1.93% of N fertilizer input to corn fields in Iowa, with values ranging from 1.66% in the northwest cropping district to 2.25% in the north-central cropping district. These values are higher than the average 1% loss rate used in the IPCC Tier 1 approach. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  2. On the constancy of the lunar cratering flux over the past 3.3 billion yr

    NASA Technical Reports Server (NTRS)

    Guinness, E. A.; Arvidson, R. E.

    1977-01-01

    Utilizing a method that minimizes random fluctuations in sampling crater populations, it can be shown that the ejecta deposit of Tycho, the floor of Copernicus, and the region surrounding the Apollo 12 landing site have incremental crater size-frequency distributions that can be expressed as log-log linear functions over the diameter range from 0.1 to 1 km. Slopes are indistinguishable for the three populations, probably indicating that the surfaces are dominated by primary craters. Treating the crater populations of Tycho, the floor of Copernicus, and Apollo 12 as primary crater populations contaminated, but not overwhelmed, with secondaries, allows an attempt at calibration of the post-heavy bombardment cratering flux. Using the age of Tycho as 109 m.y., Copernicus as 800 m.y., and Apollo 12 as 3.26 billion yr, there is no basis for assuming that the flux has changed over the past 3.3 billion yr. This result can be used for dating intermediate aged surfaces by crater density.

  3. The haemagglutination activity of equine herpesvirus type 1 glycoprotein C.

    PubMed

    Andoh, Kiyohiko; Hattori, Shiho; Mahmoud, Hassan Y A H; Takasugi, Maaya; Shimoda, Hiroshi; Bannai, Hiroshi; Tsujimura, Koji; Matsumura, Tomio; Kondo, Takashi; Kirisawa, Rikio; Mochizuki, Masami; Maeda, Ken

    2015-01-02

    Equine herpesvirus type 1 (EHV-1) has haemagglutination (HA) activity toward equine red blood cells (RBCs), but the identity of its haemagglutinin is unknown. To identify the haemagglutinin of EHV-1, the major glycoproteins of EHV-1 were expressed in 293T cells, and the cells or cell lysates were mixed with equine RBCs. The results showed that only EHV-1 glycoprotein C (gC)-producing cells adsorbed equine RBCs, and that the lysate of EHV-1 gC-expressing cells agglutinated equine RBCs. EHV-1 lacking gC did not show HA activity. HA activity was inhibited by monoclonal antibodies (MAbs) specific for gC, but not by antibodies directed against other glycoproteins. In addition, HA activity was not inhibited by the addition of heparin. These results indicate that EHV-1 gC can bind equine RBCs irrespective of heparin, in contrast to other herpesvirus gC proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Technical details concerning development of a 1200-yr proxy index for global volcanism

    NASA Astrophysics Data System (ADS)

    Crowley, T. J.; Unterman, M. B.

    2012-01-01

    This technical report describes details of developing a volcano forcing reconstruction (Crowley et al., 2008) for climate models that is based primarily on sulphate records in Antarctic and Greenland ice cores. The chronology of eruptions is considered accurate to within 1 yr for the interval AD 1104-2000 and 2 yr for AD 800-1103. The reconstruction involves: (1) calibration against satellite aerosol optical depth (AOD) estimates of the 1991 Pinatubo/Hudson eruptions; (2) partial validation against independent lunar estimates of AOD and global sulphate emissions; (3) partial assessment of uncertainties in AOD estimates; (4) assessment of possible tropical "false positives" in ice core reconstructions due to simultaneous occurrence of mid/high-latitude eruptions in each hemisphere; (5) identification of a new category of eruptions, termed "unipolar" tropical eruptions, in which the eruption plume penetrates mainly to polar regions in only the hemisphere of its eruption; (6) use of different growth curves for high- and low-latitude eruptions; (7) specification of 2/3 power shortwave scaling for eruptions larger than the 1991 Pinatubo eruption; and (8) compensatory introduction of an estimate of effective particle size that affects lifetime and scattering properties of stratospheric aerosols.

  5. Syndecan-1 alterations during the tumorigenic progression of human colonic Caco-2 cells induced by human Ha-ras or polyoma middle T oncogenes.

    PubMed Central

    Levy, P.; Munier, A.; Baron-Delage, S.; Di Gioia, Y.; Gespach, C.; Capeau, J.; Cherqui, G.

    1996-01-01

    The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21ras and pp60c-src in human colonic Caco-2 cells is associated with specific alterations of syndecan-1, a membrane-anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated (Val 12) human Ha-ras gene or with the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. Compared with control vector-transfected Caco-2 cells, both oncogene-transfected cell lines (1) contained smaller amounts of membrane-anchored PGs; (2) exhibited decreased syndecan-1 expression at the protein but not the mRNA level; (3) synthesized 35S-labelled syndecan-1 with decreased specific activity; (4) produced a syndecan-1 ectodomain with a lower molecular mass and reduced GAG chain size and sulphation; and (5) expressed heparanase degradative activity. These results show that the dramatic activation of the tumorigenic potential induced by oncogenic p21ras or Py-MT/pp60c-src in Caco-2 cells is associated with marked alterations of syndecan-1 expression at the translational and post-translational levels. Images Figure 2 PMID:8695359

  6. Effects of nitrogen and phosphorus additions on soil methane uptake in disturbed forests

    NASA Astrophysics Data System (ADS)

    Zheng, Mianhai; Zhang, Tao; Liu, Lei; Zhang, Wei; Lu, Xiankai; Mo, Jiangming

    2016-12-01

    Atmospheric nitrogen (N) deposition is generally thought to suppress soil methane (CH4) uptake in natural forests, and phosphorus (P) input may alleviate this negative effect. However, it remains unclear how N and P inputs control soil CH4 uptake in disturbed forests. In this study, soil CH4 uptake rates were measured in two disturbed forests, including a secondary forest (with previous, but not recent, disturbance) and a plantation forest (with recent continuous disturbance), in southern China for 34 months of N and/or P additions: control, N addition (150 kg N ha-1 yr-1), P addition (150 kg P ha-1 yr-1), and NP addition (150 kg N ha-1 yr-1 plus 150 kg P ha-1 yr-1). Mean CH4 uptake rate in control plots was significantly higher in the secondary forest (24.40 ± 0.81 µg CH4-C m-2 h-1) than in the plantation forest (17.07 ± 0.70 µg CH4-C m-2 h-1). CH4 uptake rate had negative relationships with soil water-filled pore space in both forests. In the secondary forest, N, P, and NP additions significantly decreased CH4 uptake by 39.7%, 27.8%, and 37.6%, respectively, but had no significant effects in the plantation forest, indicating that P input does not alleviate the suppression of CH4 uptake by N deposition. Taken together, our findings suggest that reducing anthropogenic disturbance, including harvesting of forest floor, and anthropogenic N and P inputs will increase soil CH4 uptake in disturbed forests, which is important in view of the increased trends in global warming during recent decades.

  7. Animal waste and FGD gypsum effects on bermudagrass and soil leachate nutrient contents

    USDA-ARS?s Scientific Manuscript database

    In previous experiments on newly relcaimed coal mine soils in northeastern Mississippi, applying poultry litter at 22.4 Mg ha-1 yr-1 enhanced bermudagrass (Cynodon dactylon L.) biomass and selected soil quality parameters. Additionally, co-application of 11.2 Mg ha-1 FGD gypsum and litter reduced so...

  8. Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice.

    PubMed

    Lindström, Veronica; Fagerqvist, Therese; Nordström, Eva; Eriksson, Fredrik; Lord, Anna; Tucker, Stina; Andersson, Jessica; Johannesson, Malin; Schell, Heinrich; Kahle, Philipp J; Möller, Christer; Gellerfors, Pär; Bergström, Joakim; Lannfelt, Lars; Ingelsson, Martin

    2014-09-01

    Several lines of evidence suggest that accumulation of aggregated alpha-synuclein (α-synuclein) in the central nervous system (CNS) is an early pathogenic event in Parkinson's disease and other Lewy body disorders. In recent years, animal studies have indicated immunotherapy with antibodies directed against α-synuclein as a promising novel treatment strategy. Since large α-synuclein oligomers, or protofibrils, have been demonstrated to possess pronounced cytotoxic properties, such species should be particularly attractive as therapeutic targets. In support of this, (Thy-1)-h[A30P] α-synuclein transgenic mice with motor dysfunction symptoms were found to display increased levels of α-synuclein protofibrils in the CNS. An α-synuclein protofibril-selective monoclonal antibody (mAb47) was evaluated in this α-synuclein transgenic mouse model. As measured by ELISA, 14month old mice treated for 14weeks with weekly intraperitoneal injections of mAb47 displayed significantly lower levels of both soluble and membrane-associated protofibrils in the spinal cord. Besides the lower levels of pathogenic α-synuclein demonstrated, a reduction of motor dysfunction in transgenic mice upon peripheral administration of mAb47 was indicated. Thus, immunotherapy with antibodies targeting toxic α-synuclein species holds promise as a future disease-modifying treatment in Parkinson's disease and related disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Sugar-induced conformational change found in the HA-33/HA-17 trimer of the botulinum toxin complex.

    PubMed

    Sagane, Yoshimasa; Hayashi, Shintaro; Matsumoto, Takashi; Miyashita, Shin-Ichiro; Inui, Ken; Miyata, Keita; Yajima, Shunsuke; Suzuki, Tomonori; Hasegawa, Kimiko; Yamano, Akihito; Nishikawa, Atsushi; Ohyama, Tohru; Watanabe, Toshihiro; Niwa, Koichi

    2013-08-30

    Large-sized botulinum toxin complex (L-TC) is formed by conjugation of neurotoxin, nontoxic nonhemagglutinin and hemagglutinin (HA) complex. The HA complex is formed by association of three HA-70 molecules and three HA-33/HA-17 trimers, comprised of a single HA-17 and two HA-33 proteins. The HA-33/HA-17 trimer isolated from serotype D L-TC has the ability to bind to and penetrate through the intestinal epithelial cell monolayer in a sialic acid-dependent manner, and thus it plays an important role in toxin delivery through the intestinal cell wall. In this study, we determined the solution structure of the HA-33/HA-17 trimer by using small-angle X-ray scattering (SAXS). The SAXS image of HA-33/HA-17 exhibited broadly similar appearance to the crystal image of the complex. On the other hand, in the presence of N-acetylneuraminic acid, glucose and galactose, the solution structure of the HA-33/HA-17 trimer was drastically altered compared to the structure in the absence of the sugars. Sugar-induced structural change of the HA-33/HA-17 trimer may contribute to cell binding and subsequent transport across the intestinal cell layer. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Assessment of uncertainties in soil erosion and sediment yield estimates at ungauged basins: an application to the Garra River basin, India

    NASA Astrophysics Data System (ADS)

    Swarnkar, Somil; Malini, Anshu; Tripathi, Shivam; Sinha, Rajiv

    2018-04-01

    High soil erosion and excessive sediment load are serious problems in several Himalayan river basins. To apply mitigation procedures, precise estimation of soil erosion and sediment yield with associated uncertainties are needed. Here, the revised universal soil loss equation (RUSLE) and the sediment delivery ratio (SDR) equations are used to estimate the spatial pattern of soil erosion (SE) and sediment yield (SY) in the Garra River basin, a small Himalayan tributary of the River Ganga. A methodology is proposed for quantifying and propagating uncertainties in SE, SDR and SY estimates. Expressions for uncertainty propagation are derived by first-order uncertainty analysis, making the method viable even for large river basins. The methodology is applied to investigate the relative importance of different RUSLE factors in estimating the magnitude and uncertainties in SE over two distinct morphoclimatic regimes of the Garra River basin, namely the upper mountainous region and the lower alluvial plains. Our results suggest that average SE in the basin is very high (23 ± 4.7 t ha-1 yr-1) with higher values in the upper mountainous region (92 ± 15.2 t ha-1 yr-1) compared to the lower alluvial plains (19.3 ± 4 t ha-1 yr-1). Furthermore, the topographic steepness (LS) and crop practice (CP) factors exhibit higher uncertainties than other RUSLE factors. The annual average SY is estimated at two locations in the basin - Nanak Sagar Dam (NSD) for the period 1962-2008 and Husepur gauging station (HGS) for 1987-2002. The SY at NSD and HGS are estimated to be 6.9 ± 1.2 × 105 t yr-1 and 6.7 ± 1.4 × 106 t yr-1, respectively, and the estimated 90 % interval contains the observed values of 6.4 × 105 t yr-1 and 7.2 × 106 t yr-1, respectively. The study demonstrated the usefulness of the proposed methodology for quantifying uncertainty in SE and SY estimates at ungauged basins.

  11. A Modified ELISA Accurately Measures Secretion of High Molecular Weight Hyaluronan (HA) by Graves' Disease Orbital Cells

    PubMed Central

    Krieger, Christine C.

    2014-01-01

    Excess production of hyaluronan (hyaluronic acid [HA]) in the retro-orbital space is a major component of Graves' ophthalmopathy, and regulation of HA production by orbital cells is a major research area. In most previous studies, HA was measured by ELISAs that used HA-binding proteins for detection and rooster comb HA as standards. We show that the binding efficiency of HA-binding protein in the ELISA is a function of HA polymer size. Using gel electrophoresis, we show that HA secreted from orbital cells is primarily comprised of polymers more than 500 000. We modified a commercially available ELISA by using 1 million molecular weight HA as standard to accurately measure HA of this size. We demonstrated that IL-1β-stimulated HA secretion is at least 2-fold greater than previously reported, and activation of the TSH receptor by an activating antibody M22 from a patient with Graves' disease led to more than 3-fold increase in HA production in both fibroblasts/preadipocytes and adipocytes. These effects were not consistently detected with the commercial ELISA using rooster comb HA as standard and suggest that fibroblasts/preadipocytes may play a more prominent role in HA remodeling in Graves' ophthalmopathy than previously appreciated. PMID:24302624

  12. Nitrogen availability and soil N2O emissions following conversion of forests to coffee in southern Sumatra

    NASA Astrophysics Data System (ADS)

    Verchot, Louis V.; Hutabarat, Lusida; Hairiah, Kurniatun; van Noordwijk, Meine

    2006-12-01

    Changes in land use impact on the N cycle with both local and global consequences. We examined how conversion of forest to agriculture in one catchment in southern Sumatra altered N availability and soil N2O emission. Measurements were made along a chronosequence of forest land converted to coffee gardens. A number of different management practices were also examined. Inorganic N stocks and N cycling rates were highest in the forest and lower in the coffee gardens. The forest and young conversion sites appeared to be N limited, whereas the older agricultural sites and the more intensively managed sites were not as strongly N limited. N2O emissions were low in the forest (<2 kgN ha-1yr-1) and increased sharply following deforestation. Emissions on recently cleared land were 4.6 kgN ha-1yr-1 and 8.4 kgN ha-1yr-1 in a 1-year-old coffee garden. Emissions in the older coffee gardens were lower with the lowest flux observed in a 10 year old site (1.8 kgN ha-1yr-1). We explored the effects of different types of management approaches that farmers are using in this landscape. Emissions in an 18-year-old multistrata coffee garden with a significant overstory of N fixing trees were 5 times greater (15.5 kg ha-1yr-1) than emissions from forests. We also found that intensive organic matter management produced high emissions. To understand the spatial and temporal variability of the N2O emissions we used the hole-in-the-pipe conceptual model. N2O fluxes were lowest on N limited sites. Soil water content also played an important role and emissions were highest when water filled pore space (WFPS) was between 85 and 95%. A number of formulations of this model have been applied in different ways over the years to explain spatial and temporal variation in the soil N-oxide flux, and in this study we found the mechanistic explanation useful. Our study suggests that land use change and intensification of agriculture in N limited highland landscapes may significantly increase the

  13. Quantitative remote sensing study indicates doubling of coastal erosion rate in past 50 yr along a segment of the Arctic coast of Alaska

    USGS Publications Warehouse

    Mars, J.C.; Houseknecht, D.W.

    2007-01-01

    A new quantitative coastal land gained-and-lost method uses image analysis of topographic maps and Landsat thematic mapper short-wave infrared data to document accelerated coastal land loss and thermokarst lake expansion and drainage. The data span 1955-2005 along the Beaufort Sea coast north of Teshekpuk Lake in the National Petroleum Reserve in Alaska. Some areas have undergone as much as 0.9 km of coastal erosion in the past 50 yr. Land loss attributed to coastal erosion more than doubled, from 0.48 km2 yr-1 during 1955-1985 to 1.08 km2 yr-1 during 1985-2005. Coastal erosion has breached thermokarst lakes, causing initial draining of the lakes followed by marine floodng. Although inland thermokarst lakes show some uniform expansion, lakes breached by coastal erosion display lake expansion several orders of magnitude greater than inland lakes. ?? 2007 The Geological Society of America.

  14. The reductive degradation of 1,1,1-trichloroethane by Fe(0) in a soil slurry system.

    PubMed

    Wu, Xiaoliang; Lu, Shuguang; Qiu, Zhaofu; Sui, Qian; Lin, Kuangfei; Du, Xiaoming; Luo, Qishi

    2014-01-01

    Most studies on the treatment of chlorinated contaminants by Fe(0) focus on aqueous system tests. However, few is known about the effectiveness of these tests for degrading chlorinated contaminants such as 1,1,1-trichloroethane (TCA) in soil. In this work, the reductive degradation performance of 1,1,1-TCA by Fe(0) was thoroughly investigated in a soil slurry system. The effects of various factors including acid-washed iron, the initial 1,1,1-TCA concentration, Fe(0) dosage, slurry pH, and common constituents in groundwater and soil such as Cl(-), HCO3 (-), SO4 (2-), and NO3 (-) anions and humic acid (HA) were evaluated. The experimental results showed that 1,1,1-TCA could be effectively degraded in 12 h for an initial Fe(0) dosage of 10 g L(-1) and a soil/water mass ratio of 1:5. The soil slurry experiments showed two-stage degradation kinetics: a slow reaction in the first stage and a fast reductive degradation of 1,1,1-TCA in the second stage. The reductive degradation of 1,1,1-TCA was expedited as the mass concentration of Fe(0) increased. In addition, high pHs adversely affected the degradation of 1,1,1-TCA over a pH range of 5.4-8.0 and the reductive degradation efficiency decreased with increasing slurry pH. The initial 1,1,1-TCA concentration and the presence of Cl(-) and SO4(2-) anions had negligible effects. HCO3(-) anions had a accelerative effect on 1,1,1-TCA removal, and both NO3(-) and HA had inhibitory effects. A Cl(-) mass balance showed that the amount of Cl(-) ions released into the soil slurry system during the 1,1,1-TCA degradation increased with increasing reaction time, suggesting that the main degradation mechanism of 1,1,1-TCA by Fe(0) in a soil slurry system was reductive dechlorination with 1,1-DCA as the main intermediate. In conclusion, this study provides a theoretical basis for the practical application of the remediation of contaminated sites containing chlorinated solvent.

  15. Genetic Characterization and Evolution of H1N1pdm09 after Circulation in a Swine Farm

    PubMed Central

    Boni, Arianna; Vaccari, Gabriele; Di Trani, Livia; Zaccaria, Guendalina; Alborali, Giovanni Loris; Lelli, Davide; Cordioli, Paolo; Moreno, Ana Maria

    2014-01-01

    Following the emergence of the A(H1N1)pdm09 in humans, this novel influenza virus was reverse transmitted from infected people to swine population worldwide. In this study we investigated the molecular evolution of A(H1N1)pdm09 virus identified in pigs reared in a single herd. Nasal swabs taken from pigs showing respiratory distress were tested for influenza type A and A(H1N1)pdm09 by real-time RT-PCR assays. Virus isolation from positive samples was attempted by inoculation of nasal swabs samples into specific pathogen free embryonated chicken eggs (ECE) and complete genome sequencing was performed on virus strains after replication on ECE or from original swab sample. The molecular analysis of hemagglutinin (HA) showed, in four of the swine influenza viruses under study, a unique significant amino acid change, represented by a two-amino acid insertion at the HA receptor binding site. Phylogenetic analysis of HA, neuraminidase, and concatenated internal genes revealed a very similar topology, with viruses under study forming a separate cluster, branching outside the A(H1N1)pdm09 isolates recognized until 2014. The emergence of this new cluster of A(H1N1)pdm09 in swine raises further concerns about whether A(H1N1)pdm09 with new molecular characteristics will become established in pigs and potentially transmitted to humans. PMID:25025062

  16. Safety and long-term humoral immune response in adults after vaccination with an H1N1 2009 pandemic influenza vaccine with or without AS03 adjuvant.

    PubMed

    Ferguson, Murdo; Risi, George; Davis, Matthew; Sheldon, Eric; Baron, Mira; Li, Ping; Madariaga, Miguel; Fries, Louis; Godeaux, Olivier; Vaughn, David

    2012-03-01

    In this study (NCT00985088) we evaluated different formulations of an H1N1 2009 pandemic influenza vaccine that deliver various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol-based oil-in-water adjuvant system). A total of 1340 healthy subjects aged ≥18 years were randomized to receive 1 or 2 doses of an adjuvanted (3.75-μg HA/AS03(A) or 1.9-μg HA/AS03(B)) or nonadjuvanted vaccine formulation. Safety and immunogenicity (by hemagglutination-inhibition [HI] assay) after each dose and 6 months after dose 1 are reported here. A single dose of AS03(A)-adjuvanted 3.75-μg HA H1N1 2009 induced the strongest immune responses in subjects aged 18-64 years (seroprotection rate [SPR], 97.2%; seroconversion rate [SCR], 90.1%) as well as in subjects aged >64 years (SPR, 91.1%; SCR, 78.2%) 21 days after vaccination. Six months after dose 1, subjects who received 2 doses of either the adjuvanted formulation or 1 dose of the adjuvanted 3.75-μg HA formulation continued to meet all Center for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use criteria. All formulations had clinically acceptable safety profiles. A single dose of the 3.75-μg HA AS03(A)-adjuvanted H1N1 2009 influenza vaccine was highly immunogenic in both age strata (18-64 and >64 years), inducing long-term persistence of the immune response until at least 6 months after dose 1.

  17. Quantifying nitrogen-fixation in feather moss carpets of boreal forests.

    PubMed

    DeLuca, Thomas H; Zackrisson, Olle; Nilsson, Marie-Charlotte; Sellstedt, Anita

    2002-10-31

    Biological nitrogen (N) fixation is the primary source of N within natural ecosystems, yet the origin of boreal forest N has remained elusive. The boreal forests of Eurasia and North America lack any significant, widespread symbiotic N-fixing plants. With the exception of scattered stands of alder in early primary successional forests, N-fixation in boreal forests is considered to be extremely limited. Nitrogen-fixation in northern European boreal forests has been estimated at only 0.5 kg N ha(-1) yr(-1); however, organic N is accumulated in these ecosystems at a rate of 3 kg N ha(-1) yr(-1) (ref. 8). Our limited understanding of the origin of boreal N is unacceptable given the extent of the boreal forest region, but predictable given our imperfect knowledge of N-fixation. Herein we report on a N-fixing symbiosis between a cyanobacterium (Nostoc sp.) and the ubiquitous feather moss, Pleurozium schreberi (Bird) Mitt. that alone fixes between 1.5 and 2.0 kg N ha(-1) yr(-1) in mid- to late-successional forests of northern Scandinavia and Finland. Previous efforts have probably underestimated N-fixation potential in boreal forests.

  18. Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

    PubMed Central

    Guarnaccia, Teagan; Carolan, Louise A.; Maurer-Stroh, Sebastian; Lee, Raphael T. C.; Job, Emma; Reading, Patrick C.; Petrie, Stephen; McCaw, James M.; McVernon, Jodie; Hurt, Aeron C.; Kelso, Anne; Mosse, Jennifer; Barr, Ian G.; Laurie, Karen L.

    2013-01-01

    Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance

  19. Substitutions in position 222 of haemagglutinin of pandemic influenza A (H1N1) 2009 viruses in Spain.

    PubMed

    Ledesma, Juan; Pozo, Francisco; Pérez Ruiz, Mercedes; Navarro, Jose María; Piñeiro, Luis; Montes, Milagros; Pérez Castro, Sonia; Suárez Fernández, Jonathan; García Costa, Juan; Fernández, Mirian; Galán, Juan Carlos; Cuevas, María Teresa; Casas, Inmaculada; Pérez Breña, Pilar

    2011-05-01

    A change of aspartic acid (D) to glycine (G) at position 222 in the haemagglutinin (HA) protein of pandemic influenza A (H1N1) 2009 viruses was described in Norway on November 2009 with considerable frequency in fatal and severe cases. This change was detected in other countries and was related only with severe disease. Other substitutions to glutamic acid (E) or asparagine (N) at position 222 were detected among pandemic viruses but it is unclear what implications might have in terms of severity. To analyse the appearance of amino acid substitutions at position 222 in the HA protein of circulating viruses in Spain and to determine their relationships with the disease symptoms observed. Pandemic influenza A (H1N1) 2009 viruses detected in respiratory samples of 273 severe and 533 non-severe cases from different Spanish regions were selected for sequencing of a partial segment of HA1 subunit and studied to monitor substitutions at position 222. D222G substitution was only detected in viruses from 14 severe cases (5.12%). D222E was found in viruses from 47 severe (17.21%) and from 52 non-severe cases (9.75%). D222N occurred in viruses from 3 additional severe cases (0.37%). Appearance of D222G and D222E substitution in HA of pandemic influenza A (H1N1) viruses circulating in Spain might be related with severe respiratory disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. The novel kinetics expression of Cadmium (II) removal using green adsorbent horse dung humic acid (Hd-Ha)

    NASA Astrophysics Data System (ADS)

    Basuki, Rahmat; Santosa, Sri Juari; Rusdiarso, Bambang

    2017-03-01

    Humic acid from dry horse dung powder has been prepared and this horse dung humic acid (HD-HA) was then applied as a sorbent to adsorb Cadmium(II) from a solution. Characterization of HD-HA was conducted by detection of its functional group, UV-Vis spectra, ash level, and total acidity. Result of the work showed that HD-HA had similar character compared with peat soil humic acid (PS-HA) and previous researchers. The adsorption study of this work was investigated by batch experiment in pH 5. The thermodynamics parameters in this work were determined by the Langmuir isotherm model for monolayer sorption and Freundlich isotherm model multilayer sorption. Monolayer sorption capacity (b) for HD-HA was 1.329 × 10-3 mol g-1, equilibrium constant (K) was 5.651 (mol/L)-1, and multilayer sorption capacity was 2.646 × 10-2 mol g-1. The kinetics parameters investigated in this work were determined by the novel kinetics expression resulted from the mathematical derivation the availability of binding sites of sorbent. Adsorption rate constant (ka) from this novel expression was 43.178 min-1 (mol/L)-1 and desorption rate constant (kd) was 1.250 × 10-2 min-1. Application of the kinetics model on sorption Cd(II) onto HD-HA showed the nearly all of models gave a good linearity. However, only this proposed kinetics expression has good relation with Langmuir model. The novel kinetics expression proposed in this paper seems to be more realistic and reasonable and close to the experimental real condition because the value of ka/kd (3452 (mol/L)-1) was fairly close with K from Langmuir isotherm model (5651 (mol/L)-1). Comparison of this novel kinetics expression with well-known Lagergren pseudo-first order kinetics and Ho pseudo-second order kinetics was also critically discussed in this paper.

  1. Intensive ground vegetation growth mitigates the carbon loss after forest disturbance.

    PubMed

    Zehetgruber, Bernhard; Kobler, Johannes; Dirnböck, Thomas; Jandl, Robert; Seidl, Rupert; Schindlbacher, Andreas

    2017-01-01

    Slow or failed tree regeneration after forest disturbance is increasingly observed in the central European Alps, potentially amplifying the carbon (C) loss from disturbance. We aimed at quantifying C dynamics of a poorly regenerating disturbance site with a special focus on the role of non-woody ground vegetation. Soil CO 2 efflux, fine root biomass, ground vegetation biomass, tree increment and litter input were assessed in (i) an undisturbed section of a ~ 110 years old Norway spruce stand, (ii) in a disturbed section which was clear-cut six years ago (no tree regeneration), and (iii) in a disturbed section which was clear-cut three years ago (no tree regeneration). Total soil CO 2 efflux was similar across all stand sections (8.5 ± 0.2 to 8.9 ± 0.3 t C ha -1  yr. -1 ). The undisturbed forest served as atmospheric C sink (2.1 t C ha -1  yr. -1 ), whereas both clearings were C sources to the atmosphere. The source strength three years after disturbance (-5.5 t C ha -1  yr. -1 ) was almost twice as high as six years after disturbance (-2.9 t C ha -1  yr. -1 ), with declining heterotrophic soil respiration and the high productivity of dense graminoid ground vegetation mitigating C loss. C loss after disturbance decreases with time and ground vegetation growth. Dense non-woody ground vegetation cover can hamper tree regeneration but simultaneously decrease the ecosystem C loss. The role of ground vegetation should be more explicitly taken into account in forest C budgets assessing disturbance effects.

  2. Soil organic carbon dynamics in Xilingol grassland of northern China induced by the Beijing-Tianjin Sand Source Control Program

    NASA Astrophysics Data System (ADS)

    Zhang, Liangxia; Cao, Wei; Fan, Jiangwen

    2017-06-01

    To mitigate impacts of sandstorms on northern China, the Chinese government launched the Beijing-Tianjin Sand Source Control Program (BTSSCP) in 2000. The associated practices (i.e., cultivation, enclosure, and aerial seeding) were expected to greatly enhance grassland carbon sequestration. However, the BTSSCP-induced soil organic carbon (SOC) dynamics remain elusive at a regional level. Using the Xilingol League in Inner Mongolia for a case study, we examined the impacts from 2000 to 2006 of the BTSSCP on SOC stocks using the IPCC carbon budget inventory method. Results indicated that over all practices SOC storage increased by 1.7%, but there were large differences between practices. SOC increased most rapidly at the rate of 0.3 Mg C•ha-1yr-1 under cultivation, but decreased significantly under aerial seeding with moderate or heavy grazing (0.3 vs.0.6 Mg C•ha-1yr-1). SOC increases varied slightly for grassland types, ranging from 0.10 Mg C•ha-1yr-1 for temperate desert steppe to 0.16 Mg C•ha-1yr-1 for temperate meadow steppe and lowland meadow. The overall economic benefits of the SOC sink were estimated to be 4.0 million CNY. Aerial seeding with no grazing was found to be the most cost-effective practice. Finally, we indicated that at least 55.5 years (shortest for cultivation) were needed for the grasslands to reach their potential carbon stocks. Our findings highlight the importance and effectiveness of BTSSCP in promoting terrestrial carbon sequestration which may help mitigate climate change, and further stress the need for more attention to the effectiveness of specific practices.

  3. Nitrogen critical loads for alpine vegetation and terrestrial ecosystem response: are we there yet?

    PubMed

    Bowman, William D; Gartner, Julia R; Holland, Keri; Wiedermann, Magdalena

    2006-06-01

    Increases in the deposition of anthropogenic nitrogen (N) have been linked to several terrestrial ecological changes, including soil biogeochemistry, plant stress susceptibility, and community diversity. Recognizing the need to identify sensitive indicators of biotic response to N deposition, we empirically estimated the N critical load for changes in alpine plant community composition and compared this with the estimated critical load for soil indicators of ecological change. We also measured the degree to which alpine vegetation may serve as a sink for anthropogenic N and how much plant sequestration is related to changes in species composition. We addressed these research goals by adding 20, 40, or 60 kg N x ha(-1) x yr(-1), along with an ambient control (6 kg N x ha(-1) x yr(-1) total deposition), to a species-rich alpine dry meadow for an eight-year period. Change in plant species composition associated with the treatments occurred within three years of the initiation of the experiment and were significant at all levels of N addition. Using individual species abundance changes and ordination scores, we estimated the N critical loads (total deposition) for (1) change in individual species to be 4 kg N x ha(-1) yr(-1) and (2) for overall community change to be 10 kg N x ha(-1) x yr(-1). In contrast, increases in NO3- leaching, soil solution inorganic NO3-, and net N nitrification occurred at levels above 20 kg N x ha(-1) x yr(-1). Increases in total aboveground biomass were modest and transient, occurring in only one of the three years measured. Vegetative uptake of N increased significantly, primarily as a result of increasing tissue N concentrations and biomass increases in subdominant species. Aboveground vegetative uptake of N accounted for <40% of the N added. The results of this experiment indicate that changes in vegetation composition will precede detectable changes in more traditionally used soil indicators of ecosystem responses to N deposition and

  4. Nitrogen emission and deposition budget in West and Central Africa

    NASA Astrophysics Data System (ADS)

    Galy-Lacaux, C.; Delon, C.

    2014-12-01

    Atmospheric nitrogen depends on land surface exchanges of nitrogen compounds. In Sub Saharan Africa, deposition and emission fluxes of nitrogen compounds are poorly quantified, and are likely to increase in the near future due to land use change and anthropogenic pressure. This work proposes an estimate of atmospheric N compounds budget in West and Central Africa, along an ecosystem transect, from dry savanna to wet savanna and forest, for years 2000-2007. The budget may be considered as a one point in time budget, to be included in long term studies as one of the first reference point for Sub Saharan Africa. Gaseous dry deposition fluxes are estimated by considering N compounds concentrations measured in the frame of the IDAF network (IGAC/DEBITS/AFrica) at the monthly scale and modeling of deposition velocities at the IDAF sites, taking into account the bi directional exchange of ammonia. Particulate dry deposition fluxes are calculated using the same inferential method. Wet deposition fluxes are calculated from measurements of ammonium and nitrate chemical content in precipitations at the IDAF sites combined with the annual rainfall amount. In terms of emission, biogenic NO emissions are simulated at each IDAF site with a surface model coupled to an emission module elaborated from an artificial neural network equation. Ammonia emissions from volatilization are calculated from literature data on livestock quantity in each country and N content in manure. NOx and NH3 emission from biomass burning and domestic fires are estimated from satellite data and emission factors. The total budget shows that emission sources of nitrogen compounds are in equilibrium with deposition fluxes in dry and wet savannas, with respectively 7.40 (±1.90) deposited and 9.01 (±3.44) kgN ha-1 yr-1 emitted in dry savanna, 8.38 (±2.04) kgN ha-1 yr-1 deposited and 9.60 (±0.69) kgN ha-1 yr-1 emitted in wet savanna. In forested ecosystems, the total budget is dominated by wet plus dry

  5. The duration of hyaluronidase and optimal timing of hyaluronic acid (HA) filler reinjection after hyaluronidase injection.

    PubMed

    Kim, H J; Kwon, S B; Whang, K U; Lee, J S; Park, Y L; Lee, S Y

    2018-02-01

    Hyaluronidase injection is a commonly performed treatment for overcorrection or misplacement of hyaluronic acid (HA) filler. Many patients often wants the HA filler reinjection after the use of hyaluronidase, though the optimal timing of reinjection of HA filler still remains unknown. To provide the optimal time interval between hyaluronidase injections and HA filler reinjections. 6 Sprague-Dawley rats were injected with single monophasic HA filler. 1 week after injection, the injected sites were treated with hyaluronidase. Then, HA fillers were reinjected sequentially with differing time intervals from 30 minutes to 14 days. 1 hour after the reinjection of the last HA filler, all injection sites were excised for histologic evaluation. 3 hours after reinjection of HA filler, the appearance of filler material became evident again, retaining its shape and volume. 6 hours after reinjection, the filler materials restored almost its original volume and there were no significant differences from the positive control. Our data suggest that the hyaluronidase loses its effect in dermis and subcutaneous tissue within 3-6 hours after the injection and successful engraftment of reinjected HA filler can be accomplished 6 hours after the injection.

  6. Mapping critical loads of nitrogen deposition for aquatic ecosystems in the Rocky Mountains, USA

    USGS Publications Warehouse

    Nanus, Leora; Clow, David W.; Saros, Jasmine E.; Stephens, Verlin C.; Campbell, Donald H.

    2012-01-01

    Spatially explicit estimates of critical loads of nitrogen (N) deposition (CLNdep) for nutrient enrichment in aquatic ecosystems were developed for the Rocky Mountains, USA, using a geostatistical approach. The lowest CLNdep estimates (-1 yr-1) occurred in high-elevation basins with steep slopes, sparse vegetation, and abundance of exposed bedrock and talus. These areas often correspond with areas of high N deposition (>3 kg N ha-1 yr-1), resulting in CLNdep exceedances ≥1.5 ± 1 kg N ha-1 yr-1. CLNdep and CLNdep exceedances exhibit substantial spatial variability related to basin characteristics and are highly sensitive to the NO3- threshold at which ecological effects are thought to occur. Based on an NO3- threshold of 0.5 μmol L-1, N deposition exceeds CLNdep in 21 ± 8% of the study area; thus, broad areas of the Rocky Mountains may be impacted by excess N deposition, with greatest impacts at high elevations.

  7. Glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the H1N1 influenza viruses

    PubMed Central

    Medina, Rafael A.; Stertz, Silke; Manicassamy, Balaji; Zimmermann, Petra; Sun, Xiangjie; Albrecht, Randy A.; Uusi-Kerttula, Hanni; Zagordi, Osvaldo; Belshe, Robert B.; Frey, Sharon E.; Eggink, Dirk; Tumpey, Terrence M.; García-Sastre, Adolfo

    2014-01-01

    The global spread of the 2009 pandemic H1N1 (pH1N1) virus in humans increases the likelihood that this influenza virus strain could undergo antigenic drift in the coming years. Previous seasonal H1N1 and H3N2 influenza strains acquired additional glycosylations in the globular head of their hemagglutinin (HA) proteins as they evolved over time; these are believed to shield antigenically relevant regions. We used influenza A/Netherlands/602/2009 recombinant (rpH1N1) viruses to which we added additional HA glycosylation sites reflecting their temporal appearance in previous seasonal H1N1 viruses. Additional glycosylations resulted in substantial attenuation in mice and ferrets, while deleting HA glycosylation sites from a pre-pandemic 1991 seasonal H1N1 influenza virus resulted in increased pathogenicity in mice. Sera from mice infected with wild type (WT) rpH1N1 virus showed a considerable loss of HA inhibitory (HI) activity against rpH1N1 viruses glycosylated at sites 144 or 144-172, indicating that the polyclonal antibody response elicited by WT rpH1N1 HA seems to be directed against an immunodominant region, likely site Sa, shielded by glycosylation at 144. Sera from humans vaccinated with the pH1N1 inactivated vaccine also showed reduced activity against the 144 and 144-172 mutant viruses. Remarkably, the HI activity of sera from virus-infected mice demonstrated that glycosylation at position 144 resulted in the induction of a broader polyclonal response able to cross-neutralize all WT and glycosylation mutant pH1N1 viruses. Mice infected with a recent seasonal virus in which glycosylation sites 71, 142 and 177 were removed, elicited antibodies that protected against challenge with the antigenically distant pH1N1 virus. Thus, acquisition of glycosylation sites in the HA of H1N1 human influenza viruses not only affects their pathogenicity and ability to escape from polyclonal antibodies elicited by previous influenza virus strains, but also their ability to

  8. Conformational divergence in the HA-33/HA-17 trimer of serotype C and D botulinum toxin complex.

    PubMed

    Sagane, Yoshimasa; Hayashi, Shintaro; Akiyama, Tomonori; Matsumoto, Takashi; Hasegawa, Kimiko; Yamano, Akihito; Suzuki, Tomonori; Niwa, Koichi; Watanabe, Toshihiro; Yajima, Shunsuke

    2016-08-05

    Clostridium botulinum produces a large toxin complex (L-TC) comprising botulinum neurotoxin associated with auxiliary nontoxic proteins. A complex of 33- and 17-kDa hemagglutinins (an HA-33/HA-17 trimer) enhances L-TC transport across the intestinal epithelial cell layer via binding HA-33 to a sugar on the cell surface. At least two subtypes of serotype C/D HA-33 exhibit differing preferences for the sugars sialic acid and galactose. Here, we compared the three-dimensional structures of the galactose-binding HA-33 and HA-33/HA-17 trimers produced by the C-Yoichi strain. Comparisons of serotype C/D HA-33 sequences reveal a variable region with relatively low sequence similarity across the C. botulinum strains; the variability of this region may influence the manner of sugar-recognition by HA-33. Crystal structures of sialic acid- and galactose-binding HA-33 are broadly similar in appearance. However, small-angle X-ray scattering revealed distinct solution structures for HA-33/HA-17 trimers. A structural change in the C-terminal variable region of HA-33 might cause a dramatic shift in the conformation and sugar-recognition mode of HA-33/HA-17 trimer. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain

    PubMed Central

    Caires, Rebeca; Luis, Enoch; Taberner, Francisco J.; Fernandez-Ballester, Gregorio; Ferrer-Montiel, Antonio; Balazs, Endre A.; Gomis, Ana; Belmonte, Carlos; de la Peña, Elvira

    2015-01-01

    Hyaluronan (HA) is present in the extracellular matrix of all body tissues, including synovial fluid in joints, in which it behaves as a filter that buffers transmission of mechanical forces to nociceptor nerve endings thereby reducing pain. Using recombinant systems, mouse-cultured dorsal root ganglia (DRG) neurons and in vivo experiments, we found that HA also modulates polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channels. HA diminishes heat, pH and capsaicin (CAP) responses, thus reducing the opening probability of the channel by stabilizing its closed state. Accordingly, in DRG neurons, HA decreases TRPV1-mediated impulse firing and channel sensitization by bradykinin. Moreover, subcutaneous HA injection in mice reduces heat and capsaicin nocifensive responses, whereas the intra-articular injection of HA in rats decreases capsaicin joint nociceptor fibres discharge. Collectively, these results indicate that extracellular HA reduces the excitability of the ubiquitous TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor endings underlying pain. PMID:26311398

  10. Magneto-optical and catalytic properties of Fe3O4@HA@Ag magnetic nanocomposite

    NASA Astrophysics Data System (ADS)

    Amir, Md.; Güner, S.; Yıldız, A.; Baykal, A.

    2017-01-01

    Fe3O4@HA@Ag magnetic nanocomposites (MNCs) were successfully synthesized by the simple reflux method for the removal of azo dyes from the industrial aqueous media. Fe3O4@HA@AgMNCs exhibited high catalytic activity to reduce MB within 20 min from the waste water. The obtained materials were characterized by the means of different techniques. Powder X-ray diffraction (XRD) analysis confirmed the single-phase of Fe3O4 spinel structure. SEM and TEM analysis indicated that Fe3O4@HA@AgMNCs were nanoparticles like structure with small agglomeration. TG result showed that the products contained 9% of HA. The characteristic peaks of HA at 1601 cm-1 and 1703 cm-1 was observed by the means of FT-IR spectra of Fe3O4@HA@AgMNCs. The hysteresis (σ-H) curves revealed Fe3O4@HA@Ag MNCs exhibit a typical superparamagnetic characteristic with a saturation magnetization of 59.11 emu/g and measured magnetic moment is 2.45 μB. The average magnetic particle dimension (Dmag) is 13.25 nm. In accordance, the average crystallite and particle dimensions were obtained as 11.50 nm and 13.10 nm from XRD and TEM measurements, respectively. Magnetocrystalline anisotropy was offered as uniaxial and calculated effective anisotropy constant (Keff) is 2.96×105 Erg/g. The blocking temperature was estimated as 522 K. The size-dependent saturation magnetization suggests the existence of a magnetically dead layer as 0.793 nm for Fe3O4@HA@Ag MNCs. The UV-vis diffuse reflectance spectroscopy (DRS) and Kubelka-Munk theory were applied to determine the optical properties of powder samples. The direct optical energy band gap (Eg) values were estimated from Tauc plots between 1.62 eV and 2.12 eV.

  11. Sedimentary Evidence for a Rapid Sea Level Rise at 7,600 cal yr BP from North-Central Cuba

    NASA Astrophysics Data System (ADS)

    Peros, M. C.; Agosta G'meiner, A. M.; Collins, S.

    2016-12-01

    A lack of high-resolution relative sea level (RSL) proxy data has meant that the pattern of early Holocene RSL change in the Caribbean is poorly understood. A RSL curve published by Toscano and Macintyre (2003) using inter-tidal mangrove peats and submerged corals suggests RSL underwent a relatively fast and `smooth' curvilinear increase during the Holocene. However, others, such as Blanchon and Shaw (1995), suggest that RSL increased rapidly at around 7600 cal yr BP, in response to the final stages of the melting of the Laurentide Ice Sheet (melt water pulse 1C or catastrophic rise event 3). We investigated this question using multi-proxy data from a flooded sinkhole (Cenote Jennifer) on the north coast of central Cuba. Cenote Jennifer is located 7 m above mean sea level and 2 km from the Bahamas Channel and appears to have a high degree of connectivity with the ocean through a network of underground caverns. The water depth is 13 m and the bottommost 5 m is anoxic. A sediment core collected from Cenote Jennifer was studied using loss-on-ignition, pollen analysis, high-resolution XRF core-scanning, and grain size analysis. An age-depth model was generated for the core by AMS dating. The results show that the bottommost stratigraphic unit ( 9000 to 7600 cal yr BP) is a fine-grained carbonate-rich mud (i.e., marl). This unit abruptly transitions into finely laminated organic-rich sediment from 7600 cal yr BP to the present. The pollen analysis shows that the sinkhole supported a cattail (Typha) community until 7600 cal yr BP, indicating low water levels ( 1 m). At 7600 cal yr BP, the cattail community disappeared and the vegetation of the surrounding bedrock became dominated by a thorny coastal scrubland. In addition, a 3 cm thick fining-upward siliciclastic unit is present immediately above the marl-organic contact, suggesting: 1) a marine sediment source given the limestone-dominated nature of the region, and 2) the presence of a short-duration, high

  12. Comparison of bio-mineralization behavior of Ti-6Al-4V-1Nb and Zr-1Nb nano-tubes formed by anodization

    NASA Astrophysics Data System (ADS)

    Choi, Yong; Hong, Sun I.

    2014-12-01

    Nano-tubes of titanium and zirconium alloys like Ti-6Al-4V-1Nb and Zr-1Nb were prepared by anodization followed by coating with hydroxylapatite (HA) and their bio-mineralization behaviors were compared to develop a bio-compatible material for implants in orthopedics, dentistry and cardiology. Ti-6Al-4V-1Nb weight gain in a simulated body solution increased gradually. The bigger tube diameter was, the heavier HA was deposited. Surface roughness of both alloys increased highly with the increasing diameter of nano-tube. Their surface roughness decreased by HA deposition due to the removal of the empty space of the nano-tubes. Zr-1Nb alloy had faster growth of nano-tubes layers more than Ti-6Al-4V-1Nb alloy.

  13. Homosubtypic and heterosubtypic antibodies against highly pathogenic avian influenza H5N1 recombinant proteins in H5N1 survivors and non-H5N1 subjects.

    PubMed

    Noisumdaeng, Pirom; Pooruk, Phisanu; Prasertsopon, Jarunee; Assanasen, Susan; Kitphati, Rungrueng; Auewarakul, Prasert; Puthavathana, Pilaipan

    2014-04-01

    Six recombinant vaccinia viruses containing HA, NA, NP, M or NS gene insert derived from a highly pathogenic avian influenza H5N1 virus, and the recombinant vaccinia virus harboring plasmid backbone as the virus control were constructed. The recombinant proteins were characterized for their expression and subcellular locations in TK(-) cells. Antibodies to the five recombinant proteins were detected in all 13 sequential serum samples collected from four H5N1 survivors during four years of follow-up; and those directed to rVac-H5 HA and rVac-NA proteins were found in higher titers than those directed to the internal proteins as revealed by indirect immunofluorescence assay. Although all 28 non-H5N1 subjects had no neutralizing antibodies against H5N1 virus, they did have cross-reactive antibodies to those five recombinant proteins. A significant increase in cross-reactive antibody titer to rVac-H5 HA and rVac-NA was found in paired blood samples from patients infected with the 2009 pandemic virus. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The influence of silanisation on the mechanical and degradation behaviour of PLGA/HA composites.

    PubMed

    Naik, Ashutosh; Best, Serena M; Cameron, Ruth E

    2015-03-01

    This study investigates the influence of silanisation on the mechanical and degradation behaviour of PLGA/HA composites. Three different silanes (mercaptopropyl trimethoxy silane (MPTMS), aminopropyl trimethoxy silane (APTMS) and aminopropyltriethoxy silane (APTES)) were applied to HA substrates in order to study the effect of head group (which binds to the polymer) and tail group (which binds to the surface hydroxyl groups in HA). A composite of hydroxyapatite (HA) and poly(d,l lactide-co-glycolide (50:50)) (PLGA) was investigated. The influence of concentration, the reaction time, drying temperature and substrate surface on silanisation was examined. TGA was used to detect the degree of silanisation. HA with MPTMS (1wt.% MPTMS with reaction time of 1h) was used as filler in PLGA-30wt.% HA composites for an in-vitro degradation study carried out in PBS. In addition, the mechanical properties of the composites were studied. Silanisation affects the properties of the composite by improving the bonding at the interface and hence it was found to influence the plastic mechanical properties rather than the elastic mechanical properties or the degradation profile of the composite. Copyright © 2014. Published by Elsevier B.V.

  15. Nonuniform Expansion of the Youngest Galactic Supernova Remnant G1.9+0.3

    NASA Technical Reports Server (NTRS)

    Borkowski, Kazimierz J.; Reynolds, Stephen P.; Green, David A.; Hwang, Una; Petre, Robert; Krishnamurthy, Kalyani; Willett, Rebecca

    2014-01-01

    We report measurements of the X-ray expansion of the youngest Galactic supernova remnant, G1.9+0.3, using Chandra observations in 2007, 2009, and 2011. The measured rates strongly deviate from uniform expansion, decreasing radially by about 60 along the X-ray bright SE-NW axis from 0.84 plus or minus 0.06% yr(exp -1) to 0.52% plus or minus 0.03 yr(exp -1). This corresponds to undecelerated ages of 120-190 yr, confirming the young age of G1.9+0.3 and implying a significant deceleration of the blast wave. The synchrotron-dominated X-ray emission brightens at a rate of 1.9% plus or minus 0.4% yr(exp -1). We identify bright outer and inner rims with the blast wave and reverse shock, respectively. Sharp density gradients in either the ejecta or ambient medium are required to produce the sudden deceleration of the reverse shock or the blast wave implied by the large spread in expansion ages. The blast wave could have been decelerated recently by an encounter with a modest density discontinuity in the ambient medium, such as may be found at a wind termination shock, requiring strong mass loss in the progenitor.

  16. Long term carbon fluxes in south eastern U.S. pine ecosystems.

    NASA Astrophysics Data System (ADS)

    Bracho, R. G.; Martin, T.; Gonzalez-Benecke, C. A.; Sharp, J.

    2015-12-01

    Forests in the southeastern U.S. are a critical component of the national carbon balance storing a third of the total forest carbon (C) in conterminous USA. South eastern forests occupy 60% of the land area, with a large fraction dominated by the genus Pinus distributed in almost equal proportions of naturally-regenerated and planted stands. These stands often differ in structure (e.g., stem density, leaf area index (LAI)) and in the intensity with which they are managed (e.g. naturally-regenerated, older pine stands are often managed less intensively, with prescribed fire). We measured C fluxes using the eddy covariance approach (net ecosystem production, -NEP) in planted (Pinus elliottii var. elliottii) and naturally-regenerated mixed stand of long leaf (Pinus palustris Mill) and slash pine (Pinus elliottii var. elliottii) accompanied by biometric estimations of C balance. Measurements spanned more than a decade and included interannual climatic variability ranging from severe droughts (e.g. Palmer Drought severity index (PDSI) averaged -2.7 from January 2000 to May 2002, and -3.3 from June 2006 to April 2008), to years with tropical storms. Annual NEP for the older, naturally-regenerated stand fluctuated from -1.60 to -5.38 Mg C ha-1 yr-1 with an average of -2.73 ± 1.17 Mg C ha-1 yr-1 while in plantations after canopy closure NEP fluctuated from -4.0 to -8.2 Mg C ha-1 yr-1 with an average of -6.17 ± 1.34 Mg C ha-1 yr-1. Annual NEP in naturally-regenerated pine was mainly driven by a combination of water availability and understory burning while in plantations it was driven by water availability after canopy closure. Woody and above ground net primary productivity (NPP) followed gross ecosystem carbon exchange (GEE) in both ecosystems. Naturally-regenerated and planted pine are a strong carbon sink under the current management and environmental fluctuations accumulating 28 and 130 Mg C ha-1 in a decade, respectively, and are among the most productive forests in

  17. Maintaining yields and reducing nitrogen loss in rice-wheat rotation system in Taihu Lake region with proper fertilizer management

    NASA Astrophysics Data System (ADS)

    Xue, Lihong; Yu, Yingliang; Yang, Linzhang

    2014-11-01

    In the Tailake region of China, heavy nitrogen (N) loss of rice-wheat rotation systems, due to high fertilizer-N input with low N use efficiency (NUE), was widely reported. To alleviate the detrimental impacts caused by N loss, it is necessary to improve the fertilizer management practices. Therefore, a 3 yr field experiments with different N managements including organic combined chemical N treatment (OCN, 390 kg N ha-1 yr-1, 20% organic fertilizer), control-released urea treatment (CRU, 390 kg N ha-1 yr-1, 70% resin-coated urea), reduced chemical N treatment (RCN, 390 kg N ha-1 yr-1, all common chemical fertilizer), and site-specific N management (SSNM, 333 kg N ha-1 yr-1, all common chemical fertilizer) were conducted in the Taihu Lake region with the ‘farmer’s N’ treatment (FN, 510 kg N ha-1 yr-1, all common chemical fertilizer) as a control. Grain yield, plant N uptake (PNU), NUE, and N losses via runoff, leaching, and ammonia volatilization were assessed. In the rice season, the FN treatment had the highest N loss and lowest NUE, which can be attributed to an excessive rate of N application. Treatments of OCN and RCN with a 22% reduced N rate from FN had no significant effect on PNU nor the yield of rice in the 3 yr; however, the NUE was improved and N loss was reduced 20-32%. OCN treatment achieved the highest yield, while SSNM has the lowest N loss and highest NUE due to the lowest N rate. In wheat season, N loss decreased about 28-48% with the continuous reduction of N input, but the yield also declined, with the exception of OCN treatment. N loss through runoff, leaching and ammonia volatilization was positively correlated with the N input rate. When compared with the pure chemical fertilizer treatment of RCN under the same N input, OCN treatment has better NUE, better yield, and lower N loss. 70% of the urea replaced with resin-coated urea had no significant effect on yield and NUE improvement, but decreased the ammonia volatilization loss. Soil

  18. Association between endothelial nitric oxide synthase (ENOS) G894T polymorphism and high altitude (HA) adaptation: a meta-analysis.

    PubMed

    Lu, Hong-xiang; Wang, Yu-xiao; Chen, Yu; Luo, Yong-jun

    2015-11-01

    Highland natives adapt well to the hypoxic environment at high altitude (HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial ni- tric oxide synthase (ENOS) G894T polymorphism contributed to the physiology and pathophysiology of hu- mans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894T polymorphism and HA adaptation through analyzing the published data. We searched all relevant literature about the ENOS G894T polymorphism and HA adaptation in PubMed, Med- line, and Embase before Step 2015. A random-effects model was applied (Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups (OR = 1.85; 95% Cl, 1.47-2.33; P < 0.0001). In addition, the GG genotype was significantly associated with HA adaptation (OR = 1.99; 95% Cl, 1.54-2.57; P < 0.0001). Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.

  19. Mapping soil erosion hotspots and assessing the potential impacts of land management practices in the highlands of Ethiopia

    NASA Astrophysics Data System (ADS)

    Tamene, Lulseged; Adimassu, Zenebe; Ellison, James; Yaekob, Tesfaye; Woldearegay, Kifle; Mekonnen, Kindu; Thorne, Peter; Le, Quang Bao

    2017-09-01

    An enormous effort is underway in Ethiopia to address soil erosion and restore overall land productivity. Modelling and participatory approaches can be used to delineate erosion hotspots, plan site- and context-specific interventions and assess their impacts. In this study, we employed a modelling interface developed based on the Revised Universal Soil Loss Equation adjusted by the sediment delivery ratio to map the spatial distribution of net soil loss and identify priority areas of intervention. Using the modelling interface, we also simulated the potential impacts of different soil and water conservation measures in reducing net soil loss. Model predictions showed that net soil loss in the study area ranges between 0.4 and 88 t ha- 1 yr- 1 with an average of 12 t ha- 1 yr- 1. The dominant soil erosion hotspots were associated with steep slopes, gullies, communal grazing and cultivated areas. The average soil loss observed in this study is higher than the tolerable soil loss rate estimated for the highland of Ethiopia. The scenario analysis results showed that targeting hotspot areas where soil loss exceeds 10 t ha- 1 yr- 1 could reduce net soil loss to the tolerable limit (< 2 t ha- 1 yr- 1). The spatial distribution of soil loss and the sediment yield reduction potential of different options provided essential information to guide prioritization and targeting. In addition, the results can help promoting awareness within the local community of the severity of the soil erosion problem and the potential of management interventions. Future work should include cost-benefit and tradeoff analyses of the various management options for achieving a given level of erosion reduction.

  20. Nonlinear and threshold-dominated runoff generation controls DOC export in a small peat catchment

    NASA Astrophysics Data System (ADS)

    Birkel, C.; Broder, T.; Biester, H.

    2017-03-01

    We used a relatively simple two-layer, coupled hydrology-biogeochemistry model to simultaneously simulate streamflow and stream dissolved organic carbon (DOC) concentrations in a small lead and arsenic contaminated upland peat catchment in northwestern Germany. The model procedure was informed by an initial data mining analysis, in combination with regression relationships of discharge, DOC, and element export. We assessed the internal model DOC processing based on stream DOC hysteresis patterns and 3-hourly time step groundwater level and soil DOC data for two consecutive summer periods in 2013 and 2014. The parsimonious model (i.e., few calibrated parameters) showed the importance of nonlinear and rapid near-surface runoff generation mechanisms that caused around 60% of simulated DOC load. The total load was high even though these pathways were only activated during storm events on average 30% of the monitoring time—as also shown by the experimental data. Overall, the drier period 2013 resulted in increased nonlinearity but exported less DOC (115 kg C ha-1 yr-1 ± 11 kg C ha-1 yr-1) compared to the equivalent but wetter period in 2014 (189 kg C ha-1 yr-1 ± 38 kg C ha-1 yr-1). The exceedance of a critical water table threshold (-10 cm) triggered a rapid near-surface runoff response with associated higher DOC transport connecting all available DOC pools and subsequent dilution. We conclude that the combination of detailed experimental work with relatively simple, coupled hydrology-biogeochemistry models not only allowed the model to be internally constrained but also provided important insight into how DOC and tightly coupled pollutants or trace elements are mobilized.

  1. Prediction of biological functions on glycosylation site migrations in human influenza H1N1 viruses.

    PubMed

    Sun, Shisheng; Wang, Qinzhe; Zhao, Fei; Chen, Wentian; Li, Zheng

    2012-01-01

    Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data.

  2. Chimeric Peptide Tat-HA-NR2B9c Improves Regenerative Repair after Transient Global Ischemia.

    PubMed

    Zhou, Hai-Hui; Zhang, Li; Zhang, Hai-Xia; Zhang, Jin-Ping; Ge, Wei-Hong

    2017-01-01

    Transient global ischemia (TGI) is a major public health problem, and it heightens the need of effective treatments. The present study was undertaken to investigate whether recombinant polypeptide Tat-HA-NR2B9c improves spatial learning and memory deficits in rats after TGI. Rats were subjected to 20-min ischemia induced by four-vessel occlusion (4-VO) method and daily injected with Tat-HA-NR2B9c (1.12 mg/kg) for 1 week. Tat-HA-NR2B9c increased CREB activity, upregulated B-cell lymphoma-2 (Bcl-2) expression after treated for 24 h. There was a significant increase in dendrite spine density in hippocampal CA1 region and BrdU-positive cells and BrdU/NeuN-positive cells in the dentate gyrus after Tat-HA-NR2B9c treatment, compared with ischemia group at postischemic day 28. Inhibition of the CREB activation by recombinant lentivirus, LV-CREB133-GFP, abolished the upregulation effects of Tat-HA-NR2B9c on Bcl-2 expression. Moreover, Tat-HA-NR2B9c improved the impaired spatial learning and memory ability in Morris water maze. These results suggest that Tat-HA-NR2B9c substantially ameliorated the TGI-induced loss of dendrite spine in hippocampal CA1, increased neurogenesis in dentate gyrus, and significantly improved cognitive abilities by the CREB pathway in rats after transient global cerebral ischemia. It may be served as a treatment for TGI.

  3. Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA.

    PubMed

    Lam, Kwok-Ho; Sikorra, Stefan; Weisemann, Jasmin; Maatsch, Hannah; Perry, Kay; Rummel, Andreas; Binz, Thomas; Jin, Rongsheng

    2018-04-23

    The extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a ∼2.09 Å resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites. When compared to BoNT/F5 that cleaves VAMP-2 at the same site as BoNT/HA, LC/HA displays higher affinity for VAMP-2, which could be caused by their different surface charge properties surrounding a VAMP-2 exosite-binding cleft. Furthermore, systematic mutagenesis studies on VAMP-2 and structural modeling demonstrate that residues R47 to K59 spanning the cleavage site in VAMP-2 may adopt a novel extended conformation when interacting with LC/HA and LC/F5. Taken together, our structure provides new insights into substrate-recognition of BoNT/HA and paves the way for rational design of small molecule or peptide inhibitors against LC/HA.

  4. Atmospheric Nitrogen Deposition at Two Sites in an Arid Environment of Central Asia.

    PubMed

    Li, Kaihui; Liu, Xuejun; Song, Wei; Chang, Yunhua; Hu, Yukun; Tian, Changyan

    2013-01-01

    Arid areas play a significant role in the global nitrogen cycle. Dry and wet deposition of inorganic nitrogen (N) species were monitored at one urban (SDS) and one suburban (TFS) site at Urumqi in a semi-arid region of central Asia. Atmospheric concentrations of NH3, NO2, HNO3, particulate ammonium and nitrate (pNH4 (+) and pNO3 (-)) concentrations and NH4-N and NO3-N concentrations in precipitation showed large monthly variations and averaged 7.1, 26.6, 2.4, 6.6, 2.7 µg N m(-3) and 1.3, 1.0 mg N L(-1) at both SDS and TFS. Nitrogen dry deposition fluxes were 40.7 and 36.0 kg N ha(-1) yr(-1) while wet deposition of N fluxes were 6.0 and 8.8 kg N ha(-1) yr(-1) at SDS and TFS, respectively. Total N deposition averaged 45.8 kg N ha(-1) yr(-1)at both sites. Our results indicate that N dry deposition has been a major part of total N deposition (83.8% on average) in an arid region of central Asia. Such high N deposition implies heavy environmental pollution and an important nutrient resource in arid regions.

  5. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season

    PubMed Central

    Linderman, Susanne L.; Chambers, Benjamin S.; Zost, Seth J.; Parkhouse, Kaela; Li, Yang; Herrmann, Christin; Ellebedy, Ali H.; Carter, Donald M.; Andrews, Sarah F.; Zheng, Nai-Ying; Huang, Min; Huang, Yunping; Strauss, Donna; Shaz, Beth H.; Hodinka, Richard L.; Reyes-Terán, Gustavo; Ross, Ted M.; Wilson, Patrick C.; Ahmed, Rafi; Bloom, Jesse D.; Hensley, Scott E.

    2014-01-01

    Influenza viruses typically cause the most severe disease in children and elderly individuals. However, H1N1 viruses disproportionately affected middle-aged adults during the 2013–2014 influenza season. Although H1N1 viruses recently acquired several mutations in the hemagglutinin (HA) glycoprotein, classic serological tests used by surveillance laboratories indicate that these mutations do not change antigenic properties of the virus. Here, we show that one of these mutations is located in a region of HA targeted by antibodies elicited in many middle-aged adults. We find that over 42% of individuals born between 1965 and 1979 possess antibodies that recognize this region of HA. Our findings offer a possible antigenic explanation of why middle-aged adults were highly susceptible to H1N1 viruses during the 2013–2014 influenza season. Our data further suggest that a drifted H1N1 strain should be included in future influenza vaccines to potentially reduce morbidity and mortality in this age group. PMID:25331901

  6. Effects of Land-Use Conversion from Double Rice Cropping to Vegetables on Methane and Nitrous Oxide Fluxes in Southern China.

    PubMed

    Yuan, Ye; Dai, Xiaoqin; Wang, Huimin; Xu, Ming; Fu, Xiaoli; Yang, Fengting

    2016-01-01

    Compared with CO2, methane (CH4) and nitrous oxide (N2O) are potent greenhouse gases in terms of their global warming potentials. Previous studies have indicated that land-use conversion has a significant impact on greenhouse gas emissions. However, little is known regarding the impact of converting rice (Oryza sativa L.) to vegetable fields, an increasing trend in land-use change in southern China, on CH4 and N2O fluxes. The effects of converting double rice cropping to vegetables on CH4 and N2O fluxes were examined using a static chamber method in southern China from July 2012 to July 2013. The results indicate that CH4 fluxes could reach 31.6 mg C m-2 h-1 under rice before land conversion. The cumulative CH4 emissions for fertilized and unfertilized rice were 348.9 and 321.0 kg C ha-1 yr-1, respectively. After the land conversion, the cumulative CH4 emissions were -0.4 and 1.4 kg C ha-1 yr-1 for the fertilized and unfertilized vegetable fields, respectively. Similarly, the cumulative N2O fluxes under rice were 1.27 and 0.56 kg N ha-1 yr-1 for the fertilized and unfertilized treatments before the land conversion and 19.2 and 8.5 kg N ha-1 yr-1, respectively, after the land conversion. By combining the global warming potentials (GWPs) of both gases, the overall land-use conversion effect was minor (P = 0.36) with fertilization, but the conversion reduced GWP by 63% when rice and vegetables were not fertilized. Increase in CH4 emissions increased GWP under rice compared with vegetables with non-fertilization, but increased N2O emissions compensated for similar GWPs with fertilization under rice and vegetables.

  7. Pediatric diabetes consortium type 1 diabetes new onset (NeOn) study: Factors associated with HbA1c levels one year after diagnosis

    USDA-ARS?s Scientific Manuscript database

    To identify determinants of hemoglobin A1c (HbA1c) levels 1 yr after the diagnosis of type 1 diabetes (T1D) in participants in the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) Study. Diabetes-specific as well as socioeconomic factors during the first year following diagnosis were analyze...

  8. Change in self-reported oral health in relation to use of dental services over 2 yr.

    PubMed

    Brennan, David S; Spencer, A J; Roberts-Thomson, Kaye F

    2012-10-01

    To investigate change in oral health in relation to use of dental services, a random sample of 45- to 54-yr-old subjects from Adelaide, South Australia, was surveyed in 2004-2005 (n = 986, response rate = 44.4%). Service use and a global oral-health transition (GOHT) statement were collected over 2 yr. Worsening in oral health was reported from the GOHT statement by 25% of persons, while improvement was reported by 30%. Prevalence ratios (PRs, 95% CI), adjusted for sex, education, health card status, and toothbrushing, showed that worsening oral health was inversely associated with dental visiting (PR = 0.5, 0.4-0.7) and with scaling and cleaning services (PR = 0.6, 0.4-0.9), whereas extractions (PR = 2.3, 1.6-3.4) and dentures (PR = 2.2, 1.3-3.7) were associated with a higher prevalence of worsening. Scaling and cleaning services were associated with improvement in oral health (PR = 1.5, 1.01-2.3), while endodontic services were inversely associated with improvement (PR = 0.3, 0.1-0.9). Worsening in oral health was associated with extractions and dentures and was inversely associated with visiting and preventive care. Improvement in oral health was associated with preventive care and was inversely associated with endodontic treatment. © 2012 Eur J Oral Sci.

  9. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    PubMed

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  10. Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

    PubMed

    Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

    2016-07-01

    Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

  11. Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome

    PubMed Central

    Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

    2016-01-01

    Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option. PMID:28435559

  12. Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine

    USDA-ARS?s Scientific Manuscript database

    In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared...

  13. Limits on the Majorana Neutrino Mass in the 0.1 eV Range

    NASA Astrophysics Data System (ADS)

    Baudis, L.; Dietz, A.; Heusser, G.; Klapdor-Kleingrothaus, H. V.; Krivosheina, I. V.; Kolb, St.; Majorovits, B.; Melnikov, V. F.; Päs, H.; Schwamm, F.; Strecker, H.; Alexeev, V.; Balysh, A.; Bakalyarov, A.; Belyaev, S. T.; Lebedev, V. I.; Zhukov, S.

    1999-07-01

    The Heidelberg-Moscow experiment gives the most stringent limit on the Majorana neutrino mass. After 24 kg yr of data with pulse shape measurements, we set a lower limit on the half-life of the 0νββ decay in 76Ge of T0ν1/2>=5.7×1025 yr at 90% C.L. (after PDG98 [C. Caso et al., Eur. Phys. J. C3, 1 (1998]), the sensitivity of the experiment being T0ν1/2>=1.6×1025 yr at 90% C.L. We thus exclude an effective Majorana neutrino mass greater than 0.2 eV (0.39 eV sensitivity), using the matrix elements of A. Staudt, K. Muto, and H. V. Klapdor-Kleingrothaus, Europhys. Lett. 13, 31 (1990). This limit sets strong constraints on degenerate neutrino mass models.

  14. Sustainability appraisal of shifting cultivation in the Chittagong Hill Tracts of Bangladesh.

    PubMed

    Borggaard, Ole K; Gafur, Abdul; Petersen, Leif

    2003-03-01

    An integrated socioeconomic and erosion study on the sustainability of traditional shifting cultivation (Jhum) carried out in 1998 and 1999 in the Chittagong Hill Tracts (CHT) of Bangladesh showed the system to be nonsustainable under the current conditions with fallow periods of only 3-5 years and lack of land rights. An estimated input (mainly labor) of USD 380 ha(-1) yr(-1) results in only a total output of USD 360 ha(-1) yr(-1) and Jhum cultivated areas suffer severe loss of soil and valuable plant nutrients along with runoff during the rainy season. To compensate these losses by commercial fertilizers will cost nearly USD 2 million yr(-1) for CHT. To ensure long-term productivity of the soils, Jhum should therefore be adjusted to a tolerable level and farmers should be given rights and title to the land to motivate them to switch to improved, settled farming systems.

  15. Is the permeability of naturally fractured rocks scale dependent?

    NASA Astrophysics Data System (ADS)

    Azizmohammadi, Siroos; Matthäi, Stephan K.

    2017-09-01

    The equivalent permeability, keq of stratified fractured porous rocks and its anisotropy is important for hydrocarbon reservoir engineering, groundwater hydrology, and subsurface contaminant transport. However, it is difficult to constrain this tensor property as it is strongly influenced by infrequent large fractures. Boreholes miss them and their directional sampling bias affects the collected geostatistical data. Samples taken at any scale smaller than that of interest truncate distributions and this bias leads to an incorrect characterization and property upscaling. To better understand this sampling problem, we have investigated a collection of outcrop-data-based Discrete Fracture and Matrix (DFM) models with mechanically constrained fracture aperture distributions, trying to establish a useful Representative Elementary Volume (REV). Finite-element analysis and flow-based upscaling have been used to determine keq eigenvalues and anisotropy. While our results indicate a convergence toward a scale-invariant keq REV with increasing sample size, keq magnitude can have multi-modal distributions. REV size relates to the length of dilated fracture segments as opposed to overall fracture length. Tensor orientation and degree of anisotropy also converge with sample size. However, the REV for keq anisotropy is larger than that for keq magnitude. Across scales, tensor orientation varies spatially, reflecting inhomogeneity of the fracture patterns. Inhomogeneity is particularly pronounced where the ambient stress selectively activates late- as opposed to early (through-going) fractures. While we cannot detect any increase of keq with sample size as postulated in some earlier studies, our results highlight a strong keq anisotropy that influences scale dependence.

  16. A 26,600 yr record of climate and vegetation from Rice Lake in the Eel River drainage of the northern California Coast Range

    NASA Astrophysics Data System (ADS)

    Heusser, L. E.

    2014-12-01

    Rice Lake, (40'41" N; 123'30" W, 1109 m elev.) lies in the transition zone of the precipitation dipole in the western United States, which is reflected by the present vegetation - a mosaic of mesic northern mixed hardwood-evergreen forests (Quercus spp., Pinus spp., Calocedrus/Juniperus) and more arid southern oak foothill woodlands (Quercus spp.) that borders the westernmost edge of coastal redwoods (Sequoia sempervirens) forest. The site, which lies on the active Lake Mountain fault zone, is now a large (~15 ha) sagpond that dries in summer. Between ~26,600 yr - ~15,000 yr, a permanent lake with aquatic vegetation (Isoetes) occupied the core site. Montane conifer forests, with pine (Pinus, spp.), mountain hemlock (Tsuga mertensiana), spruce (Picea spp), and western hemlock (T. heterophylla) covered the region. Climatic parameters of modern montane coniferous forest and the continued presence of aquatic vegetation (Isoetes) suggest higher precipitation and lower temperatures during the last glacial. Charcoal (fire event frequency) was minimal. Rapid oscillations of oak, the riparian alder (Alnus), pine, Cupressaceae (Juniperus, Calocedrus), Douglas fir (Pseudotsuga menzeii), and fir (Abies) characterize the deglacial, and reflect rapid changes in precipitation and temperatures, e.g, Bølling-Allerød warming and Younger Dryas cooling. Between ~15,000 yr and ~13,000 yr, aquatic vegetation of the lake abruptly decreased. Expansion of oak, tanoak (Lithocarpus), shrubs (cf. Ceanothus) and decline of pine and montane conifers, along with the development of marshes with Typha and Cyperaceae on the former lakebed, imply early Holocene warming and decreasing precipitation. This is supported by an increase in charcoal, which is attributed to forest fires. Between ~5,000 yr - ~6,000 yr, a short interval of increased precipitation (inferred from a peak in alder and decrease in Cupressaceae) initiates the development of modern mixed hardwood-evergreen forest. Correlative data

  17. The Frog Skin-Derived Antimicrobial Peptide Esculentin-1a(1-21)NH2 Promotes the Migration of Human HaCaT Keratinocytes in an EGF Receptor-Dependent Manner: A Novel Promoter of Human Skin Wound Healing?

    PubMed

    Di Grazia, Antonio; Cappiello, Floriana; Imanishi, Akiko; Mastrofrancesco, Arianna; Picardo, Mauro; Paus, Ralf; Mangoni, Maria Luisa

    2015-01-01

    One of the many functions of skin is to protect the organism against a wide range of pathogens. Antimicrobial peptides (AMPs) produced by the skin epithelium provide an effective chemical shield against microbial pathogens. However, whereas antibacterial/antifungal activities of AMPs have been extensively characterized, much less is known regarding their wound healing-modulatory properties. By using an in vitro re-epithelialisation assay employing special cell-culture inserts, we detected that a derivative of the frog-skin AMP esculentin-1a, named esculentin-1a(1-21)NH2, significantly stimulates migration of immortalized human keratinocytes (HaCaT cells) over a wide range of peptide concentrations (0.025-4 μM), and this notably more efficiently than human cathelicidin (LL-37). This activity is preserved in primary human epidermal keratinocytes. By using appropriate inhibitors and an enzyme-linked immunosorbent assay we found that the peptide-induced cell migration involves activation of the epidermal growth factor receptor and STAT3 protein. These results suggest that esculentin-1a(1-21)NH2 now deserves to be tested in standard wound healing assays as a novel candidate promoter of skin re-epithelialisation. The established ability of esculentin-1a(1-21)NH2 to kill microbes without harming mammalian cells, namely its high anti-Pseudomonal activity, makes this AMP a particularly attractive candidate wound healing promoter, especially in the management of chronic, often Pseudomonas-infected, skin ulcers.

  18. Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine.

    PubMed

    Henningson, Jamie N; Rajao, Daniela S; Kitikoon, Pravina; Lorusso, Alessio; Culhane, Marie R; Lewis, Nicola S; Anderson, Tavis K; Vincent, Amy L

    2015-03-23

    In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared lung pathology, viral replication and shedding and the antigenic relationships of four wild-type H1N1pdm09 viruses in pigs: one human (CA/09) and three isolated in swine after the pandemic (IL/09, IL/10, and MN/10). The swine strains were selected based upon unique amino acid substitutions in the HA protein. All selected viruses resulted in mild disease and viral shedding through nasal and oral fluids, however, viral replication and the degree of pathology varied between the isolates. A/Swine/IL/5265/2010 (IL/10), with substitutions I120M, S146G, S186P, V252M, had lower viral titers in the lungs and nasal secretions and fewer lung lesions. The other two swine viruses caused respiratory pathology and replicated to titers similar to the human CA/09, although MN/10 (with mutations D45Y, K304E, A425S) had lower nasal shedding. Swine-adapted H1N1pdm09 have zoonotic potential, and have reassorted with other co-circulating swine viruses, influencing the evolution of IAV in swine globally. Further, our results suggest that amino acid changes in the HA gene have the potential to alter the virulence of H1N1pdm09 in swine. Importantly, the limited clinical signs in pigs could result in continued circulation of these viruses with other endemic swine IAVs providing opportunities for reassortment. Published by Elsevier B.V.

  19. Histamine up-regulates fibroblast growth factor receptor 1 and increases FOXP2 neurons in cultured neural precursors by histamine type 1 receptor activation: conceivable role of histamine in neurogenesis during cortical development in vivo.

    PubMed

    Molina-Hernández, Anayansi; Rodríguez-Martínez, Griselda; Escobedo-Ávila, Itzel; Velasco, Iván

    2013-03-07

    During rat development, histamine (HA) is one of the first neuroactive molecules to appear in the brain, reaching its maximal value at embryonic day 14, a period when neurogenesis of deep layers is occurring in the cerebral cortex, suggesting a role of this amine in neuronal specification. We previously reported, using high-density cerebrocortical neural precursor cultures, that micromolar HA enhanced the effect of fibroblast growth factor (FGF)-2 on proliferation, and that HA increased neuronal differentiation, due to HA type 1 receptor (H(1)R) activation. Clonal experiments performed here showed that HA decreased colony size and caused a significant increase in the percentage of clones containing mature neurons through H(1)R stimulation. In proliferating precursors, we studied whether HA activates G protein-coupled receptors linked to intracellular calcium increases. Neural cells presented an increase in cytoplasmic calcium even in the absence of extracellular calcium, a response mediated by H(1)R. Since FGF receptors (FGFRs) are known to be key players in cell proliferation and differentiation, we determined whether HA modifies the expression of FGFRs1-4 by using RT-PCR. An important transcriptional increase in FGFR1 was elicited after H(1)R activation. We also tested whether HA promotes differentiation specifically to neurons with molecular markers of different cortical layers by immunocytochemistry. HA caused significant increases in cells expressing the deep layer neuronal marker FOXP2; this induction of FOXP2-positive neurons elicited by HA was blocked by the H(1)R antagonist chlorpheniramine in vitro. Finally, we found a notable decrease in FOXP2+ cortical neurons in vivo, when chlorpheniramine was infused in the cerebral ventricles through intrauterine injection. These results show that HA, by activating H(1)R, has a neurogenic effect in clonal conditions and suggest that intracellular calcium elevation and transcriptional up-regulation of FGFR1

  20. A Spodoptera exigua Cadherin Serves as a Putative Receptor for Bacillus thuringiensis Cry1Ca Toxin and Shows Differential Enhancement of Cry1Ca and Cry1Ac Toxicity

    PubMed Central

    Ren, Xiang-Liang; Chen, Rui-Rui; Zhang, Ying; Ma, Yan; Cui, Jin-Jie; Han, Zhao-Jun; Mu, Li-Li

    2013-01-01

    Crystal toxin Cry1Ca from Bacillus thuringiensis has an insecticidal spectrum encompassing lepidopteran insects that are tolerant to current commercially used B. thuringiensis crops (Bt crops) expressing Cry1A toxins and may be useful as a potential bioinsecticide. The mode of action of Cry1A is fairly well understood. However, whether Cry1Ca interacts with the same receptor proteins as Cry1A remains unproven. In the present paper, we first cloned a cadherin-like gene, SeCad1b, from Spodoptera exigua (relatively susceptible to Cry1Ca). SeCad1b was highly expressed in the larval gut but scarcely detected in fat body, Malpighian tubules, and remaining carcass. Second, we bacterially expressed truncated cadherin rSeCad1bp and its interspecific homologue rHaBtRp from Helicoverpa armigera (more sensitive to Cry1Ac) containing the putative toxin-binding regions. Competitive binding assays showed that both Cry1Ca and Cry1Ac could bind to rSeCad1bp and rHaBtRp, and they did not compete with each other. Third, Cry1Ca ingestion killed larvae and decreased the weight of surviving larvae. Dietary introduction of SeCad1b double-stranded RNA (dsRNA) reduced approximately 80% of the target mRNA and partially alleviated the negative effect of Cry1Ca on larval survival and growth. Lastly, rSeCad1bp and rHaBtRp differentially enhanced the negative effects of Cry1Ca and Cry1Ac on the larval mortalities and growth of S. exigua and H. armigera. Thus, we provide the first lines of evidence to suggest that SeCad1b from S. exigua is a functional receptor of Cry1Ca. PMID:23835184

  1. Immunization of pigs with an attenuated pseudorabies virus recombinant expressing the haemagglutinin of pandemic swine origin H1N1 influenza A virus.

    PubMed

    Klingbeil, Katharina; Lange, Elke; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2014-04-01

    Pigs can be severely harmed by influenza, and represent important reservoir hosts, in which new human pathogens such as the recent pandemic swine-origin H1N1 influenza A virus can arise by mutation and reassortment of genome segments. To obtain novel, safe influenza vaccines for pigs, and to investigate the antigen-specific immune response, we modified an established live-virus vaccine against Aujeszky's disease of swine, pseudorabies virus (PrV) strain Bartha (PrV-Ba), to serve as vector for the expression of haemagglutinin (HA) of swine-origin H1N1 virus. To facilitate transgene insertion, the genome of PrV-Ba was cloned as a bacterial artificial chromosome. HA expression occurred under control of the human or murine cytomegalovirus immediate early promoters (P-HCMV, P-MCMV), but could be substantially enhanced by synthetic introns and adaptation of the codon usage to that of PrV. However, despite abundant expression, the heterologous glycoprotein was not detectably incorporated into mature PrV particles. Replication of HA-expressing PrV in cell culture was only slightly affected compared to that of the parental virus strain. A single immunization of pigs with the PrV vector expressing the codon-optimized HA gene under control of P-MCMV induced high levels of HA-specific antibodies. The vaccinated animals were protected from clinical signs after challenge with a related swine-origin H1N1 influenza A virus, and challenge virus shedding was significantly reduced.

  2. Structural Characterization of the Hemagglutinin Receptor Specificity from the 2009 H1N1 Influenza Pandemic

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Rui; McBride, Ryan; Nycholat, Corwin M.

    2012-02-13

    Influenza virus hemagglutinin (HA) is the viral envelope protein that mediates viral attachment to host cells and elicits membrane fusion. The HA receptor-binding specificity is a key determinant for the host range and transmissibility of influenza viruses. In human pandemics of the 20th century, the HA normally has acquired specificity for human-like receptors before widespread infection. Crystal structures of the H1 HA from the 2009 human pandemic (A/California/04/2009 [CA04]) in complex with human and avian receptor analogs reveal conserved recognition of the terminal sialic acid of the glycan ligands. However, favorable interactions beyond the sialic acid are found only formore » {alpha}2-6-linked glycans and are mediated by Asp190 and Asp225, which hydrogen bond with Gal-2 and GlcNAc-3. For {alpha}2-3-linked glycan receptors, no specific interactions beyond the terminal sialic acid are observed. Our structural and glycan microarray analyses, in the context of other high-resolution HA structures with {alpha}2-6- and {alpha}2-3-linked glycans, now elucidate the structural basis of receptor-binding specificity for H1 HAs in human and avian viruses and provide a structural explanation for the preference for {alpha}2-6 siaylated glycan receptors for the 2009 pandemic swine flu virus.« less

  3. Carbon supply and storage in tilled and nontilled soils as influenced by cover crops and nitrogen fertilization.

    PubMed

    Sainju, Upendra M; Singh, Bharat P; Whitehead, Wayne F; Wang, Shirley

    2006-01-01

    Soil carbon (C) sequestration in tilled and nontilled areas can be influenced by crop management practices due to differences in plant C inputs and their rate of mineralization. We examined the influence of four cover crops {legume [hairy vetch (Vicia villosa Roth)], nonlegume [rye (Secale cereale L.)], biculture of legume and nonlegume (vetch and rye), and no cover crops (or winter weeds)} and three nitrogen (N) fertilization rates (0, 60 to 65, and 120 to 130 kg N ha(-1)) on C inputs from cover crops, cotton (Gossypium hirsutum L.), and sorghum [Sorghum bicolor (L.) Moench)], and soil organic carbon (SOC) at the 0- to 120-cm depth in tilled and nontilled areas. A field experiment was conducted on Dothan sandy loam (fine-loamy, siliceous, thermic Plinthic Paleudults) from 1999 to 2002 in central Georgia. Total C inputs to the soil from cover crops, cotton, and sorghum from 2000 to 2002 ranged from 6.8 to 22.8 Mg ha(-1). The SOC at 0 to 10 cm fluctuated with C input from October 1999 to November 2002 and was greater from cover crops than from weeds in no-tilled plots. In contrast, SOC values at 10 to 30 cm in no-tilled and at 0 to 60 cm in chisel-tilled plots were greater for biculture than for weeds. As a result, C at 0 to 30 cm was sequestered at rates of 267, 33, -133, and -967 kg C ha(-1) yr(-1) for biculture, rye, vetch, and weeds, respectively, in the no-tilled plot. In strip-tilled and chisel-tilled plots, SOC at 0 to 30 cm decreased at rates of 233 to 1233 kg C ha(-1) yr(-1). The SOC at 0 to 30 cm increased more in cover crops with 120 to 130 kg N ha(-1) yr(-1) than in weeds with 0 kg N ha(-1) yr(-1), regardless of tillage. In the subtropical humid region of the southeastern United States, cover crops and N fertilization can increase the amount of C input and storage in tilled and nontilled soils, and hairy vetch and rye biculture was more effective in sequestering C than monocultures or no cover crop.

  4. Mechanical strength of [HA/Bioplastic/Sericin] composite part printed by bioprinter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tontowi, Alva Edy, E-mail: alvaedytontowi@ugm.ac.id; Setiawan, Agris

    The aim of this research was to determine the effect of hydroxyapatite (HA) content in printed biocomposite to its mechanical strength. The biocomposite paste was prepared by composing HA, bioplastic and sericin with various ratios of [HA/Bioplastic]: 40/60, 50/50, 60,40 and 70/30. Sericin of 0.3% weight was added to the biocomposite. Mechanical test was conducted to observe tensile (ASTM D 638 type 4) and flexural strength (ASTM D 790). Both type of specimens were fabricated using 3D Printer. Printing process parameter (infill speed, print speed and layer height) were set up as 60 mm/s, 10 mm/s, 0.35 mm, respectively. Resultsmore » showed that biocomposite with [HA/Biplastic]. weight ratio of 60/40(w/w) has an optimum tensile (3.89 ± 1.26 MPa) and flexural strength (2.51 ± 0.45 MPa). Scanning electron microscope observation indicated that microstructure of specimen was influenced by the percentage of the hydroxyapatite. There was no agglomeration of HA particle within the composite.« less

  5. Synthesis and DNA binding properties of 1-(3-aminopropyl)-imidazole-containing triamide f-Im*PyIm: a novel diamino polyamide designed to target 5'-ACGCGT-3'.

    PubMed

    Satam, Vijay; Babu, Balaji; Porte, Alexander; Savagian, Mia; Lee, Megan; Smeltzer, Thomas; Liu, Yang; Ramos, Joseph; Wilson, W David; Lin, Shicai; Kiakos, Kostantinos; Hartley, John A; Lee, Moses

    2012-09-15

    A novel diamino/dicationic polyamide f-Im(*)PyIm (5) that contains an orthogonally positioned aminopropyl chain on an imidazole (Im(*)) moiety was designed to target 5'-ACGCGT-3'. The DNA binding properties of the diamino polyamide 5, determined by CD, ΔT(M), DNase I footprinting, SPR, and ITC studies, were compared with those of its monoamino/monocationic counterpart f-ImPyIm (1) and its diamino/dicationic isomer f-ImPy(*)Im (2), which has the aminopropyl group attached to the central pyrrole unit (Py(*)). The results gave evidence for the minor groove binding and selectivity of polyamide 5 for the cognate sequence 5'-ACGCGT-3', and with strong affinity (K(eq)=2.3×10(7) M(-1)). However, the binding affinities varied according to the order: f-ImPy(*)Im (2)>f-ImPyIm (1)≥f-Im(*)PyIm (5) confirming that the second amino group can improve affinity, but its position within the polyamide can affect affinity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine.

    PubMed

    Kyriakis, C S; Papatsiros, V G; Athanasiou, L V; Valiakos, G; Brown, I H; Simon, G; Van Reeth, K; Tsiodras, S; Spyrou, V; Billinis, C

    2016-08-01

    The introduction of the 2009 pandemic H1N1 (pH1N1) influenza virus in pigs changed the epidemiology of influenza A viruses (IAVs) in swine in Europe and the rest of the world. Previously, three IAV subtypes were found in the European pig population: an avian-like H1N1 and two reassortant H1N2 and H3N2 viruses with human-origin haemagglutinin (HA) and neuraminidase proteins and internal genes of avian decent. These viruses pose antigenically distinct HAs, which allow the retrospective diagnosis of infection in serological investigations. However, cross-reactions between the HA of pH1N1 and the HAs of the other circulating H1 IAVs complicate serological diagnosis. The prevalence of IAVs in Greek swine has been poorly investigated. In this study, we examined and compared haemagglutination inhibition (HI) antibody titres against previously established IAVs and pH1N1 in 908 swine sera from 88 herds, collected before and after the 2009 pandemic. While we confirmed the historic presence of the three IAVs established in European swine, we also found that 4% of the pig sera examined after 2009 had HI antibodies only against the pH1N1 virus. Our results indicate that pH1N1 is circulating in Greek pigs and stress out the importance of a vigorous virological surveillance programme. © 2015 Blackwell Verlag GmbH.

  7. Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

    PubMed

    Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

    2012-07-06

    In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

    PubMed Central

    Li, Zhuo; Mooney, Alaina J.; Gabbard, Jon D.; Gao, Xiudan; Xu, Pei; Place, Ryan J.; Hogan, Robert J.; Tompkins, S. Mark

    2013-01-01

    A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine. PMID:23077314

  9. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012

    PubMed Central

    Grgić, Helena; Costa, Marcio; Friendship, Robert M.; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors. PMID:26030614

  10. Nitrous oxide emissions from forests and pastures of various ages in the Brazilian Amazon

    NASA Astrophysics Data System (ADS)

    Melillo, J. M.; Steudler, P. A.; Feigl, B. J.; Neill, C.; Garcia, D.; Piccolo, M. C.; Cerri, C. C.; Tian, H.

    2001-12-01

    Nitrous oxide emissions from tropical forest soils are thought to account for 2.2-3.7 Tg N yr-1 of the total annual global production of 10-17 Tg N yr-1. Recent research suggests that clearing of tropical forest for pasture can increase N2O emissions but that the period of elevated emissions may be limited and fluxes from older pastures may be lower than from the original forest. Here we report N2O emissions from two land-use sequences in the Brazilian Amazon's state of Rondônia. Each sequence includes a forest and a set of pastures of different ages. One sequence contains a newly created pasture that we studied intensively through its first 2 years, including forest cutting, burning, and the planting of forage grasses. Emissions from the newly created pasture were about two and one half times the forest emissions during the first 2 years (5.0 kg N2O-N ha-1 yr-1 versus 1.9 kg N2O-N ha-1 yr-1). Nitrous oxide fluxes from pastures older than 3 years were on average about one third lower than fluxes from uncut forest (1.4 kg N2O-N ha-1 yr-1 versus 1.9 kg N2O-N ha-1 yr-1). The best predictor of N2O flux across the chronosequences was the magnitude of the NO3 pool in the upper 10 cm of soil measured at the time of gas sampling. Using a simple cohort model combined with deforestation rates estimated from satellite images by Brazil's Instituto de Pesquisas Espaciais (INPE) for the period 1978 through 1997, we estimate that for the Brazilian Amazon the basin-wide flux of N2O-N from pasture soils was 0.06 Tg in 1997. This is ˜8% of the combined forest plus pasture flux of 0.78 Tg N2O-N we estimate for the Brazilian part of the basin in 1997. In the absence of any forest-to-pasture conversion in the Brazilian part of the basin, we estimate that the basin-wide flux of N2O-N would have been only slightly larger: 0.80 Tg in 1997. Through a second modeling analysis we estimate that for the whole of the Amazon Basin, including parts of the basin outside of Brazil, the N2O

  11. Contribution of nitrous oxide and methan to the overall climate impact of maize on well-drained sandy soils of north-east Germany

    NASA Astrophysics Data System (ADS)

    Andres, M.; Hagemann, U.; Pohl, M.; Sommer, M.; Augustin, J.

    2012-04-01

    Erosion effects and the influence of organic fertiliser (fermentation residues, FR) on the climate impact and greenhouse gas (GHG) emissions of N2O, CH4 and CO2 were investigated at an experimental field side in the lowlands of north-east Germany during the years 2010 and 2011. This intensively used agricultural landscape is glacially shaped and characterized by well-drained sandy and loamy soils. Erosion effects on GHG exchange were investigated for energy maize at the CarboZALF-D project site near Dedelow, Uckermark. In addition to a non-eroded haplic luvisol (reference), emissions were measured for three eroded soil types: a) eroded haplic luvisol, b) haplic regosol (calcaric) and c) endogleyic colluvic regosol (deposition side). In a second field trial, the impact of organic fertilization on GHG emissions was assessed for a range of FR fertilization (0-200% N) and compared to a non-fertilized and a minerally fertilized control. Only 70% of the N content of the FR was assumed to be available for plants. Discontinuous measurements of N2O and CH4 were carried out bi-weekly using the closed-chamber method and 20-minute interval sampling. Gas samples were analysed using a gas chromatograph. Gas fluxes were calculated using linear regression, interpolated and finally cumulated. CO2 flux measurements of ecosystem respiration (Reco) and net ecosystem exchange (NEE) were conducted every four weeks by using a non-flow-through non-steady-state closed chamber system (Livingston and Hutchinson 1995) based on Drösler (2005). Measurement gaps of NEE were filled by modeling the Reco fluxes using the Lloyd-Taylor (Lloyd and Taylor 1994) method and the gross primary production (GPP) fluxes using Michaelis-Menten (Michaelis and Menten 1913) modeling approach. Annual NEE balances were then calculated based on the modeled Reco and GPP fluxes. All investigated soil types were C sinks, storing up to 9,6 t CO2eq ha-1 yr-1. As expected for this well-drained soils, the climate impact

  12. Nanocrystallized SrHA/SrHA SrTiO3/SrTiO3 TiO2 multilayer coatings formed by micro-arc oxidation for photocatalytic application

    NASA Astrophysics Data System (ADS)

    Han, Y.; Chen, D. H.; Zhang, L.

    2008-08-01

    Novel photocatalytic coatings containing strontium hydroxyapatite (SrHA), strontium titanate (SrTiO3), and TiO2 were formed by micro-arc oxidation (MAO) in an aqueous electrolyte containing strontium acetate and β-glycerophosphate disodium at 530 V for 0.1-5 min. The structure evolution of the coatings was investigated as a function of processing time, and the photocatalytic activity of the coatings was evaluated by measuring the decomposition rate of methyl orange under ultraviolet irradiation. During the MAO processing of the coatings, it was observed that some granules appeared in the electrolyte adjacent to the anode and they increased in amount as the processing time was prolonged. The obtained results show that the granules are amorphous and poorly crystallized SrHA with negative charges. The coating prepared for 5 min presents a microporous structure of SrHA/SrHA-SrTiO3/SrTiO3-TiO2 multilayers, in which the SrHA outermost layer and the SrHA-SrTiO3 intermediate layer are nanocrystallized. It is suggested that formation of the granules, electro-migration of the granules onto the pre-formed layer, and crystallization of the adhered granules are possible mechanisms for the formation of a SrHA/SrHA-SrTiO3/SrTiO3-TiO2 multilayer coating. This coating shows much higher photocatalytic decomposition efficiency relative to the MAO-formed TiO2 coating, and is expected to have an important photocatalytic application.

  13. Advanced dental maturity of Finnish 6- to 12-yr-old children is associated with high energy intake.

    PubMed

    Jääsaari, Päivi; Tolvanen, Mimmi; Niinikoski, Harri; Karjalainen, Sara

    2016-10-01

    We studied the association of dental maturity with body mass index (BMI), energy intake, and macronutrient intake. A randomly selected subset (n = 148) of the Special Turku Coronary Risk Factor Intervention Project (STRIP) was invited to an oral follow-up study, and the 6- and 12-yr-examination data (n = 111, 60 boys) were used. Food records for four consecutive days and BMI values were extracted from the databank of the main STRIP project. The developmental stage of seven permanent mandibular teeth was assessed using panoramic radiographs. The resulting maturity scores were converted to dental age estimates. Three dental-maturity groups (delayed, average, and advanced) and two BMI groups [normal BMI (≤mean+1SD) and high BMI (>mean+1SD)] were formed. The dental age was higher than the chronological age by 0.6-0.8 yr. Maturity scores for girls were statistically significantly higher than for boys. The distribution of girls into dental-maturity groups at age 12 yr was different from that of the boys and there were more boys than girls among the high-BMI group. Children of the advanced dental-maturity group had a statistically significantly higher energy intake than children in the other groups. We conclude that advanced dental maturity is associated with higher energy intake. © 2016 Eur J Oral Sci.

  14. Yeast Surface-Displayed H5N1 Avian Influenza Vaccines

    PubMed Central

    Lei, Han; Jin, Sha; Karlsson, Erik; Schultz-Cherry, Stacey

    2016-01-01

    Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation. PMID:28078309

  15. Deficiency of Hyaluronan Synthase 1 (Has1) Results in Chronic Joint Inflammation and Widespread Intra-Articular Fibrosis in a Murine Model of Knee Joint Cartilage Damage

    PubMed Central

    Chan, Deva D.; Xiao, Wenfeng; Li, Jun; de la Motte, Carol A.; Sandy, John D.; Plaas, Anna

    2015-01-01

    Objective Articular cartilage defects commonly result from traumatic injury and predispose to degenerative joint diseases. To test the hypothesis that aberrant healing responses and chronic inflammation lead to osteoarthritis, we examined spatiotemporal changes in joint tissues after cartilage injury in murine knees. Since intra-articular injection of hyaluronan (HA) can attenuate injury-induced osteoarthritis in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1−/−). Design Femoral groove cartilage of WT and Has1−/− mice was debrided to generate a non-bleeding wound. Macroscopic imaging, histology, and gene expression were used to evaluate naïve, sham-operated, and injured joints. Results Acute responses (1–2 weeks) in injured joints from WT mice included synovial hyperplasia with HA deposition and joint-wide increases in expression of genes associated with inflammation, fibrosis, and extracellular matrix (ECM) production. By 4 weeks, some resurfacing of damaged cartilage occurred, and early cell responses were normalized. Cartilage damage in Has1−/− mice also induced early responses; however, at 4 weeks, inflammation and fibrosis genes remained elevated with widespread cartilage degeneration and fibrotic scarring in the synovium and joint capsule. Conclusions We conclude that the ineffective repair of injured cartilage in Has1−/− joints can be at least partly explained by the markedly enhanced expression of particular genes in pathways linked to ECM turnover, IL-17/IL-6 cytokine signaling, and apoptosis. Notably, Has1 ablation does not alter gross HA content in the ECM, suggesting that HAS1 has a unique function in the metabolism of inflammatory HA matrices. PMID:26521733

  16. Effects of lunar and mars dust on HaCaT keratinocytes and CHO-K1 fibroblasts

    NASA Astrophysics Data System (ADS)

    Brix, Klaudia; Slenzka, Klaus; Rehders, Maren; Sadhukhan, Annapurna; Mistry, Rima; Duenne, Matthias; Kempf, Juergen

    Exposure to lunar dust during Apollo missions resulted in occasional reports of ocular, respira-tory and dermal irritations which showed that lunar dust has a risk potential for human health. This is caused by its high reactivity as well as its small size, leading to a wide distribution also inside habitats. Hence, detailed information regarding effects of lunar dust on human health is required to best support future missions to moon. In this study, we used different methods to assess the specific effects of lunar dust onto mammalian skin by exposing HaCaT keratinocytes and CHO-K1 fibroblasts to dusts simulating lunar or mars soils. These particular cell types were chosen because the skin protects the human body from potentially harmful substances and since a well orchestrated program ensures proper repair in cases of wounding. Keratinocytes and fibroblasts were exposed to the dusts for different durations of time and their effects on morphology, metabolic state, survival and proliferation of the cells were determined. Cytotoxi-city and proliferation were measured using the MTT assay, metabolic activity was analyzed by vital staining of mitochondria, and phalloidin staining of the actin cytoskeleton was performed to address structural integrity of the cells. It was found that the effects of the two types of soils on the different features of both cell lines varied to considerable extent, and that lunar and mars dust were specific in their effects. The obtained results will facilitate detailed inves-tigations of dust exposure during wound healing and will ease risk assessment studies for e.g. lunar lander approaches. The investigations will help to assess the risks and to determine safety measures to be taken during extraterrestrial expeditions in order to minimize risks to human health associated with exposure of human skin to dust contaminants.

  17. Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood.

    PubMed

    Ahrens, Hellen E; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2015-07-01

    Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a (51)Chromium release assay and by ex vivo kidney perfusions with human blood. Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation.

  18. Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood

    PubMed Central

    Ahrens, Hellen E.; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2015-01-01

    Background Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. Methods The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a 51Chromium release assay and by ex vivo kidney perfusions with human blood. Results Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Conclusions Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation. PMID:27500225

  19. Increasing incidence and age at diagnosis among children with type 1 diabetes mellitus over a 20-year period in Auckland (New Zealand).

    PubMed

    Derraik, José G B; Reed, Peter W; Jefferies, Craig; Cutfield, Samuel W; Hofman, Paul L; Cutfield, Wayne S

    2012-01-01

    We aimed to evaluate the incidence of type 1 diabetes mellitus in children <15 years of age (yr) in the Auckland region (New Zealand) over 20 years (1990-2009). We performed a retrospective review of all patients <15 yr diagnosed with type 1 diabetes, from an unselected complete regional cohort. There were 884 new cases of type 1 diabetes, and age at diagnosis rose from 7.6 yr in 1990/1 to 8.9 yr in 2008/9 (r(2) = 0.31, p = 0.009). There was a progressive increase in type 1 diabetes incidence among children <15 yr (p<0.0001), reaching 22.5 per 100,000 in 2009. However, the rise in incidence did not occur evenly among age groups, being 2.5-fold higher in older children (10-14 yr) than in the youngest group (0-4 yr). The incidence of new cases of type 1 diabetes was highest in New Zealand Europeans throughout the study period in all age groups (p<0.0001), but the rate of increase was similar in New Zealand Europeans and Non-Europeans. Type 1 diabetes incidence and average annual increase were similar in both sexes. There was no change in BMI SDS shortly after diagnosis, and no association between BMI SDS and age at diagnosis. There has been a steady increase in type 1 diabetes incidence among children <15 yr in Auckland over 20 years. Contrary to other studies, age at diagnosis has increased and the greatest rise in incidence occurred in children 10-14 yr. There was little change in BMI SDS in this population, providing no support for the 'accelerator hypothesis'.

  20. 7 CFR 1957.1 - General.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true General. 1957.1 Section 1957.1 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE..., 7 CFR part 1900, Subpart B. Failure of private servicers to comply with FmHA or its successor agency...

  1. Soil organic carbon sequestration in cotton production systems of the southeastern United States: a review.

    PubMed

    Causarano, H J; Franzluebbers, A J; Reeves, D W; Shaw, J N

    2006-01-01

    Past agricultural management practices have contributed to the loss of soil organic carbon (SOC) and emission of greenhouse gases (e.g., carbon dioxide and nitrous oxide). Fortunately, however, conservation-oriented agricultural management systems can be, and have been, developed to sequester SOC, improve soil quality, and increase crop productivity. Our objectives were to (i) review literature related to SOC sequestration in cotton (Gossypium hirsutum L.) production systems, (ii) recommend best management practices to sequester SOC, and (iii) outline the current political scenario and future probabilities for cotton producers to benefit from SOC sequestration. From a review of 20 studies in the region, SOC increased with no tillage compared with conventional tillage by 0.48 +/- 0.56 Mg C ha(-1) yr(-1) (H(0): no change, p < 0.001). More diverse rotations of cotton with high-residue-producing crops such as corn (Zea mays L.) and small grains would sequester greater quantities of SOC than continuous cotton. No-tillage cropping with a cover crop sequestered 0.67 +/- 0.63 Mg C ha(-1) yr(-1), while that of no-tillage cropping without a cover crop sequestered 0.34 +/- 47 Mg C ha(-1) yr(-1) (mean comparison, p = 0.04). Current government incentive programs recommend agricultural practices that would contribute to SOC sequestration. Participation in the Conservation Security Program could lead to government payments of up to Dollars 20 ha(-1). Current open-market trading of C credits would appear to yield less than Dollars 3 ha(-1), although prices would greatly increase should a government policy to limit greenhouse gas emissions be mandated.

  2. Temporal distribution and genetic variants in influenza A(H1N1)pdm09 virus circulating in Mexico, seasons 2012 and 2013.

    PubMed

    Canche-Pech, Jose Reyes; Conde-Ferraez, Laura; Puerto-Solis, Marylin; Gonzalez-Losa, Refugio; Granja-Pérez, Pilar; Villanueva-Jorge, Salha; Chan-Gasca, Maria; Gómez-Carballo, Jesus; López-Ochoa, Luisa; Jiménez-Delgadillo, Bertha; Rodríguez-Sánchez, Iram; Ramírez-Prado, Jorge; Ayora-Talavera, Guadalupe

    2017-01-01

    The 2012 and 2013 annual influenza epidemics in Mexico were characterized by presenting different seasonal patterns. In 2012 the A(H1N1)pdm09 virus caused a high incidence of influenza infections after a two-year period of low circulation; whereas the 2013 epidemic presented circulation of the A(H1N1)pdm09 virus throughout the year. We have characterized the molecular composition of the Hemagglutinin (HA) and Neuraminidase (NA) genes of the A(H1N1)pdm09 virus from both epidemic seasons, emphasizing the genetic characteristics of viruses isolated from Yucatan in Southern Mexico. The molecular analysis of viruses from the 2012 revealed that all viruses from Mexico were predominantly grouped in clade 7. Strikingly, the molecular characterization of viruses from 2013 revealed that viruses circulating in Yucatan were genetically different to viruses from other regions of Mexico. In fact, we identified the occurrence of two genetic variants containing relevant mutations at both the HA and NA surface antigens. There was a difference on the temporal circulation of each genetic variant, viruses containing the mutations HA-A141T / NA-N341S were detected in May, June and July; whereas viruses containing the mutations HA-S162I / NA-L206S circulated in August and September. We discuss the significance of these novel genetic changes.

  3. Temporal distribution and genetic variants in influenza A(H1N1)pdm09 virus circulating in Mexico, seasons 2012 and 2013

    PubMed Central

    Canche-Pech, Jose Reyes; Conde-Ferraez, Laura; Puerto-Solis, Marylin; Gonzalez-Losa, Refugio; Granja-Pérez, Pilar; Villanueva-Jorge, Salha; Chan-Gasca, Maria; Gómez-Carballo, Jesus; López-Ochoa, Luisa; Jiménez-Delgadillo, Bertha; Rodríguez-Sánchez, Iram; Ramírez-Prado, Jorge

    2017-01-01

    The 2012 and 2013 annual influenza epidemics in Mexico were characterized by presenting different seasonal patterns. In 2012 the A(H1N1)pdm09 virus caused a high incidence of influenza infections after a two-year period of low circulation; whereas the 2013 epidemic presented circulation of the A(H1N1)pdm09 virus throughout the year. We have characterized the molecular composition of the Hemagglutinin (HA) and Neuraminidase (NA) genes of the A(H1N1)pdm09 virus from both epidemic seasons, emphasizing the genetic characteristics of viruses isolated from Yucatan in Southern Mexico. The molecular analysis of viruses from the 2012 revealed that all viruses from Mexico were predominantly grouped in clade 7. Strikingly, the molecular characterization of viruses from 2013 revealed that viruses circulating in Yucatan were genetically different to viruses from other regions of Mexico. In fact, we identified the occurrence of two genetic variants containing relevant mutations at both the HA and NA surface antigens. There was a difference on the temporal circulation of each genetic variant, viruses containing the mutations HA-A141T / NA-N341S were detected in May, June and July; whereas viruses containing the mutations HA-S162I / NA-L206S circulated in August and September. We discuss the significance of these novel genetic changes. PMID:29220381

  4. Immune Escape Mutants of Highly Pathogenic Avian Influenza H5N1 Selected Using Polyclonal Sera: Identification of Key Amino Acids in the HA Protein

    PubMed Central

    Sitaras, Ioannis; Kalthoff, Donata; Beer, Martin; Peeters, Ben; de Jong, Mart C. M.

    2014-01-01

    Evolution of Avian Influenza (AI) viruses – especially of the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype – is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks) is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1), using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA) protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number. PMID:24586231

  5. HVOF-Sprayed Nano TiO2-HA Coatings Exhibiting Enhanced Biocompatibility

    NASA Astrophysics Data System (ADS)

    Lima, R. S.; Dimitrievska, S.; Bureau, M. N.; Marple, B. R.; Petit, A.; Mwale, F.; Antoniou, J.

    2010-01-01

    Biomedical thermal spray coatings produced via high-velocity oxy-fuel (HVOF) from nanostructured titania (n-TiO2) and 10 wt.% hydroxyapatite (HA) (n-TiO2-10wt.%HA) powders have been engineered as possible future alternatives to HA coatings deposited via air plasma spray (APS). This approach was chosen due to (i) the stability of TiO2 in the human body (i.e., no dissolution) and (ii) bond strength values on Ti-6Al-4V substrates more than two times higher than those of APS HA coatings. To explore the bioperformance of these novel materials and coatings, human mesenchymal stem cells (hMSCs) were cultured from 1 to 21 days on the surface of HVOF-sprayed n-TiO2 and n-TiO2-10 wt.%HA coatings. APS HA coatings and uncoated Ti-6Al-4V substrates were employed as controls. The profiles of the hMSCs were evaluated for (i) cellular proliferation, (ii) biochemical analysis of alkaline phosphatase (ALP) activity, (iii) cytoskeleton organization (fluorescent/confocal microscopy), and (iv) cell/substrate interaction via scanning electron microscopy (SEM). The biochemical analysis indicated that the hMSCs cultured on n-TiO2-10 wt.%HA coatings exhibited superior levels of bioactivity than hMSCs cultured on APS HA and pure n-TiO2 coatings. The cytoskeleton organization demonstrated a higher degree of cellular proliferation on the HVOF-sprayed n-TiO2-10wt.%HA coatings when compared to the control coatings. These results are considered promising for engineering improved performance in the next generation of thermally sprayed biomedical coatings.

  6. Hydrothermally processed 1D hydroxyapatite: mechanism of formation and biocompatibility studies

    PubMed Central

    Stojanović, Zoran S.; Ignjatović, Nenad; Wu, Victoria; Žunič, Vojka; Veselinović, Ljiljana; Škapin, Srečo; Miljković, Miroslav; Uskoković, Vuk; Uskoković, Dragan

    2016-01-01

    Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6 mg/cm2. X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37 nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P63/m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous

  7. Hanford Site Air Operating Permit Application Supplemental Information [Sec 1 Thru 5] Vol 1 Thru 3 Appendices A Thru C

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    CURN, B.L.

    2000-05-01

    This report documents radionuclide air emissions from the Hanford Site in 1998 and the resulting effective dose equivalent to the maximally exposed individual (MEI) member of the public. The report has been prepared in accordance with the Code of Federal Regulations, Title 40, Protection of the Environment, Part 61, National Emission Standards for Hazardous Air Pollutants (40 CFR 61), Subpart H: ''National Emission Standards for Emissions of Radionuclides Other than Radon from Department of Energy Facilities,'' and with the Washington Administrative Code Chapter 246247, Radiation Protection - Air Emissions. The federal regulations in 40 CFR 61, Subpart H, require themore » measurement and reporting of radionuclides emitted from Department of Energy facilities and the resulting offsite dose from those emissions. A standard of 10 mrem/yr effective dose equivalent (EDE) is imposed on them. The EDE to the MEI due to routine emissions in 1998 from Hanford Site point sources was 1.3 E-02 mrem (1.3 E-04 mSv). which is 0.13 percent of the federal standard. Chapter 246-247 of the Washington Administrative Code (WAC) requires the reporting of radionuclide emissions from all Department of Energy Hanford Site sources. The state has adopted into these regulations the 40 CFR 61 standard of 10 mrem/yr EDE. The EDE to the MEI attributable to diffuse and fugitive radionuclide air emissions from the Hanford Site in 1998 was 2.5 E-02 mrem (2.S E-04 mSv). This dose added to the dose from point sources gives a total for all sources of 3.8 E-02 mrem/yr (3.8 E-04 mSv) EDE. which is 0.38 percent of the 10 mrem/yr standard. An unplanned release on August 26, 1998, in the 300 Area of the Hanford Site resulted in a potential dose of 4.1 E-02 mrem to a hypothetical individual at the nearest point of public access to that area. This hypothetical individual was not the MEI since the wind direction on the day of the release was away from the MEI residence. The potential dose from the unplanned

  8. Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses

    PubMed Central

    McCormick, Kara; Jiang, Zhiyong; Zhu, Longchao; Lawson, Steven R.; Langenhorst, Robert; Ransburgh, Russell; Brunick, Colin; Tracy, Miranda C.; Hurtig, Heather R.; Mabee, Leah M.; Mingo, Mark; Li, Yanhua; Webby, Richard J.

    2015-01-01

    Background and Objectives Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes. Methods and Results Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates. Conclusion This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines. PMID:26061265

  9. The hot deformation behavior and microstructure evolution of HA/Mg-3Zn-0.8Zr composites for biomedical application.

    PubMed

    Liu, Debao; Liu, Yichi; Zhao, Yue; Huang, Y; Chen, Minfang

    2017-08-01

    The hot deformation behavior of nano-sized hydroxylapatite (HA) reinforced Mg-3Zn-0.8Zr composites were performed by means of Gleeble-1500D thermal simulation machine in a temperature range of 523-673K and a strain rate range of 0.001-1s -1 , and the microstructure evolution during hot compression deformation were also investigated. The results show that the flow stress increases increasing strain rates at a constant temperature, and decreases with increasing deforming temperatures at a constant strain rate. Under the same processing conditions, the flow stresses of the 1HA/Mg-3Zn-0.8Zr specimens are higher than those of the Mg-3Zn-0.8Zr alloy specimens, and the difference is getting closer with increasing deformation temperature. The hot deformation behaviors of Mg-3Zn-0.8Zr and 1HA/Mg-3Zn-0.8Zr can be described by constitutive equation of hyperbolic sine function with the hot deformation activation energy being 124.6kJ/mol and 125.3kJ/mol, respectively. Comparing with Mg-3Zn-0.8Zr alloy, the instability region in the process map of 1HA/Mg-3Zn-0.8Zr expanded to a bigger extent at the same conditions. The optimum process conditions of 1HA/Mg-3Zn-0.8Zr composite is concluded as between the temperature window of 573-623K with a strain rate range of 0.001-0.1s -1 . A higher volume fraction and smaller grain size of dynamic recrystallization (DRX) grains was observed in 1HA/Mg-3Zn-0.8Zr specimens after the hot compression deformation compared with Mg-3Zn-0.8Zr alloy, which was ascribed to the presence of the HA particles that play an important role in particle-stimulated nucleation (PSN) mechanism and can effectively hinder the migration of interfaces. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Accumulation of CD11b+Gr-1+ cells in the lung, blood and bone marrow of mice infected with highly pathogenic H5N1 and H1N1 influenza viruses

    PubMed Central

    Kotur, Mark S.; Stark, Gregory V.; Warren, Richard L.; Kasoji, Manjula; Craft, Jeremy L.; Albrecht, Randy A.; García-Sastre, Adolfo; Katze, Michael G.; Waters, Katrina M.; Vasconcelos, Daphne; Sabourin, Patrick J.; Bresler, Herbert S.; Sabourin, Carol L.

    2017-01-01

    Infection with pathogenic influenza viruses isassociated with intense inflammatory disease. Here, we investigated the innate immune response in mice infectedwith H5N1 A/Vietnam/1203/04 and with reassortanthuman H1N1 A/Texas/36/91 viruse s containing the virulence genes hemagglutinin (HA), neuraminidase (NA) and NS1 of the 1918 pandemic virus. Inclusion of the 1918 HAand NA glycoproteins rendered a seasonal H1N1 virus capable of inducing an exacerbated host innate immuneresponse similar to that observed for highly pathogenicA/Vietnam/1203/04 virus. Infection with 1918 HA/NA:Tx/91 and A/Vietnam/1203/04 were associated with severelung pathology, increased cytokine and chemokine production, and significant immune cell changes, including the presence of CD11b+Gr-1+cells in the blood, lung and bone marrow. Significant differential gene expression in the lung included pathways for cell death, apoptosis, production and response to reactive oxygen radicals, as well asarginine and proline meta bolism and chemokines associated with monocyte and neutrophil/granulocyte accumulation and/or activation. Arginase was produced in the lungof animals infected with A/Vietnam/1204. These results demonstrate that the innate immune cell response resultsin t he accumulation of CD11b+Gr-1+cells and products that have previously been shown to contribute to T cellsuppression. PMID:23397329

  11. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wörmann, Xenia; Lesch, Markus; Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA{sub 1} D130E, HA{sub 2} I91L), near the receptor binding site and themore » stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.« less

  12. Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany.

    PubMed

    Wedde, Marianne; Biere, Barbara; Wolff, Thorsten; Schweiger, Brunhilde

    2015-10-01

    This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic analysis of the hemagglutinin (HA) genes of both subtypes revealed similar evolution of the HA variants that were also seen worldwide with minor exceptions. The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since 2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were detected late in the 2009-2010 season. With respect to A(H3N2), we found herald strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were predominantly seen for minor and not for major HA clades. Generally, amino acid substitutions were most frequently found in the globular domain, including substitutions near the antigenic sites or the receptor binding site. Differences between both influenza A subtypes were seen with respect to the position of the indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more substitutions in the stem region than in the antigenic sites. In contrast, in A(H3N2) viruses most changes were identified in the major antigenic sites and five changes of potential glycosylation sites were identified in the head of the HA monomer. Interestingly, we found in seasons with less influenza activity a relatively high increase of substitutions in the head of the HA in both subtypes. This might be explained by the fact that mutations under negative selection are subsequently compensated by secondary mutations to restore important functions e.g. receptor binding properties. A better knowledge of basic evolution strategies of influenza viruses will contribute to the refinement of predictive mathematical models for identifying novel antigenic drift variants. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

    USDA-ARS?s Scientific Manuscript database

    This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

  14. Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human Keratinocytes.

    PubMed

    Kim, Hye Kyung

    2016-07-29

    Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in the cells, which induces the cellular senescence and photoaging. The present study investigated the protective effects of garlic on photo-damage and cellular senescence in UVB-exposed human keratinocytes, HaCaT cells. An in vitro cell free system was used to examine the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and nitric oxide (NO). The effect of garlic extract on ROS formation, MMP-1 protein and mRNA expressions, cytokines such as interleukin (IL)-1β and IL-6, senescence associated-β-galactosidase (SA-β-gal) activity, and silent information regulator T1 (SIRT1) activity were determined in UVB-irradiated HaCaT cells. Garlic exhibited strong DPPH radical and NO scavenging activity in cell free system exhibiting IC50 values of 2.50 mg/mL and 4.38 mg/mL, respectively. Garlic pretreatment attenuated the production of UVB-induced intracellular ROS. MMP-1 level, which has been known to be induced by ROS, was dramatically elevated by UVB irradiation, and UVB-induced MMP-1 mRNA and protein expressions were significantly reduced by garlic treatment (50 µg/mL) comparable to those of UV-unexposed control cells. UV-induced pro-inflammatory cytokine productions (IL-6 and IL-1β) were significantly inhibited by pretreatment with garlic in a dose-dependent manner. SA-β-gal activity, a classical biomarker of cellular senescence, and SIRT1 activity, which has attracted attention as an anti-aging factor in recent years, were ameliorated by garlic treatment in UV-irradiated HaCaT cells. The present study provides the first evidence of garlic inhibiting UVB-induced photoaging as a result of augmentation of cellular senescence in HaCaT human keratinocytes.

  15. Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human Keratinocytes

    PubMed Central

    Kim, Hye Kyung

    2016-01-01

    Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in the cells, which induces the cellular senescence and photoaging. The present study investigated the protective effects of garlic on photo-damage and cellular senescence in UVB-exposed human keratinocytes, HaCaT cells. An in vitro cell free system was used to examine the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and nitric oxide (NO). The effect of garlic extract on ROS formation, MMP-1 protein and mRNA expressions, cytokines such as interleukin (IL)-1β and IL-6, senescence associated-β-galactosidase (SA-β-gal) activity, and silent information regulator T1 (SIRT1) activity were determined in UVB-irradiated HaCaT cells. Garlic exhibited strong DPPH radical and NO scavenging activity in cell free system exhibiting IC50 values of 2.50 mg/mL and 4.38 mg/mL, respectively. Garlic pretreatment attenuated the production of UVB-induced intracellular ROS. MMP-1 level, which has been known to be induced by ROS, was dramatically elevated by UVB irradiation, and UVB-induced MMP-1 mRNA and protein expressions were significantly reduced by garlic treatment (50 µg/mL) comparable to those of UV-unexposed control cells. UV-induced pro-inflammatory cytokine productions (IL-6 and IL-1β) were significantly inhibited by pretreatment with garlic in a dose-dependent manner. SA-β-gal activity, a classical biomarker of cellular senescence, and SIRT1 activity, which has attracted attention as an anti-aging factor in recent years, were ameliorated by garlic treatment in UV-irradiated HaCaT cells. The present study provides the first evidence of garlic inhibiting UVB-induced photoaging as a result of augmentation of cellular senescence in HaCaT human keratinocytes. PMID:27483310

  16. Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone.

    PubMed

    Ng, Angela M H; Tan, K K; Phang, M Y; Aziyati, O; Tan, G H; Isa, M R; Aminuddin, B S; Naseem, M; Fauziah, O; Ruszymah, B H I

    2008-05-01

    Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering. Copyright 2007 Wiley Periodicals, Inc.

  17. Influence of soil texture on carbon dynamics and storage potential in tropical forest soils of Amazonia

    NASA Astrophysics Data System (ADS)

    Telles, Everaldo De Carvalho ConceiçÃ.£O.; de Camargo, PlíNio Barbosa; Martinelli, Luiz A.; Trumbore, Susan E.; da Costa, Enir Salazar; Santos, Joaquim; Higuchi, Niro; Oliveira, Raimundo Cosme

    2003-06-01

    Stable and radiocarbon isotopes were used to investigate the role of soil clay content in the storage and dynamics of soil carbon in tropical forest soils. Organic matter in clay-rich Oxisols and Ultisols contains at least two distinct components: (1) material with light δ13C signatures and turnover times of decades or less; and (2) clay-associated, 13C-enriched, carbon with turnover times of decades at the surface to millennia at depths >20 cm. Soil texture, in this case clay content, exerts a major control on the amount of slowly cycling carbon and therefore influences the storage and dynamics of carbon in tropical forest soils. Soils in primary tropical forest have been proposed as a potentially large sink for anthropogenic carbon. Comparison of carbon stocks in Oxisols sampled near Manaus, Brazil, shows no measurable change in organic carbon stocks over the past 20 years. Simple models estimating the response of soil carbon pools to a sustained 0.5% yr-1 increase in productivity result in C storage rates of 0.09 to 0.13 MgC ha-1 yr-1 in soil organic matter, with additional potential storage of 0.18 to 0.27 MgC ha-1 yr-1 in surface litter and roots. Most storage occurs in organic matter pools with turnover times less than a decade. Export of carbon in dissolved form from upland terra firme Oxisols likely accounts for <0.2 MgC ha-1 yr-1, but more work is required to assess the export potential for periodically inundated Spodosols.

  18. Increasing Incidence and Age at Diagnosis among Children with Type 1 Diabetes Mellitus over a 20-Year Period in Auckland (New Zealand)

    PubMed Central

    Derraik, José G. B.; Reed, Peter W.; Jefferies, Craig; Cutfield, Samuel W.; Hofman, Paul L.; Cutfield, Wayne S.

    2012-01-01

    Background We aimed to evaluate the incidence of type 1 diabetes mellitus in children <15 years of age (yr) in the Auckland region (New Zealand) over 20 years (1990–2009). Methods We performed a retrospective review of all patients <15 yr diagnosed with type 1 diabetes, from an unselected complete regional cohort. Results There were 884 new cases of type 1 diabetes, and age at diagnosis rose from 7.6 yr in 1990/1 to 8.9 yr in 2008/9 (r2 = 0.31, p = 0.009). There was a progressive increase in type 1 diabetes incidence among children <15 yr (p<0.0001), reaching 22.5 per 100,000 in 2009. However, the rise in incidence did not occur evenly among age groups, being 2.5-fold higher in older children (10–14 yr) than in the youngest group (0–4 yr). The incidence of new cases of type 1 diabetes was highest in New Zealand Europeans throughout the study period in all age groups (p<0.0001), but the rate of increase was similar in New Zealand Europeans and Non-Europeans. Type 1 diabetes incidence and average annual increase were similar in both sexes. There was no change in BMI SDS shortly after diagnosis, and no association between BMI SDS and age at diagnosis. Conclusions There has been a steady increase in type 1 diabetes incidence among children <15 yr in Auckland over 20 years. Contrary to other studies, age at diagnosis has increased and the greatest rise in incidence occurred in children 10–14 yr. There was little change in BMI SDS in this population, providing no support for the ‘accelerator hypothesis’. PMID:22389717

  19. Impacts of individual tree species on carbon dynamics in a moist tropical forest environment.

    PubMed

    Russell, Ann E; Raich, James W; Arrieta, Ricardo Bedoya; Valverde-Barrantes, Oscar; González, Eugenio

    2010-06-01

    In the moist tropical forest biome, which cycles carbon (C) rapidly and stores huge amounts of C, the impacts of individual species on C balances are not well known. In one of the earliest replicated experimental sites for investigating growth of native tropical trees, we examined traits of tree species in relation to their effects on forest C balances, mechanisms of influence, and consequences for C sequestration. The monodominant stands, established in abandoned pasture in 1988 at La Selva Biological Station, Costa Rica, contained five species in a complete randomized block design. Native species were: Hieronyma alchorneoides, Pentaclethra macroloba, Virola koschnyi, and Vochysia guatemalensis. The exotic species was Pinus patula. By 16 years, the lack of differences among species in some attributes suggested strong abiotic control in this environment, where conditions are very favorable for growth, These attributes included aboveground net primary productivity (ANPP), averaging 11.7 Mg C x ha(-1) x yr(-1) across species, and soil organic C (0-100 cm, 167 Mg C/ha). Other traits differed significantly, however, indicating some degree of biological control. In Vochysia plots, both aboveground biomass of 99 Mg C/ha, and belowground biomass of 20 Mg C/ha were 1.8 times that of Virola (P = 0.02 and 0.03, respectively). Differences among species in overstory biomass were not compensated by understory vegetation. Belowground NPP of 4.6 Mg C x ha(-1) yr(-1) in Hieronyma was 2.4 times that of Pinus (P < 0.01). Partitioning of NPP to belowground components in Hieronyma was more than double that of Pinus (P = 0.03). The canopy turnover rate in Hieronyma was 42% faster than that of Virola (P < 0.01). Carbon sequestration, highest in Vochysia (7.4 Mg C x ha(-1) x yr(-1), P = 0.02), averaged 5.2 Mg C x ha(-1) x yr(-1), close to the annual per capita fossil fuel use in the United States of 5.3 Mg C. Our results indicated that differences in species effects on forest C balances

  20. Potential land competition between open-pond microalgae production and terrestrial dedicated feedstock supply systems in the U.S.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Langholtz, Matthew H.; Coleman, Andre M.; Eaton, Laurence M.

    Biofuels produced from both terrestrial and algal biomass feedstocks can contribute to energy security while providing economic, environmental, and social benefits. To assess the potential for land competition between these two feedstock types in the United States, we evaluate a scenario in which 41.5 x 109 L yr-1 of second-generation biofuels are produced on pastureland, the most likely land base where both feedstock types may be deployed. This total includes 12.0 x 109 L yr-1 of biofuels from open-pond microalgae production and 29.5 x 109 L yr-1 of biofuels from terrestrial dedicated feedstock supply systems. Under these scenarios, open-pond microalgaemore » production is projected to use 1.2 million ha of private pastureland, while terrestrial dedicated feedstock supply systems would use 14.0 million ha of private pastureland. A spatial meta-analysis indicates that potential competition for land under these scenarios would be concentrated in 110 counties, containing 1.0 and 1.7 million hectares of algal and terrestrial dedicated feedstock production, respectively. A land competition index applied to these 110 counties suggests that 38 to 59 counties could experience competition for upwards of 40% of a county’s pastureland. However, this combined 2.7 million ha represents only 2%-5% of total pastureland in the U.S., with the remaining 12.5 million ha of algal or terrestrial dedicated feedstock production on pastureland in non-competing areas.« less

  1. Significant impacts of nutrient enrichment on High Arctic vegetation and soils despite two decades of recovery

    NASA Astrophysics Data System (ADS)

    Street, L. E.; Burns, N. R.; Woodin, S. J.

    2012-04-01

    We re-visit a unique field manipulation study in Svalbard to assess the long-term recovery of plant species composition, leaf tissue chemistry and total ecosystem carbon storage from nutrient enrichment. The experiment was established in 1991. The original aim was to quantify the 'critical load' of nitrogen (N) for tundra; that is, the minimum rate of N deposition affecting ecosystem structure and function. Dissolved N was applied to heath vegetation, both alone and in combination with phosphorous (P), during the growing season over three years. The rates of N addition were lower than in most other nutrient manipulation studies, and were designed to represent typical rates of deposition in the Scottish highlands (50 kg N ha-1 yr-1) and maximum deposition rates experienced in the Arctic (10 kg N ha-1 yr-1). Significant changes in shrub cover, the greenness and N content of the moss layer, and the extent of ecosystem N saturation had occurred by the end of the treatment period. After 18 years of recovery without further treatment, we assessed primary productivity using CO2 flux measurements, and the 'greenness' of vegetation using the Normalised Difference Vegetation Index. We made destructive measurements of above- and below-ground carbon and nutrient stocks, quantified species composition and sampled leaf tissue for chemical analysis. Total carbon storage in organic soils and vegetation was c. 40 % lower in the plots treated with 50 kg N ha-1 yr-1 compared to controls. Species composition in N treated plots also differed significantly, but there was no clear treatment effect on primary productivity. Where 50 kg N ha-1 yr-1 was applied in combination with P (at 5 kg P ha-1 yr-1 ), organic carbon storage was c. 70 % greater than controls, the vegetation was greener, and primary productivity higher. Effects of the treatments were also still clearly apparent in moss tissue nutrient status, even at the lower nitrogen application rate. Our results imply that the effects

  2. Evaluation of Preexisting Anti-Hemagglutinin Stalk Antibody as a Correlate of Protection in a Healthy Volunteer Challenge with Influenza A/H1N1pdm Virus

    PubMed Central

    Park, Jae-Keun; Han, Alison; Czajkowski, Lindsay; Reed, Susan; Athota, Rani; Bristol, Tyler; Rosas, Luz Angela; Cervantes-Medina, Adriana; Taubenberger, Jeffery K.

    2018-01-01

    ABSTRACT Influenza virus hemagglutinin (HA) surface glycoprotein is currently the primary target of licensed influenza vaccines. Recently, broadly reactive antibodies that target the stalk region of the HA have become a major focus of current novel vaccine development. These antibodies have been observed in humans after natural infection with influenza A virus, but the data are limited. Using samples and data from the uniquely controlled setting of an influenza A/H1N1 virus human challenge study of healthy volunteers, we performed a secondary analysis that for the first time explores the role of anti-HA stalk antibody as a human correlate of protection. An anti-HA stalk antibody enzyme-linked immunosorbent assay (ELISA) was performed on samples from 65 participants challenged with a 2009 H1N1pdm virus. Pre- and postchallenge anti-HA stalk titers were then correlated with multiple outcome measures to evaluate anti-HA stalk antibody titer as a correlate of protection. Anti-HA stalk antibody titers were present before challenge and rose in response to challenge in 64% of individuals. Those individuals with higher titers at baseline were less likely to develop shedding, but not less likely to develop symptoms. Similar to the hemagglutination inhibition (HAI) titer, the baseline anti-HA stalk antibody titer did not independently predict a decrease in the severity of influenza disease, while the antineuraminidase (neuraminidase inhibition [NAI]) titer did. As a correlate of protection, the naturally occurring anti-HA stalk antibody titer is predictive of a reduction of certain aspects of disease similar to HAI titer, but the NAI titer is the only identified correlate that is an independent predictor of a reduction of all assessed influenza clinical outcome measures. PMID:29362240

  3. Greenhouse gas balance of a Scots pine forest using biometric, eddy covariance and chamber measurements.

    NASA Astrophysics Data System (ADS)

    Gielen, Bert; De Vos, Bruno; Papale, Dario; Janssens, Ivan

    2013-04-01

    In recent years, the status of forests as sources or sinks of carbon has received much attention. Nonetheless, evidence-based long-term estimates of the magnitude of the carbon sequestration in forests are still scarce. In this study we present two independent estimates of net carbon sequestration in a temperate Scots pine dominated forest ecosystem over a 9 year period (2002-2010) and in addition, to determine the full greenhouse gas balance, the first results of automated chamber measurements of N2O and CH4. First, the net ecosystem carbon balance (NECB) was estimated from net ecosystem CO2 exchange as measured by the eddy covariance technique (NECBEC). To this end, the eddy covariance estimates were combined with non-CO2 carbon fluxes such as DOC leaching and VOC emissions. The second approach to determine the carbon sequestration was based on the changes in the ecosystem carbon stocks over time (NECBSC). For this NECBSC estimate, two assessments of the ecosystem carbon stocks (2002 and 2010) were compared. Results showed that the eddy covariance approach estimated a net uptake of 2.4 ± 1.25 tC ha-1 yr-1, while the stock based approach suggested a carbon sink of 1.8 ± 1.20 tC ha-1 yr-1. No significant change was observed in the mineral soil carbon, while the carbon stock of the litter layer slightly decreased. Phytomass was thus the main carbon sink (2.1 tC ha-1 yr-1) in the pine forest, predominantly in the stems (1.3 tC ha-1 yr-1). The fact that stem wood is the main carbon sink within the ecosystem implies that the future harvesting has the potential to fully offset the CO2 uptake by this Scots pine forest. Estimates of the impact of N2O and CH4 emissions from the soil on the total greenhouse gas budget will be presented.

  4. TSH/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis

    PubMed Central

    Krieger, Christine C.; Place, Robert F.; Bevilacqua, Carmine; Marcus-Samuels, Bernice; Abel, Brent S.; Skarulis, Monica C.; Kahaly, George J.; Neumann, Susanne

    2016-01-01

    Context: The TSH receptor (TSHR) is considered the main target of stimulatory autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also play a role. Objective: We previously demonstrated that a monoclonal stimulatory TSHR antibody, M22, activates TSHR/IGF-1R cross talk in orbital fibroblasts/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]). We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is involved in the mediation of GO pathogenesis stimulated by Graves' autoantibodies. Design/Setting/Participants: Immunoglobulins were purified from the sera of 57 GO patients (GO-Igs) and tested for their ability to activate TSHR and/or IGF-1R directly and TSHR/IGF-1R cross talk in primary cultures of GOFs. Cells were treated with M22 or GO-Igs with or without IGF-1R inhibitory antibodies or linsitinib, an IGF-1R kinase inhibitor. Main Outcome Measures: Hyaluronan (hyaluronic acid [HA]) secretion was measured as a major biological response for GOF stimulation. IGF-1R autophosphorylation was used as a measure of direct IGF-1R activation. TSHR activation was determined through cAMP production. Results: A total of 42 out of 57 GO-Ig samples stimulated HA secretion. None of the GO-Ig samples exhibited evidence for IGF-1R autophosphorylation. Both anti-IGF-1R antibodies completely inhibited IGF-1 stimulation of HA secretion. By contrast, only 1 IGF-1R antibody partially blocked HA secretion stimulated by M22 or GO-Igs in a manner similar to linsitinib, whereas the other IGF-1R antibody had no effect on M22 or GO-Ig stimulation. These findings show that the IGF-1R is involved in GO-Igs stimulation of HA secretion without direct activation of IGF-1R. Conclusions: IGF-1R activation by GO-Igs occurs via TSHR/IGF-1R cross talk rather than direct binding to IGF-1R, and this cross talk is important in the pathogenesis of GO. PMID:27043163

  5. The PA and HA Gene-Mediated High Viral Load and Intense Innate Immune Response in the Brain Contribute to the High Pathogenicity of H5N1 Avian Influenza Virus in Mallard Ducks

    PubMed Central

    Hu, Jiao; Hu, Zenglei; Mo, Yiqun; Wu, Qiwen; Cui, Zhu; Duan, Zhiqiang; Huang, Junqing; Chen, Hongzhi; Chen, Yuxin; Gu, Min; Wang, Xiaoquan; Hu, Shunlin; Liu, Huimou; Liu, Wenbo; Liu, Xiaowen

    2013-01-01

    Most highly pathogenic avian influenza A viruses cause only mild clinical signs in ducks, serving as an important natural reservoir of influenza A viruses. However, we isolated two H5N1 viruses that are genetically similar but differ greatly in virulence in ducks. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is low pathogenic. To determine the genetic basis for the high virulence of CK10 in ducks, we generated a series of single-gene reassortants between CK10 and GS10 and tested their virulence in ducks. Expression of the CK10 PA or hemagglutinin (HA) gene in the GS10 context resulted in increased virulence and virus replication. Conversely, inclusion of the GS10 PA or HA gene in the CK10 background attenuated the virulence and virus replication. Moreover, the PA gene had a greater contribution. We further determined that residues 101G and 237E in the PA gene contribute to the high virulence of CK10. Mutations at these two positions produced changes in virulence, virus replication, and polymerase activity of CK10 or GS10. Position 237 plays a greater role in determining these phenotypes. Moreover, the K237E mutation in the GS10 PA gene increased PA nuclear accumulation. Mutant GS10 viruses carrying the CK10 HA gene or the PA101G or PA237E mutation induced an enhanced innate immune response. A sustained innate response was detected in the brain rather than in the lung and spleen. Our results suggest that the PA and HA gene-mediated high virus replication and the intense innate immune response in the brain contribute to the high virulence of H5N1 virus in ducks. PMID:23926340

  6. Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.

    PubMed

    Zhang, Yulong; Dong, Rui; Park, Yujin; Bohner, Marc; Zhang, Xinli; Ting, Kang; Soo, Chia; Wu, Benjamin M

    2016-09-10

    NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. H1N1 seasonal influenza virus evolutionary rate changed over time.

    PubMed

    Suptawiwat, Ornpreya; Kongchanagul, Alita; Boonarkart, Chompunuch; Auewarakul, Prasert

    2018-05-02

    It was previously shown that the seasonal H1N1 influenza virus antigenic drift occurred at a slower rate than the seasonal H3N2 virus during the first decade of the 21th century. It was hypothesized that the slower antigenic evolution led to a decrease in average ages of infection, which in turn resulted in lower level of global viral circulation. It is unclear what caused the difference between the two viruses, but a plausible explanation may be related to the fact that the H1N1 virus had been in human population for much longer than the H3N2 virus. This would suggest that H1N1 antigenic drift in an earlier period may have been different from a more recent period. To test this hypothesis, we analyzed seasonal H1N1 influenza sequences during various time periods. In comparison to more recent H1N1 virus, the older H1N1 virus during the first half of the 20th century showed evidences of higher nonsynnonymous/synonymous ration (dN/dS) in its hemagglutinin (HA) gene. We compared amino acid sequence changes in the HA epitopes for each outbreak season and found that there were less changes in later years. Amino acid sequence diversity in the epitopes as measured by sequence entropy became smaller for each passing decade. These suggest that there might be some limit to the antigenic drift. The longer an influenza virus has drifted in human population, the less flexibility it may become. With less flexibility to adapt and escape the host immunity, the virus may have to rely more on younger naïve population. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Distribution of gene segments of the pandemic A(H1N1) 2009 virus lineage in pig populations.

    PubMed

    Okuya, K; Matsuu, A; Kawabata, T; Koike, F; Ito, M; Furuya, T; Taneno, A; Akimoto, S; Deguchi, E; Ozawa, M

    2018-05-06

    Swine influenza viruses (SIVs) are important not only for pig farming, but also for public health. In fact, pandemic A(H1N1) 2009 viruses [A(H1N1)pdm09] were derived from SIVs. Therefore, timely characterization of locally circulating SIVs is necessary for understanding the global status of SIVs. To genetically characterize SIVs circulating in Japanese pig populations, we isolated 24 SIVs of three subtypes (17 H1N1, four H1N2 and three H3N2 strains) from 14 pig farms in Japan from 2013 to 2016. Genetic analyses revealed that the haemagglutinin (HA) and neuraminidase (NA) genes of the 17 H1N1 and the HA gene of one H1N2, A/swine/Aichi/02/2016 (H1N2), SIVs belonged to the A(H1N1)pdm09 lineage. More importantly, all of the remaining six gene segments (i.e., PB1, PB1, PA, NP, M and NS) of the 24 SIVs, regardless of the HA and NA subtype, were also classified as belonging to the A(H1N1)pdm09 lineage. These results indicate that gene segments of A(H1N1)pdm09 lineage are widely distributed in SIVs circulating in Japanese pig populations In addition, the NA gene of A/swine/Aichi/02/2016 (H1N2) shared less than 88.5% nucleotide identity with that of the closest relative A/swine/Miyagi/5/2003 (H1N2), which was isolated in Japan in 2003. These results indicate the sustained circulation of classical H1N2-derived SIVs with remarkable diversity in the NA genes in Japanese pig populations. These findings highlight the necessity of both intensive biosecurity systems and active SIV surveillance in pig populations worldwide for both animal and public health. © 2018 Blackwell Verlag GmbH.

  9. Evaluation of the attenuation, immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus, in ferrets

    PubMed Central

    Broadbent, Andrew J.; Santos, Celia P.; Anafu, Amanda; Wimmer, Eckard; Mueller, Steffen; Subbarao, Kanta

    2015-01-01

    Codon-pair bias de-optimization (CPBD) of viruses involves re-writing viral genes using statistically underrepresented codon pairs, without any changes to the amino acid sequence or codon usage. Previously, this technology has been used to attenuate the influenza A/Puerto Rico/8/34 (H1N1) virus. The de-optimized virus was immunogenic and protected inbred mice from challenge. In order to assess whether CPBD could be used to produce a live vaccine against a clinically relevant influenza virus, we generated an influenza A/California/07/2009 pandemic H1N1 (2009 pH1N1) virus with de-optimized HA and NA gene segments (2009 pH1N1-(HA+NA)Min), and evaluated viral replication and protein expression in MDCK cells, and attenuation, immunogenicity, and efficacy in outbred ferrets. The 2009 pH1N1-(HA+NA)Min virus grew to a similar titer as the 2009 pH1N1 wild type (wt) virus in MDCK cells (~106 TCID50/ml), despite reduced HA and NA protein expression on western blot. In ferrets, intranasal inoculation of 2009 pH1N1-(HA+NA)Min virus at doses ranging from 103 to 105 TCID50 led to seroconversion in all animals and protection from challenge with the 2009 pH1N1 wt virus 28 days later. The 2009 pH1N1-(HA+NA)Min virus did not cause clinical illness in ferrets, but replicated to a similar titer as the wt virus in the upper and lower respiratory tract, suggesting that de-optimization of additional gene segments may be warranted for improved attenuation. Taken together, our data demonstrate the potential of using CPBD technology for the development of a live influenza virus vaccine if the level of attenuation is optimized. PMID:26655630

  10. Long-term intensive management increased carbon occluded in phytolith (PhytOC) in bamboo forest soils

    NASA Astrophysics Data System (ADS)

    Huang, Zhang-Ting; Li, Yong-Fu; Jiang, Pei-Kun; Chang, Scott X.; Song, Zhao-Liang; Liu, Juan; Zhou, Guo-Mo

    2014-01-01

    Carbon (C) occluded in phytolith (PhytOC) is highly stable at millennium scale and its accumulation in soils can help increase long-term C sequestration. Here, we report that soil PhytOC storage significantly increased with increasing duration under intensive management (mulching and fertilization) in Lei bamboo (Phyllostachys praecox) plantations. The PhytOC storage in 0-40 cm soil layer in bamboo plantations increased by 217 Mg C ha-1, 20 years after being converted from paddy fields. The PhytOC accumulated at 79 kg C ha-1 yr-1, a rate far exceeding the global mean long-term soil C accumulation rate of 24 kg C ha-1 yr-1 reported in the literature. Approximately 86% of the increased PhytOC came from the large amount of mulch applied. Our data clearly demonstrate the decadal scale management effect on PhytOC accumulation, suggesting that heavy mulching is a potential method for increasing long-term organic C storage in soils for mitigating global climate change.

  11. In vitro and in vivo evidence of a potential A(H1N1)pdm09 antigenic drift mediated by escape mutations in the haemagglutinin Sa antigenic site.

    PubMed

    Retamal, Miguel; Abed, Yacine; Rhéaume, Chantal; Baz, Mariana; Boivin, Guy

    2017-06-01

    Influenza A(H1N1)pdm09 virus continues to circulate worldwide without evidence of significant antigenic drift between 2009 and 2016. By using escape mutants, we previously identified six haemagglutinin (HA) changes (T80R, G143E, G158E, N159D, K166E and A198E) that were located within antigenic sites. Combinations of these mutations were introduced into the A(H1N1)pdm09 HA plasmid by mutagenesis. Reassortant 6 : 2 viruses containing both the HA and NA genes of the A(H1N1)pdm09 and the six internal gene segments of A/PR/8/34 were rescued by reverse genetics. In vitro, HA inhibition and microneutralization assays showed that the HA hexa-mutant reassortant virus (RG1) escaped A(H1N1)pdm09 hyper-immune ferret antiserum recognition. C57Black/6 mice that received the vaccine formulated with A/California/07/09 were challenged with 2×104 p.f.u. of either the 6 : 2 wild-type (WT) or RG1 viruses. Reductions in body weight loss, mortality rate and lung viral titre were observed in immunized animals challenged with the 6 : 2 WT virus compared to non-immunized mice. However, immunization did not protect mice challenged with RG1 virus. To further characterize the mutations causing this antigenic change, 11 additional RG viruses whose HA gene contained single or combinations of mutations were evaluated in vitro. Although the RG1 virus was still the least reactive against hyper-immune serum by HAI testing, mutations G158E and N159D within the Sa antigenic site appeared to play the major role in the altered antigenicity of the A(H1N1)pdm09 virus. These results show that the Sa antigenic site contains the most prominent epitopes susceptible to cause an antigenic drift, escaping actual vaccine protection.

  12. Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study

    PubMed Central

    Porter, John; Galanello, Renzo; Saglio, Giuseppe; Neufeld, Ellis J; Vichinsky, Elliott; Cappellini, Maria Domenica; Olivieri, Nancy; Piga, Antonio; Cunningham, Melody J; Soulières, Denis; Gattermann, Norbert; Tchernia, Gilbert; Maertens, Johan; Giardina, Patricia; Kwiatkowski, Janet; Quarta, Giovanni; Jeng, Michael; Forni, Gian Luca; Stadler, Michael; Cario, Holger; Debusscher, Louisette; Porta, Matteo Della; Cazzola, Mario; Greenberg, Peter; Alimena, Giuliana; Rabault, Bertrand; Gathmann, Insa; Ford, John Malcolm; Alberti, Daniele; Rose, Christian

    2008-01-01

    Objectives/methods This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3–81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond–Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or β-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC). Results In patients with baseline LIC ≥7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 ± 0.14 mg/kg/d; greatest in DBA: 0.4 ± 0.11 mg/kg/d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases. Conclusions Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups. PMID:18028431

  13. Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age

    PubMed Central

    Vesikari, Timo; Pepin, Stéphanie; Kusters, Inca; Hoffenbach, Agnès; Denis, Martine

    2012-01-01

    Vaccines were urgently needed in 2009 against A/H1N1 pandemic influenza. Based on the H5N1 experience, it was originally thought that 2 doses of an adjuvanted vaccine were needed for adequate immunogenicity. We tested H1N1 vaccines with or without AF03, a squalene-based adjuvant, in children. Two randomized, open-label, trials were conducted. Participants 3–17 y received two injections of 3.8 µg or 7.5 µg hemagglutinin (HA) with adjuvant or 15 µg HA without adjuvant. Participants aged 6–35 mo received two injections of 1.9 µg or 3.8 µg HA with full or half dose adjuvant or 7.5 µg HA without adjuvant. All subjects 3 to 17 y reached seroprotection (hemagglutination inhibition (HI) titer ≥ 40) after the first dose of the adjuvanted vaccine, and 94% and 98% in the 3–8 and 9–17 y groups respectively with the non-adjuvanted vaccine. In children aged 6–35 mo responses were modest after one dose, but after two doses virtually all children were seroprotected regardless of HA or adjuvant dose. In this age group, antibody titers were 5 to 7 times higher after adjuvanted than non-adjuvanted vaccine. The higher responses with the adjuvanted vaccine were also reflected as better antibody persistence. There was no clustering of adverse events that would be suggestive of a safety signal. While a single injection was sufficient in subjects from 3 y, in children aged 6–35 mo two injections of this A/H1N1 pandemic influenza vaccine were required. Formulation of this vaccine with adjuvant provided a significant advantage for immunogenicity in the latter age group. PMID:22906943

  14. New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.

    PubMed

    Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander

    2015-06-01

    Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

    PubMed Central

    Baer, Jane; Santiago, Felix W.; Fitzgerald, Theresa; Ilyushina, Natalia A.; Sundararajan, Aarthi; Henn, Alicia D.; Krammer, Florian; Yang, Hongmei; Luke, Catherine J.; Zand, Martin S.; Wright, Peter F.; Treanor, John J.; Topham, David J.

    2013-01-01

    The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and ≥70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus-specific antibody (Ab)-secreting cells and ≥4-fold increases in HAI and MN titers. However, the response was strongest in the 18- to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18- to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the anti-Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza. PMID:23576673

  16. Optimally designed collagen/polycaprolactone biocomposites supplemented with controlled release of HA/TCP/rhBMP-2 and HA/TCP/PRP for hard tissue regeneration.

    PubMed

    Kim, WonJin; Jang, Chul Ho; Kim, GeunHyung

    2017-09-01

    Collagen has been widely used as a very promising material to regenerate various tissues. It is a chief component of the extracellular matrix, and encourages various biological effects conducive to tissue regeneration. However, poor mechanical stability, low processability, and high level of water absorption can lead to impaired control of growth factor release and have impeded the use of collagen as a functional biomedical scaffold. Here, to overcome the shortcomings of collagen scaffolds, we have additively manufactured collagen/polycaprolactone (PCL) biocomposites supplemented with a bioceramic (hydroxyapatite (HA)/β-tricalcium-phosphate (TCP)) and two growth factors (recombinant human bone morphogenetic protein-2 [rhBMP-2] and platelet-rich plasma [PRP]). Various weight fractions of PCL in the collagen/PCL composites were manipulated to select optimal growth factor release and highly active cellular responses. After the optimal concentration of PCL in the collagen/PCL scaffold was determined, biocomposites supplemented with bioceramic/growth-factors were fabricated. Continuously released growth factors were assumed to increase the in vitro cellular activities of the osteoblast-like cells (MG63) cultured on the biocomposites. In vitro cellular responses, including osteogenic activities, were examined, and results showed that compared to the HA/TCP/rhBMP-2 supplemented scaffold the HA/TCP/PRP biocomposites provide significantly high cellular activities (cell proliferation: >1.3-fold) and mineralization (calcium deposition: >1.4-fold, osteocalcin: >2.6-fold) sufficient for regenerating bone tissue. Copyright © 2017. Published by Elsevier B.V.

  17. DAMA/LIBRA-phase1 results and perspectives of the phase2

    NASA Astrophysics Data System (ADS)

    Bernabei, R.; Belli, P.; Cappella, F.; Caracciolo, V.; Cerulli, R.; Dai, C. J.; d'Angelo, A.; d'Angelo, S.; Di Marco, A.; He, H. L.; Incicchitti, A.; Kuang, H. H.; Ma, X. H.; Montecchia, F.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

    2016-07-01

    The DAMA/LIBRA experiment (˜ 250 kg of highly radio-pure NaI(Tl)) is running deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N. Here we briefly recall the results obtained in its first phase of measurements (DAMA/LIBRA-phase1; total exposure: 1.04 ton × yr). DAMA/LIBRA-phase1 and the former DAMA/NaI (cumulative exposure: 1.33 ton × yr) give evidence at 9.3 σ C.L. for the presence of DM particles in the galactic halo by exploiting the model-independent DM annual modulation signature. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade. At present DAMA/LIBRA-phase2 is running with increased sensitivity.

  18. Mercury budget of an upland-peatland watershed

    Treesearch

    D. F. Grigal; Randy K. Kolka; J. A. Fleck; E. A. Nater

    2000-01-01

    Inputs, outputs, and pool sizes of total mercury (Hg) were measured in a forested 10 ha,watershed consisting of a 7 ha hardwood-dominated upland surrounding a 3 ha coniferdominated peatland. Hydrologic inputs via throughfall and stemflow, 13 +/- 0.4/ug m-2 yr-1 over the entire watershed, were about double precipitation...

  19. Nitrogen fixation in boreal peatlands: the effects of increased N deposition on N2-fixation

    NASA Astrophysics Data System (ADS)

    Popma, J. M.; Wieder, R.; Lamers, L.; Vile, M. A.

    2013-12-01

    Boreal peatlands are of great importance to global carbon and nitrogen cycling. While covering only 3-4 % of the terrestrial surface, they account for 25-30 % of the world's soil C and 9-15 % of the world's soil N. In Western Canada atmospheric dry deposition rates are extremely low: approximately 1 kg N ha-1 yr-1. Though these systems have been functioning as net sinks over the past 11,000 years, natural and anthropogenic disturbances might compromise the historical balance of C and N. Biological N2-fixation has recently been shown to represent a very significant input of N into these systems, contributing to 62% of total N in Western Canada. Interactions between N deposition and biological N2-fixation are as yet, unknown, but the impact of elevated deposition of N-compounds from increased industrial expansion of oil sands mining to peatlands, is concerning. Given that nitrogenase, the enzyme responsible for catalyzing N2-fixation, is energetically costly when active, enhanced inputs of atmospheric N deposition could be a major determinant for enzyme activity and rates of biological N input to these bogs. Understanding interactions between N deposition and N2 fixation in boreal peatlands can aid in predicting the consequences of increased N deposition and setting critical loads. We conducted a field-fertilization experiment in a poor fen in Alberta, Canada, to determine the effects of enhanced N deposition on a dominant fen species Sphagnum angustifolium. The experiment consisted of seven N treatments: Control, 0, 5, 10, 15, 20 and 25 kg N ha-1 y1, n=3. N2-fixation was measured during summer 2012 and 2013 using the acetylene reduction assay (ARA). ARA rates were converted to rates of N2-fixation by calibrating ARA with paired 15N2-incubations. In both 2012 and 2013, with increasing N deposition from 0 kg N ha-1 yr-1 to 25 kg N ha-1 yr-1, rates of N2 fixation decreased, with highest rates in the 0 kg N ha-1 yr-1 treatment mosses (54.2 × 1.40; 48.58 × 7.12 kg N ha

  20. Complete Protection against Influenza Virus H1N1 Strain A/PR/8/34 Challenge in Mice Immunized with Non-Adjuvanted Novirhabdovirus Vaccines

    PubMed Central

    Rouxel, Ronan N.; Mérour, Emilie; Biacchesi, Stéphane; Brémont, Michel

    2016-01-01

    Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to the Mononegavirales order. By reverse genetics, we previously showed that a recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve as a vaccine platform against WNV. In the current study, we aimed to evaluate the potential of the Novirhabdovirus platform as a vaccine against influenza virus. Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral surface the hemagglutinin HA ectodomain were generated and used to immunized mice. We showed that mice immunized with either, rVHSV-HA or rIHNV-HA, elicited a strong neutralizing antibody response against influenza virus. A complete protection was conferred to the immunized mice when challenged with a lethal dose of influenza H1N1 A/PR/8/34 virus. Furthermore we showed that although acting as inert antigen in mice, since naturally inactivated over 20°C, mice immunized with rVHSV-HA or rIHNV-HA in the absence of adjuvant were also completely protected from a lethal challenge. Novirhabdoviruses platform are of particular interest as vaccines for mammals since they are cost effective to produce, relatively easy to generate and very effective to protect immunized animals. PMID:27711176

  1. The Reg1-interacting proteins, Bmh1, Bmh2, Ssb1, and Ssb2, have roles in maintaining glucose repression in Saccharomyces cerevisiae.

    PubMed

    Dombek, Kenneth M; Kacherovsky, Nataly; Young, Elton T

    2004-09-10

    In Saccharomyces cerevisiae, a type 1 protein phosphatase complex composed of the Glc7 catalytic subunit and the Reg1 regulatory subunit represses expression of many glucose-regulated genes. Here we show that the Reg1-interacting proteins Bmh1, Bmh2, Ssb1, and Ssb2 have roles in glucose repression. Deleting both BMH genes causes partially constitutive ADH2 expression without significantly increasing the level of Adr1 protein, the major activator of ADH2 expression. Adr1 and Bcy1, the regulatory subunit of cAMP-dependent protein kinase, are both required for this effect indicating that constitutive expression in Deltabmh1Deltabmh2 cells uses the same activation pathway that operates in Deltareg1 cells. Deletion of both BMH genes and REG1 causes a synergistic relief from repression, suggesting that Bmh proteins also act independently of Reg1 during glucose repression. A two-hybrid interaction with the Bmh proteins was mapped to amino acids 187-232, a region of Reg1 that is conserved in different classes of fungi. Deleting this region partially releases SUC2 from glucose repression. This indicates a role for the Reg1-Bmh interaction in glucose repression and also suggests a broad role for Bmh proteins in this process. An in vivo Reg1-Bmh interaction was confirmed by copurification of Bmh proteins with HA(3)-TAP-tagged Reg1. The nonconventional heat shock proteins Ssb1 and Ssb2 are also copurified with HA(3)-TAP-tagged Reg1. Deletion of both SSB genes modestly decreases repression of ADH2 expression in the presence of glucose, suggesting that Ssb proteins, perhaps through their interaction with Reg1, play a minor role in glucose repression.

  2. Asymmetric Expansion of the Youngest Galactic Supernova Remnant G1.9+0.3

    NASA Astrophysics Data System (ADS)

    Borkowski, Kazimierz J.; Gwynne, Peter; Reynolds, Stephen P.; Green, David A.; Hwang, Una; Petre, Robert; Willett, Rebecca

    2017-03-01

    The youngest Galactic supernova remnant (SNR) G1.9+0.3, produced by a (probable) SN Ia that exploded ˜1900 CE, is strongly asymmetric at radio wavelengths, much brighter in the north, but bilaterally symmetric in X-rays. We present the results of X-ray expansion measurements that illuminate the origin of the radio asymmetry. We confirm the mean expansion rate (2011-2015) of 0.58% yr-1, but large spatial variations are present. Using the nonparametric “Demons” method, we measure the velocity field throughout the entire SNR, finding that motions vary by a factor of 5, from 0\\buildrel{\\prime\\prime}\\over{.} 09 to 0\\buildrel{\\prime\\prime}\\over{.} 44 yr-1. The slowest shocks are at the outer boundary of the bright northern radio rim, with velocities v s as low as 3600 km s-1 (for an assumed distance of 8.5 kpc), much less than v s = 12,000-13,000 km s-1 along the X-ray-bright major axis. Such strong deceleration of the northern blast wave most likely arises from the collision of SN ejecta with a much denser than average ambient medium there. This asymmetric ambient medium naturally explains the radio asymmetry. In several locations, significant morphological changes and strongly nonradial motions are apparent. The spatially integrated X-ray flux continues to increase with time. Based on Chandra observations spanning 8.3 yr, we measure its increase at 1.3 % +/- 0.8 % yr-1. The SN ejecta are likely colliding with the asymmetric circumstellar medium ejected by the SN progenitor prior to its explosion.

  3. Exotic Spartina alterniflora invasion alters ecosystem-atmosphere exchange of CH4 and N2O and carbon sequestration in a coastal salt marsh in China.

    PubMed

    Yuan, Junji; Ding, Weixin; Liu, Deyan; Kang, Hojeong; Freeman, Chris; Xiang, Jian; Lin, Yongxin

    2015-04-01

    Coastal salt marshes are sensitive to global climate change and may play an important role in mitigating global warming. To evaluate the impacts of Spartina alterniflora invasion on global warming potential (GWP) in Chinese coastal areas, we measured CH4 and N2O fluxes and soil organic carbon sequestration rates along a transect of coastal wetlands in Jiangsu province, China, including open water; bare tidal flat; and invasive S. alterniflora, native Suaeda salsa, and Phragmites australis marshes. Annual CH4 emissions were estimated as 2.81, 4.16, 4.88, 10.79, and 16.98 kg CH4 ha(-1) for open water, bare tidal flat, and P. australis, S. salsa, and S. alterniflora marshes, respectively, indicating that S. alterniflora invasion increased CH4 emissions by 57-505%. In contrast, negative N2O fluxes were found to be significantly and negatively correlated (P < 0.001) with net ecosystem CO2 exchange during the growing season in S. alterniflora and P. australis marshes. Annual N2O emissions were 0.24, 0.38, and 0.56 kg N2O ha(-1) in open water, bare tidal flat and S. salsa marsh, respectively, compared with -0.51 kg N2O ha(-1) for S. alterniflora marsh and -0.25 kg N2O ha(-1) for P. australis marsh. The carbon sequestration rate of S. alterniflora marsh amounted to 3.16 Mg C ha(-1) yr(-1) in the top 100 cm soil profile, a value that was 2.63- to 8.78-fold higher than in native plant marshes. The estimated GWP was 1.78, -0.60, -4.09, and -1.14 Mg CO2 eq ha(-1) yr(-1) in open water, bare tidal flat, P. australis marsh and S. salsa marsh, respectively, but dropped to -11.30 Mg CO2 eq ha(-1) yr(-1) in S. alterniflora marsh. Our results indicate that although S. alterniflora invasion stimulates CH4 emissions, it can efficiently mitigate increases in atmospheric CO2 and N2O along the coast of China. © 2014 John Wiley & Sons Ltd.

  4. Hyaluronic acid, HAS1, and HAS2 are significantly upregulated during muscle hypertrophy

    PubMed Central

    Calve, Sarah; Isaac, Jahdonna; Gumucio, Jonathan P.

    2012-01-01

    Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) in most vertebrate tissues and is thought to play a significant role during development, wound healing, and regeneration. In vitro studies have shown that HA enhances muscle progenitor cell recruitment and inhibits premature myotube fusion, implicating a role for this glycosaminoglycan in functional repair. However, the spatiotemporal distribution of HA during muscle growth and repair was unknown. We hypothesized that inducing hypertrophy via synergist ablation would increase the expression of HA and the HA synthases (HAS1–HAS3). We found that HA and HAS1–HAS3 were significantly upregulated within the plantaris muscle in response to Achilles tenectomy. HA concentration significantly increased 2.8-fold after 2 days but decreased towards levels comparable to age-matched controls by 14 days. Using immunohistochemistry, we found the colocalization of HAS1–HAS3 with macrophages, blood vessel epithelia, and fibroblasts varied in response to time and/or tenectomy. At the level of gene expression, only HAS1 and HAS2 significantly increased with respect to both time and tenectomy. The profiles of additional genes that influence ECM composition during muscle repair, tenascin-C, type I collagen, the HA-degrading hyaluronidases (Hyal) and matrix metalloproteinases (MMP) were also investigated. Hyal1 and Hyal2 were highly expressed in skeletal muscle but did not change after tenectomy; however, indicators of hypertrophy, MMP-2 and MMP-14, were significantly upregulated from 2 to 14 days. These results indicate that HA levels dynamically change in response to a hypertrophic stimulus and various cells may participate in this mechanism of skeletal muscle adaptation. PMID:22785117

  5. Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

    PubMed

    Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

    2017-08-01

    Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

  6. Suitability of 239+240Pu and 137Cs as tracers for soil erosion assessment in mountain grasslands.

    PubMed

    Alewell, Christine; Meusburger, Katrin; Juretzko, Gregor; Mabit, Lionel; Ketterer, Michael E

    2014-05-01

    Anthropogenic radionuclides have been distributed globally due to nuclear weapons testing, nuclear accidents, nuclear weapons fabrication, and nuclear fuel reprocessing. While the negative consequences of this radioactive contamination are self-evident, the ubiquitous fallout radionuclides (FRNs) distribution form the basis for the use as tracers in ecological studies, namely for soil erosion assessment. Soil erosion is a major threat to mountain ecosystems worldwide. We compare the suitability of the anthropogenic FRNs, 137Cs and 239+240Pu as soil erosion tracers in two alpine valleys of Switzerland (Urseren Valley, Canton Uri, Central Swiss Alps and Val Piora, Ticino, Southern Alps). We sampled reference and potentially erosive sites in transects along both valleys. 137Cs measurements of soil samples were performed with a Li-drifted Germanium detector and 239+240Pu with ICP-MS. Our data indicates a heterogeneous deposition of the 137Cs, since most of the fallout origins from the Chernobyl April/May 1986 accident, when large parts of the European Alps were still snow-covered. In contrast, 239+240Pu fallout originated mainly from 1950s to 1960s atmospheric nuclear weapons tests, resulting in a more homogenous distribution and thus seems to be a more suitable tracer in mountainous grasslands. Soil erosion assessment using 239+240Pu as a tracer pointed to a huge dynamic and high heterogeneity of erosive processes (between sedimentation of 1.9 and 7 t ha(-1) yr(-1) and erosion of 0.2-16.4 t ha(-1) yr(-1) in the Urseren Valley and sedimentation of 0.4-20.3 t ha(-1) yr(-1) and erosion of 0.1-16.4 t ha(-1) yr(-1) at Val Piora). Our study represents a novel and successful application of 239+240Pu as a tracer of soil erosion in a mountain environment. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Humic Acid Confers HIGH-AFFINITY K+ TRANSPORTER 1-Mediated Salinity Stress Tolerance in Arabidopsis.

    PubMed

    Khaleda, Laila; Park, Hee Jin; Yun, Dae-Jin; Jeon, Jong-Rok; Kim, Min Gab; Cha, Joon-Yung; Kim, Woe-Yeon

    2017-12-31

    Excessive salt disrupts intracellular ion homeostasis and inhibits plant growth, which poses a serious threat to global food security. Plants have adapted various strategies to survive in unfavorable saline soil conditions. Here, we show that humic acid (HA) is a good soil amendment that can be used to help overcome salinity stress because it markedly reduces the adverse effects of salinity on Arabidopsis thaliana seedlings. To identify the molecular mechanisms of HA-induced salt stress tolerance in Arabidopsis, we examined possible roles of a sodium influx transporter HIGH-AFFINITY K+ TRANSPORTER 1 (HKT1). Salt-induced root growth inhibition in HKT1 overexpressor transgenic plants (HKT1-OX) was rescued by application of HA, but not in wild-type and other plants. Moreover, salt-induced degradation of HKT1 protein was blocked by HA treatment. In addition, the application of HA to HKT1-OX seedlings led to increased distribution of Na+ in roots up to the elongation zone and caused the reabsorption of Na+ by xylem and parenchyma cells. Both the influx of the secondary messenger calcium and its cytosolic release appear to function in the destabilization of HKT1 protein under salt stress. Taken together, these results suggest that HA could be applied to the field to enhance plant growth and salt stress tolerance via post-transcriptional control of the HKT1 transporter gene under saline conditions.

  8. Testing the Amazon savannization hypothesis: fire effects on invasion of a neotropical forest by native cerrado and exotic pasture grasses

    PubMed Central

    Silvério, Divino V.; Brando, Paulo M.; Balch, Jennifer K.; Putz, Francis E.; Nepstad, Daniel C.; Oliveira-Santos, Claudinei; Bustamante, Mercedes M. C.

    2013-01-01

    Changes in climate and land use that interact synergistically to increase fire frequencies and intensities in tropical regions are predicted to drive forests to new grass-dominated stable states. To reveal the mechanisms for such a transition, we established 50 ha plots in a transitional forest in the southwestern Brazilian Amazon to different fire treatments (unburned, burned annually (B1yr) or at 3-year intervals (B3yr)). Over an 8-year period since the commencement of these treatments, we documented: (i) the annual rate of pasture and native grass invasion in response to increasing fire frequency; (ii) the establishment of Brachiaria decumbens (an African C4 grass) as a function of decreasing canopy cover and (iii) the effects of grass fine fuel on fire intensity. Grasses invaded approximately 200 m from the edge into the interiors of burned plots (B1yr: 4.31 ha; B3yr: 4.96 ha) but invaded less than 10 m into the unburned plot (0.33 ha). The probability of B. decumbens establishment increased with seed availability and decreased with leaf area index. Fine fuel loads along the forest edge were more than three times higher in grass-dominated areas, which resulted in especially intense fires. Our results indicate that synergies between fires and invasive C4 grasses jeopardize the future of tropical forests. PMID:23610179

  9. In vitro modulation of the interaction between HA95 and LAP2beta by cAMP signaling.

    PubMed

    Martins, Sandra B; Marstad, Anne; Collas, Philippe

    2003-09-09

    The nuclear envelope mediates key functions by interacting with chromatin. We recently reported an interaction between the chromatin- and nuclear matrix-associated protein HA95 and the inner nuclear membrane integral protein LAP2beta, implicated in initiation of DNA replication (Martins et al. (2003) J. Cell Biol. 160, 177-188). Here, we show that in vitro, interaction between HA95 and LAP2beta is modulated by cAMP signaling via PKA. Exposure of an anti-HA95 immune precipitate from interphase HeLa cells to a mitotic extract promotes ATP-dependent release of LAP2beta from the HA95 complex. This coincides with Ser and Thr phosphorylation of HA95 and LAP2beta. Inhibition of PKA with PKI abolishes phosphorylation of HA95 and dissociation of LAP2beta from HA95, although LAPbeta remains phosphorylated. Antagonizing cAMP signaling in mitotic extract also abolishes the release of LAP2beta from HA95; however, disrupting PKA anchoring to A-kinase anchoring proteins has no effect. Inhibition of CDK activity in the extract greatly reduces LAP2beta phosphorylation but does not prevent LAP2beta release from HA95. Inhibition of PKC, MAP kinase, or CaM kinase II does not affect mitotic extract-induced dissociation of LAP2beta from HA95. PKA phosphorylates HA95 but not LAP2beta in vitro and elicits a release of LAP2beta from HA95. CDK1 or PKC phosphorylates LAP2beta within the HA95 complex, but neither kinase induces LAP2beta release. Our results indicate that in vitro, the interaction between HA95 and LAP2beta is influenced by a PKA-mediated phosphorylation of HA95 rather than by CDK1- or PKC-mediated phosphorylation of LAP2beta. This suggests an additional level of regulation of a chromatin-nuclear envelope interaction in dividing cells.

  10. Evaluation of Preexisting Anti-Hemagglutinin Stalk Antibody as a Correlate of Protection in a Healthy Volunteer Challenge with Influenza A/H1N1pdm Virus.

    PubMed

    Park, Jae-Keun; Han, Alison; Czajkowski, Lindsay; Reed, Susan; Athota, Rani; Bristol, Tyler; Rosas, Luz Angela; Cervantes-Medina, Adriana; Taubenberger, Jeffery K; Memoli, Matthew J

    2018-01-23

    Influenza virus hemagglutinin (HA) surface glycoprotein is currently the primary target of licensed influenza vaccines. Recently, broadly reactive antibodies that target the stalk region of the HA have become a major focus of current novel vaccine development. These antibodies have been observed in humans after natural infection with influenza A virus, but the data are limited. Using samples and data from the uniquely controlled setting of an influenza A/H1N1 virus human challenge study of healthy volunteers, we performed a secondary analysis that for the first time explores the role of anti-HA stalk antibody as a human correlate of protection. An anti-HA stalk antibody enzyme-linked immunosorbent assay (ELISA) was performed on samples from 65 participants challenged with a 2009 H1N1pdm virus. Pre- and postchallenge anti-HA stalk titers were then correlated with multiple outcome measures to evaluate anti-HA stalk antibody titer as a correlate of protection. Anti-HA stalk antibody titers were present before challenge and rose in response to challenge in 64% of individuals. Those individuals with higher titers at baseline were less likely to develop shedding, but not less likely to develop symptoms. Similar to the hemagglutination inhibition (HAI) titer, the baseline anti-HA stalk antibody titer did not independently predict a decrease in the severity of influenza disease, while the antineuraminidase (neuraminidase inhibition [NAI]) titer did. As a correlate of protection, the naturally occurring anti-HA stalk antibody titer is predictive of a reduction of certain aspects of disease similar to HAI titer, but the NAI titer is the only identified correlate that is an independent predictor of a reduction of all assessed influenza clinical outcome measures. IMPORTANCE This is the first study to evaluate preexisting anti-HA stalk antibodies as a predictor of protection. We use a healthy volunteer influenza challenge trial for an examination of the role such antibodies

  11. Vanadium-induced apoptosis of HaCaT cells is mediated by c-fos and involves nuclear accumulation of clusterin

    PubMed Central

    Markopoulou, Soultana; Kontargiris, Evangelos; Batsi, Christina; Tzavaras, Theodore; Trougakos, Ioannis; Boothman, David A.; Gonos, Efstathios S.; Kolettas, Evangelos

    2016-01-01

    Vanadium exerts a variety of biological effects, including antiproliferative responses through activation of the respective signaling pathways and the generation of reactive oxygen species. As epidermal cells are exposed to environmental insults, human keratinocytes (HaCaT) were used to investigate the mechanism of the antiproliferative effects of vanadyl(IV) sulfate (VOSO4). Treatment of HaCaT cells with VOSO4 inhibited proliferation and induced apoptosis in a dose-dependent manner. Inhibition of proliferation was associated with downregulation of cyclins D1 and E, E2F1, and the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1. Induction of apoptosis correlated with upregulation of the c-fos oncoprotein, changes in the expression of clusterin (CLU), an altered ratio of antiapoptotic to proapoptotic Bcl-2 protein family members, and poly(ADP-ribose) poly-merase-1 cleavage. Forced overexpression of c-fos induced apoptosis in HaCaT cells that correlated with secretory CLU downregulation and upregulation of nuclear CLU (nCLU), a pro-death protein. Overexpression of Bcl-2 protected HaCaT cells from vanadium-induced apoptosis, whereas secretory CLU overexpression offered no cytoprotection. In contrast, nCLU sensitized HaCaT cells to apoptosis. Our data suggest that vanadium-mediated apoptosis was promoted by c-fos, leading to alterations in CLU isoform processing and induction of the pro-death nCLU protein. PMID:19531052

  12. A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs

    PubMed Central

    Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling

    2017-01-01

    ABSTRACT Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by

  13. Switchgrass potential on reclaimed surface mines for biofuel production in West Virginia

    NASA Astrophysics Data System (ADS)

    Marra, Michael A.

    The high cost and environmental risks associated with non-renewable energy sources has caused an increased interest in, and development of renewable biofuels. Switchgrass (Panicum virgatum L.), a warm season perennial grass, has been investigated as a source of biofuel feedstock due to its high biomass production on marginal soils, its tolerance of harsh growing conditions, and its ability to provide habitat for wildlife and soil conservation cover. West Virginia contains vast expanses of reclaimed surface mine lands and could potentially benefit from the production of switchgrass as a biofuel feedstock. Furthermore, switchgrass production could satisfy Surface Mining Reclamation and Control Act of 1977 (SMCRA) requirements for reclamation bond release to mine operators. Three separate studies will be discussed in this thesis to determine if switchgrass grown on reclaimed surface mines can produce yields similar to yields from stands grown under normal agronomic conditions and what common surface mining reclamation practices may be most appropriate for growing switchgrass. The first study examined yield production of three commercially-available, upland switchgrass varieties grown on two reclaimed surface mines in production years two, three and four. The Hampshire Hill mine site, which was reclaimed in the late 1990s using top soil and treated municipal sludge, averaged 5,800 kg (ha-yr)-1 of switchgrass compared to 803 kg (ha-yr)-1 at the Hobet 21 site which was reclaimed with crushed, unweathered rock over compacted overburden. Site and variety interacted with Cave-in-Rock as the top performer at the more fertile Hampshire Hill site and Shawnee produced the highest yields at Hobet 21 (7,853 kg ha-1 and 1,086 kg ha-1 averaged across years, respectively). Switchgrass yields increased from 2009 to 2010, but declined from 2010 to 2011. Switchgrass yields from farmlands in this region averaged about 15000 kg (ha-yr)-1 in the research literature, so switchgrass grown

  14. Antibody Pressure by a Human Monoclonal Antibody Targeting the 2009 Pandemic H1N1 Virus Hemagglutinin Drives the Emergence of a Virus with Increased Virulence in Mice

    PubMed Central

    O’Donnell, Christopher D.; Vogel, Leatrice; Wright, Amber; Das, Suman R.; Wrammert, Jens; Li, Gui-Mei; McCausland, Megan; Zheng, Nai-Ying; Yewdell, Jonathan W.; Ahmed, Rafi; Wilson, Patrick C.; Subbarao, Kanta

    2012-01-01

    ABSTRACT In 2009, a novel H1N1 influenza A virus (2009 pH1N1) emerged and caused a pandemic. A human monoclonal antibody (hMAb; EM4C04), highly specific for the 2009 pH1N1 virus hemagglutinin (HA), was isolated from a severely ill 2009 pH1N1 virus-infected patient. We postulated that under immune pressure with EM4C04, the 2009 pH1N1 virus would undergo antigenic drift and mutate at sites that would identify the antibody binding site. To do so, we infected MDCK cells in the presence of EM4C04 and generated 11 escape mutants, displaying 7 distinct amino acid substitutions in the HA. Six substitutions greatly reduced MAb binding (K123N, D131E, K133T, G134S, K157N, and G158E). Residues 131, 133, and 134 are contiguous with residues 157 and 158 in the globular domain structure and contribute to a novel pH1N1 antibody epitope. One mutation near the receptor binding site, S186P, increased the binding affinity of the HA to the receptor. 186P and 131E are present in the highly virulent 1918 virus HA and were recently identified as virulence determinants in a mouse-passaged pH1N1 virus. We found that pH1N1 escape variants expressing these substitutions enhanced replication and lethality in mice compared to wild-type 2009 pH1N1 virus. The increased virulence of these viruses was associated with an increased affinity for α2,3 sialic acid receptors. Our study demonstrates that antibody pressure by an hMAb targeting a novel epitope in the Sa region of 2009 pH1N1 HA is able to inadvertently drive the development of a more virulent virus with altered receptor binding properties. This broadens our understanding of antigenic drift. PMID:22647789

  15. Adaptation of Pandemic H1N1 Influenza Viruses in Mice▿

    PubMed Central

    Ilyushina, Natalia A.; Khalenkov, Alexey M.; Seiler, Jon P.; Forrest, Heather L.; Bovin, Nicolai V.; Marjuki, Henju; Barman, Subrata; Webster, Robert G.; Webby, Richard J.

    2010-01-01

    The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to α2,3 together with decreasing binding to α2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals. PMID:20592084

  16. Photogenotoxicity of hypericin in HaCaT keratinocytes: implications for St. John's Wort supplements and high dose UVA-1 therapy.

    PubMed

    Traynor, N J; Beattie, P E; Ibbotson, S H; Moseley, H; Ferguson, J; Woods, J A

    2005-09-15

    Extract of St. John's Wort (Hypericum perforatum) is commonly used as natural remedy for treatment of mild to moderate depression. However, it contains a powerful photoactive component, hypericin, which can cause a severe photodermatitis when eaten by grazing animals (hypericism). In humans, there is evidence that supplementation with St. John's Wort can reduce the minimal erythemal dose (MED) in patients undergoing high dose UVA-1 phototherapy. This is a recent development in phototherapy where the most erythemogenic parts of the UVA spectrum are filtered out, allowing delivery of higher doses of the longer wavelengths of UVA. Although current published evidence suggests that the plasma levels of hypericin are unlikely to cause clinical phototoxicity, it has been established that photoactive compounds can cause DNA damage at sub-toxic and sub-erythemal doses, the effects of which might not be apparent for many years after the event. The present study used HaCaT keratinocytes to investigate the photoclastogenic ability of hypericin on irradiation with UVA. The results show that although the combination of hypericin and UVA light increased the genotoxic burden, when all factors are taken into account, the risk of significant photogenotoxic damage incurred by the combination of Hypericum extracts and UVA phototherapy may be low in the majority of individuals.

  17. Broadly-reactive human monoclonal antibodies elicited following pandemic H1N1 influenza virus exposure protect mice from highly pathogenic H5N1 challenge.

    PubMed

    Nachbagauer, Raffael; Shore, David; Yang, Hua; Johnson, Scott K; Gabbard, Jon D; Tompkins, S Mark; Wrammert, Jens; Wilson, Patrick C; Stevens, James; Ahmed, Rafi; Krammer, Florian; Ellebedy, Ali H

    2018-06-13

    Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the mAbs bound HAs from multiple strains of group 1 viruses, and one mAb, 05-2G02, bound to both group 1 and group 2 influenza A HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two mAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One mAb, 70-1F02, was co-crystallized with H5 HA and showed similar heavy chain only interactions as a the previously described anti-stalk antibody CR6261. Finally, we showed that antibodies that compete with these mAbs are prevalent in serum from an individual recently infected with A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections with zoonotic or emerging pandemic influenza viruses. IMPORTANCE The rise in zoonotic infections of humans with emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually

  18. Contribution of aboveground plant respiration to carbon cycling in a Bornean tropical rainforet

    NASA Astrophysics Data System (ADS)

    Katayama, Ayumi; Tanaka, Kenzo; Ichie, Tomoaki; Kume, Tomonori; Matsumoto, Kazuho; Ohashi, Mizue; Kumagai, Tomo'omi

    2014-05-01

    Bornean tropical rainforests have a different characteristic from Amazonian tropical rainforests, that is, larger aboveground biomass caused by higher stand density of large trees. Larger biomass may cause different carbon cycling and allocation pattern. However, there are fewer studies on carbon allocation and each component in Bornean tropical rainforests, especially for aboveground plant respiration, compared to Amazonian forests. In this study, we measured woody tissue respiration and leaf respiration, and estimated those in ecosystem scale in a Bornean tropical rainforest. Then, we examined carbon allocation using the data of soil respiration and aboveground net primary production obtained from our previous studies. Woody tissue respiration rate was positively correlated with diameter at breast height (dbh) and stem growth rate. Using the relationships and biomass data, we estimated woody tissue respiration in ecosystem scale though methods of scaling resulted in different estimates values (4.52 - 9.33 MgC ha-1 yr-1). Woody tissue respiration based on surface area (8.88 MgC ha-1 yr-1) was larger than those in Amazon because of large aboveground biomass (563.0 Mg ha-1). Leaf respiration rate was positively correlated with height. Using the relationship and leaf area density data at each 5-m height, leaf respiration in ecosystem scale was estimated (9.46 MgC ha-1 yr-1), which was similar to those in Amazon because of comparable LAI (5.8 m2 m-2). Gross primary production estimated from biometric measurements (44.81 MgC ha-1 yr-1) was much higher than those in Amazon, and more carbon was allocated to woody tissue respiration and total belowground carbon flux. Large tree with dbh > 60cm accounted for about half of aboveground biomass and aboveground biomass increment. Soil respiration was also related to position of large trees, resulting in high soil respiration rate in this study site. Photosynthesis ability of top canopy for large trees was high and leaves for

  19. Centennial and millennial-scale hydroclimate changes in northwestern Patagonia since 16,000 yr BP

    NASA Astrophysics Data System (ADS)

    Moreno, Patricio I.; Videla, Javiera

    2016-10-01

    We examine hydroclimate changes at centennial/millennial timescales since 16,000 yr BP in northwestern Patagonia based on the pollen and charcoal record from Lago El Salto, a small closed-basin lake located in the Chilean Lake District (41°38‧48.02″S, 73° 5‧48.42″W). We observe cold/wet conditions between 14,500-16,000 yr BP, followed by further cooling with increased precipitation until 13,000 yr BP, enhanced precipitation seasonality and/or variability between 11,600-13,000 yr BP, and an extended warm-and-dry interval between 7600 and 11,300 yr BP with peak paleofire activity. Colder-and-wetter than present conditions and muted paleofire activity prevail between 5300 and 7600 yr BP, followed by alternating cold/wet and centennial-scale warm/dry phases starting at 5300 yr BP with three conspicuous megadroughts since 2500 yr BP. The most recent megadrought occurred during the Medieval Climate Anomaly. We identify a cold reversal that spans the Antarctic Cold Reversal (ACR) and the Younger Dryas (YD) chrons with stronger-than-present westerly influence during the former and enhanced variability during the latter. These results extend the northern limit of strong cooling and increase in precipitation during the ACR and the southern limit of influence of strong hydrologic variations during the YD in terrestrial environments, suggesting an overlap in the spheres of influence of processes originating from southern and northern polar latitudes. An extended warm southern westerly wind (SWW)-minimum interval is evident between 7600 and 11,300 yr BP, followed by a rapid shift to cool-moist conditions between 5300 and 7600 yr BP brought by a mid-Holocene SWW maximum. Since then we observe centennial-scale hydroclimate variability, which has driven biodiversity and fire-regime shifts of evergreen temperate rainforests.

  20. Effects of anodic oxidation and hydrothermal treatment on surface characteristics and biocompatibility of Ti-30Nb-1Fe-1Hf alloy

    NASA Astrophysics Data System (ADS)

    Ou, Shih-Fu; Chou, Hsin-Hua; Lin, Chao-Sung; Shih, Ching-Jui; Wang, Kuang-Kuo; Pan, Yung-Ning

    2012-06-01

    Anodic oxidation followed by hydrothermal treatment has been widely applied for surface modification of titanium alloys to precipitate a crystalline hydroxyapatite (HA) layer in order to achieve improved osteoconduction. A majority of the studies in the literature imposed relatively high powers to enhance Ca and P in the anodic oxide film (AOF). However, high powers have been found to cause deterioration of the adhesive strength in one of the author's previous study. In this study, a new electrolyte comprising calcium acetate monohydrate (CA), β-glycerophosphate disodium pentahydrate (β-GP) and HA powder was developed, and the Ti-30Nb-1Fe-1Hf alloy was anodized in this HA-containing electrolyte to a relatively low voltage. Results show that the AOF anodized in the HA-containing electrolyte exhibits a better HA forming ability during hydrothermal treatment, attributing to the presence of HA powder in the electrolyte that effectively enhances both the Ca content and Ca/P ratio in the AOF. On the other hand, the adhesive strength was little affected due to the decrease in size of the craters residing in the AOF. With respect to the biological responses, not much difference in biocompatibility of the treated and untreated Ti-Nb surfaces was obtained. However, the anodized and hydrothermally treated surface promotes the attachment of cells.

  1. High resolution stable isotopes and elemental analysis on benthic foraminifera: a 4000 yr BP record from the ria de Muros (NW Spain)

    NASA Astrophysics Data System (ADS)

    Pena, L. D.; Francés, G.; Diz, P.; Nombela, M. A.; Alejo, I.

    2003-04-01

    Carbon and oxygen stable isotopes and ICP-OES elemental ratio concentrations (Mg/Ca, Sr/Ca, Ba/Ca) from core EUGC-3B (42 45.10'N; 9 02.23'W, at 38 m.b.s.l. and 410 cm length) were measured over monospecific benthic foraminiferal samples (Nonion fabum) ranging over the last 4500 yr BP. From the oldest analysed sample (289 cm) to the core top, stable isotopes signal shows that the whole record can be separated into 4 intervals lasting each of them about 1000 yr. The lowermost interval (4300-3000 yr BP) is characterized by relatively stable delta 18O values (mean 1.77 per mil). Delta 13C is relatively low except for a maximum around 3300 cal BP (-1.50 per mil). An abrupt decrease down to the minimum value in delta 13C (-4.41 per mil) is accomplished in approximately 200 yr. Mg/Ca and Ba/Ca match perfectly this event, both of them showing the respective maxima values. Sr/Ca has a very similar behaviour to that of delta 13C but with smoother fluctuations. We attribute high values of delta 13C, Sr/Ca and Ba/Ca to periods of enhanced coastal productivity, probably due to reinforced upwelling events in the region. According to Mg/Ca signal this reinforcement took place during a relatively warmer period. The most remarkable feature during the two next periods (3000-1900 yr BP and 1900-1000 yr BP) consists of a stepwise increase of delta 13C values punctuated by a sharp decrease at the end of each interval. All the remaining proxies exhibit a nearly constant trend over these intervals. Each period can be interpreted as a weak enhance of marine productivity that the system does not hold up and finally aborts. The most recent interval represents the establishment of current conditions in the coastal system. The most conspicuous event from this interval consists of an abrupt decrease of the delta 18O that lasted for 300 yr. This event could be correlated with the well recognized warm climatic event known as the Medieval Warm Period. However the Mg/Ca ratio does not show high

  2. Divergent genetic evolution of hemagglutinin in influenza A H1N1 and A H1N2 subtypes isolated in the south-France since the winter of 2001-2002.

    PubMed

    Al Faress, Shaker; Cartet, Gaëlle; Ferraris, Olivier; Norder, Helene; Valette, Martine; Lina, Bruno

    2005-07-01

    Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization. Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses. During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes. Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity. The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.

  3. Structure, production and resource use in some old-growth spruce/fir forests in the front range of the Rocky Mountains, USA

    USGS Publications Warehouse

    Binkley, Dan; Olsson, U.; Rochelle, R.; Stohlgren, T.; Nikolov, N.

    2003-01-01

    Old-growth forests of Engelmann spruce (Picea engelmannii Parry ex. Engelm.) and subalpine fir (Abies lasiocarpa (Hook.) Nutt.) dominate much of the landscape of the Rocky Mountains. We characterized the structure, biomass and production of 18 old-growth (200-450-year-old) spruce/fir forests in Rocky Mountain National Park, Colorado, as well as the stand-level supply and use of light and nitrogen. Stands were chosen to span a broad range of elevation, aspect, and topography. Aboveground tree biomass in these old-growth forests averaged 253 Mg/ha (range 130-488 Mg/ha), with aboveground net primary production of 3700 kg ha-1 yr-1 (range from 2700 to 5200 kg ha-1 yr-1). Within stands, trees >35 cm in diameter accounted for 70% of aboveground biomass, but trees <35 cm contributed 70% of the production of woody biomass. Differences in slope and aspect among sites resulted in a range of incoming light from 58 to 74 TJ ha-1 yr-1, and tree canopies intercepted an average of 71% of incoming light (range 50-90%). Aboveground net primary production (ANPP) of trees did not relate to the supply of light or N, but ANPP correlated strongly with the amount of light and N used (r2 = 0.45-0.54, P < 0.01). Uptake of 1 kg of N was associated with about 260 kg of ANPP, and one TJ of intercepted shortwave radiation produced about 78 kg of ANPP. Across these old-growth stands, stands with greater biomass showed higher rates of both ANPP and resource use; variation in aboveground biomass was associated with 24% of the variation in N use (P = 0.04), 44% of the light use (P = 0.003), and 45% of the ANPP (P = 0.002). ?? 2002 Elsevier Science B.V. All rights reserved.

  4. The impact of papyrus wetland encroachment on the spatial and temporal variability of stream flow and sediment export in the upper Rwizi catchment, Southwest Uganda

    NASA Astrophysics Data System (ADS)

    Ryken, Nick; Vanmaercke, Matthias; Wanyama, Joshua; Deckers, Jozef; Isabirye, Moses; Poesen, Jean

    2014-05-01

    During the past 30 years, human activities in the Lake Victoria basin are responsible for eutrophication of Lake Victoria via sediment-bound nutrients. This affects food security for millions on people. Addressing this problem in this densely populated region will require adequate catchment management strategies. However, sediment yield and runoff data to develop such a strategy are currently unavailable. Also in general, sediment yields for catchments in tropical environments are very scarce, especially in East-Africa. Therefore, runoff discharge and sediment export measurements were conducted in the upper Rwizi, a representative catchment for the Lake Victoria basin which is located in Southwest Uganda. Land use in this catchment is characterized by grazing area on the high plateaus, banana cropping on the slopes and Cyperus papyrus L. wetlands in the river valleys. These papyrus wetlands are currently encroached and transformed into cropland. Eight subcatchments (99 km2 - 2120 km2), with different degrees of wetland encroachment, were monitored during the hydrological year June 2009 - May 2010. Temporal and spatial variations in runoff discharge give strong indications that papyrus wetlands are crucial for buffering runoff and sediment discharge towards Lake Victoria. Subcatchments with intact wetlands show a slower runoff response to rainfall, smaller peak runoff discharges and lower runoff coefficients. Yearly runoff depths of subcatchment with intact wetlands are three to four times smaller compared to subcatchments with encroached wetlands. Suspended sediment concentrations (SSC) show a similar result, with significant smaller SSC in the subcatchments having intact papyrus wetlands. In the subcatchments where no encroachment occurred, annual area-specific suspended sediment yields (SSY) varied between 0,26 ton ha-1 yr-1and 0,33 ton ha-1 yr-1 , while the SSY of the encroached subcatchments varied between 1,20 ton ha-1 yr-1and 2,61 ton ha-1 yr-1. This study

  5. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru; Manykin, A.A.; Rossman, J.S.

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivitymore » whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a

  6. A 3500 14C yr High-Resolution Record of Water-Level Changes in Lake Titicaca, Bolivia/Peru

    NASA Astrophysics Data System (ADS)

    Abbott, Mark B.; Binford, Michael W.; Brenner, Mark; Kelts, Kerry R.

    1997-03-01

    Sediment cores collected from the southern basin of Lake Titicaca (Bolivia/Peru) on a transect from 4.6 m above overflow level to 15.1 m below overflow level are used to identify a new century-scale chronology of Holocene lake-level variations. The results indicate that lithologic and geochemical analyses on a transect of cores can be used to identify and date century-scale lake-level changes. Detailed sedimentary analyses of subfacies and radiocarbon dating were conducted on four representative cores. A chronology based on 60 accelerator mass spectrometer radiocarbon measurements constrains the timing of water-level fluctuations. Two methods were used to estimate the 14C reservoir age. Both indicate that it has remained nearly constant at ˜250 14C yr during the late Holocene. Core studies based on lithology and geochemistry establish the timing and magnitude of five periods of low lake level, implying negative moisture balance for the northern Andean altiplano over the last 3500 cal yr. Between 3500 and 3350 cal yr B.P., a transition from massive, inorganic-clay facies to laminated organic-matter-rich silts in each of the four cores signals a water-level rise after a prolonged mid-Holocene dry phase. Evidence of other significant low lake levels occurs 2900-2800, 2400-2200, 2000-1700, and 900-500 cal yr B.P. Several of the low lake levels coincided with cultural changes in the region, including the collapse of the Tiwanaku civilization.

  7. Electrophoretic deposition of double-layer HA/Al composite coating on NiTi.

    PubMed

    Karimi, Esmaeil; Khalil-Allafi, Jafar; Khalili, Vida

    2016-01-01

    In order to improve the bioactivity of NiTi alloys, which are being known as the suitable materials for biomedical applications, numerous NiTi disks were electrophoretically coated by hetero-coagulated hydroxyapatite/aluminum composite coatings in three main voltages from suspensions with different Al concentrations. In this paper, the amount of Ni ions release and bioactivity of prepared samples as well as bonding strength of the coating to substrate were investigated. The surface characterization of the coating by XRD, EDX, SEM, and FTIR showed that HA particles bonded by Al particles. It caused the formation of a free crack coating on NiTi disks. Moreover, the bonding strength of HA/Al coatings to NiTi substrate were improved by two times as compared to that of the pure HA coatings. Immersing of coated samples in SBF for 1 week showed that apatite formation ability was improved on HA/Al composite coating and Ni ions release from the surface of composite coating decreased. These results induce the appropriate bioactivity and biocompatibility of the deposited HA/Al composite coatings on NiTi disks. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Electrochemical Characteristics of Cell Cultured Ti-Nb-Zr Alloys After Nano-Crystallized Si-HA Coating.

    PubMed

    Jeong, Yong-Hoon; Choe, Han-Cheol

    2015-01-01

    The aim of this study was to investigate the electrochemical characteristics of nano crystallized Si-HA coating on Ti-Nb-Zr alloy after human osteoblast like (HOB) cell attachment. The Ti-Nb-Zr alloy was manufactured with 35 wt.% of Nb and 10 wt.% of Zr by arc melting furnace to appropriate physical properties as biomaterials. The HA and Si-substituted coatings were prepared by electron-beam physical vapor deposition method with 0.5, 0.8 and 1.2 wt.% of Si contents, and nano aging treatment was performed 500 degrees C for 1 h. The characteristics of coating surface were analyzed by field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction, respectively. To evaluate of cell attachment on cell cultured surface, the potentiodynamic test was performed on the surface using HOB cells. The results showed that the Si-HA coating surface showed higher tendency of cell attachment than that of single HA coating, corrosion resistance value was increased by dense of cell attachment.

  9. Exergy-based efficiency and renewability assessment of biofuel production.

    PubMed

    Dewulf, J; Van Langenhove, H; Van De Velde, B

    2005-05-15

    This study presents an efficiency and renewability analysis of the production of three biofuels: rapeseed methyl ester (RME), soybean methyl ester (SME) and corn-based ethanol (EtOH). The overall production chains have been taken into account: not only the agricultural crop production and the industrial conversion into biofuel, but also production of the supply of agricultural resources (pesticides, fertilizers, fuel, seeding material) and industrial resources (energy and chemicals) to transform the crops into biofuel. Simultaneously, byproducts of the agricultural and industrial processes have been taken into account when resources have to be allocated to the biofuels. The technical analysis via the second law of thermodynamics revealed that corn-based EtOH results in the highest production rate with an exergetic fuel content of 68.8 GJ ha(-1) yr(-1), whereas the RME and SME results were limited to 47.5 and 16.4 GJ ha(-1) yr(-1). The allocated nonrenewable resource input to deliver these biofuels is significant: 16.5, 15.4, and 5.6 MJ ha(-1) yr(-1). This means that these biofuels, generally considered as renewable resources, embed a nonrenewable fraction of one-quarter for EtOH and even one-third for RME and SME. This type of analysis provides scientifically sound quantitative information that is necessarywith respect to the sustainability analysis of so-called renewable energy.

  10. Academic Performance in Human Anatomy and Physiology Classes: A 2-Yr Study of Academic Motivation and Grade Expectation

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Allen, Deborah; Gatch, Delena Bell; Shankar, Padmini

    2016-01-01

    This project used a nonexperimental design with a convenience sample and studied the relationship between academic motivation, grade expectation, and academic performance in 1,210 students enrolled in undergraduate human anatomy and physiology (HAP) classes over a 2-yr period. A 42-item survey that included 28 items of the adapted academic…

  11. A fire model with distinct crop, pasture, and non-agricultural burning: use of new data and a model-fitting algorithm for FINAL.1

    NASA Astrophysics Data System (ADS)

    Rabin, Sam S.; Ward, Daniel S.; Malyshev, Sergey L.; Magi, Brian I.; Shevliakova, Elena; Pacala, Stephen W.

    2018-03-01

    This study describes and evaluates the Fire Including Natural & Agricultural Lands model (FINAL) which, for the first time, explicitly simulates cropland and pasture management fires separately from non-agricultural fires. The non-agricultural fire module uses empirical relationships to simulate burned area in a quasi-mechanistic framework, similar to past fire modeling efforts, but with a novel optimization method that improves the fidelity of simulated fire patterns to new observational estimates of non-agricultural burning. The agricultural fire components are forced with estimates of cropland and pasture fire seasonality and frequency derived from observational land cover and satellite fire datasets. FINAL accurately simulates the amount, distribution, and seasonal timing of burned cropland and pasture over 2001-2009 (global totals: 0.434×106 and 2.02×106 km2 yr-1 modeled, 0.454×106 and 2.04×106 km2 yr-1 observed), but carbon emissions for cropland and pasture fire are overestimated (global totals: 0.295 and 0.706 PgC yr-1 modeled, 0.194 and 0.538 PgC yr-1 observed). The non-agricultural fire module underestimates global burned area (1.91×106 km2 yr-1 modeled, 2.44×106 km2 yr-1 observed) and carbon emissions (1.14 PgC yr-1 modeled, 1.84 PgC yr-1 observed). The spatial pattern of total burned area and carbon emissions is generally well reproduced across much of sub-Saharan Africa, Brazil, Central Asia, and Australia, whereas the boreal zone sees underestimates. FINAL represents an important step in the development of global fire models, and offers a strategy for fire models to consider human-driven fire regimes on cultivated lands. At the regional scale, simulations would benefit from refinements in the parameterizations and improved optimization datasets. We include an in-depth discussion of the lessons learned from using the Levenberg-Marquardt algorithm in an interactive optimization for a dynamic global vegetation model.

  12. Effect of molecular weight of hyaluronic acid (HA) on viscoelasticity and particle texturing feel of HA dermal biphasic fillers.

    PubMed

    Chun, Cheolbyong; Lee, Deuk Yong; Kim, Jin-Tae; Kwon, Mi-Kyung; Kim, Young-Zu; Kim, Seok-Soon

    2016-01-01

    Hyaluronic acid (HA) dermal biphasic fillers are synthesized for their efficacy in correcting aesthetic defects such as wrinkles, scars and facial contouring defects. The fillers consist of crosslinked HA microspheres suspended in a noncrosslinked HA. To extend the duration of HAs within the dermis and obtain the particle texturing feel, HAs are crosslinked to obtain the suitable mechanical properties. Hyaluronic acid (HA) dermal biphasic fillers are prepared by mixing the crosslinked HA microspheres and the noncrosslinked HAs. The elastic modulus of the fillers increased with raising the volume fraction of the microspheres. The mechanical properties and the particle texturing feel of the fillers made from crosslinked HA (1058 kDa) microspheres suspended in noncrosslinked HA (1368 kDa) are successfully achieved, which are adequate for the fillers. Dermal biphasic HA fillers made from 1058 kDa exhibit suitable elastic moduli (211 to 420 Pa) and particle texturing feel (scale 7 ~ 9).

  13. Nitrogen deposition in a southern hemisphere biodiversity hotspot within and surrounding Cape Town, South Africa

    NASA Astrophysics Data System (ADS)

    Angstmann, J. L.; Hall, S.; February, E.; West, A. G.; Allsopp, N.; Bond, W.

    2011-12-01

    Anthropogenic nitrogen (N) emissions have increased dramatically since the agricultural and industrial revolutions leading to N deposition in the northern hemisphere that is estimated to be an order of magnitude greater than preindustrial fluxes. N deposition rates of 5-15 kg N ha-1 yr-1 in Europe and N. America decrease plant species diversity, increase invasive species, and lead to eutrophication of surface waters. The southern hemisphere is home to over 50% of the world's biodiversity hotspots, including the 90,000 km2 Cape Floristic Region which houses 9,030 vascular plant species, 69% of which are endemic. However, to date, N deposition rates in the southern hemisphere are highly uncertain, with global models of N deposition based upon sparse datasets at best. Many terrestrial systems, such as fynbos shrublands, are adapted to low N availability and exhibit high species diversity and endemism, rendering them susceptible to ecological changes from N deposition. In this research, we quantified the spatial and temporal distribution of wet and dry N deposition across 30 protected fynbos ecosystems within the urban airshed of Cape Town, South Africa. We predicted that 1) total inorganic N deposition varies predictably along the urban-rural gradient (highest near the city centre), 2) N deposition varies seasonally, with higher fluxes in the winter months when atmospheric stability causes a build-up of N gases in and around the city, and 3) total inorganic N deposition will exceed the critical load of 10-15 kg N ha-1 yr-1 for Mediterranean shrublands, past which negative ecosystem effects have been shown to occur. Estimates of N deposition based on NO2 concentrations within the city suggest that total N deposition ranges from 8-13 kg N ha-1 yr-1 . However, we show that N deposition measured by ion-exchange resin collectors is far less than expected, averaging less than 2 kg N ha-1 yr-1 (range 0.5 - 5.5 kg N ha-1 yr-1 ), and is is dominated by NO3-, suggesting

  14. Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

    DOE PAGES

    Yao, Guorui; Lam, Kwok-ho; Perry, Kay; ...

    2017-03-08

    Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

  15. Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H.

    PubMed

    Yao, Guorui; Lam, Kwok-Ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

    2017-03-08

    Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A-G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (H C ) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the H C . Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-H C at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.

  16. Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yao, Guorui; Lam, Kwok-ho; Perry, Kay

    Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

  17. Tracking of leisure time physical activity during 28 yr in adults: the Tromsø study.

    PubMed

    Morseth, Bente; Jørgensen, Lone; Emaus, Nina; Jacobsen, Bjarne K; Wilsgaard, Tom

    2011-07-01

    Physical activity plays an important role in the prevention of many serious diseases. To develop targeted strategies that encourage physical activity, knowledge of stability of physical activity levels over time is essential. The aim of this study was to examine tracking of leisure time physical activity in adults in Northern Norway during three decades. We followed 5432 women and men who attended the Tromsø Study in 1979-1980, as well as repeated examinations after 7 and 28 yr. Baseline age was 20-54 yr (mean age=35.8 yr). Physical activity was assessed by self-administered questionnaires. Tracking of physical activity, defined as maintenance of relative rank of physical activity level, was estimated by Spearman correlation coefficient and by weighted κ statistics. Tracking in terms of predictability of later values from earlier measurements was analyzed by generalized estimating equations. A higher-than-expected proportion of subjects maintained their physical activity level from examination 1 to 2 (58%) and 3 (53%). κ statistics showed agreement of 0.41 and 0.29, respectively. Belonging to a specific physical activity level at baseline increased the odds of belonging to the same category at later examinations (sedentary odds ratio (OR)=3.9 (95% confidence interval (CI)=3.5-4.4), moderately active OR=2.2 (95% CI=2.0-2.4), active OR=2.9 (95% CI=2.6-3.3), and highly active OR=14.0 (95% CI=8.7-22.5)). Being physically active in young adulthood increased the odds of being physically active later in life (moderately active OR=3.4 (95% CI=3.0-3.9), active OR=5.4 (95% CI=4.6-6.4), and highly active OR=13.0 (95% CI=7.4-22.8)). This study showed tracking of leisure time physical activity during 28 yr in a cohort of adults.

  18. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

    PubMed Central

    Yang, Xiaoqian; lyer, Arun K.; Singh, Amit; Choy, Edwin; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

    2015-01-01

    Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer. PMID:25687880

  19. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

    NASA Astrophysics Data System (ADS)

    Yang, Xiaoqian; Lyer, Arun K.; Singh, Amit; Choy, Edwin; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

    2015-02-01

    Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer.

  20. Protection of pigs against pandemic swine origin H1N1 influenza A virus infection by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus recombinants.

    PubMed

    Klingbeil, Katharina; Lange, Elke; Blohm, Ulrike; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2015-03-02

    Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Sequence analysis, expression profiles and function of thioredoxin 2 and thioredoxin reductase 1 in resistance to nucleopolyhedrovirus in Helicoverpa armigera

    PubMed Central

    Zhang, Songdou; Li, Zhen; Nian, Xiaoge; Wu, Fengming; Shen, Zhongjian; Zhang, Boyu; Zhang, Qingwen; Liu, Xiaoxia

    2015-01-01

    The thioredoxin system, including NADPH, thioredoxin (Trx), and thioredoxin reductase (TrxR), plays significant roles in maintaining intracellular redox homeostasis and protecting organisms against oxidative damage. In this study, the characteristics and functions of H. armigera HaTrx2 and HaTrxR1 were identified. Sequence analysis showed that HaTrx2 and HaTrxR1 were both highly conserved and shared high sequence identity with other insect counterparts. The mRNA of HaTrx2 was expressed the highest in 5th instar 96 h and was mainly detected in heads and epidermis. The expression of HaTrxR1 was highly concentrated in 5th instar 72 h and 96 h, and higher in malpighian tube, midgut and hemocyte than other examined tissues. HaTrx2 and HaTrxR1 were markedly induced by various types of stress. HaTrx2- or HaTrxR1-knockdown increased ROS production in hemocytes and also increased the lipid damage in NPV infected H. armigera larvae. Furthermore, interference with expression of HaTrx2 or HaTrxR1 transcripts in H. armigera larvae resulted in increased sensitivity to NPV infection and shortened LT50 values. Our findings indicated that HaTrx2 and HaTrxR1 contribute to the susceptibility of H. armigera to NPV and also provided the theoretical basis for the in-depth study of insect thioredoxin system. PMID:26502992

  2. Cultivation, LD(50) determination and experimental model of Streptococcus suis serotype 2 strain HA9801.

    PubMed

    Zhao, Zhanzhong; Wang, Jian; Liu, Peihong; Zhang, Suhua; Gong, Jianpei; Huang, Xiqin; Li, Bin; Xue, Feiqun

    2009-04-01

    The effects of nutritional components and submerged culture conditions on colony-forming unit (CFU) counts by Streptococcus suis serotype 2 strain HA9801 in flask culture was investigated, and the optimal medium and cultivation conditions was confirmed by using a 50l bioreactor. The LD(50) values of HA9801 in pigs before and after fermentation were 1.8 x 10(7)CFU, which indicated that the virulence of HA9801 was very stable in the fermentation process. In addition, an experimental model that closely mimics naturally occurring disease in conventional pigs was established.

  3. Nutrient limitation in three lowland tropical forests in southern China receiving high nitrogen deposition: insights from fine root responses to nutrient additions.

    PubMed

    Zhu, Feifei; Yoh, Muneoki; Gilliam, Frank S; Lu, Xiankai; Mo, Jiangming

    2013-01-01

    Elevated nitrogen (N) deposition to tropical forests may accelerate ecosystem phosphorus (P) limitation. This study examined responses of fine root biomass, nutrient concentrations, and acid phosphatase activity (APA) of bulk soil to five years of N and P additions in one old-growth and two younger lowland tropical forests in southern China. The old-growth forest had higher N capital than the two younger forests from long-term N accumulation. From February 2007 to July 2012, four experimental treatments were established at the following levels: Control, N-addition (150 kg N ha(-1) yr(-1)), P-addition (150 kg P ha(-1) yr(-1)) and N+P-addition (150 kg N ha(-1) yr(-1) plus 150 kg P ha(-1) yr(-1)). We hypothesized that fine root growth in the N-rich old-growth forest would be limited by P availability, and in the two younger forests would primarily respond to N additions due to large plant N demand. Results showed that five years of N addition significantly decreased live fine root biomass only in the old-growth forest (by 31%), but significantly elevated dead fine root biomass in all the three forests (by 64% to 101%), causing decreased live fine root proportion in the old-growth and the pine forests. P addition significantly increased live fine root biomass in all three forests (by 20% to 76%). The combined N and P treatment significantly increased live fine root biomass in the two younger forests but not in the old-growth forest. These results suggest that fine root growth in all three study forests appeared to be P-limited. This was further confirmed by current status of fine root N:P ratios, APA in bulk soil, and their responses to N and P treatments. Moreover, N addition significantly increased APA only in the old-growth forest, consistent with the conclusion that the old-growth forest was more P-limited than the younger forests.

  4. The hormesis effect of plasma-elevated intracellular ROS on HaCaT cells

    NASA Astrophysics Data System (ADS)

    Szili, Endre J.; Harding, Frances J.; Hong, Sung-Ha; Herrmann, Franziska; Voelcker, Nicolas H.; Short, Robert D.

    2015-12-01

    We have examined the link between ionized-gas plasma delivery of reactive oxygen species (ROS) to immortalized keratinocyte (HaCaT) cells and cell fate, defined in terms of cell viability versus death. Phospholipid vesicles were used as cell mimics to measure the possible intracellular ROS concentration, [ROSi], delivered by various plasma treatments. Cells were exposed to a helium cold atmospheric plasma (CAP) jet for different plasma exposure times (5-60 s) and gas flow rates (50-1000 ml min-1). Based upon the [ROSi] data we argue that plasma-generated ROS in the cell culture medium can readily diffuse into real cells. Plasma exposure that equated to an [ROSi] in the range of 3.81  ×  10-10-9.47  ×  10-8 M, measured at 1 h after the plasma exposure, resulted in increased cell viability at 72 h; whereas a higher [ROSi] at 1 h decreased cell viability after 72 h of culture. This may be because of the manner in which the ROS are delivered by the plasma: HaCaT cells better tolerate a low ROS flux over an extended plasma exposure period of 1 min, compared to a high flux delivered in a few seconds, although the final [ROSi] may be the same. Our results suggest that plasma stimulation of HaCaT cells follows the principle of hormesis.

  5. J-Plus: Measuring Ha Emission Line Flux In The Nearby Universe

    NASA Astrophysics Data System (ADS)

    Logroño-García, Rafael; Vilella-Rojo, Gonzalo; López-San Juan, Carlos; Varela, Jesús; Viironen, Kerttu

    2017-10-01

    In the present presentation we aim to validate the methodology designed to extract the Ha emission line flux from J-PLUS data, a twelve optical filter survey carried out with the 2 deg² field of view T80Cam camera, mounted at the JAST/T80 telescope in the OAJ, Teruel, Spain. We use the information of the twelve J-PLUS bands, including the J0660 narrow-band filter located at rest-frame Ha, over 42 deg² to extract de-reddened and [NII] decontaminated Ha emission line fluxes of 46 star-forming regions with previous SDSS and/or CALIFA spectroscopic information. The agreement of the J-PLUS photometric Ha flux and the spectroscopic one is remarkable, with a ratio R = 1,01 +/- 0,27. This demonstrates that we are able to recover reliable Ha fluxes from J-PLUS photometric data. With an expected final area of 8,500 deg2, the large J-PLUS footprint will permit the study of the spatially resolved star formation rate of thousands nearby galaxies at z 0,015, as well as the influence of the close environment. As an illustrative example, we looked to the close pair of interacting galaxies NGC3994 and NGC3995, finding an enhancement of the star formation rate not only in the central part of NGC3994 but also in outer parts of the disc.

  6. New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A.

    PubMed

    de Alencar, J B; Macedo, L C; de Barros, M F; Rodrigues, C; Shinzato, A H; Pelissari, C B; Machado, J; Sell, A M; Visentainer, J E L

    2015-07-01

    The development of factor VIII (FVIII) inhibitor is the main complication of replacement therapy in patients with haemophilia A (HA). A ratio of 5-7% of individuals HA develops antibodies (inhibitors) against the FVIII infused during the treatment, thereby reducing their pro-coagulant activity. The immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form. We investigated the polymorphisms in regulatory regions of cytokine genes (IL1A, IL1B, IL1R, IL1RA, IL4RA, IL12, INFG, TGFB1, TNF, IL2, IL4, IL6, IL10) that could influence the risk of developing inhibitors in patients with severe HA. The genotyping of cytokine genes of 117 patients with HA was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the protocol recommended by the manufacturer (Invitrogen kit Cytokines(®) , Canoga Park, USA) RESULTS: From the cohort of 117 patients with severe HA, 35 developed inhibitors. There was a higher frequency of +874 T allele in INFG and of +869 TT and TG/TG in TGFB1 genes on patients with inhibitors. This suggests that polymorphisms in INFG and in TGFB1 genes are related to risk of developing inhibitor, and could contribute to a genetic profile of the individual HA for the risk of inhibitors development to FVIII. © 2015 John Wiley & Sons Ltd.

  7. Increased Coexpression of PD-1, TIGIT, and KLRG-1 on Tumor-Reactive CD8+ T Cells During Relapse after Allogeneic Stem Cell Transplantation.

    PubMed

    Hutten, Tim J A; Norde, Wieger J; Woestenenk, Rob; Wang, Ruo Chen; Maas, Frans; Kester, Michel; Falkenburg, J H Frederik; Berglund, Sofia; Luznik, Leo; Jansen, Joop H; Schaap, Nicolaas; Dolstra, Harry; Hobo, Willemijn

    2018-04-01

    Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for patients with a hematologic malignancy due to alloreactive T cell responses recognizing minor histocompatibility antigens (MiHA). Yet tumor immune escape mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells display low expression of costimulatory molecules and can up-regulate coinhibitory molecules that inhibit T cell functionality on ligation with their counter-receptors on the tumor-reactive T cells. The aim of this explorative study was to evaluate immune checkpoint expression profiles on T cell subsets and on cytomegalovirus (CMV)- and/or MiHA-reactive CD8 + T cells of allo-SCT recipients using a 13-color flow cytometry panel, and to correlate these expression patterns to clinical outcomes. MiHA-reactive CD8 + T cells exhibited an early differentiated CD27 ++ /CD28 ++ phenotype with low KLRG-1 and CD57 expression. These T cells also displayed increased expression of PD-1, TIM-3, and TIGIT compared with total effector memory T cells and CMV-specific CD8 + T cells in healthy donors and allo-SCT recipients. Remarkably, high coexpression of PD-1, TIGIT, and KLRG-1 on MiHA-reactive CD8 + T cells was associated with relapse after allo-SCT. Taken together, these findings indicate that MiHA-specific CD8 + T cells of relapsed patients have a distinctive coinhibitory expression signature compared with patients who stay in remission. This phenotype may serve as a potential monitoring tool in patients. Moreover, these findings suggest that PD-1 and TIGIT play important roles in regulating T cell-mediated tumor control, providing a rationale for immunotherapy with blocking antibodies to treat relapse after allo-SCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved.

  8. Hyaluronan synthase assembles hyaluronan on a [GlcNAc(β1,4)]n-GlcNAc(α1→)UDP primer and hyaluronan retains this residual chitin oligomer as a cap at the nonreducing end

    PubMed Central

    Baggenstoss, Bruce A; Washburn, Jennifer L

    2017-01-01

    Abstract Class I hyaluronan synthases (HAS) assemble [GlcNAc(β1,4)GlcUA(β1,3)]n-UDP at the reducing end and also make chitin. Streptococcus equisimilis HAS (SeHAS) also synthesizes chitin-UDP oligosaccharides, (GlcNAc-β1,4)n-GlcNAc(α1→)UDP (Weigel et al. 2015). Here we determined if HAS uses chitin-UDPs as primers to initiate HA synthesis, leaving the non-HA primer at the nonreducing (NR) end. HA made by SeHAS membranes was purified, digested with streptomyces lyase, and hydrophobic oligomers were enriched by solid phase extraction and analyzed by MALDI-TOF MS. Jack bean hexosaminidase (JBH) and MS/MS were used to analyze 19 m/z species of possible GnHn ions with clustered GlcNAc (G) residues attached to disaccharide units (H): (GlcNAcβ1,4)2–5[GlcUA(β1,3)GlcNAc]2–6. JBH digestion sequentially removed GlcNAc from the NR-end of GnHn oligomers, producing successively smaller GnH2–3 series members. Since lyase releases dehydro-oligos (dHn; M−18), only the unique NR-end oligo lacks dehydro-GlcUA. Hn oligomers were undetectable in lyase digests, whereas JBH treatment created new H2–6m/z peaks (i.e. HA tetra- through dodeca-oligomers). MS/MS of larger GnHn species produced chitin (2–5 GlcNAcs), HA oligomers and multiple smaller series members with fewer GlcNAcs. All NR-ends (97%) started with GlcNAc, as a chitin trimer (three GlcNAcs), indicating that GlcNAc(β1,4)2GlcNAc(α1→)-UDP may be optimal for initiation of HA synthesis. Also, HA made by live S. pyogenes cells had G4Hn chitin-oligo NR-ends. We conclude that chitin-UDP functions in vitro and in live cells as a primer to initiate synthesis of all HA chains and these primers remain at the NR-ends of HA chains as residual chitin caps [(GlcNAc-β1,4)3–4]. PMID:28138013

  9. Hyaluronan synthase assembles hyaluronan on a [GlcNAc(β1,4)]n-GlcNAc(α1→)UDP primer and hyaluronan retains this residual chitin oligomer as a cap at the nonreducing end.

    PubMed

    Weigel, Paul H; Baggenstoss, Bruce A; Washburn, Jennifer L

    2017-06-01

    Class I hyaluronan synthases (HAS) assemble [GlcNAc(β1,4)GlcUA(β1,3)]n-UDP at the reducing end and also make chitin. Streptococcus equisimilis HAS (SeHAS) also synthesizes chitin-UDP oligosaccharides, (GlcNAc-β1,4)n-GlcNAc(α1→)UDP (Weigel et al. 2015). Here we determined if HAS uses chitin-UDPs as primers to initiate HA synthesis, leaving the non-HA primer at the nonreducing (NR) end. HA made by SeHAS membranes was purified, digested with streptomyces lyase, and hydrophobic oligomers were enriched by solid phase extraction and analyzed by MALDI-TOF MS. Jack bean hexosaminidase (JBH) and MS/MS were used to analyze 19 m/z species of possible GnHn ions with clustered GlcNAc (G) residues attached to disaccharide units (H): (GlcNAcβ1,4)2-5[GlcUA(β1,3)GlcNAc]2-6. JBH digestion sequentially removed GlcNAc from the NR-end of GnHn oligomers, producing successively smaller GnH2-3 series members. Since lyase releases dehydro-oligos (dHn; M-18), only the unique NR-end oligo lacks dehydro-GlcUA. Hn oligomers were undetectable in lyase digests, whereas JBH treatment created new H2-6m/z peaks (i.e. HA tetra- through dodeca-oligomers). MS/MS of larger GnHn species produced chitin (2-5 GlcNAcs), HA oligomers and multiple smaller series members with fewer GlcNAcs. All NR-ends (97%) started with GlcNAc, as a chitin trimer (three GlcNAcs), indicating that GlcNAc(β1,4)2GlcNAc(α1→)-UDP may be optimal for initiation of HA synthesis. Also, HA made by live S. pyogenes cells had G4Hn chitin-oligo NR-ends. We conclude that chitin-UDP functions in vitro and in live cells as a primer to initiate synthesis of all HA chains and these primers remain at the NR-ends of HA chains as residual chitin caps [(GlcNAc-β1,4)3-4]. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Forest Carbon Storage in the Northern Midwest, USA: A Bottom-Up Scaling Approach Combining Local Meteorological and Biometric Data With Regional Forest Inventories

    NASA Astrophysics Data System (ADS)

    Curtis, P. S.; Gough, C. M.; Vogel, C. S.

    2005-12-01

    Carbon (C) storage increasingly is considered an important part of the economic return of forestlands, making easily parameterized models for assessing current and future C storage important for both ecosystem and money managers. For the deciduous forests of the northern midwest, USA, detailed information relating annual C storage to local site characteristics can be combined with spatially extensive forest inventories to produce simple, robust models of C storage useful at a variety of scales. At the University of Michigan Biological Station (45o35`' N, 84o42`' W) we measured C storage, or net ecosystem production (NEP), in 65 forest stands varying in age, disturbance history, and productivity (site index) using biometric methods, and independently measured net C exchange at the landscape level using meteorological methods. Our biometric and meteorological estimates of NEP converged to within 1% of each other over five years, providing important confirmation of the robustness of these two approaches applied within northern deciduous forests (Gough et al. 2005). We found a significant relationship between NEP, stand age ( A, yrs), and site index ( Is, m), where NEP = 0.134 + 0.022 * (LN[ A* Is]) (r2 = 0.50, P < 0.02). Site index is an integrated measure of site quality, expressed as 50 yr canopy height. We then used stand age and site index data from forests of similar species composition reported in the USDA Forest Inventory and Analysis database (ncrs2.fs.fed.us/4801/fiadb/) to estimate forest C storage at different scales across the upper midwest, Great Lakes region. Model estimates were validated against independent estimates of C storage for other forests in the region. At the local ecosystem-level (~1 km2) C storage averaged 1.52 Mg ha-1 yr-1. Scaling to the two-county area surrounding our meteorological and biometric study sites, average stand age decreased and site index increased, resulting in estimated storage of 1.62 Mg C ha-1 yr-1, or 0.22 Tg C yr-1 in

  11. Invasion chronosequence of Spartina alterniflora on methane emission and organic carbon sequestration in a coastal salt marsh

    NASA Astrophysics Data System (ADS)

    Xiang, Jian; Liu, Deyan; Ding, Weixin; Yuan, Junji; Lin, Yongxin

    2015-07-01

    Spartina alterniflora was intentionally introduced to China in 1979 for the purpose of sediment stabilization and dike protection, and has continuously replaced native plants or invaded bare mudflats in the coastal marsh. To evaluate the spatial variation of CH4 emission and soil organic carbon (SOC) storage along the invasion chronosequence, we selected four sites including bare mudflat (Control, as first year invasion), and marshes invaded by S. alterniflora in 2002 (SA-1), 1999 (SA-2) and 1995 (SA-3), respectively, in Sheyang county, Jiangsu, China and set up the marsh mesocosm system for flux measurement. The mean accumulation rate of SOC in the 0-30 cm layer exponentially increased with the invasion time, ranging from 1.08 (over the first 9 years) to 2.35 Mg C ha-1 yr-1 (over the period of 12-16 years). The cumulative CH4 emission during the growth season was 20.5, 75.4, 81.0 and 92.2 kg CH4 ha-1 in Control, SA-1, SA-2 and SA-3, respectively, and there was a binomial relationship between CH4 emission and invasion time. Cumulative CH4 emission was logarithmically increased with SOC concentration; however the ratio of CH4 emission to SOC concentration was inversely correlated with the invasion time in the S. alterniflora marsh, suggesting that the less increased SOC in the S. alterniflora marsh was converted into CH4. The net global warming potential (GWP) was estimated at 733 kg CO2-eq ha-1 yr-1 in the tidal mudflat and reduced to -1273 (SA-1) to -2233 kg CO2-eq ha-1 yr-1 (SA-3) in the S. alterniflora marsh. Our results indicated that S. alterniflora invasion effectively sequestrated atmospheric CO2 and mitigated GWP in the coastal marsh of China.

  12. Modeling the effects of different N fertilizer rates on N2O emissions and nitrate leaching from arable soils in Korea

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Berger, S.; Tenhunen, J. D.; Gebauer, G.; Kiese, R.

    2012-12-01

    interrow resulting in total direct emissions of about 1.5 to 2.3 kg N ha-1 yr-1 (area weighted average of row and interrow). Compared with the IPCC approach (EF = 0.01) these values are rather low which can be explained by high rates of simulated and measured nitrate leaching across all N treatments (row: 214 - 240 kg N ha-1 yr-1; interrow: 259 - 263 kg N ha-1 yr-1). Seasonal dynamic and magnitude of measured and simulated NO3 concentrations in soil water in different soil depths agreed well which give further evidence for the simulated nitrate leaching. Using the IPCC EF of 0.0075, nitrate leaching results in indirect N2O emissions of additionally 1.8 kg N ha-1 yr-1. Only slight increase of measured and simulated yields (4 to 5.2 t DW ha-1) with higher rates of N fertilization indicate that actual farmer practices can be improved and optimizing agricultural management considering the specific climatic and soil conditions has a high potential to reduce environmental impacts of crop cultivations in the study area of the Haean catchment.

  13. Surface coal mine land reclamation using a dry flue gas desulfurization product: Short-term and long-term water responses.

    PubMed

    Chen, Liming; Stehouwer, Richard; Tong, Xiaogang; Kost, Dave; Bigham, Jerry M; Dick, Warren A

    2015-09-01

    Abandoned coal-mined lands are a worldwide concern due to their potential negative environmental impacts, including erosion and development of acid mine drainage. A field study investigated the use of a dry flue gas desulfurization product for reclamation of abandoned coal mined land in USA. Treatments included flue gas desulfurization product at a rate of 280 Mg ha(-1) (FGD), FGD at the same rate plus 112 Mg ha(-1) yard waste compost (FGD/C), and conventional reclamation that included 20 cm of re-soil material plus 157 Mg ha(-1) of agricultural limestone (SOIL). A grass-legume sward was planted after treatment applications. Chemical properties of surface runoff and tile water (collected from a depth of 1.2m below the ground surface) were measured over both short-term (1-4 yr) and long-term (14-20 yr) periods following reclamation. The pH of surface runoff water was increased from approximately 3, and then sustained at 7 or higher by all treatments for up to 20 yr, and the pH of tile flow water was also increased and sustained above 5 for 20 yr. Compared with SOIL, concentrations of Ca, S and B in surface runoff and tile flow water were generally increased by the treatments with FGD product in both short- and long-term measurements and concentrations of the trace elements were generally not statistically increased in surface runoff and tile flow water over the 20-yr period. However, concentrations of As, Ba, Cr and Hg were occasionally elevated. These results suggest the use of FGD product for remediating acidic surface coal mined sites can provide effective, long-term reclamation. Copyright © 2015. Published by Elsevier Ltd.

  14. A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs.

    PubMed

    Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling; Chen, Hualan

    2017-11-01

    Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by

  15. Preparation and characterization of NiW-nHA composite catalyst for hydrocracking

    NASA Astrophysics Data System (ADS)

    Zhou, Gang; Hou, Yongzhao; Liu, Lei; Liu, Hongru; Liu, Can; Liu, Jing; Qiao, Huiting; Liu, Wenyong; Fan, Yubo; Shen, Shituan; Rong, Long

    2012-11-01

    The synthesis, characterization and catalytic capability of the NiW-nano-hydroxyapatite (NiW-nHA) composite were investigated in this paper. The NiW-nHA catalyst was prepared by a co-precipitation method. Then Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) and energy dispersive spectroscopy (EDX) were used to analyze this material. In addition, the catalytic capacity of the NiW-nHA composite was also examined by FT-IR and gas chromatography (GC). The results of FT-IR analysis indicated that Ni, W and nHA combined closely. TEM observation revealed that this catalyst was needle shaped and the crystal retained a nanometer size. XRD data also suggested that a new phase of CaWO4 appeared and the lattice parameters of nHA changed in this system. nHA was the carrier of metals. The rates of Ni/W-loading were 73.24% and 65.99% according to the EDX data, respectively. Furthermore, the conversion of 91.88% Jatropha oil was achieved at 360 °C and 3 MPa h-1 over NiW-nHA catalyst. The straight chain alkanes ranging from C15 to C18 were the main components in the production. The yield of C15-C18 alkanes was up to 83.56 wt%. The reaction pathway involved hydrocracking of the C&z.dbd;C bonds of these triglycerides from Jatropha oil. This paper developed a novel non-sulfided catalyst to obtain a ``green biofuel'' from vegetable oil.

  16. Lithospermic acid derivatives from Lithospermum erythrorhizon increased expression of serine palmitoyltransferase in human HaCaT cells.

    PubMed

    Thuong, Phuong Thien; Kang, Keon Wook; Kim, Jeong Kee; Seo, Dae Bang; Lee, Sang Jun; Kim, Sung Han; Oh, Won Keun

    2009-03-15

    A MeOH extract of the dry root of Lithospermum erythrorhizon showed strong increasing effect on serine palmitoyltransferase (SPT) in normal human keratinocyte cells (HaCaT cells). Bioassay-guided separation on this extract using repeated chromatography resulted in the isolation of lithospermic acid (1) and two derivative esters, 9''-methyl lithospermate (2) and 9'-methyl lithospermate (3). Compounds 1-3 significantly increased SPT expressions in the relative quantity (%) of SPT1 mRNA as well as SPT2 mRNA. These constituents also raised the level of SPT protein in HaCaT cells in a dose-dependent manner, with the increased level of SPT protein in HaCaT cells of 55%, 23%, and 81% at the concentration of 100 microg/ml, respectively. This finding suggests that lithospermic acid and its derivatives from L. erythrorhizon might improve the permeability barrier by stimulating the protein level of SPT.

  17. Activity-guided separation and characterization of new halocin HA3 from fermented broth of Haloferax larsenii HA3.

    PubMed

    Kumar, Vijay; Tiwari, Santosh Kumar

    2017-05-01

    Haloferax larsenii HA3 was able to grow optimally in HS medium containing 15% NaCl, at pH 7.2 and 42 °C in aerobic conditions. Strain HA3 was found to be round shape, Gram-negative, catalase-positive, sensitive to bile acid, and resistant to chloramphenicol, and could not utilize arginine. The lipid profile revealed the presence of glycerol diether moiety (GDEM) suggesting Haloarchaea characteristics. Phylogenetic analysis based on 16S rRNA gene sequence similarities showed that it was closely related to H. larsenii ZJ206. Interestingly, strain HA3 was found to produce halocin HA3 which was purified using ultrafiltration and chromatography. It was found to be stable up to 80 °C, pH 2.0-10.0, organic solvents, surfactants, and detergents tested. However, the activity of halocin HA3 was completely reduced in the presence of proteinase K and trypsin. It was found to be halocidal against H. larsenii HA10, rupturing cell boundary and leading to cell death. The molecular weight of halocin HA3 was found to be ~13 kDa and MALDI-TOF MS/MS analysis suggested no homology with known halocins. The N-terminal ten amino-acid residues, NH 2 MNLGIILETN-COOH, suggested a new/novel halocin. These properties of halocin HA3 may be applicable for control of Haloarchaea in environments and salted foods.

  18. Appendix 1: Regional summaries - Alaska

    Treesearch

    Jane M. Wolken; Teresa N. Hollingsworth

    2012-01-01

    Alaskan forests cover one-third of the state’s 52 million ha of land (Parson et al. 2001), and are regionally and globally significant. Ninety percent of Alaskan forests are classified as boreal, representing 4 percent of the world’s boreal forests, and are located throughout interior and south-central Alaska (fig. A1-1). The remaining 10 percent of Alaskan forests are...

  19. Mitigating nitrous oxide emissions from tea field soil using bioaugmentation with a Trichoderma viride biofertilizer.

    PubMed

    Xu, Shengjun; Fu, Xiaoqing; Ma, Shuanglong; Bai, Zhihui; Xiao, Runlin; Li, Yong; Zhuang, Guoqiang

    2014-01-01

    Land-use conversion from woodlands to tea fields in subtropical areas of central China leads to increased nitrous oxide (N2O) emissions, partly due to increased nitrogen fertilizer use. A field investigation of N2O using a static closed chamber-gas chromatography revealed that the average N2O fluxes in tea fields with 225 kg N ha(-1) yr(-1) fertilizer application were 9.4 ± 6.2 times higher than those of woodlands. Accordingly, it is urgent to develop practices for mitigating N2O emissions from tea fields. By liquid-state fermentation of sweet potato starch wastewater and solid-state fermentation of paddy straw with application of Trichoderma viride, we provided the tea plantation with biofertilizer containing 2.4 t C ha(-1) and 58.7 kg N ha(-1). Compared to use of synthetic N fertilizer, use of biofertilizer at 225 kg N ha(-1) yr(-1) significantly reduced N2O emissions by 33.3%-71.8% and increased the tea yield by 16.2%-62.2%. Therefore, the process of bioconversion/bioaugmentation tested in this study was found to be a cost-effective and feasible approach to reducing N2O emissions and can be considered the best management practice for tea fields.

  20. Sr-containing hydroxyapatite: morphologies of HA crystals and bioactivity on osteoblast cells.

    PubMed

    Aina, Valentina; Bergandi, Loredana; Lusvardi, Gigliola; Malavasi, Gianluca; Imrie, Flora E; Gibson, Iain R; Cerrato, Giuseppina; Ghigo, Dario

    2013-04-01

    . In contrast, Sr ions alone, at the concentrations released by Sr-HA (1.21-3.24 ppm), influenced neither cell proliferation nor differentiation. Thus the positive effects of Sr in Sr-HA materials are probably due to the co-action of other ions such as Ca and P. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Hyperinsulinism–hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype–phenotype correlations

    PubMed Central

    Kapoor, Ritika R; Flanagan, Sarah E; Fulton, Piers; Chakrapani, Anupam; Chadefaux, Bernadette; Ben-Omran, Tawfeg; Banerjee, Indraneel; Shield, Julian P; Ellard, Sian; Hussain, Khalid

    2009-01-01

    Background Activating mutations in the GLUD1 gene (which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase, GDH) cause the hyperinsulinism–hyperammonaemia (HI/HA) syndrome. Patients present with HA and leucine-sensitive hypoglycaemia. GDH is regulated by another intra-mitochondrial enzyme sirtuin 4 (SIRT4). Sirt4 knockout mice demonstrate activation of GDH with increased amino acid-stimulated insulin secretion. Objectives To study the genotype–phenotype correlations in patients with GLUD1 mutations. To report the phenotype and functional analysis of a novel mutation (P436L) in the GLUD1 gene associated with the absence of HA. Patients and methods Twenty patients with HI from 16 families had mutational analysis of the GLUD1 gene in view of HA (n=19) or leucine sensitivity (n=1). Patients negative for a GLUD1 mutation had sequence analysis of the SIRT4 gene. Functional analysis of the novel P436L GLUD1 mutation was performed. Results Heterozygous missense mutations were detected in 15 patients with HI/HA, 2 of which are novel (N410D and D451V). In addition, a patient with a normal serum ammonia concentration (21 μmol/l) was heterozygous for a novel missense mutation P436L. Functional analysis of this mutation confirms that it is associated with a loss of GTP inhibition. Seizure disorder was common (43%) in our cohort of patients with a GLUD1 mutation. No mutations in the SIRT4 gene were identified. Conclusion Patients with HI due to mutations in the GLUD1 gene may have normal serum ammonia concentrations. Hence, GLUD1 mutational analysis may be indicated in patients with leucine sensitivity; even in the absence of HA. A high frequency of epilepsy (43%) was observed in our patients with GLUD1 mutations. PMID:19690084

  2. [Detection of factor VIII intron 1 inversion in severe haemophilia A].

    PubMed

    Liang, Yan; Yan, Zhen-yu; Yan, Mei; Hua, Bao-lai; Xiao, Bai; Zhao, Yong-qiang; Liu, Jing-zhong

    2009-06-01

    Screening the intron 1 inversion of factor VIII (FVIII) in the population of severe haemophilia A(HA) in China and performing carrier detection and prenatal diagnosis. Using LD-PCR to detect intron 22 inversions and multiple-PCR within two tubes to intron 1 inversions in severe HA patients. Carrier detection and prenatal diagnosis were performed in affected families. Linkage analysis and DNA sequencing were used to verify these tests. One hundred and eighteen patients were seven diagnosed as intron 22 inversions and 7 were intron 1 inversions out of 247 severe HA patients. The prevalence of the intron 1 inversion in Chinese severe haemophilia A patients was 2.8% (7/247). Six women from family A and 2 from family B were diagnosed as carriers. One fetus from family A was affected fetus. Intron 1 inversion could be detected directly by multiple-PCR within two tubes. This method made the strategy more perfective in carrier and prenatal diagnosis of haemophilia A.

  3. High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex.

    PubMed

    Lee, Kwangkook; Lam, Kwok-Ho; Kruel, Anna Magdalena; Perry, Kay; Rummel, Andreas; Jin, Rongsheng

    2014-04-04

    Botulinum neurotoxins (BoNTs) are produced as progenitor toxin complexes (PTCs) by Clostridium botulinum. The PTCs are composed of BoNT and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver BoNT through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich PTC on the intestinal lumen preceding its transport across the epithelial barriers. Here, we report the crystal structure of HA33 of type B PTC (HA33/B) in complex with lactose at 1.46Å resolution. The structural comparisons among HA33 of serotypes A-D reveal two different HA33-glycan interaction modes. The glycan-binding pockets on HA33/A and B are more suitable to recognize galactose-containing glycans in comparison to the equivalent sites on HA33/C and D. On the contrary, HA33/C and D could potentially recognize Neu5Ac as an independent receptor, whereas HA33/A and B do not. These findings indicate that the different oral toxicity and host susceptibility observed among different BoNT serotypes could be partly determined by the serotype-specific interaction between HA33 and host carbohydrate receptors. Furthermore, we have identified a key structural water molecule that mediates the HA33/B-lactose interactions. It provides the structural basis for development of new receptor-mimicking compounds, which have enhanced binding affinity with HA33 through their water-displacing moiety. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. High methane emissions dominate annual greenhouse gas balances 30 years after bog rewetting

    NASA Astrophysics Data System (ADS)

    Vanselow-Algan, M.; Schmidt, S. R.; Greven, M.; Fiencke, C.; Kutzbach, L.; Pfeiffer, E.-M.

    2015-02-01

    Natural peatlands are important carbon sinks and sources of methane (CH4). In contrast, drained peatlands turn from a carbon sink to a carbon source and potentially emit nitrous oxide (N2O). Rewetting of peatlands thus implies climate change mitigation. However, data about the time span that is needed for the re-establishment of the carbon sink function by restoration is scarce. We therefore investigated the annual greenhouse gas (GHG) balances of three differently vegetated bog sites 30 years after rewetting. All three vegetation communities turned out to be sources of carbon dioxide (CO2) ranging between 0.6 ± 1.43 t CO2 ha-2 yr-1 (Sphagnum-dominated vegetation) and 3.09 ± 3.86 t CO2 ha-2 yr-1 (vegetation dominated by heath). While accounting for the different global warming potential (GWP) of the three greenhouse gases, the annual GHG balance was calculated. Emissions ranged between 25 and 53 t CO2-eq ha-1 yr-1 and were dominated by large emissions of CH4 (22 up to 51 t CO2-eq ha-1 yr-1), while highest rates were found at purple moor grass (Molinia caerulea) stands. These are to our knowledge the highest CH4 emissions so far reported for bog ecosystems in temperate Europe. As the restored area was subject to large fluctuations in water table, we conclude that the high CH4 emission rates were caused by a combination of both the temporal inundation of the easily decomposable plant litter of this grass species and the plant-mediated transport through its tissues. In addition, as a result of the land use history, the mixed soil material can serve as an explanation. With regards to the long time span passed since rewetting, we note that the initial increase in CH4 emissions due to rewetting as described in the literature is not limited to a short-term period.

  5. High methane emissions dominated annual greenhouse gas balances 30 years after bog rewetting

    NASA Astrophysics Data System (ADS)

    Vanselow-Algan, M.; Schmidt, S. R.; Greven, M.; Fiencke, C.; Kutzbach, L.; Pfeiffer, E.-M.

    2015-07-01

    Natural peatlands are important carbon sinks and sources of methane (CH4). In contrast, drained peatlands turn from a carbon sink to a carbon source and potentially emit nitrous oxide (N2O). Rewetting of peatlands thus potentially implies climate change mitigation. However, data about the time span that is needed for the re-establishment of the carbon sink function by restoration are scarce. We therefore investigated the annual greenhouse gas (GHG) balances of three differently vegetated sites of a bog ecosystem 30 years after rewetting. All three vegetation communities turned out to be sources of carbon dioxide (CO2) ranging between 0.6 ± 1.43 t CO2 ha-2 yr-1 (Sphagnum-dominated vegetation) and 3.09 ± 3.86 t CO2 ha-2 yr-1 (vegetation dominated by heath). While accounting for the different global warming potential (GWP) of CO2, CH4 and N2O, the annual GHG balance was calculated. Emissions ranged between 25 and 53 t CO2-eq ha-1 yr-1 and were dominated by large emissions of CH4 (22-51 t CO2-eq ha-1 yr-1), with highest rates found at purple moor grass (Molinia caerulea) stands. These are to our knowledge the highest CH4 emissions so far reported for bog ecosystems in temperate Europe. As the restored area was subject to large fluctuations in the water table, we assume that the high CH4 emission rates were caused by a combination of both the temporal inundation of the easily decomposable plant litter of purple moor grass and the plant-mediated transport through its tissues. In addition, as a result of the land use history, mixed soil material due to peat extraction and refilling can serve as an explanation. With regards to the long time span passed since rewetting, we note that the initial increase in CH4 emissions due to rewetting as described in the literature is not inevitably limited to a short-term period.

  6. Structure and transcription of the Helicoverpa armigera densovirus (HaDV2) genome and its expression strategy in LD652 cells.

    PubMed

    Xu, Pengjun; Graham, Robert I; Wilson, Kenneth; Wu, Kongming

    2017-02-07

    Densoviruses (DVs) are highly pathogenic to their hosts. However, we previously reported a mutualistic DV (HaDV2). Very little was known about the characteristics of this virus, so herein we undertook a series of experiments to explore the molecular biology of HaDV2 further. Phylogenetic analysis showed that HaDV2 was similar to members of the genus Iteradensovirus. However, compared to current members of the genus Iteradensovirus, the sequence identity of HaDV2 is less than 44% at the nucleotide-level, and lower than 36, 28 and 19% at the amino-acid-level of VP, NS1 and NS2 proteins, respectively. Moreover, NS1 and NS2 proteins from HaDV2 were smaller than those from other iteradensoviruses due to their shorter N-terminal sequences. Two transcripts of about 2.2 kb coding for the NS proteins and the VP proteins were identified by Northern Blot and RACE analysis. Using specific anti-NS1 and anti-NS2 antibodies, Western Blot analysis revealed a 78 kDa and a 48 kDa protein, respectively. Finally, the localization of both NS1 and NS2 proteins within the cell nucleus was determined by using Green Fluorescent Protein (GFP) labelling. The genome organization, terminal hairpin structure, transcription and expression strategies as well as the mutualistic relationship with its host, suggested that HaDV2 was a novel member of the genus Iteradensovirus within the subfamily Densovirinae.

  7. Greenhouse gas fluxes in southeastern U.S. coastal plain wetlands under contrasting land uses.

    PubMed

    Morse, Jennifer L; Ardón, Marcelo; Bernhardt, Emily S

    2012-01-01

    Whether through sea level rise or wetland restoration, agricultural soils in coastal areas will be inundated at increasing rates, renewing connections to sensitive surface waters and raising critical questions about environmental trade-offs. Wetland restoration is often implemented in agricultural catchments to improve water quality through nutrient removal. Yet flooding of soils can also increase production of the greenhouse gases nitrous oxide and methane, representing a potential environmental trade-off. Our study aimed to quantify and compare greenhouse gas emissions from unmanaged and restored forested wetlands, as well as actively managed agricultural fields within the North Carolina coastal plain, USA. In sampling conducted once every two months over a two-year comparative study, we found that soil carbon dioxide flux (range: 8000-64 800 kg CO2 x ha(-1) x yr(-1)) comprised 66-100% of total greenhouse gas emissions from all sites and that methane emissions (range: -6.87 to 197 kg CH4 x ha(-1) x yr(-1)) were highest from permanently inundated sites, while nitrous oxide fluxes (range: -1.07 to 139 kg N2O x ha(-1) x yr(-1)) were highest in sites with lower water tables. Contrary to predictions, greenhouse gas fluxes (as CO2 equivalents) from the restored wetland were lower than from either agricultural fields or unmanaged forested wetlands. In these acidic coastal freshwater ecosystems, the conversion of agricultural fields to flooded young forested wetlands did not result in increases in greenhouse gas emissions.

  8. Wisconsin Glaciation of the Sierra Nevada (79,000-15,000 yr B.P.) as Recorded by Rock Flour in Sediments of Owens Lake, California

    NASA Astrophysics Data System (ADS)

    Bischoff, James L.; Cummins, Kathleen

    2001-01-01

    Chemical analyses of the clay-sized fractions of 564 continuous sediment samples (200-yr resolution) from composite core OL90/92 allow quantification of an abundance of glacial rock flour. Rock flour produced during glacier advances is represented by clay-sized plagioclase, K-feldspar, and biotite in homogeneous internal composition. The abundance of rock flour is deemed proportional to the intensity of glacies advances. Age control for the composite section is provided by combining previously published radiocarbon dates on organics, U/Th dates on ostracode shells, and U/Th dates on saline minerals from nearby Searles Lake correlated to OL92 by pollen. The rock flour record displays three levels of variability: (1) a dominant one of about 20,000 yr related to summer insolation and precipitation; (2) an intermediate one of 3000-5000 yr, perhaps related to North Atlantic Heinrich events; and (3) a minor one of 1000-2000 yr, perhaps related to North Atlantic thermohaline-driven air-temperature variation.

  9. Wisconsin Glaciation of the Sierra Nevada (79,000-15,000 yr B.P.) as recorded by rock flour in sediments of Owens Lake, California

    USGS Publications Warehouse

    Bischoff, J.L.; Cummins, K.

    2001-01-01

    Chemical analyses of the clay-sized fractions of 564 continuous sediment samples (200-yr resolution) from composite core OL90/92 allow quantification of an abundance of glacial rock flour. Rock flour produced during glacier advances is represented by clay-sized plagioclase, K-feldspar, and biotite in homogeneous internal composition. The abundance of rock flour is deemed proportional to the intensity of glacies advances. Age control for the composite section is provided by combining previously published radiocarbon dates on organics, U/Th dates on ostracode shells, and U/Th dates on saline minerals from nearby Searles Lake correlated to OL92 by pollen. The rock flour record displays three levels of variability: (1) a dominant one of about 20,000 yr related to summer insolation and precipitation; (2) an intermediate one of 3000-5000 yr, perhaps related to North Atlantic Heinrich events; and (3) a minor one of 1000-2000 yr, perhaps related to North Atlantic thermohaline-driven air-temperature variation. ?? 2001 University of Washington.

  10. Nitrogen and phosphorus budget of a polyculture system of sea cucumber ( Apostichopus japonicus), jellyfish ( Rhopilema esculenta) and shrimp ( Fenneropenaeus chinensis)

    NASA Astrophysics Data System (ADS)

    Li, Junwei; Dong, Shuanglin; Gao, Qinfeng; Zhu, Changbo

    2014-06-01

    The nitrogen (N) and phosphorus (P) budget and the ecological efficiency of a polyculture system of sea cucumber ( Apostichopus japonicus), jellyfish ( Rhopilema esculenta) and shrimp ( Fenneropenaeus chinensis) were studied in a cofferdam, 120.2 ha in size. The nutrients were supplied by spring tide inflow. In total, 139600 kg N yr-1 and 9730 kg P yr-1 input to the system; while 118900 kg N yr-1 and 2840 kg P yr-1 outflowed from the system concurrently, thus the outflow was 85.7% (N) and 29.2% (P) of inflow. The production of N and P was 889.5 kg yr-1 and 49.28 kg yr-1 (sea cucumber) and 204 kg yr-1 and 18.03 kg yr-1 (jellyfish and shrimp), respectively. The utilization rate of N and P by polycultured animals was 7.8‰ and 6.9‰, respectively, 21.9% and 38% higher than that of monocultured sea cucumber. Our results indicated that the polyculture system was an efficient culture system of animals and a remediation system of coastal environment as well; it scavenged 14.3% and 70.8% of N and P, respectively. Such an ecological efficiency may be improved further by increasing either the stocking density or the size of sea cucumber or both.

  11. Urbanisation-related land use change from forest and pasture into turf grass modifies soil nitrogen cycling and increases N2O emissions

    NASA Astrophysics Data System (ADS)

    van Delden, Lona; Rowlings, David W.; Scheer, Clemens; Grace, Peter R.

    2016-11-01

    Urbanisation is becoming increasingly important in terms of climate change and ecosystem functionality worldwide. We are only beginning to understand how the processes of urbanisation influence ecosystem dynamics, making peri-urban environments more vulnerable to nutrient losses. Brisbane in South East Queensland has the most extensive urban sprawl of all Australian cities. This research estimated the environmental impact of land use change associated with urbanisation by examining soil nitrogen (N) turnover and subsequent nitrous oxide (N2O) emissions using a fully automated system that measured emissions on a sub-daily basis. There was no significant difference in soil N2O emissions between the native dry sclerophyll eucalypt forest and an extensively grazed pasture, wherefrom only low annual emissions were observed amounting to 0.1 and 0.2 kg N2O ha-1 yr-1, respectively. The establishment of a fertilised turf grass lawn increased soil N2O emissions 18-fold (1.8 kg N2O ha-1 yr-1), with highest emissions occurring in the first 2 months after establishment. Once established, the turf grass lawn presented relatively low N2O emissions for the rest of the year, even after fertilisation and rain events. Soil moisture was significantly higher, and mineralised N accumulated in the fallow plots, resulting in the highest N2O emissions (2.8 kg N2O ha-1 yr-1) and significant nitrate (NO3-) losses, with up to 63 kg N ha-1 lost from a single rain event due to reduced plant cover removal. The study concludes that urbanisation processes creating peri-urban ecosystems can greatly modify N cycling and increase the potential for losses in the form of N2O and NO3-.

  12. SIRT1 inhibition restores apoptotic sensitivity in p53-mutated human keratinocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herbert, Katharine J.; Cook, Anthony L., E-mail: Anthony.Cook@utas.edu.au; Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au

    2014-06-15

    Mutations to the p53 gene are common in UV-exposed keratinocytes and contribute to apoptotic resistance in skin cancer. P53-dependent activity is modulated, in part, by a complex, self-limiting feedback loop imposed by miR-34a-mediated regulation of the lysine deacetylase, SIRT1. Expression of numerous microRNAs is dysregulated in squamous and basal cell carcinomas; however the contribution of specific microRNAs to the pathogenesis of skin cancer remains untested. Through use of RNAi, miRNA target site blocking oligonucleotides and small molecule inhibitors, this study explored the influence of p53 mutational status, SIRT1 activity and miR-34a levels on apoptotic sensitivity in primary (NHEK) and p53-mutatedmore » (HaCaT) keratinocyte cell lines. SIRT1 and p53 are overexpressed in p53-mutated keratinocytes, whilst miR-34a levels are 90% less in HaCaT cells. HaCaTs have impaired responses to p53/SIRT1/miR-34a axis manipulation which enhanced survival during exposure to the chemotherapeutic agent, camptothecin. Inhibition of SIRT1 activity in this cell line increased p53 acetylation and doubled camptothecin-induced cell death. Our results demonstrate that p53 mutations increase apoptotic resistance in keratinocytes by interfering with miR-34a-mediated regulation of SIRT1 expression. Thus, SIRT1 inhibitors may have a therapeutic potential for overcoming apoptotic resistance during skin cancer treatment. - Highlights: • Impaired microRNA biogenesis promotes apoptotic resistance in HaCaT keratinocytes. • TP53 mutations suppress miR-34a-mediated regulation of SIRT1 expression. • SIRT1 inhibition increases p53 acetylation in HaCaTs, restoring apoptosis.« less

  13. Characterization of New PEEK/HA Composites with 3D HA Network Fabricated by Extrusion Freeforming.

    PubMed

    Vaezi, Mohammad; Black, Cameron; Gibbs, David M R; Oreffo, Richard O C; Brady, Mark; Moshrefi-Torbati, Mohamed; Yang, Shoufeng

    2016-05-26

    Addition of bioactive materials such as calcium phosphates or Bioglass, and incorporation of porosity into polyetheretherketone (PEEK) has been identified as an effective approach to improve bone-implant interfaces and osseointegration of PEEK-based devices. In this paper, a novel production technique based on the extrusion freeforming method is proposed that yields a bioactive PEEK/hydroxyapatite (PEEK/HA) composite with a unique configuration in which the bioactive phase (i.e., HA) distribution is computer-controlled within a PEEK matrix. The 100% interconnectivity of the HA network in the biocomposite confers an advantage over alternative forms of other microstructural configurations. Moreover, the technique can be employed to produce porous PEEK structures with controlled pore size and distribution, facilitating greater cellular infiltration and biological integration of PEEK composites within patient tissue. The results of unconfined, uniaxial compressive tests on these new PEEK/HA biocomposites with 40% HA under both static and cyclic mode were promising, showing the composites possess yield and compressive strength within the range of human cortical bone suitable for load bearing applications. In addition, preliminary evidence supporting initial biological safety of the new technique developed is demonstrated in this paper. Sufficient cell attachment, sustained viability in contact with the sample over a seven-day period, evidence of cell bridging and matrix deposition all confirmed excellent biocompatibility.

  14. Blood Leukocyte Concentrations, FEV1 Decline, and Airflow Limitation. A 15-Year Longitudinal Study of World Trade Center-exposed Firefighters.

    PubMed

    Zeig-Owens, Rachel; Singh, Ankura; Aldrich, Thomas K; Hall, Charles B; Schwartz, Theresa; Webber, Mayris P; Cohen, Hillel W; Kelly, Kerry J; Nolan, Anna; Prezant, David J; Weiden, Michael D

    2018-02-01

    Rescue/recovery work at the World Trade Center disaster site (WTC) caused a proximate decline in lung function in Fire Department of the City of New York firefighters. A subset of this cohort experienced an accelerated rate of lung function decline over 15 years of post-September 11, 2001 (9/11) follow-up. To determine if early postexposure blood leukocyte concentrations are biomarkers for subsequent FEV 1 decline and incident airflow limitation. Individual rates of forced expiratory volume in 1 second (FEV 1 ) change were calculated for 9,434 firefighters using 88,709 spirometric measurements taken between September 11, 2001, and September 10, 2016. We categorized FEV 1 change rates into three trajectories: accelerated FEV 1 decline (FEV 1 loss >64 ml/yr), expected FEV 1 decline (FEV 1 loss between 0 and 64 ml/yr), and improved FEV 1 (positive rate of change >0 ml/yr). Occurrence of FEV 1 /FVC less than 0.70 after 9/11 defined incident airflow limitation. Using regression models, we assessed associations of post-9/11 blood eosinophil and neutrophil concentrations with subsequent FEV 1 decline and airflow limitation, adjusted for age, race, smoking, height, WTC exposure level, weight change, and baseline lung function. Accelerated FEV 1 decline occurred in 12.7% of participants (1,199 of 9,434), whereas post-9/11 FEV 1 improvement occurred in 8.3% (780 of 9,434). Higher blood eosinophil and neutrophil concentrations were each associated with accelerated FEV 1 decline after adjustment for covariates (odds ratio [OR], 1.10 per 100 eosinophils/μl; 95% confidence interval [CI], 1.05-1.15; and OR, 1.10 per 1,000 neutrophils/μl; 95% CI, 1.05-1.15, respectively). Multivariable-adjusted linear regression models showed that a higher blood neutrophil concentration was associated with a faster rate of FEV 1 decline (1.14 ml/yr decline per 1,000 neutrophils/μl; 95% CI, 0.69-1.60 ml/yr; P < 0.001). Higher blood eosinophil concentrations were associated with a faster rate

  15. [Preliminary study on HA-coated titanium implants used as anchorage for protraction of dog molar teeth].

    PubMed

    Liang, X; Tang, S; Wang, H

    1998-05-01

    HA-coated titanium implants were placed surgically into dog mandible to protract the mandibular second molars with an orthodontic force of 150 g. During the force application period of 3 months, the movement of the molars was tested periodically and relevant reasons of movement were analysed. The results showed that the mesial moving distances of the second molar were respectively 1.04 mm, 1.68 mm and 1.76 mm at the first, second and third month, and the main reason of tooth mobility was ascribed to the implant anchorage. It can be concluded tiat HA-coated titanium implant can be used as anchorage for moving and fixing posterior teeth in the orthodontic treatment.

  16. Involvement of nitrergic system of CA1in harmane induced learning and memory deficits.

    PubMed

    Nasehi, Mohammad; Piri, Morteza; Abdollahian, Mojgan; Zarrindast, Mohammad Reza

    2013-01-17

    Harmane (HA) is a β-carboline alkaloid derived from the Peganum harmala plant which induces memory impairment. On the other hand some of the investigations showed that β-carboline alkaloids inhibit NO production. Thus, the aim of the present study was to investigate the role of nitrergic system of the dorsal hippocampus (CA1) in HA-induced amnesia in male adult mice. One-trial step-down passive avoidance and hole-board apparatuses were used for the assessment of memory retrieval and exploratory behaviors respectively. The data indicated that pre-training intraperitoneal (i.p.) administration of HA (12 and 16 mg/kg) decreased memory acquisition. Sole pre-training or pre-testing administration of L-NAME, a nitric oxide synthesis inhibitor (5, 10 and 15 μg/mice, intra-CA1) did not alter memory retrieval. On the other hand, pre-training (10 and 15 μg/mice, intra-CA1) and pre-testing (5, 10 μg/mice, intra-CA1) injections of L-NAME restored HA-induced amnesia (16 mg/kg, i.p.). Furthermore, neither sole pre-training nor pre-testing administration of l-arginine, a NO precursor (3, 6 and 9 μg/mice, intra-CA1), altered memory retrieval. In addition, pre-testing (6 and 9 μg/mice, intra-CA1), but not pre-training, injection of l-arginine increased HA-induced amnesia (16 mg/kg, i.p.). These results suggest that the nitrergic system of CA1 is involved in HA-induced amnesia. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Search for gravitational waves from compact binary coalescence in LIGO and Virgo data from S5 and VSR1

    NASA Astrophysics Data System (ADS)

    Abadie, J.; Abbott, B. P.; Abbott, R.; Abernathy, M.; Accadia, T.; Acernese, F.; Adams, C.; Adhikari, R.; Ajith, P.; Allen, B.; Allen, G.; Amador Ceron, E.; Amin, R. S.; Anderson, S. B.; Anderson, W. G.; Antonucci, F.; Arain, M. A.; Araya, M.; Aronsson, M.; Arun, K. G.; Aso, Y.; Aston, S.; Astone, P.; Atkinson, D. E.; Aufmuth, P.; Aulbert, C.; Babak, S.; Baker, P.; Ballardin, G.; Ballinger, T.; Ballmer, S.; Barker, D.; Barnum, S.; Barone, F.; Barr, B.; Barriga, P.; Barsotti, L.; Barsuglia, M.; Barton, M. A.; Bartos, I.; Bassiri, R.; Bastarrika, M.; Bauchrowitz, J.; Bauer, Th. S.; Behnke, B.; Beker, M. G.; Belletoile, A.; Benacquista, M.; Bertolini, A.; Betzwieser, J.; Beveridge, N.; Beyersdorf, P. T.; Bigotta, S.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Birindelli, S.; Biswas, R.; Bitossi, M.; Bizouard, M. A.; Black, E.; Blackburn, J. K.; Blackburn, L.; Blair, D.; Bland, B.; Blom, M.; Boccara, C.; Bock, O.; Bodiya, T. P.; Bondarescu, R.; Bondu, F.; Bonelli, L.; Bonnand, R.; Bork, R.; Born, M.; Bose, S.; Bosi, L.; Bouhou, B.; Boyle, M.; Braccini, S.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Brau, J. E.; Breyer, J.; Bridges, D. O.; Brillet, A.; Brinkmann, M.; Brisson, V.; Britzger, M.; Brooks, A. F.; Brown, D. A.; Budzyński, R.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Burguet–Castell, J.; Burmeister, O.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cain, J.; Calloni, E.; Camp, J. B.; Campagna, E.; Campsie, P.; Cannizzo, J.; Cannon, K. C.; Canuel, B.; Cao, J.; Capano, C.; Carbognani, F.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C.; Cesarini, E.; Chalermsongsak, T.; Chalkley, E.; Charlton, P.; Chassande-Mottin, E.; Chelkowski, S.; Chen, Y.; Chincarini, A.; Christensen, N.; Chua, S. S. Y.; Chung, C. T. Y.; Clark, D.; Clark, J.; Clayton, J. H.; Cleva, F.; Coccia, E.; Colacino, C. N.; Colas, J.; Colla, A.; Colombini, M.; Conte, R.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Costa, C. A.; Coulon, J.-P.; Coward, D.; Coyne, D. C.; Creighton, J. D. E.; Creighton, T. D.; Cruise, A. M.; Culter, R. M.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dahl, K.; Danilishin, S. L.; Dannenberg, R.; D'Antonio, S.; Danzmann, K.; Das, K.; Dattilo, V.; Daudert, B.; Davier, M.; Davies, G.; Davis, A.; Daw, E. J.; Day, R.; Dayanga, T.; de Rosa, R.; Debra, D.; Degallaix, J.; Del Prete, M.; Dergachev, V.; Derosa, R.; Desalvo, R.; Devanka, P.; Dhurandhar, S.; di Fiore, L.; di Lieto, A.; di Palma, I.; di Paolo Emilio, M.; di Virgilio, A.; Díaz, M.; Dietz, A.; Donovan, F.; Dooley, K. L.; Doomes, E. E.; Dorsher, S.; Douglas, E. S. D.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Dueck, J.; Dumas, J.-C.; Eberle, T.; Edgar, M.; Edwards, M.; Effler, A.; Ehrens, P.; Ely, G.; Engel, R.; Etzel, T.; Evans, M.; Evans, T.; Fafone, V.; Fairhurst, S.; Fan, Y.; Farr, B. F.; Fazi, D.; Fehrmann, H.; Feldbaum, D.; Ferrante, I.; Fidecaro, F.; Finn, L. S.; Fiori, I.; Flaminio, R.; Flanigan, M.; Flasch, K.; Foley, S.; Forrest, C.; Forsi, E.; Fotopoulos, N.; Fournier, J.-D.; Franc, J.; Frasca, S.; Frasconi, F.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Friedrich, D.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Galimberti, M.; Gammaitoni, L.; Garofoli, J. A.; Garufi, F.; Gemme, G.; Genin, E.; Gennai, A.; Ghosh, S.; Giaime, J. A.; Giampanis, S.; Giardina, K. D.; Giazotto, A.; Gill, C.; Goetz, E.; Goggin, L. M.; González, G.; Goßler, S.; Gouaty, R.; Graef, C.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Greverie, C.; Grosso, R.; Grote, H.; Grunewald, S.; Guidi, G. M.; Gustafson, E. K.; Gustafson, R.; Hage, B.; Hall, P.; Hallam, J. M.; Hammer, D.; Hammond, G.; Hanks, J.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G. M.; Harry, I. W.; Harstad, E. D.; Haughian, K.; Hayama, K.; Hayau, J.-F.; Hayler, T.; Heefner, J.; Heitmann, H.; Hello, P.; Heng, I. S.; Heptonstall, A.; Hewitson, M.; Hild, S.; Hirose, E.; Hoak, D.; Hodge, K. A.; Holt, K.; Hosken, D. J.; Hough, J.; Howell, E.; Hoyland, D.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh–Dinh, T.; Ingram, D. R.; Inta, R.; Isogai, T.; Ivanov, A.; Jaranowski, P.; Johnson, W. W.; Jones, D. I.; Jones, G.; Jones, R.; Ju, L.; Kalmus, P.; Kalogera, V.; Kandhasamy, S.; Kanner, J.; Katsavounidis, E.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kells, W.; Keppel, D. G.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, H.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kondrashov, V.; Kopparapu, R.; Koranda, S.; Kowalska, I.; Kozak, D.; Krause, T.; Kringel, V.; Krishnamurthy, S.; Krishnan, B.; Królak, A.; Kuehn, G.; Kullman, J.; Kumar, R.; Kwee, P.; Landry, M.; Lang, M.; Lantz, B.; Lastzka, N.; Lazzarini, A.; Leaci, P.; Leong, J.; Leonor, I.; Leroy, N.; Letendre, N.; Li, J.; Li, T. G. F.; Lin, H.; Lindquist, P. E.; Lockerbie, N. A.; Lodhia, D.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lu, P.; Luan, J.; Lubiński, M.; Lucianetti, A.; Lück, H.; Lundgren, A.; Machenschalk, B.; Macinnis, M.; Mageswaran, M.; Mailand, K.; Majorana, E.; Mak, C.; Maksimovic, I.; Man, N.; Mandel, I.; Mandic, V.; Mantovani, M.; Marchesoni, F.; Marion, F.; Márka, S.; Márka, Z.; Maros, E.; Marque, J.; Martelli, F.; Martin, I. W.; Martin, R. M.; Marx, J. N.; Mason, K.; Masserot, A.; Matichard, F.; Matone, L.; Matzner, R. A.; Mavalvala, N.; McCarthy, R.; McClelland, D. E.; McGuire, S. C.; McIntyre, G.; McIvor, G.; McKechan, D. J. A.; Meadors, G.; Mehmet, M.; Meier, T.; Melatos, A.; Melissinos, A. C.; Mendell, G.; Menéndez, D. F.; Mercer, R. A.; Merill, L.; Meshkov, S.; Messenger, C.; Meyer, M. S.; Miao, H.; Michel, C.; Milano, L.; Miller, J.; Minenkov, Y.; Mino, Y.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moe, B.; Mohan, M.; Mohanty, S. D.; Mohapatra, S. R. P.; Moraru, D.; Moreau, J.; Moreno, G.; Morgado, N.; Morgia, A.; Mors, K.; Mosca, S.; Moscatelli, V.; Mossavi, K.; Mours, B.; Mowlowry, C.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Müller-Ebhardt, H.; Munch, J.; Murray, P. G.; Nash, T.; Nawrodt, R.; Nelson, J.; Neri, I.; Newton, G.; Nishida, E.; Nishizawa, A.; Nocera, F.; Nolting, D.; Ochsner, E.; O'Dell, J.; Ogin, G. H.; Oldenburg, R. G.; O'Reilly, B.; O'Shaughnessy, R.; Osthelder, C.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Page, A.; Pagliaroli, G.; Palladino, L.; Palomba, C.; Pan, Y.; Pankow, C.; Paoletti, F.; Papa, M. A.; Pardi, S.; Pareja, M.; Parisi, M.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patel, P.; Pathak, D.; Pedraza, M.; Pekowsky, L.; Penn, S.; Peralta, C.; Perreca, A.; Persichetti, G.; Pichot, M.; Pickenpack, M.; Piergiovanni, F.; Pietka, M.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Pletsch, H. J.; Plissi, M. V.; Poggiani, R.; Postiglione, F.; Prato, M.; Predoi, V.; Price, L. R.; Prijatelj, M.; Principe, M.; Prix, R.; Prodi, G. A.; Prokhorov, L.; Puncken, O.; Punturo, M.; Puppo, P.; Quetschke, V.; Raab, F. J.; Rabeling, D. S.; Radke, T.; Radkins, H.; Raffai, P.; Rakhmanov, M.; Rankins, B.; Rapagnani, P.; Raymond, V.; Re, V.; Reed, C. M.; Reed, T.; Regimbau, T.; Reid, S.; Reitze, D. H.; Ricci, F.; Riesen, R.; Riles, K.; Roberts, P.; Robertson, N. A.; Robinet, F.; Robinson, C.; Robinson, E. L.; Rocchi, A.; Roddy, S.; Röver, C.; Rolland, L.; Rollins, J.; Romano, J. D.; Romano, R.; Romie, J. H.; Rosińska, D.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Sakata, S.; Sakosky, M.; Salemi, F.; Sammut, L.; Sancho de La Jordana, L.; Sandberg, V.; Sannibale, V.; Santamaría, L.; Santostasi, G.; Saraf, S.; Sassolas, B.; Sathyaprakash, B. S.; Sato, S.; Satterthwaite, M.; Saulson, P. R.; Savage, R.; Schilling, R.; Schnabel, R.; Schofield, R.; Schulz, B.; Schutz, B. F.; Schwinberg, P.; Scott, J.; Scott, S. M.; Searle, A. C.; Seifert, F.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sergeev, A.; Shaddock, D.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sibley, A.; Siemens, X.; Sigg, D.; Singer, A.; Sintes, A. M.; Skelton, G.; Slagmolen, B. J. J.; Slutsky, J.; Smith, J. R.; Smith, M. R.; Smith, N. D.; Somiya, K.; Sorazu, B.; Speirits, F. C.; Sperandio, L.; Stein, A. J.; Stein, L. C.; Steinlechner, S.; Steplewski, S.; Stochino, A.; Stone, R.; Strain, K. A.; Strigin, S.; Stroeer, A.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sung, M.; Susmithan, S.; Sutton, P. J.; Swinkels, B.; Talukder, D.; Tanner, D. B.; Tarabrin, S. P.; Taylor, J. R.; Taylor, R.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Thüring, A.; Titsler, C.; Tokmakov, K. V.; Toncelli, A.; Tonelli, M.; Torre, O.; Torres, C.; Torrie, C. I.; Tournefier, E.; Travasso, F.; Traylor, G.; Trias, M.; Trummer, J.; Tseng, K.; Turner, L.; Ugolini, D.; Urbanek, K.; Vahlbruch, H.; Vaishnav, B.; Vajente, G.; Vallisneri, M.; van den Brand, J. F. J.; van den Broeck, C.; van der Putten, S.; van der Sluys, M. V.; van Veggel, A. A.; Vass, S.; Vaulin, R.; Vavoulidis, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Veltkamp, C.; Verkindt, D.; Vetrano, F.; Viceré, A.; Villar, A.; Vinet, J.-Y.; Vocca, H.; Vorvick, C.; Vyachanin, S. P.; Waldman, S. J.; Wallace, L.; Wanner, A.; Ward, R. L.; Was, M.; Wei, P.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Wen, S.; Wessels, P.; West, M.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wilkinson, C.; Willems, P. A.; Williams, L.; Willke, B.; Winkelmann, L.; Winkler, W.; Wipf, C. C.; Wiseman, A. G.; Woan, G.; Wooley, R.; Worden, J.; Yakushin, I.; Yamamoto, H.; Yamamoto, K.; Yeaton-Massey, D.; Yoshida, S.; Yu, P. P.; Yvert, M.; Zanolin, M.; Zhang, L.; Zhang, Z.; Zhao, C.; Zotov, N.; Zucker, M. E.; Zweizig, J.

    2010-11-01

    We report the results of the first search for gravitational waves from compact binary coalescence using data from the Laser Interferometer Gravitational-Wave Observatory and Virgo detectors. Five months of data were collected during the Laser Interferometer Gravitational-Wave Observatory’s S5 and Virgo’s VSR1 science runs. The search focused on signals from binary mergers with a total mass between 2 and 35M⊙. No gravitational waves are identified. The cumulative 90%-confidence upper limits on the rate of compact binary coalescence are calculated for nonspinning binary neutron stars, black hole-neutron star systems, and binary black holes to be 8.7×10-3yr-1L10-1, 2.2×10-3yr-1L10-1, and 4.4×10-4yr-1L10-1, respectively, where L10 is 1010 times the blue solar luminosity. These upper limits are compared with astrophysical expectations.

  18. Serosurveillance for pandemic influenza A (H1N1) 2009 virus infection in domestic elephants, Thailand

    PubMed Central

    Paungpin, Weena; Wiriyarat, Witthawat; Chaichoun, Kridsada; Tiyanun, Ekasit; Sangkachai, Nareerat; Changsom, Don; Poltep, Kanaporn; Ratanakorn, Parntep

    2017-01-01

    The present study conducted serosurveillance for the presence of antibody to pandemic influenza A (H1N1) 2009 virus (H1N1pdm virus) in archival serum samples collected between 2009 and 2013 from 317 domestic elephants living in 19 provinces situated in various parts of Thailand. To obtain the most accurate data, hemagglutination-inhibition (HI) assay was employed as the screening test; and sera with HI antibody titers ≥20 were further confirmed by other methods, including cytopathic effect/hemagglutination based-microneutralization (microNT) and Western blot (WB) assays using H1N1pdm matrix 1 (M1) or hemagglutinin (HA) recombinant protein as the test antigen. Conclusively, the appropriate assays using HI in conjunction with WB assays for HA antibody revealed an overall seropositive rate of 8.5% (27 of 317). The prevalence of antibody to H1N1pdm virus was 2% (4/172) in 2009, 32% (17/53) in 2010, 9% (2/22) in 2011, 12% (1/8) in 2012, and 5% (3/62) in 2013. Notably, these positive serum samples were collected from elephants living in 7 tourist provinces of Thailand. The highest seropositive rate was obtained from elephants in Phuket, a popular tourist beach city. Young elephants had higher seropositive rate than older elephants. The source of H1N1pdm viral infection in these elephants was not explored, but most likely came from close contact with the infected mahouts or from the infected tourists who engaged in activities such as elephant riding and feeding. Nevertheless, it could not be excluded that elephant-to-elephant transmission did occur. PMID:29073255

  19. Serosurveillance for pandemic influenza A (H1N1) 2009 virus infection in domestic elephants, Thailand.

    PubMed

    Paungpin, Weena; Wiriyarat, Witthawat; Chaichoun, Kridsada; Tiyanun, Ekasit; Sangkachai, Nareerat; Changsom, Don; Poltep, Kanaporn; Ratanakorn, Parntep; Puthavathana, Pilaipan

    2017-01-01

    The present study conducted serosurveillance for the presence of antibody to pandemic influenza A (H1N1) 2009 virus (H1N1pdm virus) in archival serum samples collected between 2009 and 2013 from 317 domestic elephants living in 19 provinces situated in various parts of Thailand. To obtain the most accurate data, hemagglutination-inhibition (HI) assay was employed as the screening test; and sera with HI antibody titers ≥20 were further confirmed by other methods, including cytopathic effect/hemagglutination based-microneutralization (microNT) and Western blot (WB) assays using H1N1pdm matrix 1 (M1) or hemagglutinin (HA) recombinant protein as the test antigen. Conclusively, the appropriate assays using HI in conjunction with WB assays for HA antibody revealed an overall seropositive rate of 8.5% (27 of 317). The prevalence of antibody to H1N1pdm virus was 2% (4/172) in 2009, 32% (17/53) in 2010, 9% (2/22) in 2011, 12% (1/8) in 2012, and 5% (3/62) in 2013. Notably, these positive serum samples were collected from elephants living in 7 tourist provinces of Thailand. The highest seropositive rate was obtained from elephants in Phuket, a popular tourist beach city. Young elephants had higher seropositive rate than older elephants. The source of H1N1pdm viral infection in these elephants was not explored, but most likely came from close contact with the infected mahouts or from the infected tourists who engaged in activities such as elephant riding and feeding. Nevertheless, it could not be excluded that elephant-to-elephant transmission did occur.

  20. ADCYAP1R1 and asthma in Puerto Rican children.

    PubMed

    Chen, Wei; Boutaoui, Nadia; Brehm, John M; Han, Yueh-Ying; Schmitz, Cassandra; Cressley, Alex; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Baccarelli, Andrea A; Weeks, Daniel E; Kolls, Jay K; Canino, Glorisa; Celedón, Juan C

    2013-03-15

    Epigenetic and/or genetic variation in the gene encoding the receptor for adenylate-cyclase activating polypeptide 1 (ADCYAP1R1) has been linked to post-traumatic stress disorder in adults and anxiety in children. Psychosocial stress has been linked to asthma morbidity in Puerto Rican children. To examine whether epigenetic or genetic variation in ADCYAP1R1 is associated with childhood asthma in Puerto Ricans. We conducted a case-control study of 516 children ages 6-14 years living in San Juan, Puerto Rico. We assessed methylation at a CpG site in the promoter of ADCYAP1R1 (cg11218385) using a pyrosequencing assay in DNA from white blood cells. We tested whether cg11218385 methylation (range, 0.4-6.1%) is associated with asthma using logistic regression. We also examined whether exposure to violence (assessed by the Exposure to Violence [ETV] Scale in children 9 yr and older) is associated with cg11218385 methylation (using linear regression) or asthma (using logistic regression). Logistic regression was used to test for association between a single nucleotide polymorphism in ADCYAP1R1 (rs2267735) and asthma under an additive model. All multivariate models were adjusted for age, sex, household income, and principal components. EACH 1% increment in cg11218385 methylation was associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.6; P = 0.03). Among children 9 years and older, exposure to violence was associated with cg11218385 methylation. The C allele of single nucleotide polymorphism rs2267735 was significantly associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.02-1.67; P = 0.03). Epigenetic and genetic variants in ADCYAP1R1 are associated with asthma in Puerto Rican children.

  1. Overall properties of the Gaia DR1 reference frame

    NASA Astrophysics Data System (ADS)

    Liu, N.; Zhu, Z.; Liu, J.-C.; Ding, C.-Y.

    2017-03-01

    Aims: The first Gaia data release (Gaia DR1) provides 2191 ICRF2 sources with their positions in the auxiliary quasar solution and five astrometric parameters - positions, parallaxes, and proper motions - for stars in common between the Tycho-2 catalogue and Gaia in the joint Tycho-Gaia astrometric solution (TGAS). We aim to analyze the overall properties of Gaia DR1 reference frame. Methods: We compare quasar positions of the auxiliary quasar solution with ICRF2 sources using different samples and evaluate the influence on the Gaia DR1 reference frame owing to the Galactic aberration effect over the J2000.0-J2015.0 period. Then we estimate the global rotation between TGAS with Tycho-2 proper motion systems to investigate the property of the Gaia DR1 reference frame. Finally, the Galactic kinematics analysis using the K-M giant proper motions is performed to understand the property of Gaia DR1 reference frame. Results: The positional comparison between the auxiliary quasar solution and ICRF2 shows negligible orientation and validates the declination bias of -0.1mas in Gaia quasar positions with respect to ICRF2. Galactic aberration effect is thought to cause an offset 0.01mas of the Z axis direction of Gaia DR1 reference frame. The global rotation between TGAS and Tycho-2 proper motion systems, obtained by different samples, shows a much smaller value than the claimed value 0.24mas yr-1. For the Galactic kinematics analysis of the TGAS K-M giants, we find possible non-zero Galactic rotation components beyond the classical Oort constants: the rigid part ωYG = -0.38±0.15mas yr-1 and the differential part ω^primeYG = -0.29±0.19mas yr-1 around the YG axis of Galactic coordinates, which indicates possible residual rotation in Gaia DR1 reference frame or problems in the current Galactic kinematical model. Conclusions: The Gaia DR1 reference frame is well aligned to ICRF2, and the possible influence of the Galactic aberration effect should be taken into consideration

  2. Nanocomposite Porous Microcarriers Based on Strontium-Substituted HA- g-Poly(γ-benzyl-l-glutamate) for Bone Tissue Engineering.

    PubMed

    Yan, Shifeng; Xia, Pengfei; Xu, Shenghua; Zhang, Kunxi; Li, Guifei; Cui, Lei; Yin, Jingbo

    2018-05-04

    Porous microcarriers have aroused increasing attention recently, which can create a protected environment for sufficient cell seeding density, facilitate oxygen and nutrient transfer, and well support the cell attachment and growth. In this study, porous microcarriers fabricated from the strontium-substituted hydroxyapatite- graft-poly(γ-benzyl-l-glutamate) (Sr10-HA- g-PBLG) hybrid nanocomposite were developed. The surface grating of PBLG, the micromorphology and element distribution, mechanical strength, in vitro degradation, and Sr 2+ ion release of the obtained Sr10-HA- g-PBLG porous microcarriers were investigated, respectively. The grafting ratio and the molecular weight of the grafted PBLG of Sr10-HA- g-PBLG could be effectively controlled by varying the initial ratio of BLG-NCA to Sr10-HA-NH 2 . The microcarriers exhibited a highly porous and interconnected microstructure with the porosity of about 90% and overall density of 1.03-1.06 g/cm 3 . Also, the degradation rate of Sr10-HA-PBLG microcarriers could be effectively controlled and long-term Sr 2+ release was obtained. The Sr10-HA-PBLG microcarriers allowed cells adhesion, infiltration, and proliferation and promoted the osteogenic differentiation of rabbit adipose-derived stem cells (ADSCs). Successful healing of femoral bone defect was proved by injection of the ADSCs-seeded Sr10-HA-PBLG microcarriers in a rabbit model.

  3. Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

    PubMed

    Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

    2011-09-28

    Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Cost-effectiveness of an experimental caries-control regimen in a 3.4-yr randomized clinical trial among 11-12-yr-old Finnish schoolchildren.

    PubMed

    Hietasalo, Pauliina; Seppä, Liisa; Lahti, Satu; Niinimaa, Ahti; Kallio, Jouko; Aronen, Pasi; Sintonen, Harri; Hausen, Hannu

    2009-12-01

    The aim of this study was to assess the cost-effectiveness of an experimental caries-control regimen in a randomized clinical trial (RCT) conducted in Pori, Finland, in 2001-2005. Children (n = 497) who were 11-12 yr of age and had at least one active initial caries lesion at baseline were studied. The children in the experimental group (n = 250) were offered an individually designed patient-centered regimen for caries control. The children in the control group (n = 247) received standard dental care. Furthermore, the whole population was exposed to continuous community-level oral health promotion. Individual costs of treatment procedures and outcomes (DMFS increment score) for the follow-up period of 3.4 yr were calculated for each child in both groups. The incremental cost-effectiveness ratio was euro 34.07 per averted DMF surface. The experimental regimen was more effective, and also more costly. However, the total costs decreased year after year, and for the last 2 yr the experimental regimen was less expensive than the standard dental care. The experimental regimen would probably have been more cost-effective than standard dental care if the follow-up period had been longer, the regimen less comprehensive, and/or if dental nurses had conducted the preventive procedures.

  5. Diatom evidence for earthquake-induced subsidence and tsunami 300 yr ago in southern coastal Washington

    USGS Publications Warehouse

    Hemphill-Haley, E.

    1995-01-01

    Fossil diatoms from four stratigraphic sections along the tidal Niawiakum River, southwestern Washington, provide an independent paleoecological test of a relative sea-level rise that has been attributed to subsidence during an inferred earthquake in the Cascadia subduction zone about 300 yr ago. Diatom assemblages in a buried soil and overlying mud indicate a sudden and lasting shift from marshes and forests near or above highest tides to mud flats and incipient tidal marshes, with a progressive return to high-level tidal marshes by sediment aggradation and, perhaps, gradual tectonic uplift. The maount of coseismic submergence required to generate the paleoecological changes observed at these sites could have ranged from a minimum of 0.8-1.0m to a maximum of ~3.0m. The following tsunami extended farther landward than was previously inferred from the stratigraphy. These data rule out proposed alternatives to the coseismic subsidence model - that is, climatically induced sea-level rise, temporary submergence caused by storms - and support the hypothesis that a great earthquake struck southwestern Washington 300 yr ago. -from Author

  6. The Compact, ˜1 kpc Host Galaxy of a Quasar at a Redshift of 7.1

    NASA Astrophysics Data System (ADS)

    Venemans, Bram P.; Walter, Fabian; Decarli, Roberto; Bañados, Eduardo; Hodge, Jacqueline; Hewett, Paul; McMahon, Richard G.; Mortlock, Daniel J.; Simpson, Chris

    2017-03-01

    We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of the [C II] fine-structure line and the underlying far-infrared (FIR) dust continuum emission in J1120+0641, the most distant quasar currently known (z=7.1). We also present observations targeting the CO(2-1), CO(7-6), and [C I] 369 μm lines in the same source obtained at the Very Large Array and Plateau de Bure Interferometer. We find a [C II] line flux of {F}[{{C}{{II}}]}=1.11+/- 0.10 Jy {km} {{{s}}}-1 and a continuum flux density of {S}227{GHz}=0.53+/- 0.04 mJy beam-1, consistent with previous unresolved measurements. No other source is detected in continuum or [C II] emission in the field covered by ALMA (˜ 25″). At the resolution of our ALMA observations (0.″23, or 1.2 kpc, a factor of ˜70 smaller beam area compared to previous measurements), we find that the majority of the emission is very compact: a high fraction (˜80%) of the total line and continuum flux is associated with a region 1-1.5 kpc in diameter. The remaining ˜20% of the emission is distributed over a larger area with radius ≲4 kpc. The [C II] emission does not exhibit ordered motion on kiloparsec scales: applying the virial theorem yields an upper limit on the dynamical mass of the host galaxy of (4.3+/- 0.9)× {10}10 {M}⊙ , only ˜20 × higher than the central black hole (BH). The other targeted lines (CO(2-1), CO(7-6), and [C I]) are not detected, but the limits of the line ratios with respect to the [C II] emission imply that the heating in the quasar host is dominated by star formation, and not by the accreting BH. The star formation rate (SFR) implied by the FIR continuum is 105-340 {M}⊙ {{yr}}-1, with a resulting SFR surface density of ˜100-350 {M}⊙ {{yr}}-1 kpc-2, well below the value for Eddington-accretion-limited star formation.

  7. Projected Changes in Temperature and Precipitation Extremes over China as Measured by 50-yr Return Values and Periods Based on a CMIP5 Ensemble

    NASA Astrophysics Data System (ADS)

    Xu, Ying; Gao, Xuejie; Giorgi, Filippo; Zhou, Botao; Shi, Ying; Wu, Jie; Zhang, Yongxiang

    2018-04-01

    Future changes in the 50-yr return level for temperature and precipitation extremes over mainland China are investigated based on a CMIP5 multi-model ensemble for RCP2.6, RCP4.5 and RCP8.5 scenarios. The following indices are analyzed: TXx and TNn (the annual maximum and minimum of daily maximum and minimum surface temperature), RX5day (the annual maximum consecutive 5-day precipitation) and CDD (maximum annual number of consecutive dry days). After first validating the model performance, future changes in the 50-yr return values and return periods for these indices are investigated along with the inter-model spread. Multi-model median changes show an increase in the 50-yr return values of TXx and a decrease for TNn, more specifically, by the end of the 21st century under RCP8.5, the present day 50-yr return period of warm events is reduced to 1.2 yr, while extreme cold events over the country are projected to essentially disappear. A general increase in RX5day 50-yr return values is found in the future. By the end of the 21st century under RCP8.5, events of the present RX5day 50-yr return period are projected to reduce to < 10 yr over most of China. Changes in CDD-50 show a dipole pattern over China, with a decrease in the values and longer return periods in the north, and vice versa in the south. Our study also highlights the need for further improvements in the representation of extreme events in climate models to assess the future risks and engineering design related to large-scale infrastructure in China.

  8. Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

    PubMed

    Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

    2012-11-26

    Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P<0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. HST-WFC3 Near-Infrared Spectroscopy of Quenched Galaxies at zeta approx 1.5 from the WISP Survey: Stellar Populations Properties

    NASA Technical Reports Server (NTRS)

    Bedregal, A. G.; Scarlata, C.; Henry, A. L.; Atek, H.; Rafelski, M.; Teplitz, H. I.; Dominguez, A.; Siana, B.; Colbert, J. W.; Malkan, M.; hide

    2013-01-01

    We combine Hubble Space Telescope (HST) G102 and G141 near-IR (NIR) grism spectroscopy with HST/WFC3- UVIS, HST/WFC3-IR, and Spitzer/IRAC [3.6 microns] photometry to assemble a sample of massive (log(Mstar/M solar mass) at approx 11.0) and quenched (specific star formation rate < 0.01 G/yr(exp -1) galaxies at zeta approx 1.5. Our sample of 41 galaxies is the largest with G102+G141 NIR spectroscopy for quenched sources at these redshifts. In contrast to the local universe, zeta approx 1.5 quenched galaxies in the high-mass range have a wide range of stellar population properties. We find that their spectral energy distributions (SEDs) are well fitted with exponentially decreasing star formation histories and short star formation timescales (tau less than or equal to 100 M/yr). Quenched galaxies also show a wide distribution in ages, between 1 and 4 G/yr. In the (u - r)0-versus-mass space quenched galaxies have a large spread in rest-frame color at a given mass. Most quenched galaxies populate the zeta appro. 1.5 red sequence (RS), but an important fraction of them (32%) have substantially bluer colors. Although with a large spread, we find that the quenched galaxies on the RS have older median ages (3.1 G/yr) than the quenched galaxies off the RS (1.5 G/yr). We also show that a rejuvenated SED cannot reproduce the observed stacked spectra of (the bluer) quenched galaxies off the RS. We derive the upper limit on the fraction of massive galaxies on the RS at zeta approx 1.5 to be <43%.We speculate that the young quenched galaxies off the RS are in a transition phase between vigorous star formation at zeta > 2 and the zeta approx 1.5 RS. According to their estimated ages, the time required for quenched galaxies off the RS to join their counterparts on the z approx. 1.5 RS is of the order of approx. 1G/yr.

  10. Climate-induced changes in high elevation stream nitrate dynamics

    USGS Publications Warehouse

    Baron, Jill S.; Schmidt, T.M.; Hartman, M.D.

    2009-01-01

    Mountain terrestrial and aquatic ecosystems are responsive to external drivers of change, especially climate change and atmospheric deposition of nitrogen (N). We explored the consequences of a temperature-warming trend on stream nitrate in an alpine and subalpine watershed in the Colorado Front Range that has long been the recipient of elevated atmospheric N deposition. Mean annual stream nitrate concentrations since 2000 are higher by 50% than an earlier monitoring period of 1991-1999. Mean annual N export increased by 28% from 2.03 kg N ha-1yr-1 before 2000 to 2.84 kg N ha-1yr-1 in Loch Vale watershed since 2000. The substantial increase in N export comes as a surprise, since mean wet atmospheric N deposition from 1991 to 2006 (3.06 kg N ha-1 yr-1) did not increase. There has been a period of below average precipitation from 2000 to 2006 and a steady increase in summer and fall temperatures of 0.12??C yr-1 in both seasons since 1991. Nitrate concentrations, as well as the weathering products calcium and sulfate, were higher for the period 2000-2006 in rock glacier meltwater at the top of the watershed above the influence of alpine and subalpine vegetation and soils. We conclude the observed recent N increases in Loch Vale are the result of warmer summer and fall mean temperatures that are melting ice in glaciers and rock glaciers. This, in turn, has exposed sediments from which N produced by nitrification can be flushed. We suggest a water quality threshold may have been crossed around 2000. The phenomenon observed in Loch Vale may be indicative of N release from ice features such as rock glaciers worldwide as mountain glaciers retreat. ?? 2009 Blackwell Publishing Ltd.

  11. 5000 yr of paleoseismicity along the southern Dead Sea fault

    NASA Astrophysics Data System (ADS)

    Klinger, Y.; Le Béon, M.; Al-Qaryouti, M.

    2015-07-01

    The 1000-km-long left-lateral Dead Sea fault is a major tectonic structure of the oriental Mediterranean basin, bounding the Arabian Plate to the west. The fault is located in a region with an exceptionally long and rich historical record, allowing to document historical seismicity catalogues with unprecedented level of details. However, if the earthquake time series is well documented, location and lateral extent of past earthquakes remain often difficult to establish, if only based on historical testimonies. We excavated a palaeoseismic trench in a site located in a kilometre-size extensional jog, south of the Dead Sea, in the Wadi Araba. Based on the stratigraphy exposed in the trench, we present evidence for nine earthquakes that produced surface ruptures during a time period spanning 5000 yr. Abundance of datable material allows us to tie the five most recent events to historical earthquakes with little ambiguities, and to constrain the possible location of these historical earthquakes. The events identified at our site are the 1458 C.E., 1212 C.E., 1068 C.E., one event during the 8th century crisis, and the 363 C.E. earthquake. Four other events are also identified, which correlation with historical events remains more speculative. The magnitude of earthquakes is difficult to assess based on evidence at one site only. The deformation observed in the excavation, however, allows discriminating between two classes of events that produced vertical deformation with one order of amplitude difference, suggesting that we could distinguish earthquakes that started/stopped at our site from earthquakes that potentially ruptured most of the Wadi Araba fault. The time distribution of earthquakes during the past 5000 yr is uneven. The early period shows little activity with return interval of ˜500 yr or longer. It is followed by a ˜1500-yr-long period with more frequent events, about every 200 yr. Then, for the past ˜550 yr, the fault has switched back to a quieter mode

  12. Undertreatment of acute pain (oligoanalgesia) and medical practice variation in prehospital analgesia of adult trauma patients: a 10 yr retrospective study.

    PubMed

    Albrecht, E; Taffe, P; Yersin, B; Schoettker, P; Decosterd, I; Hugli, O

    2013-01-01

    Prehospital oligoanalgesia is prevalent among trauma victims, even when the emergency medical services team includes a physician. We investigated if not only patients' characteristics but physicians' practice variations contributed to prehospital oligoanalgesia. Patient records of conscious adult trauma victims transported by our air rescue helicopter service over 10 yr were reviewed retrospectively. Oligoanalgesia was defined as a numeric rating scale (NRS) >3 at hospital admission. Multilevel logistic regression analysis was used to predict oligoanalgesia, accounting first for patient case-mix, and then physician-level clustering. The intraclass correlation was expressed as the median odds ratio (MOR). A total of 1202 patients and 77 physicians were included in the study. NRS at the scene was 6.9 (1.9). The prevalence of oligoanalgesia was 43%. Physicians had a median of 5.7 yr (inter-quartile range: 4.2-7.5) of post-graduate training and 27% were female. In our multilevel analysis, significant predictors of oligoanalgesia were: no analgesia [odds ratio (OR) 8.8], National Advisory Committee for Aeronautics V on site (OR 4.4), NRS on site (OR 1.5 per additional NRS unit >4), female physician (OR 2.0), and years of post-graduate experience [>4.0 to ≤5.0 (OR 1.3), >3.0 to ≤4.0 (OR 1.6), >2.0 to ≤3.0 (OR 2.6), and ≤2.0 yr (OR 16.7)]. The MOR was 2.6, and was statistically significant. Physicians' practice variations contributed to oligoanalgesia, a factor often overlooked in analyses of prehospital pain management. Further exploration of the sources of these variations may provide innovative targets for quality improvement programmes to achieve consistent pain relief for trauma victims.

  13. Feed intake and efficiency of F1 lambs

    USDA-ARS?s Scientific Manuscript database

    Objective estimates of feed efficiency for progeny of terminal-sire breeds of sheep are needed to improve the value of market lambs. Because recent terminal-sire breed-comparison data are lacking, we determined effects of terminal-sire breed on feed efficiency of F1 lambs. Each year for 3 yr, Columb...

  14. Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration.

    PubMed

    Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C; Yang, Fan

    2017-05-01

    Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows variation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Elastin-like Protein-Hyaluronic acid (ELP-HA) Hydrogels with Decoupled Mechanical and Biochemical cues for Cartilage Regeneration

    PubMed Central

    Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C.; Yang, Fan

    2018-01-01

    Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows varyiation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. PMID:28268018

  16. HA metabolism in skin homeostasis and inflammatory disease.

    PubMed

    Kavasi, Rafaela-Maria; Berdiaki, Aikaterini; Spyridaki, Ioanna; Corsini, Emanuela; Tsatsakis, Aristidis; Tzanakakis, George; Nikitovic, Dragana

    2017-03-01

    Hyaluronan (HA), an unsulfated glycosaminoglycan, is an important component of the complex extracellular matrix network which surrounds and supports cells in tissues. HA is detected in all vertebrate tissues, but the bulk of HA is produced and deposited in the skin. In this review we focus on the role of HA in skin-associated inflammatory disease and wound healing. Properties of HA are directly dependent on its molecular weight. Thus, high molecular weight HA (HMWHA) is deposited in normal tissues during homeostasis and promotes their stability whereas low molecular weight HA fragments (LMWHA), on the other hand, may arise from enzymatic or chemical activities. The degradation of HMWHA to LMWHA fragments, often leads to the generation of biologically active oligosaccharides with different properties and postulated functions in wound scar formation and inflammation. More detailed studies of HA involvement in skin-associated inflammatory disease may result in novel treatment modalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Activation of Nrf2 Reduces UVA-Mediated MMP-1 Upregulation via MAPK/AP-1 Signaling Cascades: The Photoprotective Effects of Sulforaphane and Hispidulin

    PubMed Central

    Chaiprasongsuk, Anyamanee; Lohakul, Jinaphat; Soontrapa, Kitipong; Sampattavanich, Somponnat; Akarasereenont, Pravit

    2017-01-01

    UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates. PMID:28011874

  18. Changes in beta cell function during the proximate post-diagnosis period in persons with type 1 diabetes.

    PubMed

    DiMeglio, Linda A; Cheng, Peiyao; Beck, Roy W; Kollman, Craig; Ruedy, Katrina J; Slover, Robert; Aye, Tandy; Weinzimer, Stuart A; Bremer, Andrew A; Buckingham, Bruce

    2016-06-01

    Prior studies examining beta-cell preservation in type 1 diabetes have predominantly assessed stimulated C-peptide concentrations approximately 10 wk after diagnosis. We examined whether earlier assessments might aid in prediction of beta cell function over time. Using data from a multi-center randomized trial assessing the effect of intensive diabetes management initiated within 1 wk of diagnosis, we assessed which clinical factors predicted 90-min mixed-meal tolerance test (MMTT) stimulated C-peptide values obtained 2 and 6 wk after diagnosis. We also studied associations of these factors with C-peptide values at 1- and 2-year post-diagnosis. Data from intervention and control groups were pooled. Among 67 study participants (mean age 13.3 ± 5.7 yr, range 7.8-45.7 yr) in multivariable analyses, C-peptide increased from baseline to 2 wks and then 6 wk. C-peptide levels at these times were significantly correlated with 1- and 2-yr C-peptide concentrations (all p < 0.001), with the strongest observed associations between 6-wk C-peptide and the 1- and 2-yr values (r = 0.66 and r = 0.61, respectively). In multivariable analyses, greater baseline and 6-wk C-peptide, and older age independently predicted greater 1- and 2-yr C-peptide concentrations. C-peptide assessments close to diagnosis were predictive of subsequent C-peptide production. Our data demonstrate a clear increase in C-peptide over the initial 6 wk after diabetes diagnosis followed by a plateau. Our data do not suggest that MMTT assessments performed closer to diagnosis than 6 wk would improve prediction of subsequent residual beta cell function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in dystonia cases vs. controls.

    PubMed

    Louis, Elan D; Factor-Litvak, Pam; Michalec, Monika; Jiang, Wendy; Zheng, Wei

    2014-09-01

    Harmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson's disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness. We assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls. Blood [HA] was quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls. Mean log blood [HA] in dystonia cases was similar to that of controls (0.41±0.51g(-10)/ml vs. 0.38±0.61g(-10)/ml, t=0.42, p=0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR)unadjusted=1.11, 95% confidence interval (CI)=0.69-1.79, p=0.68; ORadjusted=1.07, 95% CI=0.58-1.97, p=0.84. In contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson's disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Blood Harmane (1-methyl-9H-pyrido[3,4-b]indole) Concentration in Dystonia Cases vs. Controls

    PubMed Central

    Louis, Elan D.; Factor-Litvak, Pam; Michalec, Monika; Jiang, Wendy; Zheng, Wei

    2014-01-01

    Background Harmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson’s disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness. Objectives We assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls. Methods Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls. Results Mean log blood [HA] in dystonia cases was similar to that of controls (0.41 ± 0.51 g −10/ml vs. 0.38 ± 0.61 g−10/ml, t = 0.42, p = 0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR) unadjusted = 1.11, 95% confidence interval (CI) = 0.69 – 1.79, p = 0.68; OR adjusted = 1.07, 95% CI = 0.58 – 1.97, p = 0.84. Conclusions In contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson’s disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders. PMID:24968164