Foot deformities, function in the lower extremities, and plantar pressure in patients with diabetes at high risk to develop foot ulcers

PubMed Central

Tang, Ulla Hellstrand; Zügner, Roland; Lisovskaja, Vera; Karlsson, Jon; Hagberg, Kerstin; Tranberg, Roy

2015-01-01

Objective Foot deformities, neuropathy, and dysfunction in the lower extremities are known risk factors that increase plantar peak pressure (PP) and, as a result, the risk of developing foot ulcers in patients with diabetes. However, knowledge about the prevalence of these factors is still limited. The aim of the present study was to describe the prevalence of risk factors observed in patients with diabetes without foot ulcers and to explore possible connections between the risk factors and high plantar pressure. Patients and methods Patients diagnosed with type 1 (n=27) or type 2 (n=47) diabetes (mean age 60.0±15.0 years) were included in this cross-sectional study. Assessments included the registration of foot deformities; test of gross function at the hip, knee, and ankle joints; a stratification of the risk of developing foot ulcers according to the Swedish National Diabetes Register; a walking test; and self-reported questionnaires including the SF-36 health survey. In-shoe PP was measured in seven regions of interests on the sole of the foot using F-Scan®. An exploratory analysis of the association of risk factors with PP was performed. Results Neuropathy was present in 28 (38%), and 39 (53%) had callosities in the heel region. Low forefoot arch was present in 57 (77%). Gait-related parameters, such as the ability to walk on the forefoot or heel, were normal in all patients. Eighty percent had normal function at the hip and ankle joints. Gait velocity was 1.2±0.2 m/s. All patients were stratified to risk group 3. Hallux valgus and hallux rigidus were associated with an increase in the PP in the medial forefoot. A higher body mass index (BMI) was found to increase the PP at metatarsal heads 4 and 5. Pes planus was associated with a decrease in PP at metatarsal head 1. Neuropathy did not have a high association with PP. Conclusions This study identified several potential risk factors for the onset of diabetic foot ulcers (DFU). Hallux valgus and hallux rigidus appeared to increase the PP under the medial forefoot and a high BMI appeared to increase the PP under the lateral forefoot. There is a need to construct a simple, valid, and reliable assessment routine to detect potential risk factors for the onset of DFU. PMID:26087865

Risk factors that affect reproductive target achievement in fertile dairy cows.

PubMed

Aungier, S P M; Roche, J F; Diskin, M G; Crowe, M A

2014-01-01

The aims of the present study were to investigate (1) the risk factors that influence the achievement of reproductive targets postpartum (pp) and (2) the key factors that influence pregnancy rate following first artificial insemination (AI) in dairy cows. Ninety-eight Holstein-Friesian pp cows were blood sampled from wk 1 to 4 pp for hematology and biochemistry. Reproductive tract health was assessed weekly by ultrasonography and vaginal mucus scoring. Body condition score (BCS), lameness score, and milk yield were assessed every 2 wk. Milk samples for progesterone assay were collected twice weekly and on d 4, 5, and 7 after AI. Risk factors associated with achieving reproductive targets depended on (1) increased metabolic activity of the liver (increased glutamate dehydrogenase at calving and increased γ-glutamyl transpeptidase in wk 4), (2) a competent immune system (increased neutrophils in wk 1; decreased α1-acid glycoprotein in wk 1, 2, and 3), (3) an endocrine system that was capable of responding by producing sufficient triiodothyronine in wk 2 and increased insulin-like growth factor I in wk 3 and 4, (4) a lower negative energy balance status (decreased nonesterified fatty acid concentration in wk 1; decreased β-hydroxybutyrate concentration in wk 2; BCS loss between calving and d 28 pp <0.5), (5) good reproductive tract health [normal uterine scan at d 45 pp; clear vaginal mucus discharge at first ovulation and at d 45 pp; resumed ovarian cyclicity by the end of the voluntary waiting period (≥ d 35 pp)], and (6) adequate diet (to ensure increased glutathione peroxidase in wk 2 and 3 and increased magnesium in wk 4). Risk factors that increased the odds of a successful first AI were previous ovulation(s) (odds ratio=3.17 per ovulation), BCS >2.5 at AI (odds ratio=3.01), and clear vaginal mucus (score=0) compared with purulent mucus (score >0) 4 d after first AI (odds ratio=2.99). In conclusion, this study identified key risk factors in the early pp period that give a higher probability of cows achieving their reproductive targets and of having a first-AI pregnancy. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An Analysis of Human Causal Factors in Unmanned Aerial Vehicle (UAV) Accidents

DTIC Science & Technology

2014-12-01

202 • Drugs/over-the-counter medication/supplements (not prescribed) PP 203 • Nutrition/ diet PP 204 • Inadequate rest (self-imposed) PP 205...2008). A survey of unmanned aircraft systems regulation: Status and future perspectives. Paper presented at 16th Mediterranean Conference on Control

[Research progresses on ergonomics assessment and measurement methods for push-pull behavior].

PubMed

Zhao, Yan; Li, Dongxu; Guo, Shengpeng

2011-10-01

Pushing and pulling (P&P) is a common operating mode of operator's physical works, and plays an important role in evaluation of human behavior health and operation performance. At present, there are many research methods of P&P, and this article is a state-of-art review of the classification of P&P research methods, the various impact factors in P&P program, technical details of internal/external P&P force measurement and evaluation, the limitation of current research methods and the future developments in the ergonomics field.

Contribution of the Δ-isobar excitation mechanism to the pp → { pp} s π0 reaction

NASA Astrophysics Data System (ADS)

Uzikov, Yu. N.; Imambekov, O.

2017-11-01

The differential cross section of the reaction pp → { pp} s π0, where { pp} s is the proton pair in the 1 S 0 state at a small excitation energy E pp < 3 MeV, is calculated using the box diagram with the excitation of the Δ-isobar. The model demonstrates a clear bump observed in the experimental data at the beam energy of ˜0.6 GeV and the zero diproton outgoing angle; however, its absolute value strongly depends on the off-shell extrapolation of the π NΔ vertex factor and underestimates the data.

Primary care patients' perspectives of barriers and enablers of primary prevention and health promotion-a meta-ethnographic synthesis.

PubMed

Moreno-Peral, Patricia; Conejo-Cerón, Sonia; Fernández, Ana; Berenguera, Anna; Martínez-Andrés, María; Pons-Vigués, Mariona; Motrico, Emma; Rodríguez-Martín, Beatriz; Bellón, Juan A; Rubio-Valera, Maria

2015-01-01

Primary care (PC) patients have difficulties in committing to and incorporating primary prevention and health promotion (PP&HP) activities into their long-term care. We aimed to re-interpret, for the first time, qualitative findings regarding factors affecting PC patients' acceptance of PP&HP activities. A meta-ethnographic synthesis was generated following electronic and manual searches that retrieved 29 articles. Papers were reviewed and translated to produce a re-interpretation of the extracted concepts. The factors affecting PC patients' receptiveness to PP&HP activities were framed in a four-level ecological model (intrapersonal, interpersonal, institutional and environment and society). Intrapersonal factors (patients' beliefs/attitudes, knowledge, skills, self-concept, motivation and resources) were the most numerous, with almost 25 different factors. Public health education to modify erroneous beliefs and values regarding PP&HP could encourage a transition to healthier lifestyles. Health care professionals' abilities to communicate and involve patients in the decision-making process can act as facilitators. Biopsychosocial training (with emphasis on communication skills) for health professionals must start with undergraduates. Increased consultation time, the use of reminders, follow-up visits and tools for communicating risk and motivating patients could be applied at the intrapersonal level. Collaborative care involving other health professionals (nutritionists or psychotherapists) and family and community stakeholders (teachers or gym trainers) was important in developing healthier habits. Patients also cited barriers related to the built environment and socioeconomic difficulties that highlighted the need for policies promoting social justice and equity. Encouraging PP&HP using social marketing strategies and regulating media to control its impact on health were also cited. Only the perspectives of PC patients in the context of chronic conditions were considered thus limiting extrapolation to other contexts. Several factors affect PP&HP. This must be taken into account when designing PP&HP activities if they are to be successfully implemented and maintained in routine practice.

Primary Care Patients’ Perspectives of Barriers and Enablers of Primary Prevention and Health Promotion—A Meta-Ethnographic Synthesis

PubMed Central

Moreno-Peral, Patricia; Conejo-Cerón, Sonia; Fernández, Ana; Berenguera, Anna; Martínez-Andrés, María; Pons-Vigués, Mariona; Motrico, Emma; Rodríguez-Martín, Beatriz; Bellón, Juan A.; Rubio-Valera, Maria

2015-01-01

Background Primary care (PC) patients have difficulties in committing to and incorporating primary prevention and health promotion (PP&HP) activities into their long-term care. We aimed to re-interpret, for the first time, qualitative findings regarding factors affecting PC patients' acceptance of PP&HP activities. Methods and Findings A meta-ethnographic synthesis was generated following electronic and manual searches that retrieved 29 articles. Papers were reviewed and translated to produce a re-interpretation of the extracted concepts. The factors affecting PC patients' receptiveness to PP&HP activities were framed in a four-level ecological model (intrapersonal, interpersonal, institutional and environment and society). Intrapersonal factors (patients' beliefs/attitudes, knowledge, skills, self-concept, motivation and resources) were the most numerous, with almost 25 different factors. Public health education to modify erroneous beliefs and values regarding PP&HP could encourage a transition to healthier lifestyles. Health care professionals' abilities to communicate and involve patients in the decision-making process can act as facilitators. Biopsychosocial training (with emphasis on communication skills) for health professionals must start with undergraduates. Increased consultation time, the use of reminders, follow-up visits and tools for communicating risk and motivating patients could be applied at the intrapersonal level. Collaborative care involving other health professionals (nutritionists or psychotherapists) and family and community stakeholders (teachers or gym trainers) was important in developing healthier habits. Patients also cited barriers related to the built environment and socioeconomic difficulties that highlighted the need for policies promoting social justice and equity. Encouraging PP&HP using social marketing strategies and regulating media to control its impact on health were also cited. Only the perspectives of PC patients in the context of chronic conditions were considered thus limiting extrapolation to other contexts. Conclusions Several factors affect PP&HP. This must be taken into account when designing PP&HP activities if they are to be successfully implemented and maintained in routine practice. PMID:25938509

Urinary tract infection after voiding cystourethrogram.

PubMed

Johnson, E K; Malhotra, N R; Shannon, R; Jacobson, D L; Green, J; Rigsby, C K; Holl, J L; Cheng, E Y

2017-08-01

Reported rates of post-procedural urinary tract infection (ppUTI) after voiding cystourethrogram (VCUG) are highly variable (0-42%). This study aimed to determine the risk of ppUTI after cystogram, and evaluate predictors of ppUTI. A retrospective cohort study of children undergoing VCUG or radionuclide cystogram (henceforth 'cystogram') was conducted. Children with neurogenic bladder who underwent cystogram in the operating room and without follow-up at the study institution were excluded. Incidence of symptomatic ppUTI within 7 days after cystogram was recorded. Predictors of ppUTI were evaluated using univariate statistics. A total of 1108 children (54% female, median age 1.1 years) underwent 1203 cystograms: 51% were on periprocedural antibiotics, 75% had a pre-existing urologic diagnosis (i.e., vesicoureteral reflux (VUR) or hydronephrosis; not UTI alone), and 18% had a clinical UTI within 30 days before cystogram. Of the cystograms, 41% had an abnormal cystogram and findings included VUR (82%), ureterocele (6%), and diverticula (6%). Twelve children had a ppUTI (1.0%; four girls, five uncircumcised boys, three circumcised boys; median age 0.9 years). Factors significantly associated with diagnosis of a ppUTI (Summary fig.) included: pre-existing urologic diagnosis prior to cystogram (12/12, 100% of patients with ppUTI), abnormal cystogram results (11/12, 92%), and use of periprocedural antibiotics (11/12, 92%). All 11 children with an abnormal cystogram had VUR ≥ Grade III. However, among all children with VUR ≥ Grade III, 4% (11/254) had a ppUTI. This is the largest study to date that has examined incidence and risk factors for ppUTI after cystogram. The retrospective nature of the study limited capture of some clinical details. This study demonstrated that the risk of ppUTI after a cystogram is very low (1.0% in this cohort). Having a pre-existing urologic diagnosis such as VUR or hydronephrosis was associated with ppUTI; therefore, children with moderate or high-grade VUR on cystogram may be at highest risk. Development of ppUTI after cystogram also highlighted the potential for a delay in diagnosis or oversight of a healthcare-associated infection due to several factors: 1) cystograms may be ordered, performed/interpreted, and followed up by multiple different providers; and 2) such infections are not captured by traditional healthcare-associated infection surveillance strategies. The risk of ppUTI after a cystogram is very low. Only children with pre-existing urologic diagnoses developed ppUTI in this study. This study's findings suggest that children undergoing a cystogram should not be given peri-procedural antibiotic prophylaxis for the sole purpose of ppUTI prevention. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Influence of PP-g-MA compatibilizer characteristics on mechanical properties of glass fiber reinforced polypropylene composites

NASA Astrophysics Data System (ADS)

Guan, Zhuo

Glass fiber (GF) reinforced polypropylene (PP) has become a common composite material used for various applications. Previous reports indicated that grafting ratio and molecular weight (MW) of znaleic anhydride grafted polypropylene (PP-g-MA) are the two most significant factors affecting the mechanical properties of PP/PP-g-MA/GF composites, but the combined effect of these two factors remains controversial. The study of the importance of MA grafting ratio and MW is continued in this work using PPIPP-g MA/GF composites containing various grades and concentrations of PP-g MA compatibilizer. First, MFR and FT1R analyses were performed to characterize the physical and chemical properties- of each PP-g-MA resin. Then, premixed PP and PP-g-MA blend were compounded with GF via twin screw extrusion, with the compounds injection molded into tensile, flexural and Izod impact specimens (all ASTM standard) for mechanical properties testing. Generally speaking, at a given GF content, higher compatibilizer concentrations led to higher tensile, flexural and notched Izod impact strength up to an optimum MA concentrations above which these properties tended to level off PP-g-MA resins with higher grafting ratio were more efficient compatibilizers as indicated by improved tensile, flexural and impact properties at lower PP-g-MA contents. In addition, MW was expected to affect properties as well, with too high and too 16w MW values leading to reduced reinforcement. While the optimum MW values for tensile and impact strength were still not clear based on present results, the estimated optimum weight average MW for maximum flexural strength was 90,000 +/- 1,400 g/mol.

Risk of Japanese carriers of hyperphosphorylated paratarg-7, the first autosomal-dominantly inherited risk factor for hematological neoplasms, to develop monoclonal gammopathy of undetermined significance and multiple myeloma.

PubMed

Grass, Sandra; Iida, Shinsuke; Wikowicz, Aleksandra; Preuss, Klaus-Dieter; Inagaki, Atsushi; Shimizu, Kazuyuki; Ziepert, Marita; Ueda, Ryuzo; Pfreundschuh, Michael

2011-03-01

Hyperphosphorylated paratarg-7 (pP-7) is a frequent target of paraproteins in German patients with monoclonal gammopathy of undetermined significance (MGUS)/multiple myeloma (MM). The frequency of MGUS/MM is lower in Japan than in Europe. As pP-7, the first molecularly defined autosomal-dominant risk factor for any hematological neoplasm, is inherited in a dominant fashion, we determined the incidence of the pP-7 carrier state in a Japanese population, and compared the frequency of pP-7-specific paraproteins and the pP-7 carrier state in Japanese and German patients with MGUS/MM. Peripheral blood from 111 Japanese patients with MGUS/MM and 278 healthy blood donors was analyzed for the pP-7 carrier state by isoelectric focusing and for pP-7-specific antibodies by ELISA. The Japanese group was compared with 252 German MGUS/MM patients and 200 healthy controls. Five of 111 (4.5%) Japanese and 35/252 (13.9%) German IgA/IgG MGUS/MM patients had a pP-7-specific paraprotein (P=0.009). The prevalence of healthy pP-7 carriers in the Japanese study group was 1/278 (0.36%), whereas it was 4/200 in the German group (P=0.166). The relative risk for pP-7 carriers developing MGUS/MM had an odds ratio of 13.1 in the Japanese and 7.9 in the German group. In conclusion, the fraction of pP-7 carriers with a pP-7-specific paraprotein is lower among Japanese than in German patients with MGUS/MM, but pP-7 carriers in both ethnic groups have a high risk of developing MGUS/MM. © 2011 Japanese Cancer Association.

Molecular Ecological Basis of Grasshopper (Oedaleus asiaticus) Phenotypic Plasticity under Environmental Selection

PubMed Central

Qin, Xinghu; Hao, Kun; Ma, Jingchuan; Huang, Xunbing; Tu, Xiongbing; Ali, Md. Panna; Pittendrigh, Barry R.; Cao, Guangchun; Wang, Guangjun; Nong, Xiangqun; Whitman, Douglas W.; Zhang, Zehua

2017-01-01

While ecological adaptation in insects can be reflected by plasticity of phenotype, determining the causes and molecular mechanisms for phenotypic plasticity (PP) remains a crucial and still difficult question in ecology, especially where control of insect pests is involved. Oedaleus asiaticus is one of the most dominant pests in the Inner Mongolia steppe and represents an excellent system to study phenotypic plasticity. To better understand ecological factors affecting grasshopper phenotypic plasticity and its molecular control, we conducted a full transcriptional screening of O. asiaticus grasshoppers reared in four different grassland patches in Inner Mongolia. Grasshoppers showed different degrees of PP associated with unique gene expressions and different habitat plant community compositions. Grasshopper performance variables were susceptible to habitat environment conditions and closely associated with plant architectures. Intriguingly, eco-transcriptome analysis revealed five potential candidate genes playing important roles in grasshopper performance, with gene expression closely relating to PP and plant community factors. By linking the grasshopper performances to gene profiles and ecological factors using canonical regression, we first demonstrated the eco-transcriptomic architecture (ETA) of grasshopper phenotypic traits (ETAGPTs). ETAGPTs revealed plant food type, plant density, coverage, and height were the main ecological factors influencing PP, while insect cuticle protein (ICP), negative elongation factor A (NELFA), and lactase-phlorizin hydrolase (LCT) were the key genes associated with PP. Our study gives a clear picture of gene-environment interaction in the formation and maintenance of PP and enriches our understanding of the transcriptional events underlying molecular control of rapid phenotypic plasticity associated with environmental variability. The findings of this study may also provide new targets for pest control and highlight the significance of ecological management practice on grassland conservation. PMID:29066978

Naval Reserve Forces throughout the World.

DTIC Science & Technology

1984-02-01

structures run the risk of an apples to oranges comparisons./ T Our lookCsuggests that the U.S. Navy has a richer mix of active to reserves than do...PP26 About Political end military Environmental Factors." 30 Pp., Thompson, Jap S.. "Seaport Dasaneence and inter-Statef Apr 1960. AG A069 099...Chemical Physics IhaMeon, Jes. Oep40enwca Risk , and ftinorablilty,’ 72(10), is May 1960) 43 OR.. Jun 1961, AD A102 09" PP 294 PP 300 pRorts, Stephen

Live-cell imaging RNAi screen identifies PP2A–B55α and importin-β1 as key mitotic exit regulators in human cells

PubMed Central

Schmitz, Michael H. A.; Held, Michael; Janssens, Veerle; Hutchins, James R. A.; Hudecz, Otto; Ivanova, Elitsa; Goris, Jozef; Trinkle-Mulcahy, Laura; Lamond, Angus I.; Poser, Ina; Hyman, Anthony A.; Mechtler, Karl; Peters, Jan-Michael; Gerlich, Daniel W.

2013-01-01

When vertebrate cells exit mitosis various cellular structures are re-organized to build functional interphase cells1. This depends on Cdk1 (cyclin dependent kinase 1) inactivation and subsequent dephosphorylation of its substrates2–4. Members of the protein phosphatase 1 and 2A (PP1 and PP2A) families can dephosphorylate Cdk1 substrates in biochemical extracts during mitotic exit5,6, but how this relates to postmitotic reassembly of interphase structures in intact cells is not known. Here, we use a live-cell imaging assay and RNAi knockdown to screen a genome-wide library of protein phosphatases for mitotic exit functions in human cells. We identify a trimeric PP2A–B55α complex as a key factor in mitotic spindle breakdown and postmitotic reassembly of the nuclear envelope, Golgi apparatus and decondensed chromatin. Using a chemically induced mitotic exit assay, we find that PP2A–B55α functions downstream of Cdk1 inactivation. PP2A–B55α isolated from mitotic cells had reduced phosphatase activity towards the Cdk1 substrate, histone H1, and was hyper-phosphorylated on all subunits. Mitotic PP2A complexes co-purified with the nuclear transport factor importin-β1, and RNAi depletion of importin-β1 delayed mitotic exit synergistically with PP2A–B55α. This demonstrates that PP2A–B55α and importin-β1 cooperate in the regulation of postmitotic assembly mechanisms in human cells. PMID:20711181

Investigating the Period of Switching Roles in Pair Programming in a Primary School

ERIC Educational Resources Information Center

Zhong, Baichang; Wang, Qiyun; Chen, Jie; Li, Yi

2017-01-01

Pair programming (PP) is a useful approach to fostering computational thinking for young students. However, there are many factors impacting on the effectiveness of PP. The period of switching roles between the driver and the navigator is often ignored by researchers. Therefore, this study aimed to explore the impact of the switching period on PP.…

AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation.

PubMed

Min, Wang; Lin, Yan; Tang, Shibo; Yu, Luyang; Zhang, Haifeng; Wan, Ting; Luhn, Tricia; Fu, Haian; Chen, Hong

2008-04-11

Previously we have shown that AIP1 (apoptosis signal-regulating kinase [ASK]1-interacting protein 1), a novel member of the Ras-GAP protein family, facilitates dephosphorylation of ASK1 at pSer967 and subsequently 14-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling. However, the phosphatase(s) responsible for ASK1 dephosphorylation at pSer967 has not been identified. In the present study, we identified protein phosphatase (PP)2A as a potential phosphatase in vascular endothelial cells (ECs). Tumor necrosis factor (TNF)-induced dephosphorylation of ASK1 pSer967 in ECs was blocked by PP2A inhibitor okadaic acid. Overexpression of PP2A catalytic subunit induced dephosphorylation of ASK1 pSer967 and activation of c-Jun N-terminal kinase (JNK). In contrast, a catalytic inactive form of PP2A or PP2A small interfering RNA blunted TNF-induced dephosphorylation of ASK1 pSer967 and activation of JNK without effects on NF-kappaB activation. Whereas AIP1, via its C2 domain, binds to ASK1, PP2A binds to the GAP domain of AIP1. Endogenous AIP1-PP2A complex can be detected in the resting state, and TNF induces a complex formation of AIP1-PP2A with ASK1. Furthermore, TNF-induced association of PP2A with ASK1 was diminished in AIP1-knockdown ECs, suggesting a critical role of AIP1 in recruiting PP2A to ASK1. TNF-signaling molecules TRAF2 and RIP1, known to be in complex with AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604, are critical for TNF-induced ASK1 dephosphorylation. Finally, PP2A and AIP1 cooperatively induce activation of ASK1-JNK signaling and EC apoptosis, as demonstrated by both overexpression and small interfering RNA knockdown approaches. Taken together, our data support a critical role of PP2A-AIP1 complex in TNF-induced activation of ASK1-JNK apoptotic signaling.

PpTFDB: A pigeonpea transcription factor database for exploring functional genomics in legumes

PubMed Central

Singh, Akshay; Sharma, Ajay Kumar; Singh, Nagendra Kumar

2017-01-01

Pigeonpea (Cajanus cajan L.), a diploid legume crop, is a member of the tribe Phaseoleae. This tribe is descended from the millettioid (tropical) clade of the subfamily Papilionoideae, which includes many important legume crop species such as soybean (Glycine max), mung bean (Vigna radiata), cowpea (Vigna ungiculata), and common bean (Phaseolus vulgaris). It plays major role in food and nutritional security, being rich source of proteins, minerals and vitamins. We have developed a comprehensive Pigeonpea Transcription Factors Database (PpTFDB) that encompasses information about 1829 putative transcription factors (TFs) and their 55 TF families. PpTFDB provides a comprehensive information about each of the identified TFs that includes chromosomal location, protein physicochemical properties, sequence data, protein functional annotation, simple sequence repeats (SSRs) with primers derived from their motifs, orthology with related legume crops, and gene ontology (GO) assignment to respective TFs. (PpTFDB: http://14.139.229.199/PpTFDB/Home.aspx) is a freely available and user friendly web resource that facilitates users to retrieve the information of individual members of a TF family through a set of query interfaces including TF ID or protein functional annotation. In addition, users can also get the information by browsing interfaces, which include browsing by TF Categories and by, GO Categories. This PpTFDB will serve as a promising central resource for researchers as well as breeders who are working towards crop improvement of legume crops. PMID:28651001

CAS or Pen-and-Paper: Factors That Influence Students' Choices

ERIC Educational Resources Information Center

Cameron, Scott; Ball, Lynda

2015-01-01

This paper reports on a study of choices about the use of a computer algebra system (CAS) or pen-and-paper (p&p) by a class of seven Year 11 Mathematical Methods (CAS) students as they completed a calculus worksheet. Factors that influenced students' choices are highlighted by comparing and contrasting the use of CAS and p&p between…

Influences of Display Design and Task Management Strategy on Situation Awareness, Performance, and Workload in Process Control Environments

DTIC Science & Technology

2014-12-26

and Ergonomics Society 54th Annual Meeting (pp. 284-288). Human Factors and Ergonomics Society. Miller, C. A., & Parasuraman, R. (2007). Designing ...Factors and Ergonomics Society, 37 (1), 32-64. Gould, J. (1988). How to design usable systems (excerpt). IBM Research Center Hawthorne. In M...Research Past, Present, and Future. Ergonomics in Design : The Quarterly of Human Factors Applications , 21(2), pp. 9-14. Handal, C., & Ikuma, L. H

Parameters Comparsion of Leads Detection in Arctic Sea Ice Using CRYOSAT-2 Waveform Data

NASA Astrophysics Data System (ADS)

Li, J.; Zhang, S.; Xiao, F.; Zhu, C.; Zhang, Y.; Zhu, T.; Yuan, L.

2018-04-01

Leads are only a small part of the polar sea ice structure, but they play a dominant role on the turbulence exchange between the ocean and the atmosphere, they are also important factors about sea ice thickness inversion. Since the early 2000s, Satellite altimetry has been applied to monitor the Arctic sea ice thickness, Satellite altimetry data can be used to distinguish leads and sea ice. In this paper, four parameters including Pulse peakiness (PP), stack standard deviation (SSD), stack kurtosis (SKU) and stack skewness (SSK) are extracted from CryoSat-2 satellite altimetry waveform data. The four parameters are combined into five combinations (PP, PP&SSD, PP&SSD&SKU, PP&SSD&SSK, PP&SSD&SSK&SKU) with constrain conditions to detect the leads. The results of the five methods are compared with MODIS (moderate-resolution imagining spectroradiometer) images and show that, the combination of PP&SSD is better than the single PP, the rest of combinations are the same as the combination of PP&SSD. It turns out, there is no promotion when we add SSK and SKU, successively or simultaneously.

Mechanical properties of PP/PA blends in addition with PP-g-MAH with different PP molecular weight and MAH content

NASA Astrophysics Data System (ADS)

Tokumitsu, Katuhisa; Nakajima, Yuki; Aoki, Kenji

2016-03-01

The mechanical properties and morphological changes of PP/PA6/PP-g-MAH blends were investigated. In particular, various kinds of PP-g-MAH, which have a series of different Mw of PP and MAH content, were investigated. From the tensile test results of PP/PA6 blends, although the elongation at break and yield stress can be improved by adding PP-g-MAH, modulus slightly decreased. In particular, elongation at break of PP/PA in addition with PP-g-MAH increased twentyfold from 27.0% (without PP-g-MAH) to 570%. On the basis of Charpy impact test results, the impact strength can also be improved by adding PP-g-MAH. From SEM observation, it was found that the diameter of the dispersed PA6 phase in PP matrix was getting much smaller with PP-g-MAH content. From the TEM observation, the boundary of the PA phase in PP/PA blends without PP-g-MAH compatibilizer can be observed clearly, but it becomes hard to see the boundary part of the PA phase in PP/PA blend with compatibilizer. Furthermore, when comparing the inside of the PA phase, small amount of PP phase can be observed in the PA phase of PP/PA blend with compatibilizer. Here, we defined a parameter, Comprehensive Mechanical Property Factor (CMPF), which can be calculated by multiple each mechanical property (elongation at break, yield stress, modulus and impact strength) against each maximum value, and it was found that CMPF has a good correlation with the diameter of PA6 phase. In conclusion, an optimum mechanical property of PP/PA6 can be obtained by using PP-g-MAH with Mw around 35,000 ˜ 50,000 g mol-1 and MAH content around 2.0 ˜ 3.5 %.

Arabidopsis PHOSPHOTYROSYL PHOSPHATASE ACTIVATOR Is Essential for PROTEIN PHOSPHATASE 2A Holoenzyme Assembly and Plays Important Roles in Hormone Signaling, Salt Stress Response, and Plant Development1[W][OPEN

PubMed Central

Chen, Jian; Hu, Rongbin; Zhu, Yinfeng; Shen, Guoxin; Zhang, Hong

2014-01-01

PROTEIN PHOSPHATASE 2A (PP2A) is a major group of serine/threonine protein phosphatases in eukaryotes. It is composed of three subunits: scaffolding subunit A, regulatory subunit B, and catalytic subunit C. Assembly of the PP2A holoenzyme in Arabidopsis (Arabidopsis thaliana) depends on Arabidopsis PHOSPHOTYROSYL PHOSPHATASE ACTIVATOR (AtPTPA). Reduced expression of AtPTPA leads to severe defects in plant development, altered responses to abscisic acid, ethylene, and sodium chloride, and decreased PP2A activity. In particular, AtPTPA deficiency leads to decreased methylation in PP2A-C subunits (PP2Ac). Complete loss of PP2Ac methylation in the suppressor of brassinosteroid insensitive1 mutant leads to 30% reduction of PP2A activity, suggesting that PP2A with a methylated C subunit is more active than PP2A with an unmethylated C subunit. Like AtPTPA, PP2A-A subunits are also required for PP2Ac methylation. The interaction between AtPTPA and PP2Ac is A subunit dependent. In addition, AtPTPA deficiency leads to reduced interactions of B subunits with C subunits, resulting in reduced functional PP2A holoenzyme formation. Thus, AtPTPA is a critical factor for committing the subunit A/subunit C dimer toward PP2A heterotrimer formation. PMID:25281708

Selective activators of protein phosphatase 5 target the auto-inhibitory mechanism.

PubMed

Haslbeck, Veronika; Drazic, Adrian; Eckl, Julia M; Alte, Ferdinand; Helmuth, Martin; Popowicz, Grzegorz; Schmidt, Werner; Braun, Frank; Weiwad, Matthias; Fischer, Gunter; Gemmecker, Gerd; Sattler, Michael; Striggow, Frank; Groll, Michael; Richter, Klaus

2015-04-20

Protein phosphatase 5 (PP5) is an evolutionary conserved serine/threonine phosphatase. Its dephosphorylation activity modulates a diverse set of cellular factors including protein kinases and the microtubule-associated tau protein involved in neurodegenerative disorders. It is auto-regulated by its heat-shock protein (Hsp90)-interacting tetratricopeptide repeat (TPR) domain and its C-terminal α-helix. In the present study, we report the identification of five specific PP5 activators [PP5 small-molecule activators (P5SAs)] that enhance the phosphatase activity up to 8-fold. The compounds are allosteric modulators accelerating efficiently the turnover rate of PP5, but do barely affect substrate binding or the interaction between PP5 and the chaperone Hsp90. Enzymatic studies imply that the compounds bind to the phosphatase domain of PP5. For the most promising compound crystallographic comparisons of the apo PP5 and the PP5-P5SA-2 complex indicate a relaxation of the auto-inhibited state of PP5. Residual electron density and mutation analyses in PP5 suggest activator binding to a pocket in the phosphatase/TPR domain interface, which may exert regulatory functions. These compounds thus may expose regulatory mechanisms in the PP5 enzyme and serve to develop optimized activators based on these scaffolds. © 2015 Authors.

Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli

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

Fan, Haitian; Hahm, Joseph; Diggs, Stephen

The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes tomore » small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. Finally, this molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.« less

Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli

DOE PAGES

Fan, Haitian; Hahm, Joseph; Diggs, Stephen; ...

2015-07-10

The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes tomore » small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. Finally, this molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.« less

Search for the standard model higgs Boson in the ZH-->nunubb channel in 5.2 fb{-1} of pp collisions at sqrt[s]=1.96 TeV.

PubMed

Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Ancu, L S; Aoki, M; Arnoud, Y; Arov, M; Askew, A; Asman, B; Atramentov, O; Avila, C; Backusmayes, J; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Barfuss, A-F; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Bu, X B; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Calfayan, P; Calpas, B; Calvet, S; Camacho-Pérez, E; Cammin, J; Carrasco-Lizarraga, M A; Carrera, E; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Cheu, E; Chevalier-Théry, S; Cho, D K; Cho, S W; Choi, S; Choudhary, B; Christoudias, T; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Cutts, D; Cwiok, M; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; Devaughan, K; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dorland, T; Dubey, A; Dudko, L V; Duflot, L; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fuess, S; Gadfort, T; Galea, C F; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Geng, W; Gerbaudo, D; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Golovanov, G; Gómez, B; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Haefner, P; Hagopian, S; Haley, J; Hall, I; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinson, A P; Heintz, U; Hensel, C; Heredia-De La Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hohlfeld, M; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Huske, N; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jamin, D; Jesik, R; Johns, K; Johnson, C; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Juste, A; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Khatidze, D; Kirby, M H; Kirsch, M; Kohli, J M; Kozelov, A V; Kraus, J; Kumar, A; Kupco, A; Kurca, T; Kuzmin, V A; Kvita, J; Lam, D; Lammers, S; Landsberg, G; Lebrun, P; Lee, H S; Lee, W M; Leflat, A; Lellouch, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Mackin, D; Mättig, P; Magaña-Villalba, R; Mal, P K; Malik, S; Malyshev, V L; Maravin, Y; Martínez-Ortega, J; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Mendoza, L; Menezes, D; Mercadante, P G; Merkin, M; Meyer, A; Meyer, J; Mommsen, R K; Mondal, N K; Moulik, T; Muanza, G S; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nogima, H; Novaes, S F; Nunnemann, T; Obrant, G; Ochando, C; Onoprienko, D; Orduna, J; Osman, N; Osta, J; Otec, R; Otero Y Garzón, G J; Owen, M; Padilla, M; Padley, P; Pangilinan, M; Parashar, N; Parihar, V; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Penning, B; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pol, M-E; Polozov, P; Popov, A V; Prewitt, M; Price, D; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Ranjan, K; Ratoff, P N; Razumov, I; Renkel, P; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rominsky, M; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shary, V; Shchukin, A A; Shivpuri, R K; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Stolin, V; Stoyanova, D A; Strandberg, J; Strang, M A; Strauss, E; Strauss, M; Ströhmer, R; Strom, D; Stutte, L; Svoisky, P; Takahashi, M; Tanasijczuk, A; Taylor, W; Tiller, B; Titov, M; Tokmenin, V V; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; van den Berg, P J; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vilanova, D; Vint, P; Vokac, P; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Wetstein, M; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Xu, C; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, Z; Yin, H; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zeitnitz, C; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L; Zutshi, V; Zverev, E G

2010-02-19

A search is performed for the standard model Higgs boson in 5.2 fb{-1} of pp collisions at sqrt[s]=1.96 TeV, collected with the D0 detector at the Fermilab Tevatron Collider. The final state considered is a pair of b jets and large missing transverse energy, as expected from pp-->ZH-->nunubb production. The search is also sensitive to the WH-->lnubb channel when the charged lepton is not identified. For a Higgs boson mass of 115 GeV, a limit is set at the 95% C.L. on the cross section multiplied by branching fraction for [pp-->(Z/W)H](H-->bb) that is a factor of 3.7 larger than the standard model value, consistent with the factor of 4.6 expected.

Meet the terminator: The phosphatase PP2A puts brakes on IRF-3 activation.

PubMed

Chattopadhyay, Saurabh; Sen, Ganes C

2014-04-24

Cellular interferon response to microbial infection is transient. In a recent paper in Immunity, Long et al. (2014) identify protein phosphatase 2A (PP2A) as a deactivator of phospho-interferon regulatory factor 3, the key transcription factor for interferon synthesis, thus providing one basis for the observed transiency. Copyright © 2014 Elsevier Inc. All rights reserved.

G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases

PubMed Central

Chen, Ruming; Rato, Cláudia; Yan, Yahui; Crespillo-Casado, Ana; Clarke, Hanna J; Harding, Heather P; Marciniak, Stefan J; Read, Randy J; Ron, David

2015-01-01

Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity. However, selectivity was restored by crude cell lysate or purified G-actin, which joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple surface contacts with PP1G, but at a distance from the active site, whereas in the substrate-selective ternary complex, actin contributes to one face of a platform encompassing the active site. Computational docking of the N-terminal lobe of eIF2a at this platform placed phosphorylated serine 51 near the active site. Mutagenesis of predicted surface-contacting residues enfeebled dephosphorylation, suggesting that avidity for the substrate plays an important role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex. DOI: http://dx.doi.org/10.7554/eLife.04871.001 PMID:25774600

Central precocious puberty: from physiopathological mechanisms to treatment.

PubMed

Chirico, V; Lacquaniti, A; Salpietro, V; Buemi, M; Salpietro, C; Arrigo, T

2014-01-01

Puberty is a complex, coordinated biological process with multiple levels of regulations. The timing of puberty varies greatly in children and it is influenced by environmental, endocrine and genetic factors. Precocious puberty (PP) is an important issue, affecting between 1 in 5.000-10.000 children. The physiopathological mechanism is still unknown. From an etiological point of view, PP may be subdivided into gonadotropin-releasing hormone (GnRH) -dependent and independent causes. GnRH-dependent PP, often called central precocious puberty (CPP), is based on hypothalamic-pituitary-gonadal axis activation associated with progressive pubertal development, accelerated growth rate and advancement of skeletal age. Conversely, peripheral precocious puberty (PPP) is related to sex steroid exposure, independently of hypothalamic-–pituitary-–gonadal (HPG) axis activation. Kisspeptins play a central role in the modulation of GnRH secretion with peripheral factors that influence the timing of puberty, such as adipokines and endocrine disrupting chemicals. Moreover, PP could be related to genetic disorders, involving pivotal genes of the HPG axis. The standard test used to verify HPG activity is the gonadotropin response to administered GnRH analogs. We describe the physiopathological mechanisms of PP and its clinical implications, analysing diagnostic flow-chart and new potential biomarkers that could reveal PP. An update of the current literature was also carried out regarding the recent novelty for treatment.

Arsenic Metabolism in Children Differs From That in Adults

PubMed Central

Skröder Löveborn, Helena; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

2016-01-01

Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12. Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children’s arsenic methylation; an increase in Ery-Se from the 5–95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and −3.2 pp for %DMA (P  <  .001). Despite this, Ery-Se was positively associated with U-As (5–95th percentile: +41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5–95th percentile: −1.9 pp, P  =  .001) and positively associated with %DMA (5–95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. PMID:27056082

Nuclear modification factor of D$^0$ mesons in PbPb collisions at $$\\sqrt{s_\\mathrm{NN}} = 5.02$$ TeV

DOE PAGES

Sirunyan, Albert M; et al.

2018-07-10

The transverse momentum (pt) spectrum of prompt D0 mesons and their antiparticles has been measured via the hadronic decay channels D0 to K- pi+ and D0-bar to K+ pi- in pp and PbPb collisions at a centre-of-mass energy of 5.02 TeV per nucleon pair with the CMS detector at the LHC. The measurement is performed in the D0 meson pt range of 2-100 GeV and in the rapidity range of abs(y)<1. The pp (PbPb) dataset used for this analysis corresponds to an integrated luminosity of 27.4 inverse picobarns (530 inverse microbarns). The measured D0 meson pt spectrum in pp collisionsmore » is well described by perturbative QCD calculations. The nuclear modification factor, comparing D0 meson yields in PbPb and pp collisions, was extracted for both minimum-bias and the 10% most central PbPb interactions. For central events, the D0 meson yield in the PbPb collisions is suppressed by a factor of 5-6 compared to the pp reference in the pt range of 6-10 GeV. For D0 mesons in the high-pt range of 60-100 GeV, a significantly smaller suppression is observed. The results are also compared to theoretical calculations.« less

Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis.

PubMed

Shimizu, Toshio; Bokuda, Kota; Kimura, Hideki; Kamiyama, Tsutomu; Nakayama, Yuki; Kawata, Akihiro; Isozaki, Eiji; Ugawa, Yoshikazu

2018-05-01

To investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS). A total of 145 patients with sporadic ALS and 73 healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale-Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model. Compared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years, p = 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival ( p = 0.002). Sensory cortex hyperexcitability predicts short survival in patients with ALS. © 2018 American Academy of Neurology.

Nuclear modification factor of D0 mesons in PbPb collisions at sqrt(s[NN]) = 5.02 TeV

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

Sirunyan, Albert M; et al.

2017-08-16

The transverse momentum (pt) spectrum of prompt D0 mesons and their antiparticles has been measured via the hadronic decay channels D0 to K- pi+ and D0-bar to K+ pi- in pp and PbPb collisions at a centre-of-mass energy of 5.02 TeV per nucleon pair with the CMS detector at the LHC. The measurement is performed in the D0 meson pt range of 2-100 GeV and in the rapidity range of abs(y)<1. The pp (PbPb) dataset used for this analysis corresponds to an integrated luminosity of 27.4 inverse picobarns (530 inverse microbarns). The measured D0 meson pt spectrum in pp collisionsmore » is well described by perturbative QCD calculations. The nuclear modification factor, comparing D0 meson yields in PbPb and pp collisions, was extracted for both minimum-bias and the 10% most central PbPb interactions. For central events, the D0 meson yield in the PbPb collisions is suppressed by a factor of 5-6 compared to the pp reference in the pt range of 6-10 GeV. For D0 mesons in the high-pt range of 60-100 GeV, a significantly smaller suppression is observed. The results are also compared to theoretical calculations.« less

On the mechanism of polypropylene fibres in preventing fire spalling in self-compacting and high-performance cement paste

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

Liu, X.; Magnel Laboratory for Concrete Research, Department of Structural Engineering, Ghent University, Technologiepark-Zwijnaarde 904 B-9052, Ghent; Ye, G.

2008-04-15

With the increasing application of self-compacting concrete (SCC) in construction and infrastructure, the fire spalling behavior of SCC has been attracting due attention. In high performance concrete (HPC), addition of polypropylene fibers (PP fibers) is widely used as an effective method to prevent explosive spalling. Hence, it would be useful to investigate whether the PP fibers are also efficient in SCC to avoid explosive spalling. However, no universal agreement exists concerning the fundamental mechanism of reducing the spalling risk by adding PP fiber. For SCC, the reduction of flowability should be considered when adding a significant amount of fibres. Inmore » this investigation, both the micro-level and macro-level properties of pastes with different fiber contents were studied in order to investigate the role of PP fiber at elevated temperature in self-compacting cement paste samples. The micro properties were studied by backscattering electron microscopy (BSE) and mercury intrusion porosimetry (MIP) tests. The modification of the pore structure at elevated temperature was investigated as well as the morphology of the PP fibers. Some macro properties were measured, such as the gas permeability of self-compacting cement paste after heating at different temperatures. The factors influencing gas permeability were analyzed. It is shown that with the melting of PP fiber, no significant increase in total pore volume is obtained. However, the connectivity of isolated pores increases, leading to an increase of gas permeability. With the increase of temperature, the addition of PP fibers reduces the damage of cement pastes, as seen from the total pore volume and the threshold pore diameter changes. From this investigation, it is concluded that the connectivity of pores as well as the creation of micro cracks are the major factors which determine the gas permeability after exposure to high temperatures. Furthermore, the connectivity of the pores acts as a dominant factor for temperatures below 300 deg. C. For higher temperatures micro cracks are becoming the major factor which influences the gas permeability.« less

Factors Affecting Pro- and Anti-Oxidant Properties of Fragments of the b-Protein Precursor (bPP): Implication for Alzheimer's Disease.

PubMed

Andorn, Anne C.; Kalaria, Rajesh N.

2000-06-01

Oxidative stress may have a key pathogenetic role in neurodegenerative diseases including Alzheimer's disease (AD). While there is evidence that some amyloid-b (Ab) peptides can initiate oxidative stress at micromolar doses, there is also some evidence that oxidative stress increases the concentration of the b-protein precursor (bPP) and the potential for increased formation of the Ab peptides. The following studies were performed to test the hypothesis that fragments of bPP could be antioxidants and hence that oxidative stress might be an early event in AD. We found that several fragments of bPP, including the Ab peptides, inhibit ascorbate-stimulated lipid peroxidation (ASLP) in membrane fragment preparations of postmortem human brain. In contrast, other fragments of bPP enhance ASLP. These data indicate that bPP or fragments of bPP could play a key role in the redox status of cells and that alterations in bPP processing could have profound effects on the cellular response to oxidative stress.

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.

PubMed

Niemiec, Joanna; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Majchrzyk, Kaja; Kruczak, Anna; Sas-Korczyńska, Beata; Ryś, Janusz

2018-04-01

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Highly acidic C-terminal domain of pp32 is required for the interaction with histone chaperone, TAF-Ibeta.

PubMed

Lee, In-Seon; Oh, Sang-Min; Kim, Sung-Mi; Lee, Dong-Seok; Seo, Sang-Beom

2006-12-01

We have previously reported that INHAT (inhibitor of acetyltransferases) complex subunits, TAF (template activating factor)-Ialpha, TAF-Ibeta and pp32 can inhibit histone acetylation and HAT (histone acetyltransferase)-dependent transcription by binding to histones. Evidences are accumulating that INHAT complex subunits have important regulatory roles in various cellular activities such as replication, transcription, and apoptosis etc. However, how these subunits interact each other remains largely unknown. Using immunoprecipitation (IP) and protein-protein interaction assays with TAF-Ibeta and pp32 deletion mutant proteins, we identify INHAT complex subunits, TAF-Ibeta and pp32 interaction requires highly acidic C-terminal domain of pp32. We also show that the interaction between the INHAT complex subunits is stronger in the presence of histones. In this study, we report that the synergistic inhibition of HAT-mediated transcription by TAF-Ibeta and pp32 is dependent on the highly acidic C-terminal domain of pp32.

The Relationship of Socioeconomic and Behavioral Risk Factors With Trends of Overweight in Korea.

PubMed

Shin, Jin Hee; Dupre, Matthew E; Østbye, Truls; Murphy, Gwen; Silberberg, Mina

2015-11-01

Previous studies have shown that overweight (including obesity) has increased significantly in Korea in recent decades. However, it remains unclear whether this change has been uniform among all Koreans and to what extent socioeconomic and behavioral factors have contributed to this increase. Changes in overweight were estimated using data from the 1998, 2001, 2005, 2007-2009, and 2010-2012 Korea National Health and Nutrition Examination Survey (n=55 761). Overweight increased significantly among men but not among women between 1998 and 2012. Changes in socioeconomic and behavioral factors over the time period were not associated with overall trends for both men and women. However, we found significant differences in the prevalence of overweight relative to key risk factors. For men, overweight increased at a significantly greater rate among the non-exercising (predicted probability [PP] from 0.23 to 0.32] and high-calorie (PP from 0.18 to 0.37) groups compared to their active and lower-calorie counterparts, respectively. For women, overweight increased only among the non-exercising (PP from 0.27 to 0.28) and low-income (PP from 0.31 to 0.36) groups during this period. These findings suggest that programs aimed at reducing overweight should target Korean men and women in specific socioeconomic and behavioral risk groups differentially.

The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

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

Peng, Yi; Zhou, Yajuan; Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071

Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, wemore » showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo.« less

Nano-sized calcium phosphate particles for periodontal gene therapy.

PubMed

Elangovan, Satheesh; Jain, Shardool; Tsai, Pei-Chin; Margolis, Henry C; Amiji, Mansoor

2013-01-01

Growth factors such as platelet-derived growth factor (PDGF) have significantly enhanced periodontal therapy outcomes with a high degree of variability, mostly due to the lack of continual supply for a required period of time. One method to overcome this barrier is gene therapy. The aim of this in vitro study is to evaluate PDGF-B gene delivery in fibroblasts using nano-sized calcium phosphate particles (NCaPP) as vectors. NCaPP incorporating green fluorescent protein (NCaPP-GFP) and PDGF-B (NCaPP-PDGF-B) plasmids were synthesized using an established precipitation system and characterized using transmission electron microscopy and 1.2% agarose gel electrophoresis. Biocompatibility and transfection of the nanoplexes in fibroblasts were evaluated using cytotoxicity assay and florescence microscopy, respectively. Polymerase chain reaction and enzyme-linked immunosorbent assay were performed to evaluate PDGF-B transfection after different time points of treatments, and the functionality of PDGF-B transfection was evaluated using the cell proliferation assay. Synthesized NCaPP nanoplexes incorporating the genes of GFP and PDGF-B were spherical in shape and measured about 30 to 50 nm in diameter. Gel electrophoresis confirmed DNA incorporation and stability within the nanoplexes, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium reagent assay demonstrated their biocompatibility in fibroblasts. In vitro transfection studies revealed a higher and longer lasting transfection after NCaPP-PDGF-B treatment, which lasted up to 96 hours. Significantly enhanced fibroblast proliferation observed in NCaPP-PDGF-B-treated cells confirmed the functionality of these nanoplexes. NCaPP demonstrated higher levels of biocompatibility and efficiently transfected PDGF plasmids into fibroblasts under described in vitro conditions.

Clinically Determined and Self-Reported Dental Caries Status During and After Pregnancy Among Low-Income Hispanic Women

PubMed Central

Weintraub, Jane A.; Gansky, Stuart A.; Santo, William; Ramos-Gomez, Francisco

2014-01-01

Objectives This analysis assessed, during and one-year after pregnancy: 1) the prevalence of and relationship between self-reported and clinically determined dental caries and oral health status, and whether self-reports are a potential proxy for professional determination; 2) factors associated with high levels of professionally determined or self-reported oral disease. Methods Data are from a randomized clinical trial of 301 pregnant, low-income Hispanic women at the California-Mexico border to compare two interventions to prevent early childhood caries. Interviews and dental examinations were conducted at enrollment (second trimester) and one-year post-partum (PP). Results During pregnancy and PP, 93% had untreated caries and most had gingival inflammation. Sensitivity and specificity of self-reported measures compared to dentists’ determinations were modest (ranging from 45–80% for sensitivity and 41–77% for specificity at both time points); positive predictive values for women reporting current tooth decay or fair/poor oral health were high (>94%), but negative predictive values were low (<23%). In a bivariate GEE model, factors associated with fair/poor self-reported oral health during and after pregnancy included self-reported dental symptoms (current tooth decay, bleeding gums without brushing), dental behaviors (not flossing) and number of decayed tooth surfaces. In a logistic regression model, the only significant factor PP associated with less extensive untreated disease was if women ever had their teeth cleaned professionally (OR=0.44). Conclusions There is a great need for dental treatment in this underserved population both during pregnancy and PP. Women may not be able to accurately recognize or act on their treatment needs. At baseline and PP, few demographic or behavioral factors were associated with either self-reported or clinically-determined oral disease (e.g., being less educated or acculturated and not flossing) in the bivariate analyses. Ever having a professional teeth cleaning significantly predicted less disease PP. PMID:23889689

Clinically determined and self-reported dental status during and after pregnancy among low-income Hispanic women.

PubMed

Weintraub, Jane A; Finlayson, Tracy L; Gansky, Stuart A; Santo, William; Ramos-Gomez, Francisco

2013-01-01

This analysis assessed, during and 1 year after pregnancy: a) the prevalence of and relationship between self-reported and clinically determined dental caries and oral health status, and whether self-reports are a potential proxy for professional determination; and b) factors associated with high levels of professionally determined or self-reported oral disease. Data are from a randomized clinical trial of 301 pregnant, low-income Hispanic women at the California-Mexico border to compare two interventions to prevent early childhood caries. Interviews and dental examinations were conducted at enrollment (second trimester) and 1-year postpartum (PP). During pregnancy and PP, 93 percent had untreated caries and most had gingival inflammation. Sensitivity and specificity of self-reported measures compared to dentists' determinations were modest (ranging from 45-80 percent for sensitivity and 41-77 percent for specificity at both time points); positive predictive values for women reporting current tooth decay or fair/poor oral health were high (>94 percent), but negative predictive values were low (<23 percent). In a bivariate GEE model, factors associated with fair/poor self-reported oral health during and after pregnancy included self-reported dental symptoms (current tooth decay, bleeding gums without brushing), dental behaviors (not flossing) and number of decayed tooth surfaces. In a logistic regression model, the only significant factor PP associated with less extensive untreated disease was if women ever had their teeth cleaned professionally (OR = 0.44). There is a great need for dental treatment in this underserved population both during pregnancy and PP. Women may not be able to accurately recognize or act on their treatment needs. At baseline and PP, few demographic or behavioral factors were associated with either self-reported or clinically determined oral disease (e.g., being less educated or acculturated and not flossing) in the bivariate analyses. Ever having a professional teeth cleaning significantly predicted less disease PP. © 2013 American Association of Public Health Dentistry.

Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression.

PubMed

McCarrel, Taralyn; Fortier, Lisa

2009-08-01

Platelet-rich plasma (PRP) has generated substantial interest for tendon and ligament regeneration because of the high concentrations of growth factors in platelet alpha-granules. This study compared the temporal release of growth factors from bone marrow aspirate (BMA), PRP, and lyophilized platelet product (PP), and measured their effects on tendon and ligament gene expression. Blood and BMA were collected and processed to yield PRP and plasma. Flexor digitorum superficialis tendon (FDS) and suspensory ligament (SL) explants were cultured in 10% plasma in DMEM (control), BMA, PRP, or PP. TGF-beta1 and PDGF-BB concentrations were determined at 0, 24, and 96 h of culture using ELISA. Quantitative RT-PCR for collagen types I and III (COL1A1, COL3A1), cartilage oligomeric matrix protein (COMP), decorin, and matrix metalloproteinases-3 and 13 (MMP-3, MMP-13) was performed. TGF-beta1 and PDGF-BB concentrations were highest in PRP and PP. Growth factor quantity was unchanged in BMA, increased in PRP, and decreased in PP over 4 days. TGF-beta1 and platelet concentrations were positively correlated. Lyophilized PP and PRP resulted in increased COL1A1:COL3A1 ratio, increased COMP, and decreased MMP-13 expression. BMA resulted in decreased COMP and increased MMP-3 and MMP-13 gene expression. Platelet concentration was positively correlated with COL1A1, ratio of COL1A1:COL3A1, and COMP, and negatively correlated with COL3A1, MMP-13, and MMP-3. White blood cell concentration was positively correlated with COL3A1, MMP3, and MMP13, and negatively correlated with a ratio of COL1A1:COL3A1, COMP, and decorin. These findings support further in vivo investigation of PRP and PP for treatment of tendonitis and desmitis. Copyright 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

PubMed Central

2012-01-01

Background Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3–6 months and analyzed using repeated-measures ANOVA. Results Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (−1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness. Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC. Conclusions We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely. PMID:23013746

Role of Scd5, a protein phosphatase-1 targeting protein, in phosphoregulation of Sla1 during endocytosis

PubMed Central

Chi, Richard J.; Torres, Onaidy T.; Segarra, Verónica A.; Lansley, Tanya; Chang, Ji Suk; Newpher, Thomas M.; Lemmon, Sandra K.

2012-01-01

Summary Phosphorylation regulates assembly and disassembly of proteins during endocytosis. In yeast, Prk1 and Ark1 phosphorylate factors after vesicle internalization leading to coat disassembly. Scd5, a protein phosphatase-1 (PP1)-targeting subunit, is proposed to regulate dephosphorylation of Prk1/Ark1 substrates to promote new rounds of endocytosis. In this study we analyzed scd5-PP1Δ2, a mutation causing impaired PP1 binding. scd5-PP1Δ2 caused hyperphosphorylation of several Prk1 endocytic targets. Live-cell imaging of 15 endocytic components in scd5-PP1Δ2 revealed that most factors arriving before the invagination/actin phase of endocytosis had delayed lifetimes. Severely affected were early factors and Sla2 (Hip1R homolog), whose lifetime was extended nearly fourfold. In contrast, the lifetime of Sla1, a Prk1 target, was extended less than twofold, but its cortical recruitment was significantly reduced. Delayed Sla2 dynamics caused by scd5-PP1Δ2 were suppressed by SLA1 overexpression. This was dependent on the LxxQxTG repeats (SR) of Sla1, which are phosphorylated by Prk1 and bind Pan1, another Prk1 target, in the dephosphorylated state. Without the SR, Sla1ΔSR was still recruited to the cell surface, but was less concentrated in cortical patches than Pan1. sla1ΔSR severely impaired endocytic progression, but this was partially suppressed by overexpression of LAS17, suggesting that without the SR region the SH3 region of Sla1 causes constitutive negative regulation of Las17 (WASp). These results demonstrate that Scd5/PP1 is important for recycling Prk1 targets to initiate new rounds of endocytosis and provide new mechanistic information on the role of the Sla1 SR domain in regulating progression to the invagination/actin phase of endocytosis. PMID:22825870

Crizotinib in patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer versus chemotherapy as a first-line treatment.

PubMed

Zhou, Jianya; Zheng, Jing; Zhang, Xiaochen; Zhao, Jing; Zhu, Yanping; Shen, Qian; Wang, Yuehong; Sun, Ke; Zhang, Zeying; Pan, Zhijie; Shen, Yihong; Zhou, Jianying

2018-01-03

To compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86-571-87,236,876 predictive clinical factors of the efficacy of crizotinib. The 73 patients with ALK-positive advanced NSCLC were divided into three groups based on the first-line treatment: first-line crizotinib group (1-CRZ group, n = 32); first-line platinum-based pemetrexed treatment group (1-PP group, n = 28), and first-line chemotherapy platinum-based non-pemetrexed group (N1-PP, n = 12). Sixty eight of the 73 patients received crizotinib treatment and followed up in our hospital. Differences in the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared in the different groups. The clinical factors were evaluated to predict the efficacy of crizotinib by the Kaplan-Meier survival analysis and Cox proportional hazards model. The PFS, ORR, DCR were 16.1 months, 78.1% (25/32) and 100% (32/32) in the 1-CRZ group; were 6.0 months, 17.9% (5/28) and 57.2% (16/28) in the 1-PP group; and were 2.9 months, 15.4% (2/13) and 46.2% (6/13) in the N1-PP group. The PFS of the 1-CRZ group was significantly longer than that of the 1-PP group (P < 0.001) and the N1-PP group (P < 0.001). The ORR and DCR of the 1-CRZ group was significantly greater than that of the 1-PP group and the N1-PP group (all the P < 0.001). Higher Eastern Cooperative Oncology Group (ECOG) performance status score (> = 2) (HR 2.345, 95% CI 1.137-4.834, P = 0.021) and patients received crizotinib after N1-PP chemotherapy (HR 2.345, 95% CI 1.137-4.834, P = 0.021) were two factors associated with shorter PFS after crizotinib treatment. In patients with ALK-positive NSCLC who did not receive previous treatment, crizotinib was superior to standard chemotherapy for the longer PFS and greater ORR and DCR. Higher ECOG score (> = 2) and patients received crizotinib after N1-PP chemotherapy predict poor efficacy of crizotinib.

Gadolinium and 5-Aminolevulinic Acid-induced Protoporphyrin IX Levels in Human Gliomas: An Ex Vivo Quantitative Study to Correlate Protoporphyrin IX Levels and Blood-Brain Barrier Breakdown

PubMed Central

Valdés, Pablo A.; Moses, Ziev B.; Kim, Anthony; Belden, Clifford J.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2012-01-01

In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence guidance has been used as a surgical adjunct to improve the extent of resection of gliomas. Exogenous administration of ALA prior to surgery leads to the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can visualize and thereby discriminate between normal and tumor tissue. Selective accumulation of PpIX has been linked to numerous factors, of which blood-brain barrier (BBB) breakdown has been suggested to be a key factor. To test the hypothesis that PpIX concentration (CPpIX) positively correlates with gadolinium (Gd) concentrations (CGd), we performed ex vivo measurements of PpIX and of Gd using Inductively-Coupled Plasma Mass Spectrometry (ICP-MS) the latter as a quantitative biomarker of BBB breakdown; this was corroborated with immunohistochemistry of microvascular density in surgical biopsies of patients undergoing fluorescence guided surgery for glioma .We found positive correlations between CPpIX and CGd (r = 0.58, p < 0.0001), and between CPpIX and microvascular density (r = 0.55, p < 0.0001), suggesting a significant, yet limited association between BBB breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first time that Gd measurements by ICP-MS have been used in human gliomas. PMID:22878664

Factors that determine academic versus private practice career interest in radiation oncology residents in the United States: results of a nationwide survey.

PubMed

Chang, Daniel T; Shaffer, Jenny L; Haffty, Bruce G; Wilson, Lynn D

2013-11-01

To determine what factors US radiation oncology residents consider when choosing academic or nonacademic careers. A 20-question online survey was developed and sent to all US radiation oncology residents to assess factors that influence their career interest. Residents were asked to rate their interest in academics (A) versus private practice (PP) on a 0 (strong interest in A) to 100 (strong interest in PP) scale. Responses were classified as A (0-30), undecided (40-60), and PP (70-100). Residents were also asked to rank 10 factors that most strongly influenced their career interest. Three hundred thirty-one responses were collected, of which 264 were complete and form the basis for this analysis. Factors that correlated with interest in A included having a PhD (P=.018), postgraduate year level (P=.0006), research elective time (P=.0003), obtaining grant funding during residency (P=.012), and number of publications before residency (P=.0001), but not number of abstracts accepted in the past year (P=.65) or publications during residency (P=.67). The 3 most influential factors for residents interested in A were: (1) baseline interest before residency; (2) academic role models; and (3) research opportunities during residency. The 3 most influential factors for residents interested in PP were: (1) baseline interest before residency; (2) academic role models; and (3) academic pressure and obligations. Interest in A correlated with postgraduate year level, degree, and research time during residency. Publications before but not during residency correlated with academic interest, and baseline interest was the most influential factor. These data can be used by residency program directors to better understand what influences residents' career interest. Copyright © 2013 Elsevier Inc. All rights reserved.

Factors that Determine Academic Versus Private Practice Career Interest in Radiation Oncology Residents in the United States: Results of a Nationwide Survey

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

Chang, Daniel T., E-mail: dtchang@stanford.edu; Shaffer, Jenny L.; Haffty, Bruce G.

Purpose: To determine what factors US radiation oncology residents consider when choosing academic or nonacademic careers. Methods and Materials: A 20-question online survey was developed and sent to all US radiation oncology residents to assess factors that influence their career interest. Residents were asked to rate their interest in academics (A) versus private practice (PP) on a 0 (strong interest in A) to 100 (strong interest in PP) scale. Responses were classified as A (0-30), undecided (40-60), and PP (70-100). Residents were also asked to rank 10 factors that most strongly influenced their career interest. Results: Three hundred thirty-one responsesmore » were collected, of which 264 were complete and form the basis for this analysis. Factors that correlated with interest in A included having a PhD (P=.018), postgraduate year level (P=.0006), research elective time (P=.0003), obtaining grant funding during residency (P=.012), and number of publications before residency (P=.0001), but not number of abstracts accepted in the past year (P=.65) or publications during residency (P=.67). The 3 most influential factors for residents interested in A were: (1) baseline interest before residency; (2) academic role models; and (3) research opportunities during residency. The 3 most influential factors for residents interested in PP were: (1) baseline interest before residency; (2) academic role models; and (3) academic pressure and obligations. Conclusions: Interest in A correlated with postgraduate year level, degree, and research time during residency. Publications before but not during residency correlated with academic interest, and baseline interest was the most influential factor. These data can be used by residency program directors to better understand what influences residents' career interest.« less

Oligomerization reactions of ribonucleotides - The reaction of the 5'-phosphorimidazolide of adenosine with diadenosine pyrophosphate on montmorillonite and other minerals

NASA Technical Reports Server (NTRS)

Ferris, James P.; Ertem, Gozen

1993-01-01

The overall regiospecificity of the 3',5'-phosphodiester bond formation is shown to be increased from 64 to 83 percent when a 9:1 ratio of ImpA to A5'ppA instead of ImpA alone is reacted in the presence of Na(+)-montmorillonite. The major factor in the regiospecificity increase is the formation of 3',5'-linked A5'ppA3'pA and A5'pp-A3'pA3'pA. The results obtained show that ImpA reacts more readily with A5'ppA than it does with another ImpA molecule and that A5'ppA plays a central role in directing the formation of 3',5'-phosphodiester bonds.

Progesterone-associated proteins PP12 and PP14 in the human endometrium.

PubMed

Rutanen, E M; Koistinen, R; Seppälä, M; Julkunen, M; Suikkari, A M; Huhtala, M L

1987-01-01

Two proteins, designated as PP12 and PP14 were originally isolated from soluble extracts of the human placenta and its adjacent membranes. We have shown that they are synthesized by decidualized/secretory endometrium and not by placenta. Both proteins occur at high concentrations in human amniotic fluid, which is therefore an excellent source for purification. PP12 is a 34-kDa glycoprotein, which has an N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala. This is identical with that of somatomedin-binding protein purified from the amniotic fluid. PP12 too binds somatomedin-C, or IGF-I (insulin-like growth factor-I). Human secretory endometrium synthesizes and secretes PP12, and progesterone stimulates its secretion. PP14 is a 28-kDa glycoprotein. Its N-terminal sequence shows homology to that of beta-lactoglobulins from various species. We have found PP14 in the human endometrium, serum and milk. Immunologically, PP14 is related to progestagen-associated endometrial protein (PEP), alpha-2 pregnancy-associated endometrial protein (alpha-2, PEG), endometrial protein 15 (EP15), alpha-uterine protein (AUP) and chorionic alpha-2 microglobulin (CAG-2). In ovulatory menstrual cycles, the concentration of PP14 increases in endometrial tissue as the secretory changes advance. In serum, the PP14 concentration begins to rise later than the progesterone levels, and high serum PP14 levels are maintained for the first days of the next cycle. By contrast, no elevation of serum PP14 level is seen in anovulatory cycles. Our results show that progesterone-associated proteins are synthesized by the human endometrium and appear in the peripheral circulation, where they can be quantitatively measured using immunochemical techniques.

Intermittent Induction of HIF-1α Produces Lasting Effects on Malignant Progression Independent of Its Continued Expression

PubMed Central

Choi, Hyunsung; Gillespie, David L.; Berg, Shauna; Rice, Christopher; Couldwell, Sandrine; Gu, Jie; Colman, Howard; Jensen, Randy L.; Huang, L. Eric

2015-01-01

Dysregulation of hypoxia-inducible transcription factors HIF-1α and HIF-2α correlates with poor prognosis in human cancers; yet, divergent and sometimes opposing activities of these factors in cancer biology have been observed. Adding to this complexity is that HIF-1α apparently possesses tumor-suppressing activities, as indicated by the loss-of-function mutations or even homozygous deletion of HIF1A in certain human cancers. As a step towards understanding this complexity, we employed 8-week intermittent induction of a stable HIF-1α variant, HIF1α(PP), in various cancer cell lines and examined the effects on malignant progression in xenografts of immunocompromised mice in comparison to those of HIF2α(PP). Although 8-week treatment led to eventual loss of HIF1α(PP) expression, treated osteosarcoma U-2 OS cells acquired tumorigenicity in the subcutaneous tissue. Furthermore, the prior treatment resulted in widespread invasion of malignant glioma U-87 MG cells in the mouse brain and sustained growth of U-118 MG glioma cells. The lasting effects of HIF-1α on malignant progression are specific because neither HIF2α(PP) nor β-galactosidase yielded similar effects. By contrast, transient expression of HIF1α(PP) in U-87 MG cells or constitutive expression of HIF1α(PP) but not HIF2α(PP) in a patient-derived glioma sphere culture inhibited tumor growth and spread. Our results indicate that intermittent induction of HIF-1α produces lasting effects on malignant progression even at its own expense. PMID:25893706

Efficacy of dietary spray dried plasma protein to mitigate the negative effects on performance of pigs fed diets with corn naturally contaminated with multiple mycotoxins.

PubMed

Weaver, A C; Campbell, J M; Crenshaw, J D; Polo, J; Kim, S W

2014-09-01

The ability of spray dried plasma protein (SDPP) to reduce the negative effects of multiple mycotoxins from naturally contaminated corn on weaned pig performance and health was investigated (n = 180; 6.84 ± 0.11 kg). For 12 d after weaning, pigs were fed phase 1 nursery diets with either 0% SDPP (PP0) or 6% SDPP (PP6). After 12 d, pigs were fed phase 2 diets for 3 wk. Pigs fed PP0 in phase 1 continued to be fed a phase 2 diet with no SDPP (PP0/PP0) or were fed a diet including corn naturally contaminated with multiple mycotoxins (M), labeled PP0/PP0M. Pigs fed SDPP in phase 1 were fed either a diet with no SDPP (PP6/PP0), a diet with M and no SDPP (PP6/PP0M), a diet with M and 3% SDPP (PP6/PP3M), or a diet with M and 6% SDPP (PP6/PP6M). During phase 1, pigs fed PP6 had increased (P < 0.05) ADG, ADFI, and G:F, whereas immunological parameters were not altered. During phase 2, pigs consuming PP0/PP0M had reduced ADG (P < 0.01) and ADFI (P < 0.05) in contrast to pigs fed PP0/PP0, whereas the performance of pigs fed PP6/PP0M was intermediate to pigs fed PP0/PP0M and PP6/PP0. The ADG and ADFI did not differ for pigs fed PP0/PP0M and PP6/PP0M during phase 2. Performance of pigs fed PP6/PP3M in contrast to pigs fed PP6/PP0M during phase 2 did not differ; however, these pigs had lower (P < 0.05) tumor necrosis factor α and tended (P = 0.094) to have lower DNA damage. During phase 2, ADG and ADFI of pigs fed PP6/PP6M did not differ from pigs fed PP6/PP0M, but G:F tended (P = 0.067) to be increased in pigs fed PP6/PP6M. Over the entire study period, pigs fed PP0/PP0M had reduced (P < 0.05) ADG and tended (P = 0.067) to have reduced ADFI. During this time, pigs fed PP6/PP0M tended to have greater ADG and ADFI (P = 0.093 and P = 0.067, respectively) compared with pigs fed PP0/PP0M. Overall, feeding a diet with SDPP improved growth performance and feed intake of young pigs directly after weaning. Feeding multiple M had a negative impact on growth performance of pigs during this trial. This response was more significant when pigs were not fed SDPP in phase 1. Overall, when combining phase 1 and 2 performance data, daily gain and feed intake tended to be reduced when pigs were not fed 6% SDPP in phase 1. This study indicates that the composition of diets fed immediately after weaning may be important for pigs that subsequently are under a M challenge.

Stability-driven nonnegative matrix factorization to interpret spatial gene expression and build local gene networks.

PubMed

Wu, Siqi; Joseph, Antony; Hammonds, Ann S; Celniker, Susan E; Yu, Bin; Frise, Erwin

2016-04-19

Spatial gene expression patterns enable the detection of local covariability and are extremely useful for identifying local gene interactions during normal development. The abundance of spatial expression data in recent years has led to the modeling and analysis of regulatory networks. The inherent complexity of such data makes it a challenge to extract biological information. We developed staNMF, a method that combines a scalable implementation of nonnegative matrix factorization (NMF) with a new stability-driven model selection criterion. When applied to a set ofDrosophilaearly embryonic spatial gene expression images, one of the largest datasets of its kind, staNMF identified 21 principal patterns (PP). Providing a compact yet biologically interpretable representation ofDrosophilaexpression patterns, PP are comparable to a fate map generated experimentally by laser ablation and show exceptional promise as a data-driven alternative to manual annotations. Our analysis mapped genes to cell-fate programs and assigned putative biological roles to uncharacterized genes. Finally, we used the PP to generate local transcription factor regulatory networks. Spatially local correlation networks were constructed for six PP that span along the embryonic anterior-posterior axis. Using a two-tail 5% cutoff on correlation, we reproduced 10 of the 11 links in the well-studied gap gene network. The performance of PP with theDrosophiladata suggests that staNMF provides informative decompositions and constitutes a useful computational lens through which to extract biological insight from complex and often noisy gene expression data.

Epidermal growth factor-stimulated protein phosphorylation in rat hepatocytes

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

Connelly, P.A.; Sisk, R.B.; Johnson, R.M.

1987-05-01

Epidermal growth factor (EGF) causes a 6-fold increase in the phosphorylation state of a cytosolic protein (pp36, M/sub r/ = 36,000, pI = 5.5) in hepatocytes isolated from fasted, male, Wistar rats. Stimulation of /sup 32/P incorporation is observed as early as 1 min following treatment of hepatocytes with EGF and is still present at 30 min after exposure to the growth factor. The phosphate incorporated into pp36 in response to EGF is located predominantly in serine but not tyrosine residues. Phosphorylation of pp36 does not occur in response to insulin or to agents which specifically activate the cAMP-dependent proteinmore » kinase (S/sub p/ -cAMPS), protein kinase C (PMA) or Ca/sup 2 +//calmodulin-dependent protein kinases (A23187) in these cells. Prior treatment of hepatocytes with the cAMP analog, S/sub p/-cAMPS, or ADP-ribosylation of N/sub i/, the inhibitory GTP-binding protein of the adenylate cyclase complex, does not prevent EGF-stimulated phosphorylation of pp36. However, as seen in other cell types, pretreatment of hepatocytes with PMA abolishes all EGF-mediated responses including phosphorylation of pp36. These results suggest that EGP specifically activates an uncharacterized, serine protein kinase in hepatocytes that is distal to the intrinsic EGF receptor tyrosine protein kinase. The rapid activation of this kinase suggests that it may play an important role in the early response of the cell to EGF.« less

PP2ARts1 is a master regulator of pathways that control cell size

PubMed Central

Zapata, Jessica; Dephoure, Noah; MacDonough, Tracy; Yu, Yaxin; Parnell, Emily J.; Mooring, Meghan; Gygi, Steven P.; Stillman, David J.

2014-01-01

Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth. PMID:24493588

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

PubMed Central

Tao, Min; Liu, Lu; Shen, Meng; Zhi, Qiaoming; Gong, Fei-Ran; Zhou, Binhua P.; Wu, Yadi; Liu, Haiyan; Chen, Kai; Shen, Bairong; Wu, Meng-Yao; Shou, Liu-Mei; Li, Wei

2016-01-01

ABSTRACT Previous studies have indicated that inflammatory stimulation represses protein phosphatase 2A (PP2A), a well-known tumor suppressor. However, whether PP2A repression participates in pancreatic cancer progression has not been verified. We used lipopolysaccharide (LPS) and macrophage-conditioned medium (MCM) to establish in vitro inflammation models, and investigated whether inflammatory stimuli affect pancreatic cancer cell growth and invasion PP2A catalytic subunit (PP2Ac)-dependently. Via nude mouse models of orthotopic tumor xenografts and dibutyltin dichloride (DBTC)-induced chronic pancreatitis, we evaluated the effect of an inflammatory microenvironment on PP2Ac expression in vivo. We cloned the PP2Acα and PP2Acβ isoform promoters to investigate the PP2Ac transcriptional regulation mechanisms. MCM accelerated pancreatic cancer cell growth; MCM and LPS promoted cell invasion. DBTC promoted xenograft growth and metastasis, induced tumor-associated macrophage infiltration, promoted angiogenesis, activated the nuclear factor-κB (NF-κB) pathway, and repressed PP2Ac expression. In vitro, LPS and MCM downregulated PP2Ac mRNA and protein. PP2Acα overexpression attenuated JNK, ERK, PKC, and IKK phosphorylation, and impaired LPS/MCM-stimulated cell invasion and MCM-promoted cell growth. LPS and MCM activated the NF-κB pathway in vitro. LPS and MCM induced IKK and IκB phosphorylation, leading to p65/RelA nuclear translocation and transcriptional activation. Overexpression of the dominant negative forms of IKKα attenuated LPS and MCM downregulation of PP2Ac, suggesting inflammatory stimuli repress PP2Ac expression NF-κB pathway–dependently. Luciferase reporter gene assay verified that LPS and MCM downregulated PP2Ac transcription through an NF-κB–dependent pathway. Our study presents a new mechanism in inflammation-driven cancer progression through NF-κB pathway–dependent PP2Ac repression. PMID:26761431

On the difficulties of detecting PP precursors

NASA Astrophysics Data System (ADS)

Lessing, Stephan; Thomas, Christine; Saki, Morvarid; Schmerr, Nicholas; Vanacore, Elizabeth

2015-06-01

The PP precursors are seismic waves that form from underside reflections of P waves off discontinuities in the upper mantle transition zone (MTZ). These seismic phases are used to map discontinuity topography, sharpness, and impedance contrasts; the resulting structural variations are then often interpreted as evidence for temperature and/or mineralogy variations within the mantle. The PP precursors as well as other seismic phases have been used to establish the global presence of seismic discontinuities at 410 and 660 km depth. Intriguingly, in more than 80 per cent of PP precursor observations the seismic wave amplitudes are significantly weaker than the amplitudes predicted by seismic reference models. Even more perplexing is the observation that 1-5 per cent of all earthquakes (which are 20-25 per cent of earthquakes with clear PP waveforms) do not show any evidence for the PP precursors from the discontinuities even in the presence of well-developed PP waveforms. Non-detections are found in six different data sets consisting of tens to hundreds of events. We use synthetic modelling to examine a suite of factors that could be responsible for the absence of the PP precursors. The take-off angles for PP and the precursors differ by only 1.2-1.5°; thus source-related complexity would affect PP and the precursors. A PP wave attenuated in the upper mantle would increase the relative amplitude of the PP precursors. Attenuation within the transition zone could reduce precursor amplitudes, but this would be a regional phenomenon restricted to particular source receiver geometries. We also find little evidence for deviations from the theoretical travel path of seismic rays expected for scattered arrivals. Factors that have a strong influence include the stacking procedures used in seismic array techniques in the presence of large, interfering phases, the presence of topography on the discontinuities on the order of tens of kilometres, and 3-D lateral heterogeneity in the velocity and density changes with depth across the transition zone. We also compare the observed precursors' amplitudes with seismic models from calculations of phase equilibria and find that a seismic velocity model derived from a pyrolite composition reproduces the data better than the currently available 1-D earth models. This largely owes to the pyrolite models producing a stronger minimum in the reflection coefficient across the epicentral distances where the reduction in amplitudes of the PP precursors is observed. To suppress the precursors entirely in a small subset of earthquakes, other effects, such as localized discontinuity topography and seismic signal processing effects are required in addition to the changed velocity model.

Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer

PubMed Central

Golden, Teresa; Aragon, Ileana V.; Rutland, Beth; Tucker, J. Allan; Shevde, Lalita A.; Samant, Rajeev S.; Zhou, Guofei; Amable, Lauren; Skarra, Danalea; Honkanen, Richard E.

2008-01-01

Ser/Thr protein phosphatase 5 (PP5) regulates several signaling-cascades that suppress growth and/or facilitate apoptosis in response to genomic stress. The expression of PP5 is responsive to hypoxia inducible factor-1 (HIF-1) and estrogen, which have both been linked to the progression of human breast cancer. Still, it is not clear if PP5 plays a role in the development of human cancer. Here, immunostaining of breast cancer tissue-microarrays (TMAs) revealed a positive correlation between PP5 overexpression and ductal carcinoma in situ (DCIS; P value 0.0028), invasive ductal carcinoma (IDC; P value 0.012) and IDC with metastases at the time of diagnosis (P value 0.0001). In a mouse xenograft model, the constitutive overexpression of PP5 was associated with an increase in the rate of tumor growth. In a MCF-7 cell culture model overexpression correlated with both an increase in the rate of proliferation and protection from cell death induced by oxidative stress, UVC-irradiation, adriamycin, and vinblastine. PP5 overexpression had no apparent effect on the sensitivity of MCF-7 cells to taxol or rapamycin. Western analysis of extracts from cells over-expressing PP5 revealed a decrease in the phosphorylation of known substrates for PP5. Together, these studies indicate that elevated levels of PP5 protein occur in human breast cancer and suggest that PP5 overexpression may aid tumor progression. PMID:18280813

ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid-mediated photodynamic therapy.

PubMed

Palasuberniam, Pratheeba; Yang, Xue; Kraus, Daniel; Jones, Patrick; Myers, Kenneth A; Chen, Bin

2015-08-18

Photosensitizer protoporphyrin IX (PpIX) fluorescence, intracellular localization and cell response to photodynamic therapy (PDT) were analyzed in MCF10A normal breast epithelial cells and a panel of human breast cancer cells including estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) positive and triple negative breast cancer (TNBC) cells after treatment with PpIX precursor aminolevulinic acid (ALA). Although PpIX fluorescence was heterogeneous in different cells, TNBC cells showed significantly lower PpIX level than MCF10A and ER- or HER2-positive cells. PpIX fluorescence in TNBC cells also had much less mitochondrial localization than other cells. There was an inverse correlation between PpIX fluorescence and cell viability after PDT. Breast cancer cells with the highest PpIX fluorescence were the most sensitive to ALA-PDT and TNBC cells with the lowest PpIX level were resistant to PDT. Treatment of TNBC cells with ABCG2 transporter inhibitor Ko143 significantly increased ALA-PpIX fluorescence, enhanced PpIX mitochondrial accumulation and sensitized cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. These results demonstrate that enhanced ABCG2 activity renders TNBC cell resistance to ALA-PDT and inhibiting ABCG2 transporter is a promising approach for targeting TNBC with ALA-based modality.

Relations between a novel, reliable, and rapid index of arterial compliance (PP-HDI) and well-established inidices of arterial blood pressure (ABP) in a sample of hypertensive elderly subjects.

PubMed

Bergamini, L; Finelli, M E; Bendini, C; Ferrari, E; Veschi, M; Neviani, F; Manni, B; Pelosi, A; Rioli, G; Neri, M

2009-01-01

Hypertension is a risk factor for a long-lasting arterial wall-remodelling leading to stiffness. The rapid method measuring the pulse pressure (PP) by means of the tool of Hypertension Diagnostic Instruments (HDI) called PP-HDI, overcomes some of the problems arising with more-time consuming methods, like ambulatory blood pressure monitoring (ABPM), and give information about the elasticity of the arterial walls. We studied the relationship between the PP-HDI, the large artery compliance (LA-C) and small artery compliance (SA-C) and few well-established indices of arterial blood pressure (ABP) in a sample of 75 hypertensive subjects, aged 65 years and over. Significant correlations between LA-C and heart rate (HR), PP-ABPM and PP-HDI were found. SA-C relates with HR and systolic blood pressure (SBP) measured in lying and standing positions. Applying a stepwise regression analysis, we found that LA-C variance stems from PP-HDI and HR, while SA-C variance stems from SBP in lying position. Receiver operator characteristic (ROC) curves for thresholds of PP showed that PP-HDI reached levels of sensitivity/specificity similar to PP-ABPM. In conclusion, surveillance of ABP through hemo-dynamic indices, in particular of SBP, is essential, nevertheless the advantage of this control is not known in an elderly population where the organ damage is already evident. PP needs necessarily an instrumental measurement. The PP-HDI result is similar in reliability with respect to PPABPM, but is more rapid and well applicable in an elderly population.

Influence of Knee Joint Extension on Submaximal Oxygen Consumption and Anaerobic Power in Cyclists

DTIC Science & Technology

1991-06-05

Cycling (pp. 91-122). Champaign, IL: Human Kinetics Books. Cavanagh, P.R. & Kram, R. (1985). Mechanical and muscular factors affecting the efficiency...M.L. (1986). Flexibility standards of the U.S. cycling team. In E.R. Burke (Ed.). Science of Cycling (pp. 47-68). Champaign, IL: Human Kinetics Books...height and pedaling cadence on power output and efficiency. In E.R. Burke (Ed.). Science of Cycling (pp. 69-907). Champaign, IL: Human Kinetics Books

The Navy Enlistment Field Marketing Experiment. Volume 3. An Empirical Investigation of Navy Recruiter Productivity

DTIC Science & Technology

1982-10-15

Individual Difference, Interpersonal, and Situational Factors’, Journal of Marketing Research , Vol. 15, November, pp. 517-531. 2. Beswick, C. A., and...D. W. Cravens (1977), "A Multistage Decision Model 7, for Salesforce Management", Journal of Marketing Research , Vol 14, May, pp 135-144. 3. Brown, A...Jr. (1976), "Organi- zational Climate and Job Satisfaction in the Salesforce," Journal of Marketing Research , Vol. 13, November, pp. 323-332. 6

Cyclin B Translation Depends on mTOR Activity after Fertilization in Sea Urchin Embryos

PubMed Central

Boulben, Sandrine; Glippa, Virginie; Morales, Julia; Cormier, Patrick

2016-01-01

The cyclin B/CDK1 complex is a key regulator of mitotic entry. Using PP242, a specific ATP-competitive inhibitor of mTOR kinase, we provide evidence that the mTOR signalling pathway controls cyclin B mRNA translation following fertilization in Sphaerechinus granularis and Paracentrotus lividus. We show that PP242 inhibits the degradation of the cap-dependent translation repressor 4E-BP (eukaryotic initiation factor 4E-Binding Protein). PP242 inhibits global protein synthesis, delays cyclin B accumulation, cyclin B/CDK1 complex activation and consequently entry into the mitotic phase of the cell cycle triggered by fertilization. PP242 inhibits cyclin B mRNA recruitment into active polysomes triggered by fertilization. An amount of cyclin B mRNA present in active polysomes appears to be insensitive to PP242 treatment. Taken together, our results suggest that, following sea urchin egg fertilization, cyclin B mRNA translation is controlled by two independent mechanisms: a PP242-sensitive and an additional PP242-insentitive mechanism. PMID:26962866

Control of plant phosphate homeostasis by inositol pyrophosphates and the SPX domain.

PubMed

Jung, Ji-Yul; Ried, Martina K; Hothorn, Michael; Poirier, Yves

2018-02-01

Proteins containing a SPX domain are involved in phosphate (Pi) homeostasis, including Pi transport and adaptation to Pi deficiency. The SPX domain harbors a basic surface binding Pi at low affinity and inositol pyrophosphates (PP-InsPs) at high affinity. Genetic and biochemical studies revealed that PP-InsPs serve as ligands for the SPX domain. Residues in the PHO1 SPX domain involved in PP-InsPs binding are critical for its Pi export activity, and the interaction between SPX proteins and the PHR1 transcription factor, which results in PHR1 inactivation, is promoted by PP-InsPs. Changes in PP-InsPs levels in response to Pi deficiency may thus contribute to the adaptation of plants to stress via the modulation of the activity of SPX-containing proteins and their interactors. Modulating PP-InsP levels or the affinity/specificity of the SPX domain for PP-InsP could potentially be used to engineer crops to maintain high yield under reduced Pi fertilizer input. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genomic characteristics of vB_PpaP_PP74, a T7-like Autographivirinae bacteriophage infecting a potato pathogen of the newly proposed species Pectobacterium parmentieri.

PubMed

Kabanova, Anastasia; Shneider, Mikhail; Bugaeva, Eugenia; Ha, Vo Thi Ngoc; Miroshnikov, Kirill; Korzhenkov, Aleksei; Kulikov, Eugene; Toschakov, Stepan; Ignatov, Alexander; Miroshnikov, Konstantin

2018-06-01

Bacteriophage vB_PpaP_PP74 (PP74) is a novel virulent phage that infects members of the species Pectobacterium parmentieri, a newly established species of soft-rot-causing bacteria in the family Pectobacteriaceae, derived from potato-specific Pectobacterium wasabiae. vB_PpaP_PP74 was identified as a member of the family Podoviridae by transmission electron microscopy. The phage has a 39,790-bp dsDNA genome containing 50 open reading frames (ORFs). Because of the absence of genes encoding toxins or lysogeny factors, PP74 may be considered a candidate phage for pathogen biocontrol applications. The genome layout is similar to genomes of T7-like phages within the subfamily Autographivirinae, and therefore, functions can be attributed to most of ORFs. However, the closest nucleotide sequence homologs of phage PP74 are unclassified Escherichia phages. Based on phylogenetic analysis, vB_PpaP_PP74 is a sensu lato T7-like phage, but it forms a distant subgenus group together with homologous enterobacterial phages.

The NAC transcription factor family in maritime pine (Pinus Pinaster): molecular regulation of two genes involved in stress responses.

PubMed

Pascual, Ma Belén; Cánovas, Francisco M; Ávila, Concepción

2015-10-24

NAC transcription factors comprise a large plant-specific gene family involved in the regulation of diverse biological processes. Despite the growing number of studies on NAC transcription factors in various species, little information is available about this family in conifers. The goal of this study was to identify the NAC transcription family in maritime pine (Pinus pinaster), to characterize ATAF-like genes in response to various stresses and to study their molecular regulation. We have isolated two maritime pine NAC genes and using a transient expression assay in N. benthamiana leaves estudied the promoter jasmonate response. In this study, we identified 37 NAC genes from maritime pine and classified them into six main subfamilies. The largest group includes 12 sequences corresponding to stress-related genes. Two of these NAC genes, PpNAC2 and PpNAC3, were isolated and their expression profiles were examined at various developmental stages and in response to various types of stress. The expression of both genes was strongly induced by methyl jasmonate (MeJA), mechanical wounding, and high salinity. The promoter regions of these genes were shown to contain cis-elements involved in the stress response and plant hormonal regulation, including E-boxes, which are commonly found in the promoters of genes that respond to jasmonate, and binding sites for bHLH proteins. Using a transient expression assay in N. benthamiana leaves, we found that the promoter of PpNAC3 was rapidly induced upon MeJA treatment, while this response disappeared in plants in which the transcription factor NbbHLH2 was silenced. Our results suggest that PpNAC2 and PpNAC3 encode stress-responsive NAC transcription factors involved in the jasmonate response in pine. Furthermore, these data also suggest that the jasmonate signaling pathway is conserved between angiosperms and gymnosperms. These findings may be useful for engineering stress tolerance in pine via biotechnological approaches.

Arsenic Metabolism in Children Differs From That in Adults.

PubMed

Skröder Löveborn, Helena; Kippler, Maria; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

2016-07-01

Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12.Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children's arsenic methylation; an increase in Ery-Se from the 5-95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and -3.2 pp for %DMA (P  <  .001). Despite this, Ery-Se was positively associated with U-As (5-95th percentile: +41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5-95th percentile: -1.9 pp, P  =  .001) and positively associated with %DMA (5-95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice.

PubMed

Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Lütjohann, Dieter; Veltien, Andor; Heerschap, Arend; Kiliaan, Amanda J

2017-01-01

Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPP swe /PS1 dE9 (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF. Furthermore, using advanced MRI techniques, decline of functional and structural connectivity was revealed in the AD-like mice coupled to impaired cognition, increased locomotor activity, and anxiety-related behavior. Post mortem analyses demonstrated also increased neuroinflammation, and both decreased synaptogenesis and neurogenesis in the AβPP/PS1 mice. Additionally, deviant levels of fatty acids and sterols were present in the brain tissue of the AβPP/PS1 mice indicating maladapted brain fatty acid metabolism. Our findings suggest a link between increased SBP, decreased cerebral hemodynamics and connectivity in an AD mouse model during aging, leading to behavioral and cognitive impairments. As these results mirror the complex clinical symptomatology in the prodromal phase of AD, we suggest that this AD-like murine model could be used to investigate prevention and treatment strategies for early AD patients. Moreover, this study helps to develop more efficient therapies and diagnostics for this very early stage of AD.

Nerve Growth Factor Increases mRNA Levels for the Prion Protein and the β -amyloid Protein Precursor in Developing Hamster Brain

NASA Astrophysics Data System (ADS)

Mobley, William C.; Neve, Rachael L.; Prusiner, Stanley B.; McKinley, Michael P.

1988-12-01

Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the β protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the β -protein precursor (β -PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and β -PP mRNAs. The increases in PrP and β -PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and β -PP mRNA levels. Increased PrP and β -PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and β -PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes.

Transfer function-derived central pressure and cardiovascular disease events: the Framingham Heart Study.

PubMed

Mitchell, Gary F; Hwang, Shih-Jen; Larson, Martin G; Hamburg, Naomi M; Benjamin, Emelia J; Vasan, Ramachandran S; Levy, Daniel; Vita, Joseph A

2016-08-01

Relations between central pulse pressure (PP) or pressure amplification and major cardiovascular disease (CVD) events are controversial. Estimates of central aortic pressure derived using radial artery tonometry and a generalized transfer function may better predict CVD risk beyond the predictive value of brachial SBP. Augmentation index, central SBP, central PP, and central-to-peripheral PP amplification were evaluated using radial artery tonometry and a generalized transfer function as implemented in the SphygmoCor device (AtCor Medical, Itasca, Illinois, USA). We used proportional hazards models to examine relations between central hemodynamics and first-onset major CVD events in 2183 participants (mean age 62 years, 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (limits 0.2-8.9) years, 149 participants (6.8%) had an incident event. Augmentation index (P = 0.6), central aortic systolic pressure (P = 0.20), central aortic PP (P = 0.24), and PP amplification (P = 0.15) were not related to CVD events in multivariable models that adjusted for age, sex, brachial cuff systolic pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes. In a model that included standard risk factors, model fit was improved (P = 0.03) when brachial systolic pressure was added after central, whereas model fit was not improved (P = 0.30) when central systolic pressure was added after brachial. After considering standard risk factors, including brachial cuff SBP, augmentation index, central PP and PP amplification derived using radial artery tonometry, and a generalized transfer function were not predictive of CVD risk.

Protein Phosphatase 2A Antagonizes ATM and ATR in a Cdk2- and Cdc7-Independent DNA Damage Checkpoint

PubMed Central

Petersen, Paris; Chou, Danny M.; You, Zhongsheng; Hunter, Tony; Walter, Johannes C.; Walter, Gernot

2006-01-01

We previously used a soluble cell-free system derived from Xenopus eggs to investigate the role of protein phosphatase 2A (PP2A) in chromosomal DNA replication. We found that immunodepletion of PP2A or inhibition of PP2A by okadaic acid (OA) inhibits initiation of DNA replication by preventing loading of the initiation factor Cdc45 onto prereplication complexes. Evidence was provided that PP2A counteracts an inhibitory protein kinase that phosphorylates and inactivates a crucial Cdc45 loading factor. Here, we report that the inhibitory effect of OA is abolished by caffeine, an inhibitor of the checkpoint kinases ataxia-telangiectasia mutated protein (ATM) and ataxia-telangiectasia related protein (ATR) but not by depletion of ATM or ATR from the extract. Furthermore, we demonstrate that double-strand DNA breaks (DSBs) cause inhibition of Cdc45 loading and initiation of DNA replication and that caffeine, as well as immunodepletion of either ATM or ATR, abolishes this inhibition. Importantly, the DSB-induced inhibition of Cdc45 loading is prevented by addition of the catalytic subunit of PP2A to the extract. These data suggest that DSBs and OA prevent Cdc45 loading through different pathways, both of which involve PP2A, but only the DSB-induced checkpoint implicates ATM and ATR. The inhibitory effect of DSBs on Cdc45 loading does not result from downregulation of cyclin-dependent kinase 2 (Cdk2) or Cdc7 activity and is independent of Chk2. However, it is partially dependent on Chk1, which becomes phosphorylated in response to DSBs. These data suggest that PP2A counteracts ATM and ATR in a DNA damage checkpoint in Xenopus egg extracts. PMID:16479016

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

Sirunyan, Albert M; et al.

The transverse momentum (pt) spectrum of prompt D0 mesons and their antiparticles has been measured via the hadronic decay channels D0 to K- pi+ and D0-bar to K+ pi- in pp and PbPb collisions at a centre-of-mass energy of 5.02 TeV per nucleon pair with the CMS detector at the LHC. The measurement is performed in the D0 meson pt range of 2-100 GeV and in the rapidity range of abs(y)<1. The pp (PbPb) dataset used for this analysis corresponds to an integrated luminosity of 27.4 inverse picobarns (530 inverse microbarns). The measured D0 meson pt spectrum in pp collisionsmore » is well described by perturbative QCD calculations. The nuclear modification factor, comparing D0 meson yields in PbPb and pp collisions, was extracted for both minimum-bias and the 10% most central PbPb interactions. For central events, the D0 meson yield in the PbPb collisions is suppressed by a factor of 5-6 compared to the pp reference in the pt range of 6-10 GeV. For D0 mesons in the high-pt range of 60-100 GeV, a significantly smaller suppression is observed. The results are also compared to theoretical calculations.« less

PpNAC1, a main regulator of phenylalanine biosynthesis and utilization in maritime pine.

PubMed

Pascual, María Belén; Llebrés, María-Teresa; Craven-Bartle, Blanca; Cañas, Rafael A; Cánovas, Francisco M; Ávila, Concepción

2018-05-01

The transcriptional regulation of phenylalanine metabolism is particularly important in conifers, long-lived species that use large amounts of carbon in wood. Here, we show that the Pinus pinaster transcription factor, PpNAC1, is a main regulator of phenylalanine biosynthesis and utilization. A phylogenetic analysis classified PpNAC1 in the NST proteins group and was selected for functional characterization. PpNAC1 is predominantly expressed in the secondary xylem and compression wood of adult trees. Silencing of PpNAC1 in P. pinaster results in the alteration of stem vascular radial patterning and the down-regulation of several genes associated with cell wall biogenesis and secondary metabolism. Furthermore, transactivation and EMSA analyses showed that PpNAC1 is able to activate its own expression and PpMyb4 promoter, while PpMyb4 is able to activate PpMyb8, a transcriptional regulator of phenylalanine and lignin biosynthesis in maritime pine. Together, these results suggest that PpNAC1 is a functional ortholog of the ArabidopsisSND1 and NST1 genes and support the idea that key regulators governing secondary cell wall formation could be conserved between gymnosperms and angiosperms. Understanding the molecular switches controlling wood formation is of paramount importance for fundamental tree biology and paves the way for applications in conifer biotechnology. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.

PubMed

Fang, Jun; Tsukigawa, Kenji; Liao, Long; Yin, Hongzhuan; Eguchi, Kanami; Maeda, Hiroshi

2016-01-01

Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.

Pulse pressure independently predicts major cardiovascular events in younger but not in older subjects with erectile dysfunction.

PubMed

Corona, Giovanni; Monami, Matteo; Boddi, Valentina; Rastrelli, Giulia; Melani, Cecilia; Balzi, Daniela; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2011-01-01

Pulse pressure (PP; i.e., the arithmetic difference between systolic and diastolic blood pressure) has been suggested to be an independent cardiovascular risk (CV) factor in the general population. We previously also reported a negative association between PP and arteriogenic erectile dysfunction (ED). This finding has recently been questioned. To verify the association of PP with ED severity and to evaluate its role in predicting forthcoming CV events. This is an observational prospective cohort study evaluating a consecutive series of 1,687 patients attending our Andrological Unit for ED. Several hormonal and biochemical parameters were studied, along with SIEDY structured interviews and penile Doppler ultrasound. Subjects with PP in the lowest quartile (I: 20-45; II: 46-55; III: 56-62; IV: 63-115 mm Hg) had a significant reduction in the risk of severe ED (RR = 0.60[0.47-0.76]; P < 0.0001). When the same analysis was repeated as a function of age quartile (I = 17-44, II = 45-55, III = 56-62, and IV = 63-88 years old), after adjusting for testosterone levels, mean blood pressure, Chronic Disease Score, and body mass index, PP was inversely related to ED only in the youngest age group. During a mean follow up of 4.4 ± 2.6 years, 147 major cardiovascular events (MACE) were observed. In a Cox regression model, after adjusting for possible confounding factors, a lower PP was associated with a lower risk of MACE in the whole sample and in younger subjects, but not in the older ones. Checking for blood pressure in ED subjects and calculating PP should become a routine practice in sexual medicine. In younger individuals, low PP reflects not only sexual health (better erection) but also cardiovascular health (less prevalence of MACE). © 2010 International Society for Sexual Medicine.

RSL genes are sufficient for rhizoid system development in early diverging land plants.

PubMed

Jang, Geupil; Yi, Keke; Pires, Nuno D; Menand, Benoît; Dolan, Liam

2011-06-01

Land plants are anchored to their substratum from which essential inorganic nutrients are taken up. These functions are carried out by a system of rhizoids in early diverging groups of land plants, such as mosses, liverworts and hornworts. Physcomitrella patens RHD SIX-LIKE1 (PpRSL1) and PpRSL2 transcription factors are necessary for rhizoid development in mosses. Similar proteins, AtRHD6 and AtRSL1, control the development of root hairs in Arabidopsis thaliana. Auxin positively regulates root hair development independently of AtRHD6 and AtRSL1 in A. thaliana but the regulatory interactions between auxin and PpRSL1 and PpRSL2 are unknown. We show here that co-expression of PpRSL1 and PpRSL2 is sufficient for the development of the rhizoid system in the moss P. patens; constitutive expression of PpRSL1 and PpRSL2 converts developing leafy shoot axes (gametophores) into rhizoids. During wild-type development, PpRSL1 and PpRSL2 are expressed in the specialized cells that develop rhizoids, indicating that cell-specific expression of PpRSL1 and PpRSL2 is sufficient to promote rhizoid differentiation during wild-type P. patens development. In contrast to A. thaliana, auxin promotes rhizoid development by positively regulating PpRSL1 and PpRSL2 activity in P. patens. This indicates that even though the same genes control the development of root hairs and rhizoids, the regulation of this transcriptional network by auxin is different in these two species. This suggests that auxin might have controlled the development of the first land plant soil anchoring systems that evolved 465 million years ago by regulating the expression of RSL genes and that this regulatory network has changed since mosses and angiosperms last shared a common ancestor.

SCF E3 ligase PP2-B11 plays a positive role in response to salt stress in Arabidopsis

PubMed Central

Jia, Fengjuan; Wang, Chunyan; Huang, Jinguang; Yang, Guodong; Wu, Changai; Zheng, Chengchao

2015-01-01

Skp1–Cullin–F-box (SCF) E3 ligases are essential to the post-translational regulation of many important factors involved in cellular signal transduction. In this study, we identified an F-box protein from Arabidopsis thaliana, AtPP2-B11, which was remarkably induced with increased duration of salt treatment in terms of both transcript and protein levels. Transgenic Arabidopsis plants overexpressing AtPP2-B11 exhibited obvious tolerance to high salinity, whereas the RNA interference line was more sensitive to salt stress than wild-type plants. Isobaric tag for relative and absolute quantification analysis revealed that 4311 differentially expressed proteins were regulated by AtPP2-B11 under salt stress. AtPP2-B11 could upregulate the expression of annexin1 (AnnAt1) and function as a molecular link between salt stress and reactive oxygen species accumulation in Arabidopsis. Moreover, AtPP2-B11 influenced the expression of Na+ homeostasis genes under salt stress, and the AtPP2-B11 overexpressing lines exhibited lower Na+ accumulation. These results suggest that AtPP2-B11 functions as a positive regulator in response to salt stress in Arabidopsis. PMID:26041321

I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort apoptosis.

PubMed

Liu, Gong-Ping; Wei, Wei; Zhou, Xin; Zhang, Yao; Shi, Hai-Hong; Yin, Jun; Yao, Xiu-Qing; Peng, Cai-Xia; Hu, Juan; Wang, Qun; Li, Hong-Lian; Wang, Jian-Zhi

2012-02-01

A chronic neuron loss is the cardinal pathology in Alzheimer disease (AD), but it is still not understood why most neurons in AD brain do not accomplish apoptosis even though they are actually exposed to an environment with enriched proapoptotic factors. Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)), an endogenous PP2A inhibitor, is significantly increased in AD brain, but the role of I(2)(PP2A) in AD-like neuron loss is elusive. Here, we show that I(2)(PP2A) regulates p53 and Akt correlatively. The mechanisms involve activated transcription and p38 MAPK activities. More importantly, we demonstrate that the simultaneous activation of Akt induced by I(2)(PP2A) counteracts the hyperactivated p53-induced cell apoptosis. Furthermore, I(2)(PP2A), p53 and Akt are all elevated in the brain of mouse model and AD patients. Our results suggest that the increased I(2)(PP2A) may trigger apoptosis by p53 upregulation, but due to simultaneous activation of Akt, the neurons are aborted from the apoptotic pathway. This finding contributes to the understanding of why most neurons in AD brain do not undergo apoptosis. Copyright © 2010. Published by Elsevier Inc.

Stability-driven nonnegative matrix factorization to interpret spatial gene expression and build local gene networks

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

Wu, Siqi; Joseph, Antony; Hammonds, Ann S.

Spatial gene expression patterns enable the detection of local covariability and are extremely useful for identifying local gene interactions during normal development. The abundance of spatial expression data in recent years has led to the modeling and analysis of regulatory networks. The inherent complexity of such data makes it a challenge to extract biological information. We developed staNMF, a method that combines a scalable implementation of nonnegative matrix factorization (NMF) with a new stability-driven model selection criterion. When applied to a set of Drosophila early embryonic spatial gene expression images, one of the largest datasets of its kind, staNMF identifiedmore » 21 principal patterns (PP). Providing a compact yet biologically interpretable representation of Drosophila expression patterns, PP are comparable to a fate map generated experimentally by laser ablation and show exceptional promise as a data-driven alternative to manual annotations. Our analysis mapped genes to cell-fate programs and assigned putative biological roles to uncharacterized genes. Finally, we used the PP to generate local transcription factor regulatory networks. Spatially local correlation networks were constructed for six PP that span along the embryonic anterior-posterior axis. Using a two-tail 5% cutoff on correlation, we reproduced 10 of the 11 links in the well-studied gap gene network. In conclusion, the performance of PP with the Drosophila data suggests that staNMF provides informative decompositions and constitutes a useful computational lens through which to extract biological insight from complex and often noisy gene expression data.« less

Stability-driven nonnegative matrix factorization to interpret spatial gene expression and build local gene networks

DOE PAGES

Wu, Siqi; Joseph, Antony; Hammonds, Ann S.; ...

2016-04-06

Spatial gene expression patterns enable the detection of local covariability and are extremely useful for identifying local gene interactions during normal development. The abundance of spatial expression data in recent years has led to the modeling and analysis of regulatory networks. The inherent complexity of such data makes it a challenge to extract biological information. We developed staNMF, a method that combines a scalable implementation of nonnegative matrix factorization (NMF) with a new stability-driven model selection criterion. When applied to a set of Drosophila early embryonic spatial gene expression images, one of the largest datasets of its kind, staNMF identifiedmore » 21 principal patterns (PP). Providing a compact yet biologically interpretable representation of Drosophila expression patterns, PP are comparable to a fate map generated experimentally by laser ablation and show exceptional promise as a data-driven alternative to manual annotations. Our analysis mapped genes to cell-fate programs and assigned putative biological roles to uncharacterized genes. Finally, we used the PP to generate local transcription factor regulatory networks. Spatially local correlation networks were constructed for six PP that span along the embryonic anterior-posterior axis. Using a two-tail 5% cutoff on correlation, we reproduced 10 of the 11 links in the well-studied gap gene network. In conclusion, the performance of PP with the Drosophila data suggests that staNMF provides informative decompositions and constitutes a useful computational lens through which to extract biological insight from complex and often noisy gene expression data.« less

Aircraft Alerting Systems Criteria Study. Volume II. Human Factors Guidelines for Aircraft Alerting Systems

DTIC Science & Technology

1977-05-01

Effect of Mixing Flashing and Steady Irrelevant Lights, Ergonomics, Vol. 6 (3), 1963, pp. 27-294. Creelman , C. D., Detection of Signals of Uncertain...Frequency, Acoustical Sok. America-J, Vol. 32 (7), July 1960, pp. 805-10. Creelman , C. D., Detection, Discrimination, and Loudness of Short Tones

Psychophysical and Patient Factors as Determinants of Pain, Function and Health Status in Shoulder Disorders

PubMed Central

Uddin, Zakir; MacDermid, Joy C.; Moro, Jaydeep; Galea, Victoria; Gross, Anita R.

2016-01-01

Objective: To estimate the extent to which psychophysical quantitative sensory test (QST) and patient factors (gender, age and comorbidity) predict pain, function and health status in people with shoulder disorders. To determine if there are gender differences for QST measures in current perception threshold (CPT), vibration threshold (VT) and pressure pain (PP) threshold and tolerance. Design: A cross-sectional study design. Setting: MacHAND Clinical Research Lab at McMaster University. Subjects: 34 surgical and 10 nonsurgical participants with shoulder pain were recruited. Method: Participants completed the following patient reported outcomes: pain (Numeric Pain Rating, Pain Catastrophizing Scale, Shoulder Pain and Disability Index) and health status (Short Form-12). Participants completed QST at 4 standardized locations and then an upper extremity performance-based endurance test (FIT-HaNSA). Pearson r’s were computed to determine the relationships between QST variables and patient factors with either pain, function or health status. Eight regression models were built to analysis QST’s and patient factors separately as predictors of either pain, function or health status. An independent sample t-test was done to evaluate the gender effect on QST. Results: Greater PP threshold and PP tolerance was significantly correlated with higher shoulder functional performance on the FIT-HANSA (r =0.31-0.44) and lower self-reported shoulder disability (r = -0.32 to -0.36). Higher comorbidity was consistently correlated (r =0.31-0.46) with more pain, and less function and health status. Older age was correlated to more pain intensity and less function (r =0.31-0.57). In multivariate models, patient factors contributed significantly to pain, function or health status models (r2 =0.19-0.36); whereas QST did not. QST was significantly different between males and females [in PP threshold (3.9 vs. 6.2, p < .001) and PP tolerance (7.6 vs. 2.6, p < .001) and CPT (1.6 vs. 2.3, p =.02)]. Conclusion: Psychophysical dimensions and patient factors (gender, age and comorbidity) affect self-reported and performance-based outcome measures in people with shoulder disorders. PMID:29399220

Validity of a scale of neighbourhood informal social control relevant to pre-schoolers' physical activity: A cross-sectional study.

PubMed

Cerin, Ester; Suen, Yi Nam; Barnett, Anthony; Huang, Wendy Y J; Mellecker, Robin R

2017-12-01

Childhood physical activity (PA) is important for health across the lifespan. Time pre-schoolers spend outdoors, which has been associated with more PA, is likely influenced by parents' perception of neighbourhood informal social control relevant to pre-schoolers' PA, defined as the willingness of neighbours to intervene to ensure social order and a safe community environment for young children's active play. To advance measurement of this construct, we assessed factorial and construct validities of the PA-related neighbourhood informal social control scale for parents of pre-schoolers (PANISC-PP). In 2013-2014, Hong Kong primary caregivers (n=394) of 3-5 year-old children completed a socio-demographic questionnaire, the preliminary version of the PANISC-PP, and self-report measures of theoretical neighbourhood correlates of PA-related neighbourhood informal social control (perceived signs of physical and social disorder, community cohesion, perceived stranger danger, risk of unintentional injury and traffic safety). The fit of the data to an a priori measurement model of the PANISC-PP was examined using confirmatory factor analyses. As the a priori model showed inadequate fit to the data, the factor structure was re-specified based on theoretical considerations. The final measurement models of the PANISC-PP showed acceptable fit to the data and consisted of three correlated latent factors: "General informal supervision", "Civic engagement for the creation of a better neighbourhood environment" and "Educating and assisting neighbourhood children". The internal reliability of the subscales was good (Cronbach's α values 0.82-0.89). Generalised additive mixed models indicated that all subscales were positively associated with community cohesion and scores on the subscale "Educating and assisting neighbourhood children" were related in the expected direction to all indicators of traffic and personal safety, supporting construct validity of the PANISC-PP. This study suggests that the PANISC-PP is a reliable and valid instrument for assessing parents' perceived neighbourhood informal social control related to pre-schoolers' PA.

The targeting expression of the vascular endothelial growth factor gene in endothelial cells regulated by HRE.ppET-1.

PubMed

Zheng, Xiangrong; Zhang, Shangshang; Yang, Yujia; Wang, Xia; Zhong, Le; Yu, Xiaohe

2008-11-01

The success of gene therapy depends largely on the efficacy of gene delivery vector systems that can deliver genes to target organs or cells selectively and efficiently with minimal toxicity. Here, we show that by using the HRE.ppET-1 regulatory element, we were able to restrict expression of the transgene of vascular endothelial growth factor (VEGF) to endothelial cells exclusively in hypoxic conditions. Eukaryotic expression vectors such as pEGFP-HRE.ppET-1, pcDNA3.1-VEGF+Pa, pcDNA3.1-ppET-1+ EGF+Pa, and pcDNA3.1-HRE.ppET-1+VEGF+Pa were constructed by using a series of nuclear molecule handling methods like PCR, enzyme digestion. The recombinant vectors were transfected into HUVEC cells and HL7702 cells by the lipofectin method. GFP expression was observed with a fluorescence microscope to validate the specificity of expression in endothelial cells under the regulation of HRE.ppET-1 element. Cobalt chloride (final concentration 100 mumol/L) was added to the medium to mimic hypoxia in vitro. After transfection of vectors, the expression of VEGF mRNA was detected by RT-PCR, and the expression of VEGF was detected by Western blotting and ELISA methods under normoxia and hypoxia, respectively. The cell proliferation rate was detected by the MTT test. The expression of GFP revealed that the exterior gene was transcripted effectively in endothelial cells regulated by the HRE.ppET-1 element, while the expression of GFP was very weak in nonendothelial cells. The results of RT-PCR, Western blotting and ELISA showed that VEGF gene expression in the pcDNA3.1-HRE.ppET-1+VEGF+Pa group and in the pcDNA3.1-ppET-1+VEGF+Pa group was higher in hypoxia than it was in normoxia (P<0.05). The MTT test showed that the proliferation rate of HUVEC transfected with HPVA under hypoxia exceeded that of the control group. We conclude that the HRE.ppET-1 element was expressed specifically in endothelial cells, and can increase the expression of VEGF in hypoxia and stimulate proliferation of endothelial cells. Taking advantage of these facts could greatly improve the efficiency of gene therapy. The vector would be valuable for various gene transfer studies targeting endothelial cells.

Dormancy-Associated MADS-Box (DAM) and the Abscisic Acid Pathway Regulate Pear Endodormancy Through a Feedback Mechanism.

PubMed

Tuan, Pham Anh; Bai, Songling; Saito, Takanori; Ito, Akiko; Moriguchi, Takaya

2017-08-01

In the pear 'Kosui' (Pyrus pyrifolia Nakai), the dormancy-associated MADS-box (PpDAM1 = PpMADS13-1) gene has been reported to play an essential role in bud endodormancy. Here, we found that PpDAM1 up-regulated expression of 9-cis-epoxycarotenoid dioxygenase (PpNCED3), which is a rate-limiting gene for ABA biosynthesis. Transient assays with a dual luciferase reporter system (LUC assay) and electrophoretic mobility shift assay (EMSA) showed that PpDAM1 activated PpNCED3 expression by binding to the CArG motif in the PpNCED3 promoter. PpNCED3 expression was increased toward endodormancy release in lateral flower buds of 'Kosui', which is consistent with the induced levels of ABA, its catabolism (ABA 8'-hydroxylase) and signaling genes (type 2C protein phosphatase genes and SNF1-related protein kinase 2 genes). In addition, we found that an ABA response element (ABRE)-binding transcription factor, PpAREB1, exhibiting high expression concomitant with endodormancy release, bound to three ABRE motifs in the promoter region of PpDAM1 and negatively regulated its activity. Taken together, our results suggested a feedback regulation between PpDAM1 and the ABA metabolism and signaling pathway during endodormancy of pear. This first evidence of an interaction between a DAM and ABA biosynthesis in vitro will provide further insights into bud endodormancy regulatory mechanisms of deciduous trees including pear. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs

PubMed Central

Waadt, Rainer; Schroeder, Julian I.

2016-01-01

The phytohormone abscisic acid (ABA) is critical to plant development and stress responses. Abiotic stress triggers an ABA signal transduction cascade, which is comprised of the core components PYL/RCAR ABA receptors, PP2C-type protein phosphatases, and protein kinases. Small GTPases of the ROP/RAC family act as negative regulators of ABA signal transduction. However, the mechanisms by which ABA controls the behavior of ROP/RACs have remained unclear. Here, we show that an Arabidopsis guanine nucleotide exchange factor protein RopGEF1 is rapidly sequestered to intracellular particles in response to ABA. GFP-RopGEF1 is sequestered via the endosome-prevacuolar compartment pathway and is degraded. RopGEF1 directly interacts with several clade A PP2C protein phosphatases, including ABI1. Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated degradation. Interestingly, ABA-mediated degradation of RopGEF1 also plays an important role in ABA-mediated inhibition of lateral root growth. The presented findings point to a PP2C-RopGEF-ROP/RAC control loop model that is proposed to aid in shutting off ABA signal transduction, to counteract leaky ABA signal transduction caused by “monomeric” PYL/RCAR ABA receptors in the absence of stress, and facilitate signaling in response to ABA. PMID:27192441

The protein phosphatase 2A catalytic subunit StPP2Ac2b acts as a positive regulator of tuberization induction in Solanum tuberosum L.

PubMed

Muñiz García, María Noelia; Muro, María Catalina; Mazzocchi, Luciana Carla; País, Silvia Marina; Stritzler, Margarita; Schlesinger, Mariana; Capiati, Daniela Andrea

2017-02-01

This study provides the first genetic evidence for the role of PP2A in tuberization, demonstrating that the catalytic subunit StPP2Ac2b positively modulates tuber induction, and that its function is related to the regulation of gibberellic acid metabolism. The results contribute to a better understanding of the molecular mechanism controlling tuberization induction, which remains largely unknown. The serine/threonine protein phosphatases type 2A (PP2A) are implicated in several physiological processes in plants, playing important roles in hormone responses. In cultivated potato (Solanum tuberosum), six PP2A catalytic subunits (StPP2Ac) were identified. The PP2Ac of the subfamily I (StPP2Ac1, 2a and 2b) were suggested to be involved in the tuberization signaling in leaves, where the environmental and hormonal signals are perceived and integrated. The aim of this study was to investigate the role of PP2A in the tuberization induction in stolons. We selected one of the catalytic subunits of the subfamily I, StPP2Ac2b, to develop transgenic plants overexpressing this gene (StPP2Ac2b-OE). Stolons from StPP2Ac2b-OE plants show higher tuber induction rates in vitro, as compared to wild type stolons, with no differences in the number of tubers obtained at the end of the process. This effect is accompanied by higher expression levels of the gibberellic acid (GA) catabolic enzyme StGA2ox1. GA up-regulates StPP2Ac2b expression in stolons, possibly as part of the feedback system by which the hormone regulates its own level. Sucrose, a tuber-promoting factor in vitro, increases StPP2Ac2b expression. We conclude that StPP2Ac2b acts in stolons as a positive regulator tuber induction, integrating different tuberization-related signals mainly though the modulation of GA metabolism.

Peach MYB7 activates transcription of the proanthocyanidin pathway gene encoding leucoanthocyanidin reductase, but not anthocyanidin reductase

PubMed Central

Zhou, Hui; Lin-Wang, Kui; Liao, Liao; Gu, Chao; Lu, Ziqi; Allan, Andrew C.; Han, Yuepeng

2015-01-01

Proanthocyanidins (PAs) are a group of natural phenolic compounds that have a great effect on both flavor and nutritious value of fruit. It has been shown that PA synthesis is regulated by R2R3-MYB transcription factors (TFs) via activation of PA-specific pathway genes encoding leucoanthocyanidin reductase and anthocyanidin reductase. Here, we report the isolation and characterization of a MYB gene designated PpMYB7 in peach. The peach PpMYB7 represents a new group of R2R3-MYB genes regulating PA synthesis in plants. It is able to activate transcription of PpLAR1 but not PpANR, and has a broader selection of potential bHLH partners compared with PpMYBPA1. Transcription of PpMYB7 can be activated by the peach basic leucine-zipper 5 TF (PpbZIP5) via response to ABA. Our study suggests a transcriptional network regulating PA synthesis in peach, with the results aiding the understanding of the functional divergence between R2R3-MYB TFs in plants. PMID:26579158

Amyloid-β production via cleavage of amyloid-β protein precursor is modulated by cell density.

PubMed

Zhang, Can; Browne, Andrew; Divito, Jason R; Stevenson, Jesse A; Romano, Donna; Dong, Yuanlin; Xie, Zhongcong; Tanzi, Rudolph E

2010-01-01

Mounting evidence suggests that Alzheimer's disease (AD) is caused by the accumulation of the small peptide, amyloid-β (Aβ), a proteolytic cleavage product of amyloid-β protein precursor (AβPP). Aβ is generated through a serial cleavage of AβPP by β- and γ-secretase. Aβ40 and Aβ42 are the two main components of amyloid plaques in AD brains, with Aβ42 being more prone to aggregation. AβPP can also be processed by α-secretase, which cleaves AβPP within the Aβ sequence, thereby preventing the generation of Aβ. Little is currently known regarding the effects of cell density on AβPP processing and Aβ generation. Here we assessed the effects of cell density on AβPP processing in neuronal and non-neuronal cell lines, as well as mouse primary cortical neurons. We found that decreased cell density significantly increases levels of Aβ40, Aβ42, total Aβ, and the ratio of Aβ42: Aβ40. These results also indicate that cell density is a significant modulator of AβPP processing. Overall, these findings carry profound implications for both previous and forthcoming studies aiming to assess the effects of various conditions and genetic/chemical factors, e.g., novel drugs on AβPP processing and Aβ generation in cell-based systems. Moreover, it is interesting to speculate whether cell density changes in vivo may also affect AβPP processing and Aβ levels in the AD brain.

The Evolution of Soviet Requirements for Naval Forces - Solving the Problems of the Early 1960s.

DTIC Science & Technology

1982-12-01

the military sector ) or more than that response (additional factors having served as stimuli). And even where the magnitude of expenditures for...34Alternative Approaches to Attrition Utgoff. Kathy and Thaler, Dick, "The Economicos of Multi Year Minagemont," 30 pp., Jan 1982 (Iontracting," 47 pp

FOXA1 and SOX9 Expression in the Developing Urogenital Sinus of the Tammar Wallaby (Macropus eugenii).

PubMed

Gamat, Melissa; Chew, Keng Yih; Shaw, Geoffrey; Renfree, Marilyn B

2015-01-01

The mammalian prostate is a compact structure in humans but multi-lobed in mice. In humans and mice, FOXA1 and SOX9 play pivotal roles in prostate morphogenesis, but few other species have been examined. We examined FOXA1 and SOX9 in the marsupial tammar wallaby, Macropus eugenii, which has a segmented prostate more similar to human than to mouse. In males, prostatic budding in the urogenital epithelium (UGE) was initiated by day 24 postpartum (pp), but in the female the UGE remained smooth and had begun forming the marsupial vaginal structures. FOXA1 was upregulated in the male urogenital sinus (UGS) by day 51 pp, whilst in the female UGS FOXA1 remained basal. FOXA1 was localised in the UGE in both sexes between day 20 and 80 pp. SOX9 was upregulated in the male UGS at day 21-30 pp and remained high until day 51-60 pp. SOX9 protein was localised in the distal tips of prostatic buds which were highly proliferative. The persistent upregulation of the transcription factors SOX9 and FOXA1 after the initial peak and fall of androgen levels suggest that in the tammar, as in other mammals, these factors are required to sustain prostate differentiation, development and proliferation as androgen levels return to basal levels. © 2015 S. Karger AG, Basel.

Ongoing advances in quantitative PpIX fluorescence guided intracranial tumor resection (Conference Presentation)

NASA Astrophysics Data System (ADS)

Olson, Jonathan D.; Kanick, Stephen C.; Bravo, Jaime J.; Roberts, David W.; Paulsen, Keith D.

2016-03-01

Aminolevulinc-acid induced protoporphyrin IX (ALA-PpIX) is being investigated as a biomarker to guide neurosurgical resection of brain tumors. ALA-PpIX fluorescence can be observed visually in the surgical field; however, raw fluorescence emissions can be distorted by factors other than the fluorophore concentration. Specifically, fluorescence emissions are mixed with autofluorescence and attenuated by background absorption and scattering properties of the tissue. Recent work at Dartmouth has developed advanced fluorescence detection approaches that return quantitative assessments of PpIX concentration, which are independent of background optical properties. The quantitative fluorescence imaging (qFI) approach has increased sensitivity to residual disease within the resection cavity at the end of surgery that was not visible to the naked eye through the operating microscope. This presentation outlines clinical observations made during an ongoing investigation of ALA-PpIX based guidance of tumor resection. PpIX fluorescence measurements made in a wide-field hyperspectral imaging approach are co-registered with point-assessment using a fiber optic probe. Data show variations in the measured PpIX accumulation among different clinical tumor grades (i.e. high grade glioma, low grade glioma), types (i.e. primary tumors. metastases) and normal structures of interest (e.g. normal cortex, hippocampus). These results highlight the contrast enhancement and underscore the potential clinical benefit offered from quantitative measurements of PpIX concentration during resection of intracranial tumors.

Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex.

PubMed

Hiraga, Shin-Ichiro; Alvino, Gina M; Chang, Fujung; Lian, Hui-Yong; Sridhar, Akila; Kubota, Takashi; Brewer, Bonita J; Weinreich, Michael; Raghuraman, M K; Donaldson, Anne D

2014-02-15

Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.

Abscisic acid affects transcription of chloroplast genes via protein phosphatase 2C-dependent activation of nuclear genes: repression by guanosine-3'-5'-bisdiphosphate and activation by sigma factor 5.

PubMed

Yamburenko, Maria V; Zubo, Yan O; Börner, Thomas

2015-06-01

Abscisic acid (ABA) represses the transcriptional activity of chloroplast genes (determined by run-on assays), with the exception of psbD and a few other genes in wild-type Arabidopsis seedlings and mature rosette leaves. Abscisic acid does not influence chloroplast transcription in the mutant lines abi1-1 and abi2-1 with constitutive protein phosphatase 2C (PP2C) activity, suggesting that ABA affects chloroplast gene activity by binding to the pyrabactin resistance (PYR)/PYR1-like or regulatory component of ABA receptor protein family (PYR/PYL/RCAR) and signaling via PP2Cs and sucrose non-fermenting protein-related kinases 2 (SnRK2s). Further we show by quantitative PCR that ABA enhances the transcript levels of RSH2, RSH3, PTF1 and SIG5. RelA/SpoT homolog 2 (RSH2) and RSH3 are known to synthesize guanosine-3'-5'-bisdiphosphate (ppGpp), an inhibitor of the plastid-gene-encoded chloroplast RNA polymerase. We propose, therefore, that ABA leads to an inhibition of chloroplast gene expression via stimulation of ppGpp synthesis. On the other hand, sigma factor 5 (SIG5) and plastid transcription factor 1 (PTF1) are known to be necessary for the transcription of psbD from a specific light- and stress-induced promoter (the blue light responsive promoter, BLRP). We demonstrate that ABA activates the psbD gene by stimulation of transcription initiation at BLRP. Taken together, our data suggest that ABA affects the transcription of chloroplast genes by a PP2C-dependent activation of nuclear genes encoding proteins involved in chloroplast transcription. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Plasma fatty acid ethanolamides are associated with postprandial triglycerides, ApoCIII and ApoE in humans consuming high fructose corn syrup-sweetened beverage.

PubMed

Allister Price, Candice; Argueta, Donovan A; Medici, Valentina; Bremer, Andrew A; Lee, Vivien; Nunez, Marinelle V; Chen, Guoxia X; Keim, Nancy L; Havel, Peter J; Stanhope, Kimber L; DiPatrizio, Nicholas V

2018-04-10

Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages (SSB) increases risk factors involved in the development of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD). Our previous study demonstrated that when compared to aspartame (Asp), two weeks of high-fructose corn syrup (HFCS)-sweetened beverages provided at 25% of daily energy requirement (Ereq) was associated with increased body weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors in young adults. The fatty acid ethanolamide, anandamide (AEA), and the monoacylglycerol, 2-arachidonoyl-sn-glycerol (2-AG), are two primary endocannabinoids (ECs) that play a role in regulating food intake, increasing adipose storage, and regulating lipid metabolism. Therefore, we measured plasma concentrations of ECs and their analogs, oleoylethanolamide (OEA), docosahexaenoyl ethanolamide (DHEA), and docosahexaenoyl glycerol (DHG), in participants from our previous study who consumed HFCS- or Asp-sweetened beverages to determine associations with weight gain and CVD risk factors. Two-week exposure to either HFCS- or Asp-sweetened beverages resulted in significant differences in the changes in fasting levels of OEA and DHEA between groups after the testing period. Subjects who consumed Asp, but not HFCS, displayed a reduction in AEA, OEA and DHEA after the testing period. In contrast, there were significant positive relationships between AEA, OEA, and DHEA versus ppTG, ppApoCIII and ppApoE in those consuming HFCS, but not in those consuming Asp. Our findings reveal previously unknown associations between circulating ECs and EC-related molecules with markers of lipid metabolism and CVD risk after HFCS-consumption.

Which type of placenta previa requires blood transfusion more frequently? A new concept of indiscernible edge total previa.

PubMed

Baba, Yosuke; Takahashi, Hironori; Ohkuchi, Akihide; Usui, Rie; Matsubara, Shigeki

2016-11-01

During cesarean section (CS) for placenta previa (PP), the size/area/portion of the lower uterine segment occupied by the placenta may affect the bleeding amount and the subsequent need for a blood transfusion (BT). We propose a new concept, indiscernible edge total PP (IEPP), when vaginal ultrasound does not discern the lower placental edge because the placenta covers the visible lower segment. We characterized IEPP, focusing on its allogeneic BT requirement. We classified PP (n = 307) into four types: marginal, partial, discernible edge total PP (DEPP) and IEPP: internal ostium (os)-placental edge distance measurable or unmeasurable on vaginal ultrasound in DEPP or IEPP, respectively. We determined the clinical characteristics according to the four types; the relationship between the intraoperative blood loss and os-edge distance in DEPP; and risk factors for allogeneic BT. The following were significantly higher/larger in cases of IEPP: previous CS; anterior placentation; lacunae; elective cesarean hysterectomy; intraoperative blood loss; autologous BT; allogeneic BT; intensive care unit admission; and an abnormally invasive placenta (AIP). In DEPP, the os-edge distance was weakly correlated with the bleeding amount (r = 0.214). Multivariate logistic regression analysis showed that previous CS, lacunae, AIP and IEPP were independent risk factors for allogeneic BT (odds ratios 3.8, 3.1, 13.8 and 4.6, respectively). After excluding patients undergoing hemostatic procedures during CS, IEPP remained the only independent risk factor for allogeneic BT (odds ratio 5.2). The new concept of IEPP may be useful for predicting BT in CS for patients with PP. © 2016 Japan Society of Obstetrics and Gynecology.

Effect of pre- and postpartum supplementation with lipid-encapsulated conjugated linoleic acid on reproductive performance and the growth hormone-insulin-like growth factor-I axis in multiparous high-producing dairy cows.

PubMed

Csillik, Z; Faigl, V; Keresztes, M; Galamb, E; Hammon, H M; Tröscher, A; Fébel, H; Kulcsár, M; Husvéth, F; Huszenicza, Gy; Butler, W R

2017-07-01

The objective of the study was to evaluate the effect of prepartum and postpartum (PP) supplementation with 2 isomers of conjugated linoleic acid (CLA) on reproductive parameters and some related metabolic factors in dairy cows. High-producing, multiparous Holstein Friesian cows (n = 60) were allotted to 3 treatment groups: the CLA1 group (n = 20) was supplemented with 70 g of lipid-encapsulated CLA providing 7 g each of cis-9,trans-11 and trans-10,cis-12 CLA from d 21 (d 21) before expected calving until d 7 after artificial insemination (AI), that is, until 77 to 91 d PP; the CLA2 group (n = 20) was supplemented with the same amount of CLA beginning at calving until d 7 after AI; and the control group (n = 20) received an isocaloric, isonitrogenous, and isolipidic diet. Blood samples were taken weekly to measure glucose, insulin, insulin-like growth factor-I (IGF-I), and leptin. Liver biopsy was performed in 10 cows per group for growth hormone receptor 1A and IGF-I mRNA analyses. At d 49 to 63 PP, ovulation was synchronized with the Pre-Synch protocol followed by fixed-time AI. Milk progesterone was monitored from calving until d 35 post-AI. Cows returning to estrus following AI were inseminated. Supplementation with CLA before calving improved the recovery of plasma leptin levels in the early PP period (from the day of calving until wk 3 PP; treatment effect). Later PP (wk 5), plasma IGF-I, and leptin remained significantly higher in both CLA1 and CLA2 groups compared with control, although hepatocellular IGF-I mRNA was not different among groups. Plasma IGF-I levels remained higher in both CLA-treated groups on the day of AI. Growth hormone receptor 1A mRNA levels in hepatic tissue decreased in all groups, reaching a nadir in the first week PP. Days to first PP ovulation did not differ between groups; however, both supplemented groups conceived earlier compared with control (d 97 ± 19, d 97 ± 23, and d 113 ± 30 for CLA1, CLA2, and control, respectively). Plasma progesterone concentration was higher in both supplemented groups on d 2 to 5 following the synchronized ovulation than in controls. We concluded that CLA supplementation around calving alters PP metabolic signals as reflected by higher plasma leptin and IGF-I levels. Conjugated linoleic acid stimulated early luteal function and reduced the PP interval to conception. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Baseline and projected future carbon storage and carbon fluxes in ecosystems of Hawai‘i

USGS Publications Warehouse

Selmants, Paul C.; Giardina, Christian P.; Jacobi, James D.; Zhu, Zhiliang

2017-05-04

This assessment was conducted to fulfill the requirements of section 712 of the Energy Independence and Security Act of 2007 and to improve understanding of factors influencing carbon balance in ecosystems of Hawai‘i. Ecosystem carbon storage, carbon fluxes, and carbon balance were examined for major terrestrial ecosystems on the seven main Hawaiian islands in two time periods: baseline (from 2007 through 2012) and future (projections from 2012 through 2061). The assessment incorporated observed data, remote sensing, statistical methods, and simulation models. The national assessment has been completed for the conterminous United States, using methodology described in SIR 2010-5233, with results provided in three regional reports (PP 1804, PP 1797, and PP 1897), and for Alaska, with results provided in PP 1826.

A case report of uncompensated alkalosis induced by daily plasmapheresis in a patient with thrombotic thrombocytopenic purpura.

PubMed

Nagai, Yoshiko; Itabashi, Mitsuyo; Mizutani, Mayuko; Ogawa, Tetsuya; Yumura, Wako; Tsuchiya, Ken; Nitta, Kosaku

2008-02-01

Plasmapheresis (PP) is widely known as the standard therapy for thrombotic thrombocytopenic purpura (TTP). Citrate is used as an anticoagulant in fresh frozen plasma, and the large amount of citrate infused during PP induces metabolic alkalosis. A 29-year-old woman was diagnosed with TTP associated with systemic lupus erythematosus, and was treated by daily PP in addition to a steroid, an immunosuppressant, vincristine, and cyclophosphamide. Uncompensated alkalosis caused by a combination of metabolic and respiratory alkalosis developed after artificial ventilation was discontinued. Her metabolic status improved after controlling her respiratory status and the activity of the TTP. Metabolic alkalosis is a common complication in TTP patients treated by frequent PP, but several factors that affect metabolic status may aggravate the alkalosis and induce uncompensated alkalosis.

Key factors limiting the open circuit voltage of n(+)pp(+) indium phosphide solar cells

NASA Technical Reports Server (NTRS)

Goradia, Chandra; Thesling, William; Weinberg, Irving

1991-01-01

Solar cells made from gallium arsenide (GaAs), with a room temperature bandgap of E(sub g) = 1.43 eV have exhibited the best measured open circuit voltage (V sub OC) of 1.05 V at 1 AMO, 25 C. The material InP is in many ways similar to GaAs. A simple calculation comparing InP to GaAs then shows that solar cells made from InP, with E(sub g) = 1.35 at 300 K, should exhibit the best measured (V sub OC) of approximately 950 mV at 1 AMO, 300 K. However, to date, the best measured V(sub OC) for InP solar cells made by any fabrication method is 899 mV at AM1.5, 25 C which would translate to 912 mV at 1 AMO, 25 C. The V(sub OC) of an n(+)pp(+) InP solar cell is governed by several factors. Of these, some factors, such as the thickness and doping of the emitter and base regions, are easily controlled and can be adjusted to desired values dictated by a good performance optimizing model. Such factors were not considered. There are other factors which also govern V(sub OC), and their values are not so easily controlled. The primary ones among these are (1) the indirect or Hall-Shockley-Read lifetimes in the various regions of the cell, (2) the low-doping intrinsic carrier concentration n(sub i) of the InP material, (3) the heavy doping factors in the emitter and BSF regions, and (4) the front surface recombination velocity S(sub F). The influence of these latter factors on the V(sub OC) of the n(+)pp(+) InP solar cell and the results were used to produce a near-optimum design of the n(+)pp(+) InP solar cell.

Negative Regulation of Abscisic Acid Signaling by the Fagus sylvatica FsPP2C1 Plays A Role in Seed Dormancy Regulation and Promotion of Seed Germination1

PubMed Central

González-García, Mary Paz; Rodríguez, Dolores; Nicolás, Carlos; Rodríguez, Pedro Luis; Nicolás, Gregorio; Lorenzo, Oscar

2003-01-01

FsPP2C1 was previously isolated from beech (Fagus sylvatica) seeds as a functional protein phosphatase type-2C (PP2C) with all the conserved features of these enzymes and high homology to ABI1, ABI2, and PP2CA, PP2Cs identified as negative regulators of ABA signaling. The expression of FsPP2C1 was induced upon abscisic acid (ABA) treatment and was also up-regulated during early weeks of stratification. Furthermore, this gene was specifically expressed in ABA-treated seeds and was hardly detectable in vegetative tissues. In this report, to provide genetic evidence on FsPP2C1 function in seed dormancy and germination, we used an overexpression approach in Arabidopsis because transgenic work is not feasible in beech. Constitutive expression of FsPP2C1 under the cauliflower mosaic virus 35S promoter confers ABA insensitivity in Arabidopsis seeds and, consequently, a reduced degree of seed dormancy. Additionally, transgenic 35S:FsPP2C1 plants are able to germinate under unfavorable conditions, as inhibitory concentrations of mannitol, NaCl, or paclobutrazol. In vegetative tissues, Arabidopsis FsPP2C1 transgenic plants show ABA-resistant early root growth and diminished induction of the ABA-response genes RAB18 and KIN2, but no effect on stomatal closure regulation. Seed and vegetative phenotypes of Arabidopsis 35S:FsPP2C1 plants suggest that FsPP2C1 negatively regulates ABA signaling. The ABA inducibility of FsPP2C1 expression, together with the transcript accumulation mainly in seeds, suggest that it could play an important role modulating ABA signaling in beechnuts through a negative feedback loop. Finally, we suggest that negative regulation of ABA signaling by FsPP2C1 is a factor contributing to promote the transition from seed dormancy to germination during early weeks of stratification. PMID:12970481

Nutritional geometry of calcium and phosphorus nutrition in broiler chicks. Growth performance, skeletal health and intake arrays.

PubMed

Bradbury, E J; Wilkinson, S J; Cronin, G M; Thomson, P C; Bedford, M R; Cowieson, A J

2014-07-01

The interaction between calcium (Ca) and non-phytate phosphorus (nPP) in broiler nutrition and skeletal health is highly complex with many factors influencing their digestion, absorption and utilisation. The use of an investigative model such as the geometric framework allows a graphical approach to explore these complex interactions. A total of 600 Ross 308-day-old male broiler chicks were allocated to one of 15 dietary treatments with five replicates and eight birds per replicate. Dietary treatments were formulated to one of three total densities of total Ca+nPP; high (15 g/kg), medium (13.5 g/kg) and low (12 g/kg) and at each density there were five different ratios of Ca : nPP (4, 2.75, 2.1, 1.5 and 1.14 : 1). Weekly performance data was collected and at the end of the experiment birds were individually weighed and the right leg removed for tibia ash analysis. Skeletal health was assessed using the latency to lie (LTL) at day 27. At low Ca and high nPP as well as high Ca and low nPP diets, birds had reduced feed intake, BW gain, poorer feed efficiency and lower tibia ash, resulting in a significant interaction between dietary Ca and nPP (P<0.05). LTL times were negatively influenced by diets having either a broad ratio (high Ca, low nPP) or too narrow a ratio (low Ca, high nPP) indicating that shorter LTL times may be influenced by the ratio of Ca : nPP rather than absolute concentrations of either mineral. The calculated intake arrays show that broilers more closely regulate Ca intake than nPP intake. Broilers are willing to over consume nPP to defend a Ca intake target more so than they are willing to over consume Ca to defend an nPP target. Overall dietary nPP was more influential on performance metrics, however, from the data it may appear that birds prioritise Ca intake over nPP and broadly ate to meet this requirement. As broilers are more willing to eat to a Ca intake target rather than an nPP intake target, this emphasises the importance of formulating diets to a accurately balanced density of Ca : nPP considering the biological importance of both minerals.

Effects of Polypropylene Orientation on Mechanical and Heat Seal Properties of Polymer-Aluminum-Polymer Composite Films for Pouch Lithium-Ion Batteries.

PubMed

Zeng, Fangxinyu; Chen, Jinyao; Yang, Feng; Kang, Jian; Cao, Ya; Xiang, Ming

2018-01-16

In this study, polyamide-aluminum foil-polypropylene (PA-Al-PP) composite films with different orientation status of the PP layer were prepared, and their morphology, tensile, peeling and heat seal behavior were studied. The comparative study of tensile and fracture behaviors of single-layer film of PA, Al and PP, as well as the composite films of PA-Al, PP-Al and PA-Al-PP revealed that in PA-Al-PP composite film, the PA layer with the highest tensile strength can share the tensile stress from the Al layer during stretching, while the PP layer with the lowest tensile strength can prevent further development of the small cracks on boundary of the Al layer during stretching. Moreover, the study of heat seal behavior suggested that both the orientation status and the heat seal conditions were important factors in determining the heat seal strength ( HSS ) and failure behavior of the sample. Four failure types were observed, and a clear correspondence between HSS and failure types was found. The results also elucidated that for the composite film, only in the cases where the tensile stress was efficiently released by each layer during HSS measurement could the composite film exhibit desired high HSS that was even higher than its tensile strength.

Enhanced ethylene responsiveness in the Arabidopsis eer1 mutant results from a loss-of-function mutation in the protein phosphatase 2A A regulatory subunit, RCN1.

PubMed

Larsen, Paul Brian; Cancel, Jesse Daniel

2003-06-01

Ethylene signaling in Arabidopsis begins with a family of five ethylene receptors that regulate the activity of the Raf-like kinase, CTR1. Recent work to identify novel factors required for modulating ethylene signaling resulted in the isolation of enhanced ethylene response 1 (eer1), a mutant that displays both increased sensitivity and increased amplitude of response to ethylene. Molecular cloning of eer1 reveals that its mutant phenotype results from a loss-of-function mutation in the previously characterized RCN1, one of three PP2A A regulatory subunits in Arabidopsis. Our analysis shows that neither RCN1 expression nor PP2A activity is regulated by ethylene. Instead, we found that Arabidopsis PP2A-1C, a PP2A catalytic subunit previously characterized as interacting with RCN1, associates strongly with the kinase domain of CTR1 in vitro. This likely represents a role for PP2A in modulation of CTR1 activity because an in vitro kinase assay did not reveal phosphorylation of either RCN1 or PP2A-1C by CTR1, indicating that neither of them is a substrate for CTR1. PP2A activity is required for Ras-dependent activation of mammalian Raf, with reductions in PP2A activity significantly compromising the effectiveness of this mechanism. Our genetic and biochemical results suggest that a similar requirement for PP2A activity exists for ethylene signaling, with loss-of-function mutations affecting PP2A activity possibly reducing the effectiveness of CTR1 activation, thus lowering the threshold required for manifestation of ethylene response.

PP2A regulates SCF-induced cardiac stem cell migration through interaction with p38 MAPK.

PubMed

Wang, Ying; Xia, Yanli; Kuang, Dong; Duan, Yaqi; Wang, Guoping

2017-12-15

Previous studies have shown that stem cell factor (SCF) induces the migration of cardiac stem cells (CSCs) and helps to repair myocardial infarctions. Earlier studies on the migration mechanism only focused on the activation of kinases; here, we aimed to explore the functional role of protein phosphatase 2A (PP2A) in SCF-induced CSC migration. CSCs were treated with SCF, PP2A enzymatic activity was measured, the phosphorylation levels of PP2A, p38 MAPK and cofilin were evaluated using western blot. Transwell assay was used to determine the migratory ability of CSCs. In vitro, SCF induced the phosphorylation of p38 MAPK and cofilin, leading to the migration of CSCs. Cofilin acted as a downstream signal of p38 MAPK. PP2A was involved in this process. Further studies revealed that PP2A was inactivated via phosphorylation at Tyr307 by SCF and the inactivation/phosphorylation was mediated by activated p38 MAPK, as p38 MAPK inhibitor SB203580 or siRNA prevented SCF-induced inactivation and phosphorylation of PP2A. When CSCs were pretreated with PP2A inhibitor (okadaic acid, OA), SCF-induced CSC migration and the downstream signals were enhanced, and the enhancement was reversed when p38 MAPK was blocked. Additionally, co-immunoprecipitation showed a direct interaction of PP2A with p38 MAPK. Our results indicated that PP2A regulated the SCF-induced activation of p38 MAPK/cofilin signaling pathway and subsequent migration of CSCs by interaction with p38 MAPK. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Time trends in utilization of G-CSF prophylaxis and risk of febrile neutropenia in a Medicare population receiving adjuvant chemotherapy for early-stage breast cancer.

PubMed

Goyal, Ravi K; Tzivelekis, Spiros; Rothman, Kenneth J; Candrilli, Sean D; Kaye, James A

2018-02-01

The purpose of this study is to assess temporal trends in the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis and risk of febrile neutropenia (FN) among older women receiving adjuvant chemotherapy for early-stage breast cancer. Women aged ≥ 66 years with diagnosis of early-stage breast cancer who initiated selected adjuvant chemotherapy regimens were identified using the SEER-Medicare data from 2002 to 2012. Adjusted, calendar-year-specific proportions were estimated for use of G-CSF primary prophylaxis (PP) and secondary prophylaxis and FN risk in the first and the second/subsequent cycles during the first course of chemotherapy, using logistic regression models. calendar-year-specific mean probabilities were estimated with covariates set to modal values. Among 11,107 eligible patients (mean age 71.7 years), 74% received G-CSF in the first course of chemotherapy. Of all patients, 5819 (52%) received G-CSF PP, and among those not receiving G-CSF PP, only 5% received G-CSF secondary prophylaxis. The adjusted proportion using G-CSF PP increased from 6% in 2002 to 71% in 2012. During the same period, the adjusted risk of FN in the first cycle increased from 2% to 3%; the adjusted risk increased from 1.5% to 2.9% among those receiving G-CSF PP and from 2.3% to 3.5% among those not receiving G-CSF PP. The use of G-CSF PP increased substantially during the study period. Although channeling of higher-risk patients to treatment with G-CSF PP is expected, the adjusted risk of FN among patients treated with G-CSF PP tended to be lower than among those not receiving G-CSF PP.

Modulation of PPAR Expression and Activity in Response to Polyphenolic Compounds in High Fat Diets

PubMed Central

Domínguez-Avila, J. Abraham; González-Aguilar, Gustavo A.; Alvarez-Parrilla, Emilio; de la Rosa, Laura A.

2016-01-01

Peroxisome proliferator-activated receptors (PPAR) are transcription factors that modulate energy metabolism in liver, adipose tissue and muscle. High fat diets (HFD) can negatively impact PPAR expression or activity, favoring obesity, dyslipidemia, insulin resistance and other conditions. However, polyphenols (PP) found in vegetable foodstuffs are capable of positively modulating this pathway. We therefore focused this review on the possible effects that PP can have on PPAR when administered together with HFD. We found that PP from diverse sources, such as coffee, olives, rice, berries and others, are capable of inducing the expression of genes involved in a decrease of adipose mass, liver and serum lipids and lipid biosynthesis in animal and cell models of HFD. Since cells or gut bacteria can transform PP into different metabolites, it is possible that a synergistic or antagonistic effect ultimately occurs. PP molecules from vegetable sources are an interesting option to maintain or return to a state of energy homeostasis, possibly due to an adequate PPAR expression and activity. PMID:27367676

Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression

PubMed Central

Park, Mi-Ju; Lee, Kyu Sup; Yoon, Youngjin; Kim, Hyung Sik; Lee, Jun Hee; Kwon, Sang-Mo; Lee, Syng-Ook; Kim, Keuk-Jun; Baek, Jin-Ho; Ha, Ki-Tae

2016-01-01

In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins β3 and β5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells. PMID:26839969

Modulation of PPAR Expression and Activity in Response to Polyphenolic Compounds in High Fat Diets.

PubMed

Domínguez-Avila, J Abraham; González-Aguilar, Gustavo A; Alvarez-Parrilla, Emilio; de la Rosa, Laura A

2016-06-29

Peroxisome proliferator-activated receptors (PPAR) are transcription factors that modulate energy metabolism in liver, adipose tissue and muscle. High fat diets (HFD) can negatively impact PPAR expression or activity, favoring obesity, dyslipidemia, insulin resistance and other conditions. However, polyphenols (PP) found in vegetable foodstuffs are capable of positively modulating this pathway. We therefore focused this review on the possible effects that PP can have on PPAR when administered together with HFD. We found that PP from diverse sources, such as coffee, olives, rice, berries and others, are capable of inducing the expression of genes involved in a decrease of adipose mass, liver and serum lipids and lipid biosynthesis in animal and cell models of HFD. Since cells or gut bacteria can transform PP into different metabolites, it is possible that a synergistic or antagonistic effect ultimately occurs. PP molecules from vegetable sources are an interesting option to maintain or return to a state of energy homeostasis, possibly due to an adequate PPAR expression and activity.

Organochlorine pesticides accumulation and breast cancer: A hospital-based case-control study.

PubMed

He, Ting-Ting; Zuo, An-Jun; Wang, Ji-Gang; Zhao, Peng

2017-05-01

The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. We conducted a hospital-based case-control study in 56 patients with breast cancer and 46 patients with benign breast disease. We detected the accumulation level of several organochlorine pesticides products (β-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp'-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients using gas chromatography. Thereafter, we examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, we analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Our data showed that breast cancer patients suffered high accumulation levels of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp'-dichlorodiphenyldichloroethane were risk factors for breast cancer. Our results provide new evidence on etiology of breast cancer.

Organochlorine pesticide levels in umbilical cord blood of newborn in Veracruz, Mexico.

PubMed

Herrero-Mercado, Margarita; Waliszewski, S M; Caba, M; Martínez-Valenzuela, C; Hernández-Chalate, F

2010-10-01

Organochlorine pesticides accumulate in lipid rich compartments of organisms. During pregnancy, the compounds pass through the placental barrier appear in cord blood. The aim of this study was to monitor the levels of organochlorine pesticides in 70 umbilical cord blood samples taken during deliveries in Veracruz in 2009. For organochlorine pesticides, only the presence β-HCH (4%, 3.9 μg/L median concentration on wet weight), pp'DDE (100%, 0.7 μg/L) and pp'DDT (4%, 1.4 μg/L) were detected. The total pool of samples divided according to sex of new born babies, showed no statistical differences among median concentrations. The number of deliveries considered as a determinant contamination factor affirmed there were no statistical differences among median concentrations; however pp'DDE levels increased from the one to two childbirth groups. Age of pregnant women as a discriminate factor manifests in a significant increase in contamination levels among first, second and third tertile. In general, umbilical cord blood samples in Veracruz contained organochlorine pesticides, especially pp'DDE, confirming the presence of these compounds in the environment and their transfer from the mother to the developing fetus.

Predicting the pain continuum after adolescent idiopathic scoliosis surgery: A prospective cohort study

PubMed Central

Chidambaran, V.; Ding, L.; Moore, D.L.; Spruance, K.; Cudilo, E.M.; Pilipenko, V.; Hossain, M.; Sturm, P.; Kashikar-Zuck, S.; Martin, L.J.; Sadhasivam, S.

2017-01-01

Background Chronic postsurgical pain (CPSP) affects half a million children annually in the United States, with dire socioeconomic consequences, including long-term disability into adulthood. The few studies of CPSP in children are limited by sample size, follow-up duration, non-homogeneity of surgical procedure and factors evaluated. Methods In a prospective study of 144 adolescents undergoing a single major surgery (spine fusion), we evaluated demographic, perioperative, surgical and psychosocial factors as predictors of a continuum of postsurgical pain: immediate, pain maintenance at 2–3 months (chronic pain/CP) and persistence of pain a year (persistent pain/PP) after surgery. Results We found an incidence of 37.8% and 41.8% for CP and PP. CP and acute pain were both significant predictors for developing PP (p-value <0.001 and 0.003). Preoperative pain and higher postoperative opioid requirement was significantly associated with CP (p = 0.015, p = 0.002), while Childhood Anxiety Sensitivity Index (p = 0.002) and surgical duration (p = 0.014) predicted PP. The final regression models had reasonable predictive accuracy (c-statistic of 0.73 and 0.83 for CP and PP, respectively). Anxiety scores and catastrophizing for child and parent were found to be significantly correlated (p = 0.005, p = 0.013 respectively). Pain trajectories revealed that 65% of patients who developed PP reported CP and high pain trends; however, 33% of those who developed PP could not be identified using solely pain criteria. Conclusion Persistent postsurgical pain in children is a significant problem. It can be predicted in part by combinations of psychological and clinical variables, which may provide evidence-based measures to prevent development of CPSP in the future. Significance In a homogeneous cohort of adolescents undergoing spine fusion, we report a high incidence of persistent postsurgical pain (41.8%) predicted by child anxiety, perioperative pain, and surgical duration. Our results stress timely preventive and therapeutic strategies. PMID:28346762

The B55α Regulatory Subunit of Protein Phosphatase 2A Mediates Fibroblast Growth Factor-Induced p107 Dephosphorylation and Growth Arrest in Chondrocytes

PubMed Central

Daempfling, Lea

2013-01-01

Fibroblast growth factor (FGF)-induced growth arrest of chondrocytes is a unique cell type-specific response which contrasts with the proliferative response of most cell types and underlies several genetic skeletal disorders caused by activating FGF receptor (FGFR) mutations. We have shown that one of the earliest key events in FGF-induced growth arrest is dephosphorylation of the retinoblastoma protein (Rb) family member p107 by protein phosphatase 2A (PP2A), a ubiquitously expressed multisubunit phosphatase. In this report, we show that the PP2A-B55α holoenzyme (PP2A containing the B55α subunit) is responsible for this phenomenon. Only the B55α (55-kDa regulatory subunit, alpha isoform) regulatory subunit of PP2A was able to bind p107, and this interaction was induced by FGF in chondrocytes but not in other cell types. Small interfering RNA (siRNA)-mediated knockdown of B55α prevented p107 dephosphorylation and FGF-induced growth arrest of RCS (rat chondrosarcoma) chondrocytes. Importantly, the B55α subunit bound with higher affinity to dephosphorylated p107. Since the p107 region interacting with B55α is also the site of cyclin-dependent kinase (CDK) binding, B55α association may also prevent p107 phosphorylation by CDKs. FGF treatment induces dephosphorylation of the B55α subunit itself on several serine residues that drastically increases the affinity of B55α for the PP2A A/C dimer and p107. Together these observations suggest a novel mechanism of p107 dephosphorylation mediated by activation of PP2A through B55α dephosphorylation. This mechanism might be a general signal transduction pathway used by PP2A to initiate cell cycle arrest when required by external signals. PMID:23716589

The Relationship Between Pulse Pressure, the Estimated Glomerular Filtration Rate, and Urine Microalbumin/Creatinine Ratio in Korean Adults.

PubMed

Seong, Jeong Min; Park, Chang Eun; Gi, Mi Young; Sun, Kwang Soon; Kim, Yu Jeong; Yoon, Hyun

2017-01-01

Pulse pressure (PP) is a predictor of adverse outcomes in patients on haemodialysis. Thus, the present study was conducted to assess the relationship between PP, estimated glomerular filtration rate (eGFR), and urine microalbumin/creatinine ratio (uACR) in Korean adults. Data of 9,409 adults (4,206 men and 5,203 women) aged ≥ 20 years from the Sixth Korean National Health and Nutrition Examination Survey (2013-2014) were analyzed. A multivariate analysis revealed that systolic blood pressure (SBP) (β = -0.170, 95% confidence interval [CI], -0.216 to -0.159), diastolic blood pressure (DBP) (β = 0.088, 95% CI 0.108-0.200; p < 0.001), and PP (β = -0.134, 95% CI -0.215 to -0.157) were significant factors determining eGFR. In contrast, SBP (β = 0.152, 95% CI, 0.985-1.456; p < 0.001), DBP (β = -0.062, 95% CI -1.141 to -0.442; p < 0.001), and PP (β = 0.118, 95% CI 0.965-1.436; p < 0.001) were the significant factors determining uACR. The odds ratios (ORs) of a high PP (PP ≥ 60 mmHg) with a normal group [eGFR ≥ 60 ml/min/1.73 m2 and uACR < 30 mg/g] as a reference were significant for decreased eGFR [eGFR < 60 ml/min/1.73 m2, 1.484 (95% CI, 1.003-2.196)], elevated uACR [uACR ≥ 30 mg/g, 2.592 (95% CI, 2.085-3.223)], and decreased eGFR plus elevated uACR [eGFR < 60 ml/min/1.73 m2 and uACR ≥ 30 mg/g, 3.889 (95% CI, 2.519-6.004)]. Enhanced PP was associated with a decreased eGFR and an increase in uACR in Korean adults. In addition, the PP increased greatly when a decrease in eGFR and an increase in uACR appeared simultaneously. © 2017 The Author(s). Published by S. Karger AG, Basel.

Polypharmacy and Unplanned Hospitalizations in Patients with Rheumatoid Arthritis.

PubMed

Filkova, Maria; Carvalho, João; Norton, Sam; Scott, David; Mant, Tim; Molokhia, Mariam; Cope, Andrew; Galloway, James

2017-12-01

Polypharmacy (PP), the prescribing of multiple drugs for an individual, is rising in prevalence. PP associates with an increased risk of adverse drug reactions (ADR) and hospital admissions. We investigated the relationship between PP, characteristics of rheumatoid arthritis (RA), and the risk of unplanned hospital admissions. Patients from a hospital RA cohort were retrospectively analyzed. Information was collected from electronic medical records. Cox proportional hazards were used to compare hospitalization risk according to levels of PP. Admissions were adjudicated to determine whether an ADR was implicated. The study included 1101 patients; the mean number of all medications was 5. PP correlated with increasing age, disease duration, disease activity, and disability. At least 1 unplanned admission occurred for 16% of patients. Patients taking ≥ 10 medications had an adjusted HR for hospitalization of 3.1 (95% CI 2.1-4.5), compared to those taking 0-5 medications. Corticosteroid use associated with a doubling in adjusted risk of admission of 1.7 (95% CI 1.2-2.4). The most common reason for hospitalization was infection (28%). While in half of all admissions an ADR was a possible contributing factor, only 2% of admissions were found to directly result from an ADR. PP is common in RA and is a prognostic marker associated with increased risk of acute hospitalizations. Our data suggest that PP may be an indicator of comorbidity burden rather than a contributing cause of a drug-related toxicity. PP should be monitored to minimize inappropriate combination of prescribed medications. PP may be a useful predictor of clinical outcomes in epidemiologic studies.

Regulatory Subunit B′γ of Protein Phosphatase 2A Prevents Unnecessary Defense Reactions under Low Light in Arabidopsis1[W][OA

PubMed Central

Trotta, Andrea; Wrzaczek, Michael; Scharte, Judith; Tikkanen, Mikko; Konert, Grzegorz; Rahikainen, Moona; Holmström, Maija; Hiltunen, Hanna-Maija; Rips, Stephan; Sipari, Nina; Mulo, Paula; Weis, Engelbert; von Schaewen, Antje; Aro, Eva-Mari; Kangasjärvi, Saijaliisa

2011-01-01

Light is an important environmental factor that modulates acclimation strategies and defense responses in plants. We explored the functional role of the regulatory subunit B′γ (B′γ) of protein phosphatase 2A (PP2A) in light-dependent stress responses of Arabidopsis (Arabidopsis thaliana). The predominant form of PP2A consists of catalytic subunit C, scaffold subunit A, and highly variable regulatory subunit B, which determines the substrate specificity of PP2A holoenzymes. Mutant leaves of knockdown pp2a-b′γ plants show disintegration of chloroplasts and premature yellowing conditionally under moderate light intensity. The cell-death phenotype is accompanied by the accumulation of hydrogen peroxide through a pathway that requires CONSTITUTIVE EXPRESSION OF PR GENES5 (CPR5). Moreover, the pp2a-b′γ cpr5 double mutant additionally displays growth suppression and malformed trichomes. Similar to cpr5, the pp2a-b′γ mutant shows constitutive activation of both salicylic acid- and jasmonic acid-dependent defense pathways. In contrast to cpr5, however, pp2a-b′γ leaves do not contain increased levels of salicylic acid or jasmonic acid. Rather, the constitutive defense response associates with hypomethylation of DNA and increased levels of methionine-salvage pathway components in pp2a-b′γ leaves. We suggest that the specific B′γ subunit of PP2A is functionally connected to CPR5 and operates in the basal repression of defense responses under low irradiance. PMID:21571669

Structure-Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins.

PubMed

Twiner, Michael J; Doucette, Gregory J; Pang, Yucheng; Fang, Chao; Forsyth, Craig J; Miles, Christopher O

2016-11-04

Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2- epi -DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 > 2- epi -DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs' activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors.

Solid-state drawing of post-consumer isotactic poly(propylene): Effect of melt filtration and carbon black on structural and mechanical properties.

PubMed

Luijsterburg, B J; Jobse, P S; Spoelstra, A B; Goossens, J G P

2016-08-01

Post-consumer plastic waste obtained via mechanical recycling is usually applied in thick-walled products, because of the low mechanical strength due to the presence of contaminants. In fact, sorted post-consumer isotactic poly(propylene) (i-PP) can be considered as a blend of 95% i-PP and 5% poly(ethylene), with traces of poly(ethylene terephthalate) (PET). By applying a treatment such as solid-state drawing (SSD) after melt extrusion, the polymer chains can be oriented in one direction, thereby improving the stiffness and tensile strength. In this research, molecular processes such as crystal break-up and chain orientation of these complex blends were monitored as a function of draw ratio. The melt filter mesh size - used to exclude rigid PET particles - and the addition of carbon black (CB) - often added for coloration in the recycling industry - were varied to investigate their influence on the SSD process. This research shows that despite the blend complexity, the molecular processes during SSD compare to virgin i-PP and that similar draw ratios can be obtained (λmax=20), albeit at reduced stiffness and strength as a result of the foreign polymers present in post-consumer i-PP. It is observed that the process stability improves with decreasing mesh size and that higher draw ratios can be obtained. The addition of carbon black, which resides in the dispersed PE phase, also stabilizes the SSD process. Compared to isotropic post-consumer i-PP, the stiffness can be improved by a factor 10 to over 11GPa, while the tensile strength can be improved by a factor 15-385MPa, which is approx. 70% of the maximum tensile strength achieved for virgin i-PP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Does insulin-like growth factor 1 genotype influence muscle power response to strength training in older men and women?

PubMed

Sood, Suchi; Hanson, Erik D; Delmonico, Matthew J; Kostek, Matthew C; Hand, Brian D; Roth, Stephen M; Hurley, Ben F

2012-02-01

The CA-repeat polymorphism in the insulin-like growth factor 1 (IGF1) gene promoter region has been associated with strength and circulating IGF-I protein levels. The purpose of the study was to determine if the IGF1 CA-repeat polymorphism influences muscle power at baseline and in response to ST in older adults. Knee extensor peak power (PP) was measured at 50, 60, and 70% of 1-RM strength before and after 10 weeks of unilateral knee extensor ST in older adults, aged 50-85 years, to determine the changes in absolute and relative PP with ST. Subjects (N = 114) were genotyped for the IGF1 CA-repeat polymorphism and grouped as homozygous for the 192 allele, heterozygous, or non-carriers of the 192 allele. The 192 homozygotes had significantly lower baseline PP at 50, 60, and 70% of 1-RM strength than the non-carriers when age, sex, and baseline fat-free mass were covaried (all P < 0.05). This same relationship was observed when the highest PP within these ranges was compared (e.g., 317.6 ± 13.5 for 192 homozygotes and 380.2 ± 16.3 for non-carriers of the 192 allele, P < 0.05). Both absolute and relative PP increased significantly with ST in all genotype groups as expected, but there were no significant relationships among IGF1 genotypes and any of the PP changes. Despite a significant relationship between IGF1 genotype and knee extensor peak power at baseline, IGF1 genotype does not appear to influence changes in knee extensor peak power with ST.

Increased Foxo3a Nuclear Translocation and Activity is an Early Neuronal Response to βγ-Secretase-Mediated Processing of the Amyloid-β Protein Precursor: Utility of an AβPP-GAL4 Reporter Assay.

PubMed

Law, Bernard M; Guest, Amy L; Pullen, Matthew W J; Perkinton, Michael S; Williams, Robert J

2018-01-01

Sequential cleavage of the amyloid-β protein precursor (AβPP) by BACE1 (β-secretase) followed by theγ-secretase complex, is strongly implicated in Alzheimer's disease (AD) but the initial cellular responses to these cleavage events are not fully defined. β-secretase-mediated AβPP processing yields an extracellular domain (sAβPPβ) and a C-terminal fragment of AβPP of 99 amino acids (C99). Subsequent cleavage by γ-secretase produces amyloid-β (Aβ) and an AβPP intracellular domain (AICD). A cellular screen based on the generation of AICD from an AβPP-Gal4 fusion protein was adapted by introducing familial AD (FAD) mutations into the AβPP sequence and linking the assay to Gal4-UAS driven luciferase and GFP expression, to identify responses immediately downstream of AβPP processing in neurons with a focus on the transcription factor Foxo3a which has been implicated in neurodegeneration. The K670N/M671L, E682K, E693G, and V717I FAD mutations and the A673T protective mutation, were introduced into the AβPP sequence by site directed mutagenesis. When expressed in mouse cortical neurons, AβPP-Gal4-UAS driven luciferase and GFP expression was substantially reduced by γ-secretase inhibitors, lowered by β-secretase inhibitors, and enhanced by α-secretase inhibitors suggesting that AICD is a product of the βγ-secretase pathway. AβPP-Gal4-UAS driven GFP expression was exploited to identify individual neurons undergoing amyloidogenic AβPP processing, revealing increased nuclear localization of Foxo3a and enhanced Foxo3a-mediated transcription downstream of AICD production. Foxo3a translocation was not driven by AICD directly but correlated with reduced Akt phosphorylation. Collectively this suggests that βγ-secretase-mediated AβPP processing couples to Foxo3a which could be an early neuronal signaling response in AD.

Negative regulation of protein phosphatase 2Cbeta by ISG15 conjugation.

PubMed

Takeuchi, Tomoharu; Kobayashi, Takayasu; Tamura, Shinri; Yokosawa, Hideyoshi

2006-08-07

ISG15, an interferon-upregulated ubiquitin-like protein, is covalently conjugated to various cellular proteins (ISGylation). In this study, we found that protein phosphatase 2Cbeta (PP2Cbeta), which functions in the nuclear factor kappaB (NF-kappaB) pathway via dephosphorylation of TGF-beta-activated kinase, was ISGylated, and analysis by NF-kappaB luciferase reporter assay revealed that PP2Cbeta activity was suppressed by co-expression of ISG15, UBE1L, and UbcH8. We determined the ISGylation sites of PP2Cbeta and constructed its ISGylation-resistant mutant. In contrast to the wild type, this mutant suppressed the NF-kappaB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, we propose that ISGylation negatively regulates PP2Cbeta activity.

Consideration of air quality standards for vegetation with respect to ozone

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

Heggestad, H.E.

1968-01-01

There is an increasing body of evidence that ozone is the most damaging of all air pollutants affecting vegetation. It is the principal oxidant in the photochemical smog complex. Concentrations measured with an ultraviolet photometer, considered specific for ozone, have exceeded 0.5 part per million (ppM) in the Los Angeles area. Only one-tenth of this level, or 0.05 ppM, for 8 hours is known to injure very sensitive tobacco varieties. Studies in several laboratories show that a broad spectrum of plant species is visibly affected after a few hours exposure at concentrations much lower than 0.5 ppM. There is alsomore » some evidence that ozone reduces plant growth. Many factors must be taken into account in considering standards for possible use in the protection of vegetation from ozone damage. These include ozone concentration and methods of measurement, time of exposure, possible additive effects of other pollutants, sensitivity of species to ozone, their economic value, and the extent of injury which can be tolerated. The response of a species to the pollutant is conditioned by genetic factors and environmental conditions. The lack of routine, specific methods for measuring ozone in ambient air is a handicap. California and Colorado established standards for oxidants at 0.15 ppM and 0.10 ppM, respectively, for 1 hour. How these standards relate to the dosage of ozone that causes acute and chronic injury to various plant species is discussed. 28 references.« less

Prediction of maternal near-miss in placenta previa: a retrospective analysis from a tertiary center in Ankara, Turkey.

PubMed

Coskun, Bora; Akkurt, Iltac; Dur, Rıza; Akkurt, Mehmet O; Ergani, Seval Y; Turan, Ozerk T; Coskun, Bugra

2018-02-01

To determine risk factors for severe complications during and after cesarean delivery (CD) in placenta previa (PP). We reviewed retrospectively collected data from women with PP who underwent CD during a 6-year study period. We identified the complicated group based on the modified WHO near-miss criteria. Complicated and noncomplicated groups were compared considering clinical, laboratory, and sonographic features. Thirty-seven of 256 cases classified as near miss consisting of 14 peripartum hysterectomies, 12 uterine balloon placements, 10 great artery ligations, and four B-lynch suture placement procedures without maternal mortality. Perioperative complications included surgical wound infections (n = 5), bladder injury (n = 4), pelvic abscess (n = 1), and uterine rupture (n = 1). Logistic regression analyses demonstrated following features to be associated with maternal near miss in PP: (1) coexistent abruption (aOR 13.2, 95% CI 5.8-75.3), (2) morbidly adherent placenta (aOR 11.92, 95% CI 3.24-43.82), (3) number of hospitalizations for vaginal bleeding (≥3) (aOR 8.88, 95% CI 3.32-26.69), and (4) transvaginal cervical length (CL) measurement <10th percentile (aOR 5.5, 95% CI 2.1-15.4). Short cervical length, recurrent vaginal bleeding, morbidly adherent placenta, and concurrent placental abruption are independent predictors for subsequent severe maternal morbidity in PP cases. Early identification of these risk factors during PP follow-up may improve maternal outcome.

Encouraging Reactivity to Create Robust Machines

DTIC Science & Technology

2013-07-01

Performance Evaluation and Benchmarking of Intelligent Systems, 113 137. Baldwin, J. (1896). A new factor in evolution. The American Naturalist, 30(355...Once more unto the breach: Co evolving a robot and its simulator. In Proceed ings of the international conference on artifical life (alife9) (pp.57...Pfeifer, R. (2003). Evolving complete agents using artificial ontogeny. In (pp. 237 258). Springer Verlag. Brooks, R. (1994). Artifical life and

'Big bang' of B-cell development revealed.

PubMed

Murre, Cornelis

2018-01-15

Earlier studies have identified transcription factors that specify B-cell fate, but the underlying mechanisms remain to be revealed. Two new studies by Miyai and colleagues (pp. 112-126) and Li and colleagues (pp. 96-111) in this issue of Genes & Development provide new and unprecedented insights into the genetic and epigenetic mechanisms that establish B-cell identity. © 2018 Murre; Published by Cold Spring Harbor Laboratory Press.

Prediction of the production of nitrogen oxide (NOx) in turbojet engines

NASA Astrophysics Data System (ADS)

Tsague, Louis; Tsogo, Joseph; Tatietse, Thomas Tamo

Gaseous nitrogen oxides (NO+NO2=NOx) are known as atmospheric trace constituent. These gases remain a big concern despite the advances in low NOx emission technology because they play a critical role in regulating the oxidization capacity of the atmosphere according to Crutzen [1995. My life with O 3, NO x and other YZO x S; Nobel Lecture; Chemistry 1995; pp 195; December 8, 1995] . Aircraft emissions of nitrogen oxides ( NOx) are regulated by the International Civil Aviation Organization. The prediction of NOx emission in turbojet engines by combining combustion operational data produced information showing correlation between the analytical and empirical results. There is close similarity between the calculated emission index and experimental data. The correlation shows improved accuracy when the 2124 experimental data from 11 gas turbine engines are evaluated than a previous semi empirical correlation approach proposed by Pearce et al. [1993. The prediction of thermal NOx in gas turbine exhausts. Eleventh International Symposium on Air Breathing Engines, Tokyo, 1993, pp. 6-9]. The new method we propose predict the production of NOx with far more improved accuracy than previous methods. Since a turbojet engine works in an atmosphere where temperature, pressure and humidity change frequently, a correction factor is developed with standard atmospheric laws and some correlations taken from scientific literature [Swartwelder, M., 2000. Aerospace engineering 410 Term Project performance analysis, November 17, 2000, pp. 2-5; Reed, J.A. Java Gas Turbine Simulator Documentation. pp. 4-5]. The new correction factor is validated with experimental observations from 19 turbojet engines cruising at altitudes of 9 and 13 km given in the ICAO repertory [Middleton, D., 1992. Appendix K (FAA/SETA). Section 1: Boeing Method Two Indices, 1992, pp. 2-3]. This correction factor will enable the prediction of cruise NOx emissions of turbojet engines at cruising speeds. The ICAO database [Goehlich, R.A., 2000. Investigation into the applicability of pollutant emission models for computer aided preliminary aircraft design, Book number 175654, 4.2.2000, pp. 57-79] can now be completed using the approach we propose to complete the whole mission flight NOx emissions.

Control of rRNA and tRNA syntheses in Escherichia coli by guanosine tetraphosphate.

PubMed Central

Ryals, J; Little, R; Bremer, H

1982-01-01

The expression of stable RNA (rRNA and tRNA) genes and the concentration of guanosine tetraphosphate (ppGpp) were measured in an isogenic pair of relA+ and relA derivatives of Escherichia coli B/r. The cells were either growing exponentially at different rates or subject to amino acid starvation when they were measured. The specific stable RNA gene activity (rs/rt, the rate of rRNA and tRNA synthesis relative to the total instantaneous rate of RNA synthesis) was found to decrease from 1.0 at a ppGpp concentration of 0 (extrapolated value) to 0.24 at saturating concentrations of ppGpp (above 100 pmoles per optical density at 460 nm unit of cell mass). The same relationship between the rs/rt ratio and ppGpp concentration was obtained independent of the physiological state of the bacteria (i.e., independent of the growth rate or of amino acid starvation) and independent of the relA allele. It can be concluded that ppGpp is an effector for stable RNA gene control and that stable RNA genes are not controlled by factors other than the ppGpp-mediated system. The results were shown to be qualitatively and quantitatively consistent with data on in vitro rRNA gene control by ppGpp, and they were interpreted in the light of reported ideas derived from those in vitro experiments. PMID:6179924

Effects of Polypropylene Orientation on Mechanical and Heat Seal Properties of Polymer-Aluminum-Polymer Composite Films for Pouch Lithium-Ion Batteries

PubMed Central

Chen, Jinyao; Yang, Feng; Kang, Jian; Cao, Ya; Xiang, Ming

2018-01-01

In this study, polyamide-aluminum foil-polypropylene (PA-Al-PP) composite films with different orientation status of the PP layer were prepared, and their morphology, tensile, peeling and heat seal behavior were studied. The comparative study of tensile and fracture behaviors of single-layer film of PA, Al and PP, as well as the composite films of PA-Al, PP-Al and PA-Al-PP revealed that in PA-Al-PP composite film, the PA layer with the highest tensile strength can share the tensile stress from the Al layer during stretching, while the PP layer with the lowest tensile strength can prevent further development of the small cracks on boundary of the Al layer during stretching. Moreover, the study of heat seal behavior suggested that both the orientation status and the heat seal conditions were important factors in determining the heat seal strength (HSS) and failure behavior of the sample. Four failure types were observed, and a clear correspondence between HSS and failure types was found. The results also elucidated that for the composite film, only in the cases where the tensile stress was efficiently released by each layer during HSS measurement could the composite film exhibit desired high HSS that was even higher than its tensile strength. PMID:29337881

Structure–Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins

PubMed Central

Twiner, Michael J.; Doucette, Gregory J.; Pang, Yucheng; Fang, Chao; Forsyth, Craig J.; Miles, Christopher O.

2016-01-01

Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure–activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2-epi-DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 >> 2-epi-DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs’ activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors. PMID:27827901

G-protein control of the ribosome-associated stress response protein SpoT.

PubMed

Jiang, Mengxi; Sullivan, Susan M; Wout, Patrice K; Maddock, Janine R

2007-09-01

The bacterial response to stress is controlled by two proteins, RelA and SpoT. RelA generates the alarmone (p)ppGpp under amino acid starvation, whereas SpoT is responsible for (p)ppGpp hydrolysis and for synthesis of (p)ppGpp under a variety of cellular stress conditions. It is widely accepted that RelA is associated with translating ribosomes. The cellular location of SpoT, however, has been controversial. SpoT physically interacts with the ribosome-associated GTPase CgtA, and we show here that, under an optimized salt condition, SpoT is also associated with a pre-50S particle. Analysis of spoT and cgtA mutants and strains overexpressing CgtA suggests that the ribosome associations of SpoT and CgtA are mutually independent. The steady-state level of (p)ppGpp is increased in a cgtA mutant, but the accumulation of (p)ppGpp during amino acid starvation is not affected, providing strong evidence that CgtA regulates the (p)ppGpp level during exponential growth but not during the stringent response. We show that CgtA is not associated with pre-50S particles during amino acid starvation, indicating that under these conditions in which (p)ppGpp accumulates, CgtA is not bound either to the pre-50S particle or to SpoT. We propose that, in addition to its role as a 50S assembly factor, CgtA promotes SpoT (p)ppGpp degradation activity on the ribosome and that the loss of CgtA from the ribosome is necessary for maximal (p)ppGpp accumulation under stress conditions. Intriguingly, we found that in the absence of spoT and relA, cgtA is still an essential gene in Escherichia coli.

Deferiprone and Gallium-Protoporphyrin Have the Capacity to Potentiate the Activity of Antibiotics in Staphylococcus aureus Small Colony Variants

PubMed Central

Richter, Katharina; Thomas, Nicky; Zhang, Guimin; Prestidge, Clive A.; Coenye, Tom; Wormald, Peter-John; Vreugde, Sarah

2017-01-01

Small colony variants (SCVs) of bacteria like Staphylococcus aureus are characterized by a reduced colony size and are linked to increased antibiotic tolerance and resistance. Their altered expression of virulence factors, slow growing properties and their ability to form biofilms make the eradication of SCVs challenging. In the context of biofilm-related infectious diseases involving S. aureus SCVs, a therapy targeting bacterial iron metabolism was evaluated. The combination of the iron-chelator deferiprone (Def) and the heme-analog gallium-protoporphyrin (GaPP), in solution and incorporated in a surgical wound gel, was tested for activity against planktonic and sessile SCVs. To this end, the activity of Def-GaPP was assessed against planktonic S. aureus SCVs, as well as against in vitro and in vivo biofilms in the colony biofilm model, an artificial wound model and a Caenorhabditis elegans infection model. While Def alone failed to show substantial antibacterial activity, GaPP and the combination of Def-GaPP demonstrated concentration- and strain-dependent antibacterial properties. Specifically, the Def-GaPP combination significantly reduced the bacterial load in an artificial wound model and increased the survival of S. aureus SCV infected C. elegans. When Def-GaPP were combined with gentamicin or ciprofloxacin, the triple combinations exceeded the antibiofilm activity of the individual compounds in the colony biofilm model. In targeting bacterial iron metabolism, Def-GaPP showed significant activity against planktonic and sessile SCVs. Moreover, Def-GaPP could potentiate the activity of gentamicin and ciprofloxacin. Delivered in a wound healing gel, Def-GaPP showed promise as a new topical strategy against infections with S. aureus SCVs. PMID:28690982

PpCBF3 from Cold-Tolerant Kentucky Bluegrass Involved in Freezing Tolerance Associated with Up-Regulation of Cold-Related Genes in Transgenic Arabidopsis thaliana

PubMed Central

Chen, Yu; Xu, Bin; Yang, Zhimin; Huang, Bingru

2015-01-01

Dehydration-Responsive Element Binding proteins (DREB)/C-repeat (CRT) Binding Factors (CBF) have been identified as transcriptional activators during plant responses to cold stress. The objective of this study was to determine the physiological roles of a CBF gene isolated from a cold-tolerant perennial grass species, Kentucky bluegrass (Poa pratensis L.), which designated as PpCBF3, in regulating plant tolerance to freezing stress. Transient transformation of Arabidopsis thaliana mesophyll protoplast with PpCBF3-eGFP fused protein showed that PpCBF3 was localized to the nucleus. RT-PCR analysis showed that PpCBF3 was specifically induced by cold stress (4°C) but not by drought stress [induced by 20% polyethylene glycol 6000 solution (PEG-6000)] or salt stress (150 mM NaCl). Transgenic Arabidopsis overexpressing PpCBF3 showed significant improvement in freezing (-20°C) tolerance demonstrated by a lower percentage of chlorotic leaves, lower cellular electrolyte leakage (EL) and H2O2 and O2 .- content, and higher chlorophyll content and photochemical efficiency compared to the wild type. Relative mRNA expression level analysis by qRT-PCR indicated that the improved freezing tolerance of transgenic Arabidopsis plants overexpressing PpCBF3 was conferred by sustained activation of downstream cold responsive (COR) genes. Other interesting phenotypic changes in the PpCBF3-transgenic Arabidopsis plants included late flowering and slow growth or ‘dwarfism’, both of which are desirable phenotypic traits for perennial turfgrasses. Therefore, PpCBF3 has potential to be used in genetic engineering for improvement of turfgrass freezing tolerance and other desirable traits. PMID:26177510

PP2B and PP1α cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling

PubMed Central

Chen, Ruichuan; Liu, Min; Li, Huan; Xue, Yuhua; Ramey, Wanichaya N.; He, Nanhai; Ai, Nanping; Luo, Haohong; Zhu, Ying; Zhou, Nan; Zhou, Qiang

2008-01-01

The positive transcription elongation factor b (P-TEFb), consisting of Cdk9 and cyclin T, stimulates RNA polymerase II elongation and cotranscriptional pre-mRNA processing. To accommodate different growth conditions and transcriptional demands, a reservoir of P-TEFb is kept in an inactive state in the multisubunit 7SK snRNP. Under certain stress or disease conditions, P-TEFb is released to activate transcription, although the signaling pathway(s) that controls this is largely unknown. Here, through analyzing the UV- or hexamethylene bisacetamide (HMBA)-induced release of P-TEFb from 7SK snRNP, an essential role for the calcium ion (Ca2+)–calmodulin–protein phosphatase 2B (PP2B) signaling pathway is revealed. However, Ca2+ signaling alone is insufficient, and PP2B must act sequentially and cooperatively with protein phosphatase 1α (PP1α) to disrupt 7SK snRNP. Activated by UV/HMBA and facilitated by a PP2B-induced conformational change in 7SK snRNP, PP1α releases P-TEFb through dephosphorylating phospho-Thr186 in the Cdk9 T-loop. This event is also necessary for the subsequent recruitment of P-TEFb by the bromodomain protein Brd4 to the preinitiation complex, where Cdk9 remains unphosphorylated and inactive until after the synthesis of a short RNA. Thus, through cooperatively dephosphorylating Cdk9 in response to Ca2+ signaling, PP2B and PP1α alter the P-TEFb functional equilibrium through releasing P-TEFb from 7SK snRNP for transcription. PMID:18483222

Antidiabetic Polypill Improves Central Pathology and Cognitive Impairment in a Mixed Model of Alzheimer's Disease and Type 2 Diabetes.

PubMed

Infante-Garcia, Carmen; Ramos-Rodriguez, Juan Jose; Hierro-Bujalance, Carmen; Ortegon, Esperanza; Pickett, Eleanor; Jackson, Rosemary; Hernandez-Pacho, Fernando; Spires-Jones, Tara; Garcia-Alloza, Monica

2018-07-01

Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor. In order to test the effects of PP at the central level, we have long-term treated a new mixed model of AD-T2D, the APP/PS1xdb/db mouse. We have analyzed AD pathological features and the underlying specific characteristics that relate AD and T2D. As expected, metabolic alterations were ameliorated after PP treatment in diabetic mice, supporting a role for PP in maintaining pancreatic activity. At central level, PP reduced T2D-associated brain atrophy, showing both neuronal and synaptic preservation. Tau and amyloid pathologies were also reduced after PP treatment. Furthermore, we observed a reduction of spontaneous central bleeding and inflammation after PP treatment in diabetic mice. As consequence, learning and memory processes were improved after PP treatment in AD, T2D, and AD-T2D mice. Our data provide the basis to further analyze the role of PP, as an alternative or adjuvant, to slow down or delay the central complications associated with T2D and AD.

Deferiprone and Gallium-Protoporphyrin Have the Capacity to Potentiate the Activity of Antibiotics in Staphylococcus aureus Small Colony Variants.

PubMed

Richter, Katharina; Thomas, Nicky; Zhang, Guimin; Prestidge, Clive A; Coenye, Tom; Wormald, Peter-John; Vreugde, Sarah

2017-01-01

Small colony variants (SCVs) of bacteria like Staphylococcus aureus are characterized by a reduced colony size and are linked to increased antibiotic tolerance and resistance. Their altered expression of virulence factors, slow growing properties and their ability to form biofilms make the eradication of SCVs challenging. In the context of biofilm-related infectious diseases involving S. aureus SCVs, a therapy targeting bacterial iron metabolism was evaluated. The combination of the iron-chelator deferiprone (Def) and the heme-analog gallium-protoporphyrin (GaPP), in solution and incorporated in a surgical wound gel, was tested for activity against planktonic and sessile SCVs. To this end, the activity of Def-GaPP was assessed against planktonic S. aureus SCVs, as well as against in vitro and in vivo biofilms in the colony biofilm model, an artificial wound model and a Caenorhabditis elegans infection model. While Def alone failed to show substantial antibacterial activity, GaPP and the combination of Def-GaPP demonstrated concentration- and strain-dependent antibacterial properties. Specifically, the Def-GaPP combination significantly reduced the bacterial load in an artificial wound model and increased the survival of S. aureus SCV infected C. elegans . When Def-GaPP were combined with gentamicin or ciprofloxacin, the triple combinations exceeded the antibiofilm activity of the individual compounds in the colony biofilm model. In targeting bacterial iron metabolism, Def-GaPP showed significant activity against planktonic and sessile SCVs. Moreover, Def-GaPP could potentiate the activity of gentamicin and ciprofloxacin. Delivered in a wound healing gel, Def-GaPP showed promise as a new topical strategy against infections with S. aureus SCVs.

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

Bahig, Houda; Simard, Dany; Létourneau, Laurent

Purpose: To determine the incidence of pseudoprogression (PP) after spine stereotactic body radiation therapy based on a detailed and quantitative assessment of magnetic resonance imaging (MRI) morphologic tumor alterations, and to identify predictive factors distinguishing PP from local recurrence (LR). Methods and Materials: A retrospective analysis of 35 patients with 49 spinal segments treated with spine stereotactic body radiation therapy, from 2009 to 2014, was conducted. The median number of follow-up MRI studies was 4 (range, 2-7). The gross tumor volumes (GTVs) within each of the 49 spinal segments were contoured on the pretreatment and each subsequent follow-up T1- andmore » T2-weighted MRI sagittal sequence. T2 signal intensity was reported as the mean intensity of voxels constituting each volume. LR was defined as persistent GTV enlargement on ≥2 serial MRI studies for ≥6 months or on pathologic confirmation. PP was defined as a GTV enlargement followed by stability or regression on subsequent imaging within 6 months. Kaplan-Meier analysis was used for estimation of actuarial local control, disease-free survival, and overall survival. Results: The median follow-up was 23 months (range, 1-39 months). PP was identified in 18% of treated segments (9 of 49) and LR in 29% (14 of 49). Earlier volume enlargement (5 months for PP vs 15 months for LR, P=.005), greater GTV to reference nonirradiated vertebral body T2 intensity ratio (+30% for PP vs −10% for LR, P=.005), and growth confined to 80% of the prescription isodose line (80% IDL) (8 of 9 PP cases vs 1 of 14 LR cases, P=.002) were associated with PP on univariate analysis. Multivariate analysis confirmed an earlier time to volume enlargement and growth within the 80% IDL as significant predictors of PP. LR involved the epidural space in all but 1 lesion, whereas PP was confined to the vertebral body in 7 of 9 cases. Conclusions: PP was observed in 18% of treated spinal segments. Tumor growth confined to the 80% IDL and earlier time to tumor enlargement were predictive for PP.« less

Organochlorine pesticide level differences among female inhabitants from Veracruz, Puebla and Tabasco, Mexico.

PubMed

Waliszewski, Stefan M; Caba, M; Saldarriaga-Noreña, H; Martínez, A J; Meza, E; Valencia Quintana, R; Zepeda, R

2014-08-01

Organochlorine pesticides have been used in Mexico in malaria control programs and against ectoparasites. The objective of this study was to compare the levels of organochlorine pesticides: HCB, α-β-γ-HCH, pp'-DDE, op'-DDT and pp'-DDT in adipose tissue of female inhabitants from three Mexican states: Veracruz, Puebla and Tabasco. Data analyses indicated higher β-HCH levels in Puebla inhabitants. When comparing the mean values of the pp'-DDE concentrations among the three states, no statistically significant differences were noted. A trend of increasing concentrations of op'-DDT from Veracruz to Puebla and Tabasco was observed. Significantly higher pp'-DDT concentrations in Veracruz as compared to Puebla and Tabasco were determined. Using factorial analysis of three age categories (>30, 31-50, <51) organochlorine pesticide concentrations increases with age of participants, indicating time of exposure as a principal factor of organochlorine pesticides accumulation in adipose tissue.

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

Adare, A.; Afanasiev, S.; Aidala, C.

Measurements of bottomonium production in heavy-ion and p+p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three Υ states, Υ(1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au+Au and p+p collisions at \\(\\sqrt{s_{\\mathrm{NN}}}=200\\) GeV. The Υ(1S + 2S + 3S) → e⁺e⁻ differential cross section at midrapidity was found to be B eedσ/dy = 108 ± 38 (stat) ± 15 (syst) ± 11 (luminosity) pb in p+p collisions. The nuclear modification factor in the 30% most central Au+Au collisions indicates a suppression ofmore » the total Υ state yield relative to the extrapolation from p+p collision data. Thus, the suppression is consistent with measurements at higher energies by the CMS experiment at the Large Hadron Collider.« less

A signaling role of histone-binding proteins and INHAT subunits pp32 and Set/TAF-Ibeta in integrating chromatin hypoacetylation and transcriptional repression.

PubMed

Kutney, Sara N; Hong, Rui; Macfarlan, Todd; Chakravarti, Debabrata

2004-07-16

Various post-translational modifications of histones significantly influence gene transcription. Although un- or hypoacetylated histones are tightly linked to transcriptional repression, the mechanisms and identities of chromatin signal transducer proteins integrating histone hypoacetylation into repression in humans have remained largely unknown. Here we show that the mammalian histone-binding proteins and inhibitor of acetyltransferases (INHAT) complex subunits, Set/template-activating factor-Ibeta (TAF-Ibeta) and pp32, specifically bind to unacetylated, hypoacetylated, and repressively marked histones but not to hyperacetylated histones. Additionally, Set/TAF-Ibeta and pp32 associate with histone deacetylases in vitro and in vivo and repress transcription from a chromatin-integrated template in vivo. Finally, Set/TAF-Ibeta and pp32 associate with an endogenous estrogen receptor-regulated gene, EB1, in the hypoacetylated transcriptionally inactive state but not with the hyperacetylated transcriptionally active form. Together, these data define a novel in vivo mechanistic role for the mammalian Set/TAF-Ibeta and pp32 proteins as transducers of chromatin signaling by integrating chromatin hypoacetylation and transcriptional repression.

Exploring hotspots of pneumococcal pneumonia and potential impacts of ejecta dust exposure following the Christchurch earthquakes.

PubMed

Pearson, Amber L; Kingham, Simon; Mitchell, Peter; Apparicio, Philippe

2013-12-01

The etiology of pneumococcal pneumonia (PP) is well-known. Yet, some events may increase its incidence. Natural disasters may worsen air quality, a risk factor for PP. We investigated spatial/spatio-temporal clustering of PP pre- and post-earthquakes in Christchurch, New Zealand. The earthquakes resulted in deaths, widespread damage and liquefaction ejecta (a source of air-borne dust). We tested for clusters and associations with ejecta, using 97 cases (diagnosed 10/2008-12/2011), adjusted for age and area-level deprivation. The strongest evidence to support the potential role of ejecta in clusters of PP cases was the: (1) geographic shift in the spatio-temporal cluster after deprivation adjustment to match the post-earthquake clusters and; (2) increased relative risk in the fully-adjusted post-earthquake compared to the pre-earthquake cluster. The application of spatial statistics to study PP and ejecta are novel. Further studies to assess the long-term impacts of ejecta inhalation are recommended particularly in Christchurch, where seismic activity continues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Thctf1 transcription factor of Trichoderma harzianum is involved in 6-pentyl-2H-pyran-2-one production and antifungal activity.

PubMed

Rubio, M Belén; Hermosa, Rosa; Reino, José Luis; Collado, Isidro G; Monte, Enrique

2009-01-01

We describe the cloning and characterization of the Trichoderma harzianum Thctf1 gene, which shows high sequence identity with a transcription factor gene of Fusarium solani f. sp. pisi. In T. harzianum, disruption of the Thctf1 gene by homologous recombination gave rise to transformants that in plate experiments did not show the yellow pigmentation observed in the wild-type strain. In several Trichoderma spp. a yellow pigmentation and a coconut aroma have been related to the production of 6-pentyl-2H-pyran-2-one (6PP) compounds. Prompted by this, we explored whether the loss of pigmentation in the Thctf1 null mutants of T. harzianum might be related to the synthesis of 6PP. Chromatographic and spectroscopic analyses revealed that the disruptants did not produce two secondary metabolites, derived from 6PP and not previously described in the Trichoderma genus, that are present in wild-type culture filtrates. Since 6PP is a recognized antifungal compound, this ability was analyzed in both the disruptants and wild-type, observing that the Thctf1 null mutants of T. harzianum had reduced antimicrobial capacity. Our results point to the significant role of THCTF1 in the production of secondary metabolites and in the antifungal activity of T. harzianum.

Human cytomegalovirus DNA polymerase catalytic subunit pUL54 possesses independently acting nuclear localization and ppUL44 binding motifs.

PubMed

Alvisi, Gualtiero; Ripalti, Alessandro; Ngankeu, Apollinaire; Giannandrea, Maila; Caraffi, Stefano G; Dias, Manisha M; Jans, David A

2006-10-01

The catalytic subunit of human cytomegalovirus (HCMV) DNA polymerase pUL54 is a 1242-amino-acid protein, whose function, stimulated by the processivity factor, phosphoprotein UL44 (ppUL44), is essential for viral replication. The C-terminal residues (amino acids 1220-1242) of pUL54 have been reported to be sufficient for ppUL44 binding in vitro. Although believed to be important for functioning in the nuclei of infected cells, no data are available on either the interaction of pUL54 with ppUL44 in living mammalian cells or the mechanism of pUL54 nuclear transport and its relationship with that of ppUL44. The present study examines for the first time the nuclear import pathway of pUL54 and its interaction with ppUL44 using dual color, quantitative confocal laser scanning microscopy on live transfected cells and quantitative gel mobility shift assays. We showed that of two nuclear localization signals (NLSs) located at amino acids 1153-1159 (NLSA) and 1222-1227 (NLSB), NLSA is sufficient to confer nuclear localization on green fluorescent protein (GFP) by mediating interaction with importin alpha/beta. We also showed that pUL54 residues 1213-1242 are sufficient to confer ppUL44 binding abilities on GFP and that pUL54 and ppUL44 can be transported to the nucleus as a complex. Our work thus identified distinct sites within the HCMV DNA polymerase, which represent potential therapeutic targets and establishes the molecular basis of UL54 nuclear import.

Monitoring of organochlorine pesticide residue levels in adipose tissue of Veracruz, Mexico inhabitants.

PubMed

Waliszewski, Stefan M; Caba, M; Herrero-Mercado, M; Saldariaga-Noreña, H; Meza, E; Zepeda, R; Martínez-Valenzuela, C; Infanzon, R; Hernández-Chalate, F

2011-11-01

The objective of the present study was to monitor the levels of organochlorine pesticides HCB, α-β-γ-HCH, pp'DDE, op'DDT and pp'DDT in 150 adipose tissue samples of Veracruz, Mexico inhabitants. In analyzed samples, the following pesticides were detected: p,p'-DDE in 100% of the samples at mean 1.643 mg/kg; p,p'-DDT in 99.3.% of the samples at mean 0.227 mg/kg; β-HCH in 97.3% of the samples at mean 0.063 mg/kg; and op'DDT in 93.3% of the samples at mean 0.022 mg/kg. Comparing mean, median and geometric mean concentrations of organochlorine pesticides shows a decrease in values from mean to median and to geometric mean which points out a prevalence of lower concentrations among the total samples and the existence of occasional cases of extreme exposure expressed in range values. The pooled samples divided according to sex, showed only significant differences of pp'DDE median concentrations between sexes. The other organochlorine pesticides indicated no statistical differences between sexes, including the pp'DDE/pp'DDT ratio. The samples grouped according to age, showed that the third tertile was more contaminated for both sexes, indicating age as a positively associated factor with organochlorine pesticide levels in adipose tissue of Veracruz inhabitants. Comparing organochlorine pesticide levels between 2008 and 2010 years, a decreased tendency for β-HCH, pp'DDE, Σ-DDT and pp'DDE/pp'DDT ratio levels was observed.

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

PubMed

Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew

2017-04-11

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

Location of intense electromagnetic ion cyclotron (EMIC) wave events relative to the plasmapause: Van Allen Probes observations

NASA Astrophysics Data System (ADS)

Tetrick, S. S.; Engebretson, M. J.; Posch, J. L.; Olson, C. N.; Smith, C. W.; Denton, R. E.; Thaller, S. A.; Wygant, J. R.; Reeves, G. D.; MacDonald, E. A.; Fennell, J. F.

2017-04-01

We have studied the spatial location relative to the plasmapause (PP) of the most intense electromagnetic ion cyclotron (EMIC) waves observed on Van Allen Probes A and B during their first full precession in local time. Most of these waves occurred over an L range of from -1 to +2 RE relative to the PP. Very few events occurred only within 0.1 RE of the PP, and events with a width in L of < 0.2 RE occurred both inside and outside the PP. Wave occurrence was always associated with high densities of ring current ions; plasma density gradients or enhancements were associated with some events but were not dominant factors in determining the sites of wave generation. Storm main and recovery phase events in the dusk sector were often inside the PP, and dayside events during quiet times and compressions of the magnetosphere were more evenly distributed both inside and outside the PP. Superposed epoch analyses of the dependence of wave onset on solar wind dynamic pressure (Psw), the SME (SuperMAG auroral electrojet) index, and the SYM-H index showed that substorm injections and solar wind compressions were temporally closely associated with EMIC wave onset but to an extent that varied with frequency band, magnetic local time, and storm phase, and location relative to the PP. The fact that increases in SME and Psw were less strongly correlated with events at the PP than with other events might suggest that the occurrence of those events was affected by the density gradient.

Ambulatory arterial stiffness index and 24-hour ambulatory pulse pressure as predictors of mortality in Ohasama, Japan.

PubMed

Kikuya, Masahiro; Staessen, Jan A; Ohkubo, Takayoshi; Thijs, Lutgarde; Metoki, Hirohito; Asayama, Kei; Obara, Taku; Inoue, Ryusuke; Li, Yan; Dolan, Eamon; Hoshi, Haruhisa; Hashimoto, Junichiro; Totsune, Kazuhito; Satoh, Hiroshi; Wang, Ji-Guang; O'Brien, Eoin; Imai, Yutaka

2007-04-01

Ambulatory arterial stiffness index (AASI) and pulse pressure (PP) are indexes of arterial stiffness and can be computed from 24-hour blood pressure recordings. We investigated the prognostic value of AASI and PP in relation to fatal outcomes. In 1542 Ohasama residents (baseline age, 40 to 93 years; 63.4% women), we applied Cox regression to relate mortality to AASI and PP while adjusting for sex, age, BMI, 24-hour MAP, smoking and drinking habits, diabetes mellitus, and a history of cardiovascular disease. During 13.3 years (median), 126 cardiovascular and 63 stroke deaths occurred. The sex- and age-standardized incidence rates of cardiovascular and stroke mortality across quartiles were U-shaped for AASI and J-shaped for PP. Across quartiles, the multivariate-adjusted hazard ratios for cardiovascular and stroke death significantly deviated from those in the whole population in a U-shaped fashion for AASI, whereas for PP, none of the HRs departed from the overall risk. The hazard ratios for cardiovascular mortality across ascending AASI quartiles were 1.40 (P=0.04), 0.82 (P=0.25), 0.64 (P=0.01), and 1.35 (P=0.03). Additional adjustment of AASI for PP and sensitivity analyses by sex, excluding patients on antihypertensive treatment or with a history of cardiovascular disease, or censoring deaths occurring within 2 years of enrollment, produced confirmatory results. In a Japanese population, AASI predicted cardiovascular and stroke mortality over and beyond PP and other risk factors, whereas in adjusted analyses, PP did not carry any prognostic information.

Effect of total solids content on biohydrogen production and lactic acid accumulation during dark fermentation of organic waste biomass.

PubMed

Ghimire, Anish; Trably, Eric; Frunzo, Luigi; Pirozzi, Francesco; Lens, Piet N L; Esposito, Giovanni; Cazier, Elisabeth A; Escudié, Renaud

2018-01-01

Production of biohydrogen and related metabolic by-products was investigated in Solid State Dark Fermentation (SSDF) of food waste (FW) and wheat straw (WS). The effect of the total solids (TS) content and H 2 partial pressure (pp H2 ), two of the main operating factors of SSDF, were investigated. Batch tests with FW at 10, 15, 20, 25 and 30% TS showed considerable effects of the TS on metabolites distribution. H 2 production was strongly inhibited for TS contents higher than 15% with a concomitant accumulation of lactic acid and a decrease in substrate conversion. Varying the pp H2 had no significant effect on the conversion products and overall degradation of FW and WS, suggesting that pp H2 was not the main limiting factor in SSDF. This study showed that the conversion of complex substrates by SSDF depends on the substrate type and is limited by the TS content. Copyright © 2017 Elsevier Ltd. All rights reserved.

Higgs radiation off top quarks at the Tevatron and the LHC.

PubMed

Beenakker, W; Dittmaier, S; Krämer, M; Plümper, B; Spira, M; Zerwas, P M

2001-11-12

Higgs bosons can be searched for in the channels pp macro/pp-->tt macro H + X at the Fermilab Tevatron and the Cern Large Hadron Collider (LHC). We have calculated the QCD corrections to these processes in the standard model at next-to-leading order. The higher-order corrections reduce the renormalization and factorization scale dependence considerably and stabilize the theoretical predictions for the cross sections. At the central scale mu = (2m(t)+M(H))/2 the properly defined K factors are slightly below unity for the Tevatron (K approximately 0.8) and slightly above unity for the LHC (K approximately 1.2).

The small-x gluon distribution in centrality biased pA and pp collisions

DOE PAGES

Dumitru, Adrian; Kapilevich, Gary; Skokov, Vladimir

2018-04-04

Here, the nuclear modification factor R pA(p T) provides information on the small- x gluon distribution of a nucleus at hadron colliders. Several experiments have recently measured the nuclear modification factor not only in minimum bias but also for central pA collisions. In this paper we analyze the bias on the configurations of soft gluon fields introduced by a centrality selection via the number of hard particles. Such bias can be viewed as reweighting of configurations of small- x gluons. We find that the biased nuclear modification factor Q pA(p T) for central collisions is above R pA(p T) formore » minimum bias events, and that it may redevelop a “Cronin peak” even at small x . The magnitude of the peak is predicted to increase approximately like 1/A ⊥ ν, ν~0.6±0.1 , if one is able to select more compact configurations of the projectile proton where its gluons occupy a smaller transverse area A ⊥. We predict an enhanced Q pp(p T)–1~1/(p T 2) ν and a Cronin peak even for central pp collisions.« less

The small-x gluon distribution in centrality biased pA and pp collisions

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

Dumitru, Adrian; Kapilevich, Gary; Skokov, Vladimir

Here, the nuclear modification factor R pA(p T) provides information on the small- x gluon distribution of a nucleus at hadron colliders. Several experiments have recently measured the nuclear modification factor not only in minimum bias but also for central pA collisions. In this paper we analyze the bias on the configurations of soft gluon fields introduced by a centrality selection via the number of hard particles. Such bias can be viewed as reweighting of configurations of small- x gluons. We find that the biased nuclear modification factor Q pA(p T) for central collisions is above R pA(p T) formore » minimum bias events, and that it may redevelop a “Cronin peak” even at small x . The magnitude of the peak is predicted to increase approximately like 1/A ⊥ ν, ν~0.6±0.1 , if one is able to select more compact configurations of the projectile proton where its gluons occupy a smaller transverse area A ⊥. We predict an enhanced Q pp(p T)–1~1/(p T 2) ν and a Cronin peak even for central pp collisions.« less

First Person Perspective of Seated Participants Over a Walking Virtual Body Leads to Illusory Agency Over the Walking.

PubMed

Kokkinara, Elena; Kilteni, Konstantina; Blom, Kristopher J; Slater, Mel

2016-07-01

Agency, the attribution of authorship to an action of our body, requires the intention to carry out the action, and subsequently a match between its predicted and actual sensory consequences. However, illusory agency can be generated through priming of the action together with perception of bodily action, even when there has been no actual corresponding action. Here we show that participants can have the illusion of agency over the walking of a virtual body even though in reality they are seated and only allowed head movements. The experiment (n = 28) had two factors: Perspective (1PP or 3PP) and Head Sway (Sway or NoSway). Participants in 1PP saw a life-sized virtual body spatially coincident with their own from a first person perspective, or the virtual body from third person perspective (3PP). In the Sway condition the viewpoint included a walking animation, but not in NoSway. The results show strong illusions of body ownership, agency and walking, in the 1PP compared to the 3PP condition, and an enhanced level of arousal while the walking was up a virtual hill. Sway reduced the level of agency. We conclude with a discussion of the results in the light of current theories of agency.

Maintenance dose conversion between oral risperidone and paliperidone palmitate 1 month: Practical guidance based on pharmacokinetic simulations.

PubMed

Russu, Alberto; Kern Sliwa, Jennifer; Ravenstijn, Paulien; Singh, Arun; Mathews, Maju; Kim, Edward; Gopal, Srihari

2018-06-01

We assessed the dosage strengths of paliperidone palmitate 1-month (PP1M) long-acting injectable resulting in similar steady-state (SS) exposures to the dosage strengths of oral risperidone using pharmacokinetic (PK) simulations. Population PK simulations of SS PK were performed using the PK models of oral risperidone and PP1M. The concentrations of active moiety (risperidone + paliperidone) from risperidone were compared to paliperidone concentrations resulting from PP1M administration. Similarity was assessed via graphical evaluation of median and 90% prediction intervals of SS PK profiles over 28 days. Oral risperidone doses of 1, 2, 3, 4, and 6 mg/d are expected to result in similar SS PK as PP1M doses of 25, 50, 75, 100, and 150 mg eq. (which correspond to 39, 78, 117, 156, and 234 mg of paliperidone palmitate) respectively (ie 25-fold dose conversion factor from oral risperidone to PP1M). This study provides clinicians with a practical guidance to establish suitable maintenance dose levels of PP1M and oral risperidone when transitioning patients from one formulation to another. © 2018 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

A Cdk9-PP1 switch regulates the elongation-termination transition of RNA polymerase II.

PubMed

Parua, Pabitra K; Booth, Gregory T; Sansó, Miriam; Benjamin, Bradley; Tanny, Jason C; Lis, John T; Fisher, Robert P

2018-06-13

The end of the RNA polymerase II (Pol II) transcription cycle is strictly regulated to prevent interference between neighbouring genes and to safeguard transcriptome integrity 1 . The accumulation of Pol II downstream of the cleavage and polyadenylation signal can facilitate the recruitment of factors involved in mRNA 3'-end formation and termination 2 , but how this sequence is initiated remains unclear. In a chemical-genetic screen, human protein phosphatase 1 (PP1) isoforms were identified as substrates of positive transcription elongation factor b (P-TEFb), also known as the cyclin-dependent kinase 9 (Cdk9)-cyclin T1 (CycT1) complex 3 . Here we show that Cdk9 and PP1 govern phosphorylation of the conserved elongation factor Spt5 in the fission yeast Schizosaccharomyces pombe. Cdk9 phosphorylates both Spt5 and a negative regulatory site on the PP1 isoform Dis2 4 . Sites targeted by Cdk9 in the Spt5 carboxy-terminal domain can be dephosphorylated by Dis2 in vitro, and dis2 mutations retard Spt5 dephosphorylation after inhibition of Cdk9 in vivo. Chromatin immunoprecipitation and sequencing analysis indicates that Spt5 is dephosphorylated as transcription complexes traverse the cleavage and polyadenylation signal, concomitant with the accumulation of Pol II phosphorylated at residue Ser2 of the carboxy-terminal domain consensus heptad repeat 5 . A conditionally lethal Dis2-inactivating mutation attenuates the drop in Spt5 phosphorylation on chromatin, promotes transcription beyond the normal termination zone (as detected by precision run-on transcription and sequencing 6 ) and is genetically suppressed by the ablation of Cdk9 target sites in Spt5. These results suggest that the transition of Pol II from elongation to termination coincides with a Dis2-dependent reversal of Cdk9 signalling-a switch that is analogous to a Cdk1-PP1 circuit that controls mitotic progression 4 .

v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

PubMed

Xie, W; Fletcher, B S; Andersen, R D; Herschman, H R

1994-10-01

We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.

Trends in Penile Prosthetics: Influence of Patient Demographics, Surgeon Volume, and Hospital Volume on Type of Penile Prosthesis Inserted in New York State.

PubMed

Kashanian, James A; Golan, Ron; Sun, Tianyi; Patel, Neal A; Lipsky, Michael J; Stahl, Peter J; Sedrakyan, Art

2018-02-01

Penile prostheses (PPs) are a discrete, well-tolerated treatment option for men with medical refractory erectile dysfunction. Despite the increasing prevalence of erectile dysfunction, multiple series evaluating inpatient data have found a decrease in the frequency of PP surgery during the past decade. To investigate trends in PP surgery and factors affecting the choice of different PPs in New York State. This study used the New York State Department of Health Statewide Planning and Research Cooperative (SPARCS) data cohort that includes longitudinal information on hospital discharges, ambulatory surgery, emergency department visits, and outpatient services. Patients older than 18 years who underwent inflatable or non-inflatable PP insertion from 2000 to 2014 were included in the study. Influence of patient demographics, surgeon volume, and hospital volume on type of PP inserted. Since 2000, 14,114 patients received PP surgery in New York State; 12,352 PPs (88%) were inflatable and 1,762 (12%) were non-inflatable, with facility-level variation from 0% to 100%. There was an increasing trend in the number of annual procedures performed, with rates of non-inflatable PP insertion decreasing annually (P < .01). More procedures were performed in the ambulatory setting over time (P < .01). Important predictors of device choice were insurance type, year of insertion, hospital and surgeon volume, and the presence of comorbidities. Major influences in choice of PP inserted include racial and socioeconomic factors and surgeon and hospital surgical volume. Use of the SPARCS database, which captures inpatient and outpatient services, allows for more accurate insight into trends in contrast to inpatient sampling alone. However, SPARCS is limited to patients within New York State and the results might not be generalizable to men in other states. Also, patient preference was not accounted for in these analyses, which can play a role in PP selection. During the past 14 years, there has been an increasing trend in inflatable PP surgery for the management of erectile dysfunction. Most procedures are performed in the ambulatory setting and not previously captured by prior studies using inpatient data. Kashanian JA, Golan R, Sun T, et al. Trends in Penile Prosthetics: Influence of Patient Demographics, Surgeon Volume, and Hospital Volume on Type of Penile Prosthesis Inserted in New York State. J Sex Med 2018;15:245-250. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl.

PubMed

Odai, H; Sasaki, K; Iwamatsu, A; Nakamoto, T; Ueno, H; Yamagata, T; Mitani, K; Yazaki, Y; Hirai, H

1997-04-15

Grb2/Ash and Shc are the adapter proteins that link tyrosine-kinase receptors to Ras and make tyrosine-kinase functionally associated with receptors and Ras in fibroblasts and hematopoietic cells. Grb2/Ash and Shc have the SH3, SH2, or phosphotyrosine binding domains. These domains bind to proteins containing proline-rich regions or tyrosine-phosphorylated proteins and contribute to the association of Grb2/Ash and Shc with other signaling molecules. However, there could remain unidentified signaling molecules that physically and functionally interact with these adapter proteins and have biologically important roles in the signaling pathways. By using the GST fusion protein including the full length of Grb2/Ash, we have found that c-Cbl and an unidentified 135-kD protein (pp135) are associated with Grb2/Ash. We have also found that they become tyrosine-phosphorylated by treatment of a human leukemia cell line, UT-7, with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have purified the pp135 by using GST-Grb2/Ash affinity column and have isolated the full-length complementary DNA (cDNA) encoding the pp135 using a cDNA probe, which was obtained by the degenerate polymerase chain reaction based on a peptide sequence of the purified pp135. The cloned cDNA has 3,958 nucleotides that contain a single long open reading frame of 3,567 nucleotides, encoding a 1,189 amino acid protein with a predicted molecular weight of approximately 133 kD. The deduced amino acid sequence reveals that pp135 is a protein that has one SH2, one SH3, and one proline-rich domain. The pp135, which contains two motifs conserved among the inositol polyphosphate-5-phosphatase proteins, was shown to have the inositol polyphosphate-5-phosphatase activity. The pp135 was revealed to associate constitutively with Grb2/Ash and inducibly with Shc using UT-7 cells stimulated with GM-CSF. In the cell lines derived from human chronic myelogenous leukemia, pp135 was constitutively tyrosine-phosphorylated and associated with Shc and Bcr-Abl. These facts suggest that pp135 is a signaling molecule that has a unique enzymatic activity and should play an important role in the signaling pathway triggered by GM-CSF and in the transformation of hematopoietic cells caused by Bcr-Abl.

Maternally derived anti-fibroblast growth factor 23 antibody as new tool to reduce phosphorus requirement of chicks.

PubMed

Ren, Zhouzheng; Bütz, Daniel E; Sand, Jordan M; Cook, Mark E

2017-04-01

Novel means to reduce phosphate input into poultry feeds and increase its retention would preserve world phosphate reserves and reduce environmental impact of poultry production. Here we show that a maternally derived antibody to a fibroblast growth factor-23 (FGF-23) peptide (GMNPPPYS) alleviated phosphorus deficiency in chicks fed low non-phytate phosphorus (nPP) diets. White Leghorn laying hens were vaccinated with either an adjuvant control or the synthetic FGF-23 peptide, and chicks with control or anti-FGF-23 maternal antibodies were fed a diet containing either 0.13 or 0.45% nPP (experiment 1), and 0.20 or 0.45% nPP (experiment 2) for 14 d. In both experiments, decreasing nPP from 0.45 to 0.13 or 0.20% decreased BW gain, G:F, excreta phosphorus, plasma phosphate, and plasma FGF-23 at all time periods examined (nPP main effect, P < 0.05). In experiment 1, chicks with maternal anti-FGF-23 antibody had increased tibiotarsi ash (d 14), and decreased excreta phosphate (d 7, 14) and plasma intact parathyroid hormone (d 7) when compared to chicks with control antibody (antibody main effect, P < 0.05). Mortality (d 7 to 14, 1 to 14), posture scores (d 7, 14) and bone lesion scores (d 14) decreased and plasma phosphate (d 14) increased in anti-FGF-23 chicks fed 0.13% nPP, compared to those with control antibody on the same diet (P < 0.05). In experiment 2, chicks with maternal anti-FGF-23 antibody had increased tibiotarsi ash (d 14), and plasma phosphate (d 14) and 1,25(OH)2D3 (d 14) levels, compared to chicks with control antibody (antibody main effect, P < 0.05). BW gain and G:F were increased in chicks with anti-FGF-23 antibody fed 0.20% nPP, compared to control antibody chicks on the same diet, at all time periods examined (P < 0.05). In conclusion, maternally-derived anti-FGF-23 antibody increased phosphorus retention in chicks fed diets containing either 0.13 or 0.20% nPP and thereby, reduced signs of phosphorus deficiency. © 2016 Poultry Science Association Inc.

Link Between Perceived Body Weight and Smoking Behavior Among Adolescents.

PubMed

Yoon, Jangho; Bernell, Stephanie L

2016-11-01

This study investigates a relationship between overweight perception and smoking among adolescents. Data were retrieved from the Youth Risk Behavior Survey (YRBS), a biennial survey of a nationally representative sample of students in grades 9 through 12 in the United States. We analyze five waves of repeated cross-sections (N = 73 376) for the years 2005-2013. We estimate a recursive simultaneous-equations system in which body weight perception, which is a function of actual weight, influences smoking status. Outcome measures are binary indicators for current smoking and frequent current smoking. Perceived weight is categorized into very overweight perception, slightly overweight perception, and about the right weight/underweight perception. In comparison to adolescents who perceive themselves to be the right weight or underweight, adolescents who perceive themselves to be very overweight are 6.1 percentage points (pp) (standard error [SE] = 1.6pp) more likely to currently smoking and 3.3pp (SE = 1.2pp) more likely to frequently smoke. Adolescents with slightly overweight perception are 7.9pp (SE = 1.0pp) and 2.5pp (SE = 0.6pp) more likely to currently smoke and frequently smoke, respectively, as compared to those with the right weight/underweight perception. The relationships are larger for females, and appear to be mediated by weight-loss activity. In an era of tight budgets, it is crucial to address both obesity and smoking in manners that do not work at cross purposes. Strategies to combat youth smoking may be more effective if the perception of being overweight is considered an important risk factor, especially among female adolescents. We find that perception of being overweight is an important causal risk factor for adolescent smoking. Main findings of this study imply that even a slight change in the perception of body weight may lead to a significant change in smoking behavior among adolescents, especially among females and that the perception of being overweight induces adolescents to smoke regularly. Unlike most prior studies, we discovered a positive effect of slight overweight perception on smoking for adolescent males. Our findings emphasize the importance of addressing both obesity and smoking in manners that do not work at cross purposes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Study of light mesons with WASA-at-COSY

NASA Astrophysics Data System (ADS)

Prencipe, Elisabetta

2014-06-01

The WASA detector, operating at the COSY facility in Jülich (Germany) has been collecting data since 2007. The experiment allows to perform studies of light mesons, such as π0, η and ω rare decay processes, in order to perform precise measurements of branching ratios, determine Dalitz plot parameters, test symmetry and symmetry breaking, and evaluate transition form factors. In the experiments a proton or deuteron beam impinged on a pellet target of hydrogen or deuterium, which allows the reactions proton-proton (pp) or proton-deuteron (pd). A high-statistics sample of η mesons has been collected: in the reaction pd →3He η, 3×107η mesons were tagged at a beam energy of 1.0 GeV, while 5×108η mesons were produced in the reaction pp → ppη at 1.4 GeV. This corresponds to the production of 10 η/s and 100 η/s, respectively, for the two reaction processes. In the pp dataset a higher background level is found compared to the pd data set. In both cases, we identify the η mesons by means of the missing mass derived from the recoil particles. A kinematic fit largely rejects the background in our analysis. The advantage in using the pp dataset is that the production of η mesons is almost a factor of 10 higher than in the pd fusion to 3He. As we plan to measure the branching ratios of very rare processes, high statistics is needed. A summary of the recent activity on the study of light mesons with WASA-at-COSY here is given.

The Effect of Rotation on Legibility of Dot-Matrix Characters

DTIC Science & Technology

1991-02-01

National Standard for human factors engineering of visual display terminal workstations . Paper presented at the meeting of the Human Factors Society...Ed.), Modern issues in perception (pp. 217-226). Amsterdam: North Holland. Human Factors Society, HFS/ANSI VDT Standards Committee. (1988). American

JPRS Report, Science & Technology. China.

DTIC Science & Technology

1989-03-29

Commun ., Vol COM-29, No 6, pp 895-901, June 1981. [4] R.C. Titsworth , "A Boolean-Function-Multiplexed Telemetry System," IEEE Trans, on SET, pp 42...Reagents 39 Gene-Engineered Human Epithelium Growth Factor (hEGF) 39 Superfine Snake Venom 39 COMPUTERS Ai Computer System LISP-MI [Zheng Shouqi, et...XUEBAO, No 3, Jun 88] 134 Coordinated Development of Microwave, Optical Communications [Zhang Xu; DIANXIN KUAIBAO, No 11, Nov 88] 143 Error

Effects of Computer Architecture on FFT (Fast Fourier Transform) Algorithm Performance.

DTIC Science & Technology

1983-12-01

Criteria for Efficient Implementation of FFT Algorithms," IEEE Transactions on Acoustics, Speech, and Signal Processing, Vol. ASSP-30, pp. 107-109, Feb...1982. Burrus, C. S. and P. W. Eschenbacher. "An In-Place, In-Order Prime Factor FFT Algorithm," IEEE Transactions on Acoustics, Speech, and Signal... Transactions on Acoustics, Speech, and Signal Processing, Vol. ASSP-30, pp. 217-226, Apr. 1982. Control Data Corporation. CDC Cyber 170 Computer Systems

The Shock and Vibration Digest. Volume 14, Number 5

DTIC Science & Technology

1982-05-01

Engrg., Santiago de Chile ,_[_, paper B3, pp 117- 129(1969). 13. Crandall, S.H., Lee, S.S., and Williams, J.H., Jr., "Accumulated Slip of a...Temperature, en - vironment, cumulative damage, and shock loading factors can also contribute to Cf depending on the operating conditions of the...Cycle Fatigue," ASME Proc. Intl. Conf. Reliability, Stress Analy- sis Failure Prevention Methods Mech. Des ., pp 237-245 (1980). 18. Shure, J.R. and

Maternal and Cord Serum Cytokine Changes with Continuous and Intermittent Labor Epidural Analgesia: A Randomized Study

PubMed Central

Mantha, Venkat R.; Vallejo, Manuel C.; Ramesh, Vimala; Jones, Bobby L.; Ramanathan, Sivam

2012-01-01

Background. Maternal fever during labor epidural analgesia (LEA) may cause increased maternal and cord serum inflammatory cytokines. We report the effects of intermittent and continuous LEA on these cytokines. Methods. Ninety-two women were randomly assigned to continuous (CLEA) or intermittent (ILEA) groups, 46 in each. Maternal temperature was checked and blood drawn at epidural insertion (baseline) and four-hourly until 4 h postpartum (4 PP). Cord blood was drawn after placental delivery. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte macrophage-colony stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) were measured and analyzed according to group randomization, and then combined and reanalyzed as febrile (temperature ≥38°C) or afebrile groups. Results. Significant intragroup changes from baseline were noted in some groups. Data are pg/mL, median (Q1/Q3). IL-6 rose at all time points in all groups. CLEA: baseline: 18.5 (12.5/31.1), 4 h: 80.0 (46.3/110.8), 8 h: 171.9 (145.3/234.3), and 4 PP: 81 (55.7/137.4). ILEA: baseline: 15.7 (10.2/27.1), 4 h: 68.2 (33.3/95.0), 8 h: 125.0 (86.3/195.0), and 4 PP: 70.2 (54.8/103.6). Febrile group: baseline: 21.6 (13.8/40.9), 4 h: 83.9 (47.5/120.8), 8 h: 186.7 (149.6/349.9), and 4 PP: 105.8 (65.7/158.8). Afebrile group: baseline: 10.9 (2.1/17.4), 4 h: 38.2 (15.0/68.2), 8 h: 93.8 (57.1/135.7), and 4 PP: 52.9 (25.1/78). IL-8 rose at all time points in CLEA: baseline: 2.68 (0.0/4.3), 4 h: 3.7 (0.0/6.5), 8 h: 6.0 (3.3/9.6), 4 PP: 5.6 (0.8/8.0), and afebrile group baseline: 2.5 (0.0/4.7), 4 h: 3.3 (0.0/6.2), 8 h: 5.3 (1.9/9.8), and 4 PP: 4.7 (0.0/7.6). It fell at 4 PP in febrile group: baseline: 4.1 (0.0/6.4), 4 h: 3.8 (0.0/6.5), 8 h: 5.2 (2.5/8.0), and 4 PP: 2.9 (0.0/4.0). GM-CSF increased at 8 h and decreased at 4 PP in ILEA baseline: 2.73 (0.0/7.2), 4 h: 2.73 (0.0/7.9), 8 h: 3.9 (2.7/11.5), and 4 PP: 2.0 (0.0/7.2). It increased at 4 h and 8 h and decreased at 4 PP in febrile group: baseline: 2.6 (0.0/4.2), 4 h: 3.2 (2.1/7.0), 8 h: 4.0 (3.2/12.3), and 4 PP: 2.4 (1.7/12.6). There were no intergroup cytokine changes in maternal or cord serum in CLEA versus ILEA or febrile versus afebrile groups. Conclusions. Some cytokines, especially IL-6, rise physiologically during labor epidural analgesia. PMID:22629160

Development of Risk Uncertainty Factors from Historical NASA Projects

NASA Technical Reports Server (NTRS)

Amer, Tahani R.

2011-01-01

NASA is a good investment of federal funds and strives to provide the best value to the nation. NASA has consistently budgeted to unrealistic cost estimates, which are evident in the cost growth in many of its programs. In this investigation, NASA has been using available uncertainty factors from the Aerospace Corporation, Air Force, and Booz Allen Hamilton to develop projects risk posture. NASA has no insight into the developmental of these factors and, as demonstrated here, this can lead to unrealistic risks in many NASA Programs and projects (P/p). The primary contribution of this project is the development of NASA missions uncertainty factors, from actual historical NASA projects, to aid cost-estimating as well as for independent reviews which provide NASA senior management with information and analysis to determine the appropriate decision regarding P/p. In general terms, this research project advances programmatic analysis for NASA projects.

Retinoic Acid Protects Cardiomyocytes from High Glucose-Induced Apoptosis via Inhibition of Sustained Activation of NF-κB Signaling

PubMed Central

Nizamutdinova, Irina T.; Guleria, Rakeshwar S.; Singh, Amar B.; Kendall, Jonathan A.; Baker, Kenneth M.; Pan, Jing

2012-01-01

We have previously shown that retinoic acid (RA) has protective effects on high glucose (HG)-induced cardiomyocyte apoptosis. To further elucidate the molecular mechanisms of RA effects, we determined the interaction between nuclear factor (NF)-κB and RA signaling. HG induced a sustained phosphorylation of IKK/IκBα and transcriptional activation of NF-κB in cardiomyocytes. Activated NF-κB signaling has an important role in HG-induced cardiomyocyte apoptosis and gene expression of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1 (MCP-1). All-trans RA (ATRA) and LGD1069, through activation of RAR/RXR-mediated signaling, inhibited the HG-mediated effects in cardiomyocytes. The inhibitory effect of RA on NF-κB activation was mediated through inhibition of IKK/IκBα phosphorylation. ATRA and LGD1069 treatment promoted protein phosphatase 2A (PP2A) activity, which was significantly suppressed by HG stimulation. The RA effects on IKK and IκBα were blocked by okadaic acid or silencing the expression of PP2Ac-subunit, indicating that the inhibitory effect of RA on NF-κB is regulated through activation of PP2A and subsequent dephosphorylation of IKK/IκBα. Moreover, ATRA and LGD1069 reversed the decreased PP2A activity and inhibited the activation of IKK/IκBα and gene expression of MCP-1, IL-6 and TNF-α in the hearts of Zucker diabetic fatty rats. In summary, our findings suggest that the suppressed activation of PP2A contributed to sustained activation of NF-κB in HG-stimulated cardiomyocytes; and that the protective effect of RA on hyperglycemia-induced cardiomyocyte apoptosis and inflammatory responses is partially regulated through activation of PP2A and suppression of NF-κB-mediated signaling and downstream targets. PMID:22718360

Rotational Uniqueness Conditions under Oblique Factor Correlation Metric

ERIC Educational Resources Information Center

Peeters, Carel F. W.

2012-01-01

In an addendum to his seminal 1969 article Joreskog stated two sets of conditions for rotational identification of the oblique factor solution under utilization of fixed zero elements in the factor loadings matrix (Joreskog in "Advances in factor analysis and structural equation models," pp. 40-43, 1979). These condition sets, formulated under…

Cytokines Alter Glucocorticoid Receptor Phosphorylation in Airway Cells

PubMed Central

Bouazza, Belaid; Krytska, Kateryna; Debba-Pavard, Manel; Amrani, Yassine; Honkanen, Richard E.; Tran, Jennifer

2012-01-01

Corticosteroid insensitivity (CSI) represents a profound challenge in managing patients with asthma. We recently demonstrated that short exposure of airway smooth muscle cells (ASMCs) to proasthmatic cytokines drastically reduced their responsiveness to glucocorticoids (GCs), an effect that was partially mediated via interferon regulatory factor-1, suggesting the involvement of additional mechanisms (Am J Respir Cell Mol Biol 2008;38:463–472). Although GC receptor (GR) can be phosphorylated at multiple serines in the N-terminal region, the major phosphorylation sites critical for GR transcriptional activity are serines 211 (Ser211) and 226 (Ser226). We tested the novel hypothesis that cytokine-induced CSI in ASMCs is due to an impaired GR phosphorylation. Cells were treated with TNF-α (10 ng/ml) and IFN-γ (500 UI/ml) for 6 hours and/or fluticasone (100 nm) added 2 hours before. GR was constitutively phosphorylated at Ser226 but not at Ser211 residues. Cytokines dramatically suppressed fluticasone-induced phosphorylation of GR on Ser211 but not on Ser226 residues while increasing the expression of Ser/Thr protein phosphatase (PP)5 but not that of PP1 or PP2A. Transfection studies using a reporter construct containing GC responsive elements showed that the specific small interfering RNA–induced mRNA knockdown of PP5, but not that of PP1 or PP2A, partially prevented the cytokine suppressive effects on GR-meditated transactivation activity. Similarly, cytokines failed to inhibit GC-induced GR-Ser211 phosphorylation when expression of PP5 was suppressed. We propose that the novel mechanism that proasthmatic cytokine-induced CSI in ASMCs is due, in part, to PP5-mediated impairment of GR-Ser211 phosphorylation. PMID:22592921

Changes in body composition in apparently healthy urban Indian women up to 3 years postpartum.

PubMed

Kajale, Neha A; Khadilkar, Anuradha V; Chiplonkar, Shashi A; Khadilkar, Vaman

2015-01-01

Dietary and life style practices differ in postpartum (PP) and nonpregnant Indian women. Effect of these practices on postpartum weight retention (PPWR) and development of cardio-metabolic risk (CMR) has been scarcely studied in urban women. Aims of this study were to (i) compare anthropometry, biochemical parameters and body composition up to 3 years PP (ii) effect of PPWR, dietary fat intake and physical activity on CMR factors. Cross-sectional, 300-fullterm, apparently healthy primi-parous women (28.6 ± 3.4 years) randomly selected. 128 women within 7-day of delivery (Group-A), 88 with 1-2 years (Group-B) and 84 with 3-4-year-old-children (Group-C) were studied. Anthropometry, sociodemographic status, physical activity, diet, clinical examination, biochemical tests, body composition, at total body (TB), by dual energy X-ray absorptiometry (GE-Lunar DPX) were collected. Women at 3-year PP showed higher weight retention (6.5[10] kg) than at 1-year (3.0[7] kg) (median [IQR]). Android fat % (central obesity) increased (P < 0.05) at 1-year PP (47 ± 10.0%) when compared to 1-week PP (44.3 ± 6.7%) and remained elevated at 3-year PP (45.6 ± 10.2%). Regression analysis revealed that at 1-year PP, increase in PPWR (Odd Ratio [OR] 1.8, 95% confidence interval [CI] = [1.2, 2.5], P < 0.001) and inactivity (OR 1.4, 95% CI= (0.97, 2.0), P < 0.1) were predictors for CMR. At 3-year PP, only PPWR was responsible for increase in CMR parameters (OR 1.6, 95% CI = (1.3, 2.3), P < 0.001) and not inactivity (P > 0.1). Postdelivery, low physical activity and higher PPWR may increase CMR in Indian women.

Development of temperature-based algorithms for the estimation of microphytobenthic primary production in a tidal flat: A case study in Daebu mudflat, Korea.

PubMed

Kwon, Bong-Oh; Kim, Hae-Cheol; Koh, Chul-Hwan; Ryu, Jongseong; Son, SeungHyun; Kim, Yong Hoon; Khim, Jong Seong

2018-05-23

This study presents the results of field experiments that were designed to investigate the photophysiological characteristics of microphytobenthos (MPB) and to estimate primary production (PP) in Daebu mudflat, which is located at the west coast of Korea. A typical seasonal (or monthly) fluctuation of intertidal MPB PP was found in association with biotic (benthic Chl-a) and/or abiotic parameters (irradiance and temperature) over a period of three years. From a series of field-laboratory experiments using the oxygen micro-profiling method (totaling 28 surveys), three consistent phenomena were observed: 1) winter to early spring algal blooms, 2) seasonal changes in Q 10 , and 3) temperature dependent MPB photosynthesis-irradiance (P-I). In particular, both the chlorophyll-specific maximum photosynthetic capacity (P b max ) and the saturated light intensity (I k ), derived from 126 P-I curves (1870 data sets of oxygen micro-profiling in the sediment), were significantly correlated with sediment temperature (p < 0.01). To develop an empirical MPB PP model, the relationships between P-I parameters and environmental variables were parameterized following established exponential forms (e.g., Q 10 ). It was possible to estimate the MPB PP in Daebu mudflat area by using easily accessible explanatory factor, suitable to be used for future explorations of parameters such as sediment temperature, irradiance, chlorophyll concentration, and tidal height. The estimated annual MPB PP based on the empirical PP model were found to be greater than that in the Wadden Sea and average annual PP in the temperate zones of the world. Authors believe that the present approach of the MPB PP estimation could be combined with remote-sensing techniques (e.g., satellites) to support coastal ecosystem management. Copyright © 2018 Elsevier Ltd. All rights reserved.

Location of intense electromagnetic ion cyclotron (EMIC) wave events relative to the plasmapause: Van Allen Probes observations

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

Tetrick, S. S.; Engebretson, M. J.; Posch, J. L.

In this paper, we have studied the spatial location relative to the plasmapause (PP) of the most intense electromagnetic ion cyclotron (EMIC) waves observed on Van Allen Probes A and B during their first full precession in local time. Most of these waves occurred over an L range of from -1 to +2 R E relative to the PP. Very few events occurred only within 0.1 R E of the PP, and events with a width in L of < 0.2 R E occurred both inside and outside the PP. Wave occurrence was always associated with high densities of ringmore » current ions; plasma density gradients or enhancements were associated with some events but were not dominant factors in determining the sites of wave generation. Storm main and recovery phase events in the dusk sector were often inside the PP, and dayside events during quiet times and compressions of the magnetosphere were more evenly distributed both inside and outside the PP. Superposed epoch analyses of the dependence of wave onset on solar wind dynamic pressure (Psw), the SME (SuperMAG auroral electrojet) index, and the SYM-H index showed that substorm injections and solar wind compressions were temporally closely associated with EMIC wave onset but to an extent that varied with frequency band, magnetic local time, and storm phase, and location relative to the PP. Finally, the fact that increases in SME and Psw were less strongly correlated with events at the PP than with other events might suggest that the occurrence of those events was affected by the density gradient.« less

Location of intense electromagnetic ion cyclotron (EMIC) wave events relative to the plasmapause: Van Allen Probes observations

DOE PAGES

Tetrick, S. S.; Engebretson, M. J.; Posch, J. L.; ...

2017-03-17

In this paper, we have studied the spatial location relative to the plasmapause (PP) of the most intense electromagnetic ion cyclotron (EMIC) waves observed on Van Allen Probes A and B during their first full precession in local time. Most of these waves occurred over an L range of from -1 to +2 R E relative to the PP. Very few events occurred only within 0.1 R E of the PP, and events with a width in L of < 0.2 R E occurred both inside and outside the PP. Wave occurrence was always associated with high densities of ringmore » current ions; plasma density gradients or enhancements were associated with some events but were not dominant factors in determining the sites of wave generation. Storm main and recovery phase events in the dusk sector were often inside the PP, and dayside events during quiet times and compressions of the magnetosphere were more evenly distributed both inside and outside the PP. Superposed epoch analyses of the dependence of wave onset on solar wind dynamic pressure (Psw), the SME (SuperMAG auroral electrojet) index, and the SYM-H index showed that substorm injections and solar wind compressions were temporally closely associated with EMIC wave onset but to an extent that varied with frequency band, magnetic local time, and storm phase, and location relative to the PP. Finally, the fact that increases in SME and Psw were less strongly correlated with events at the PP than with other events might suggest that the occurrence of those events was affected by the density gradient.« less

[Central pulse pressure but not brachial blood pressure is the predominant factor affecting aortic arterial stiffness].

PubMed

Xiao, Wen-Kai; Ye, Ping; Bai, Yong-Yi; Luo, Lei-Ming; Wu, Hong-Mei; Gao, Peng

2015-01-01

To investigate the differences in central hemodynamic indices between hypertensive and normotensive subjects and identify the blood pressure index that the most strongly correlate with arterial stiffness and vascular damage markers. A cohort of 820 hypertensive patients and 820 normotensive individuals matched for age and gender were enrolled in this study. We measured carotid-femoral and carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and central blood pressures using pulse wave analysis and applanation tonometry. Plasma homocysteine (HCY), high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also tested in these subjects. In both hypertensive and normotensive subjects, the central systolic blood pressure (SBP) and pulse pressure (PP) were significantly lower than brachial SBP and PP; this PP amplification was significantly lower in the normotensives (9.85∓6.55 mmHg) than in the hypertensives (12.64∓6.69 mmHg), but the amplification ratios were comparable between the two groups. Blood pressure and age were closely related with aortic arterial stiffness. Compared with normotensive subjects, hypertensive subjects had higher carotid-femoral PWV and AIx, and showed significantly lowered PP amplification ratio with age. Central PP was more strongly related to arterial stiffness and vascular damage markers than the other pressure indices. Multivariate analyses revealed that carotid-femoral PWV and aortic AIx were strongly influenced by central PP but not by the mean blood pressure or brachial PP. The central PP is a more direct indicator of central arterial stiffness and a better marker of vascular aging than other blood pressure variables. These findings support the use of central blood pressure as a treatment target in future trials.

Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress.

PubMed

Sripathi, Srinivas R; He, Weilue; Um, Ji-Yeon; Moser, Trevor; Dehnbostel, Stevie; Kindt, Kimberly; Goldman, Jeremy; Frost, Megan C; Jahng, Wan Jin

2012-01-01

Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress.

Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress

PubMed Central

Um, Ji-Yeon; Moser, Trevor; Dehnbostel, Stevie; Kindt, Kimberly; Goldman, Jeremy; Frost, Megan C.; Jahng, Wan Jin

2016-01-01

Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress. PMID:27974994

Charged-particle nuclear modification factors in PbPb and pPb collisions at √{s_{NN}}=5.02 TeV

NASA Astrophysics Data System (ADS)

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T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Rossini, M.; Schönenberger, M.; Starodumov, A.; Tavolaro, V. R.; Theofilatos, K.; Wallny, R.; Aarrestad, T. K.; Amsler, C.; Caminada, L.; Canelli, M. F.; De Cosa, A.; Galloni, C.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Yang, Y.; Zucchetta, A.; Candelise, V.; Doan, T. H.; Jain, Sh.; Khurana, R.; Konyushikhin, M.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Moya, M. Miñano; Paganis, E.; Psallidas, A.; Tsai, J. f.; Tzeng, Y. M.; Asavapibhop, B.; Singh, G.; Srimanobhas, N.; Suwonjandee, N.; Adiguzel, A.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Cerci, D. Sunar; Tali, B.; Topakli, H.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Bilmis, S.; Isildak, B.; Karapinar, G.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Yetkin, E. A.; Yetkin, T.; Cakir, A.; Cankocak, K.; Sen, S.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; El Nasr-storey, S. Seif; Smith, D.; Smith, V. J.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. 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I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Berry, E.; Cutts, D.; Garabedian, A.; Hakala, J.; Heintz, U.; Hogan, J. M.; Jesus, O.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Piperov, S.; Sagir, S.; Spencer, E.; Syarif, R.; Breedon, R.; Breto, G.; Burns, D.; De La Barca Sanchez, M. Calderon; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Bravo, C.; Cousins, R.; Dasgupta, A.; Everaerts, P.; Florent, A.; Hauser, J.; Ignatenko, M.; Mccoll, N.; Saltzberg, D.; Schnaible, C.; Takasugi, E.; Valuev, V.; Weber, M.; Bouvier, E.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Shirazi, S. M. A. 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B.; Ferguson, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Kaufman, G. Nicolas; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Winn, D.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Cremonesi, M.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hare, D.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; De Sá, R. Lopes; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Wu, Y.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Low, J. F.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Shchutska, L.; Sperka, D.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, J. R.; Adams, T.; Askew, A.; Bein, S.; Diamond, B.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Prosper, H.; Santra, A.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Jung, K.; Kurt, P.; O'Brien, C.; Gonzalez, I. D. Sandoval; Turner, P.; Varelas, N.; Wang, H.; Wu, Z.; Zakaria, M.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Anderson, I.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Martin, C.; Osherson, M.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; Xin, Y.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Bruner, C.; Castle, J.; Forthomme, L.; Kenny, R. P.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Sanders, S.; Stringer, R.; Takaki, J. D. Tapia; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Kellogg, R. G.; Kolberg, T.; Kunkle, J.; Lu, Y.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Apyan, A.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; Demiragli, Z.; Di Matteo, L.; Ceballos, G. Gomez; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Krajczar, K.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Sumorok, K.; Tatar, K.; Varma, M.; Velicanu, D.; Veverka, J.; Wang, J.; Wang, T. W.; Wyslouch, B.; Yang, M.; Zhukova, V.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Finkel, A.; Gude, A.; Hansen, P.; Kalafut, S.; Kao, S. C.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bartek, R.; Bloom, K.; Claes, D. R.; Dominguez, A.; Fangmeier, C.; Suarez, R. Gonzalez; Kamalieddin, R.; Kravchenko, I.; Rodrigues, A. Malta; Meier, F.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; George, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kaisen, J.; Kharchilava, A.; Kumar, A.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; De Lima, R. Teixeira; Trocino, D.; Wang, R.-J.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Kubik, A.; Kumar, A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Anampa, K. Hurtado; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Hughes, R.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Lange, D.; Luo, J.; Marlow, D.; Medvedeva, T.; Mei, K.; Mooney, M.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Svyatkovskiy, A.; Tully, C.; Zuranski, A.; Malik, S.; Barker, A.; Barnes, V. E.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Schulte, J. 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G.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Juska, E.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Rose, A.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Cowden, C.; Damgov, J.; De Guio, F.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Sturdy, J.; Belknap, D. A.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.

2017-04-01

The spectra of charged particles produced within the pseudorapidity window | η| < 1 at √{s_{NN}}=5.02 TeV are measured using 404 μb-1 of PbPb and 27.4 pb-1 of pp data collected by the CMS detector at the LHC in 2015. The spectra are presented over the transverse momentum ranges spanning 0 .5 < p T < 400 GeV in pp and 0 .7 < p T < 400 GeV in PbPb collisions. The corresponding nuclear modification factor, R AA, is measured in bins of collision centrality. The R AA in the 5% most central collisions shows a maximal suppression by a factor of 7-8 in the p T region of 6-9 GeV. This dip is followed by an increase, which continues up to the highest p T measured, and approaches unity in the vicinity of p T = 200 GeV. The R AA is compared to theoretical predictions and earlier experimental results at lower collision energies. The newly measured pp spectrum is combined with the pPb spectrum previously published by the CMS collaboration to construct the pPb nuclear modification factor, R pA, up to 120 GeV. For p T > 20 GeV, R pA exhibits weak momentum dependence and shows a moderate enhancement above unity. [Figure not available: see fulltext.

Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis.

PubMed

Ao, M; Chavez, M B; Chu, E Y; Hemstreet, K C; Yin, Y; Yadav, M C; Millán, J L; Fisher, L W; Goldberg, H A; Somerman, M J; Foster, B L

2017-12-01

Although acellular cementum is essential for tooth attachment, factors directing its development and regeneration remain poorly understood. Inorganic pyrophosphate (PP i ), a mineralization inhibitor, is a key regulator of cementum formation: tissue-nonspecific alkaline phosphatase (Alpl/TNAP) null mice (increased PP i ) feature deficient cementum, while progressive ankylosis protein (Ank/ANK) null mice (decreased PP i ) feature increased cementum. Bone sialoprotein (Bsp/BSP) and osteopontin (Spp1/OPN) are multifunctional extracellular matrix components of cementum proposed to have direct and indirect effects on cell activities and mineralization. Studies on dentoalveolar development of Bsp knockout (Bsp -/- ) mice revealed severely reduced acellular cementum, however underlying mechanisms remain unclear. The similarity in defective cementum phenotypes between Bsp -/- mice and Alpl -/- mice (the latter featuring elevated PP i and OPN), prompted us to examine whether BSP is operating by modulating PP i -associated genes. Genetic ablation of Bsp caused a 2-fold increase in circulating PP i , altered mRNA expression of Alpl, Spp1, and Ank, and increased OPN protein in the periodontia. Generation of a Bsp knock-out (KO) cementoblast cell line revealed significantly decreased mineralization capacity, 50% increased PP i in culture media, and increased Spp1 and Ank mRNA expression. While addition of 2μg/ml recombinant BSP altered Spp1, Ank, and Enpp1 expression in cementoblasts, changes resulting from this dose were not dependent on the integrin-binding RGD motif or MAPK/ERK signaling pathway. Decreasing PP i by genetic ablation of Ank on the Bsp -/- mouse background reestablished cementum formation, allowing >3-fold increased acellular cementum volume compared to wild-type (WT). However, deleting Ank did not fully compensate for the absence of BSP. Bsp -/- ; Ank -/- double-deficient mice exhibited mean 20-27% reduced cementum thickness and volume compared to Ank -/- mice. From these data, we conclude that the perturbations in PP i metabolism are not solely driving the cementum pathology in Bsp -/- mice, and that PP i is more potent than BSP as a cementum regulator, as shown by the ability to override loss of BSP by lowering PP i . We propose that BSP and PP i work in concert to direct mineralization in cementum and likely other mineralized tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

Mir-338-3p Mediates Tnf-A-Induced Hepatic Insulin Resistance by Targeting PP4r1 to Regulate PP4 Expression.

PubMed

Dou, Lin; Wang, Shuyue; Sun, Libo; Huang, Xiuqing; Zhang, Yang; Shen, Tao; Guo, Jun; Man, Yong; Tang, Weiqing; Li, Jian

2017-01-01

Insulin resistance is a critical factor contributing to the pathogenesis of type 2 diabetes and other metabolic diseases. Recent studies have indicated that miR-338-3p plays an important role in cancer. Here, we investigated whether miR-338-3p mediates tumour necrosis factor-α (TNF-α)-induced hepatic insulin resistance. The activation of the insulin signalling pathway and the level of glycogenesis were examined in the livers of the db/db and high fat diet (HFD)-fed mice and in HEP1-6 cells transfected with miR-338-3p mimic or inhibitor. Computational prediction of microRNA target, luciferase assay and Western blot were used to assess the miR-338-3p target. Chromatin immunoprecipitation (ChIP) assay was used to determine the transcriptional regulator of miR-338-3p. miR-338-3p was down-regulated in the livers of the db/db, HFD-fed and TNF-α-treated C57BL/6J mice, as well as in mouse HEP1-6 hepatocytes treated with TNF-α. Importantly the down-regulation of miR-338-3p induced insulin resistance, as indicated by impaired glucose tolerance and insulin tolerance. Further research showed that the down-regulated miR-338-3p resulted in the impaired AKT/ glycogen synthase kinase 3 beta (GSl·Gβ) signalling pathway and glycogen synthesis. In contrast, hepatic over-expression of miR-338-3p rescued the TNF-α-induced insulin resistance. Moreover, protein phosphatase 4 regulator subunit 1 (PP4R1) was identified as a direct target of miR-338-3p that mediated hepatic insulin signalling by regulating protein phosphatase 4 (PP4). Finally we identified hepatic nuclear factor 4 alpha (HNF-4α) as the transcriptional regulator of miRNA-338-3p. Our studies provide novel insight into the critical role and molecular mechanism by which miR-338-3p is involved in TNF-α-induced hepatic insulin resistance. miR-338-3p might mediate TNF-α-induced hepatic insulin resistance by targeting PP4R1 to regulate PP4 expression. © 2017 The Author(s). Published by S. Karger AG, Basel.

Energy dependence of the transverse momentum distributions of charged particles in pp collisions measured by ALICE.

PubMed

Abelev, B; Adam, J; Adamová, D; Adare, A M; Aggarwal, M M; Aglieri Rinella, G; Agnello, M; Agocs, A G; Agostinelli, A; Ahammed, Z; Ahmad, N; Ahmad Masoodi, A; Ahmed, I; Ahn, S A; Ahn, S U; Aimo, I; Aiola, S; Ajaz, M; Akindinov, A; Aleksandrov, D; Alessandro, B; Alexandre, D; Alici, A; Alkin, A; Alme, J; Alt, T; Altini, V; Altinpinar, S; Altsybeev, I; Alves Garcia Prado, C; Andrei, C; Andronic, A; Anguelov, V; Anielski, J; Antičić, T; Antinori, F; Antonioli, P; Aphecetche, L; Appelshäuser, H; Arbor, N; Arcelli, S; Armesto, N; Arnaldi, R; Aronsson, T; Arsene, I C; Arslandok, M; Augustinus, A; Averbeck, R; Awes, T C; Äystö, J; Azmi, M D; Bach, M; Badalà, A; Baek, Y W; Bailhache, R; Bala, R; Baldisseri, A; Baltasar Dos Santos Pedrosa, F; Bán, J; Baral, R C; Barbera, R; Barile, F; Barnaföldi, G G; Barnby, L S; Barret, V; Bartke, J; Basile, M; Bastid, N; Basu, S; Bathen, B; Batigne, G; Batyunya, B; Batzing, P C; Baumann, C; Bearden, I G; Beck, H; Bedda, C; Behera, N K; Belikov, I; Bellini, F; Bellwied, R; Belmont-Moreno, E; Bencedi, G; Beole, S; Berceanu, I; Bercuci, A; Berdnikov, Y; Berenyi, D; Bergognon, A A E; Bertens, R A; Berzano, D; Betev, L; Bhasin, A; Bhati, A K; Bhom, J; Bianchi, L; Bianchi, N; Bianchin, C; Bielčík, J; Bielčíková, J; Bilandzic, A; Bjelogrlic, S; Blanco, F; Blanco, F; Blau, D; Blume, C; Bock, F; Bogdanov, A; Bøggild, H; Bogolyubsky, M; Boldizsár, L; Bombara, M; Book, J; Borel, H; Borissov, A; Bornschein, J; Botje, M; Botta, E; Böttger, S; Braidot, E; Braun-Munzinger, P; Bregant, M; Breitner, T; Broker, T A; Browning, T A; Broz, M; Brun, R; Bruna, E; Bruno, G E; Budnikov, D; Buesching, H; Bufalino, S; Buncic, P; Busch, O; Buthelezi, Z; Caffarri, D; Cai, X; Caines, H; Caliva, A; Calvo Villar, E; Camerini, P; Canoa Roman, V; Cara Romeo, G; Carena, F; Carena, W; Carminati, F; Casanova Díaz, A; Castillo Castellanos, J; Casula, E A R; Catanescu, V; Cavicchioli, C; Ceballos Sanchez, C; Cepila, J; Cerello, P; Chang, B; Chapeland, S; Charvet, J L; Chattopadhyay, S; 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Grigoriev, V; Grigoryan, A; Grigoryan, S; Grinyov, B; Grion, N; Grosse-Oetringhaus, J F; Grossiord, J-Y; Grosso, R; Guber, F; Guernane, R; Guerzoni, B; Guilbaud, M; Gulbrandsen, K; Gulkanyan, H; Gunji, T; Gupta, A; Gupta, R; Khan, K H; Haake, R; Haaland, Ø; Hadjidakis, C; Haiduc, M; Hamagaki, H; Hamar, G; Hanratty, L D; Hansen, A; Harris, J W; Harton, A; Hatzifotiadou, D; Hayashi, S; Hayrapetyan, A; Heckel, S T; Heide, M; Helstrup, H; Herghelegiu, A; Herrera Corral, G; Herrmann, N; Hess, B A; Hetland, K F; Hicks, B; Hippolyte, B; Hori, Y; Hristov, P; Hřivnáčová, I; Huang, M; Humanic, T J; Hutter, D; Hwang, D S; Ichou, R; Ilkaev, R; Ilkiv, I; Inaba, M; Incani, E; Innocenti, G M; Ionita, C; Ippolitov, M; Irfan, M; Ivanov, V; Ivanov, M; Ivanytskyi, O; Jachołkowski, A; Jahnke, C; Jang, H J; Janik, M A; Jayarathna, P H S Y; Jena, S; Jimenez Bustamante, R T; Jones, P G; Jung, H; Jusko, A; Kalcher, S; Kaliňák, P; Kalliokoski, T; Kalweit, A; Kang, J H; Kaplin, V; Kar, S; Karasu Uysal, A; Karavichev, O; Karavicheva, T; Karpechev, E; Kazantsev, A; Kebschull, U; Keidel, R; Ketzer, B; Khan, S A; Khan, M M; Khan, P; Khanzadeev, A; Kharlov, Y; Kileng, B; Kim, S; Kim, D W; Kim, D J; Kim, B; Kim, T; Kim, M; Kim, M; Kim, J S; Kirsch, S; Kisel, I; Kiselev, S; Kisiel, A; Kiss, G; Klay, J L; Klein, J; Klein-Bösing, C; Kluge, A; Knichel, M L; Knospe, A G; Köhler, M K; Kollegger, T; Kolojvari, A; Kondratiev, V; Kondratyeva, N; Konevskikh, A; Kovalenko, V; Kowalski, M; Kox, S; Koyithatta Meethaleveedu, G; Kral, J; Králik, I; Kramer, F; Kravčáková, A; Krelina, M; Kretz, M; Krivda, M; Krizek, F; Krus, M; Kryshen, E; Krzewicki, M; Kucera, V; Kucheriaev, Y; Kugathasan, T; Kuhn, C; Kuijer, P G; Kulakov, I; Kumar, J; Kurashvili, P; Kurepin, A B; Kurepin, A; Kuryakin, A; Kushpil, S; Kushpil, V; Kweon, M J; Kwon, Y; Ladrón de Guevara, P; Lagana Fernandes, C; Lakomov, I; Langoy, R; Lara, C; Lardeux, A; La Pointe, S L; La Rocca, P; Lea, R; Lechman, M; Lee, S C; Lee, G R; Legrand, I; Lehnert, J; Lemmon, R C; Lenhardt, M; Lenti, V; León Monzón, I; Lévai, P; Li, S; Lien, J; Lietava, R; Lindal, S; Lindenstruth, V; Lippmann, C; Lisa, M A; Ljunggren, H M; Lodato, D F; Loenne, P I; Loggins, V R; Loginov, V; Lohner, D; Loizides, C; Loo, K K; Lopez, X; López Torres, E; Løvhøiden, G; Lu, X-G; Luettig, P; Lunardon, M; Luo, J; Luparello, G; Luzzi, C; Jacobs, P M; Ma, R; Maevskaya, A; Mager, M; Mahapatra, D P; Maire, A; Malaev, M; Maldonado Cervantes, I; Malinina, L; Mal'Kevich, D; Malzacher, P; Mamonov, A; Manceau, L; Manko, V; Manso, F; Manzari, V; Marchisone, M; Mareš, J; Margagliotti, G V; Margotti, A; Marín, A; Markert, C; Marquard, M; Martashvili, I; Martin, N A; Martinengo, P; Martínez, M I; Martínez García, G; Martin Blanco, J; Martynov, Y; Mas, A; Masciocchi, S; Masera, M; Masoni, A; Massacrier, L; Mastroserio, A; Matyja, A; Mazer, J; Mazumder, R; Mazzoni, M A; Meddi, F; Menchaca-Rocha, A; Mercado Pérez, J; Meres, M; Miake, Y; Mikhaylov, K; Milano, L; Milosevic, J; Mischke, A; Mishra, A N; Miśkowiec, D; 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Soltz, R; Song, M; Song, J; Soos, C; Soramel, F; Spacek, M; Sputowska, I; Spyropoulou-Stassinaki, M; Srivastava, B K; Stachel, J; Stan, I; Stefanek, G; Steinpreis, M; Stenlund, E; Steyn, G; Stiller, J H; Stocco, D; Stolpovskiy, M; Strmen, P; Suaide, A A P; Subieta Vásquez, M A; Sugitate, T; Suire, C; Suleymanov, M; Sultanov, R; Šumbera, M; Susa, T; Symons, T J M; Szanto de Toledo, A; Szarka, I; Szczepankiewicz, A; Szymański, M; Takahashi, J; Tangaro, M A; Tapia Takaki, J D; Tarantola Peloni, A; Tarazona Martinez, A; Tauro, A; Tejeda Muñoz, G; Telesca, A; Terrevoli, C; Ter Minasyan, A; Thäder, J; Thomas, D; Tieulent, R; Timmins, A R; Toia, A; Torii, H; Trubnikov, V; Trzaska, W H; Tsuji, T; Tumkin, A; Turrisi, R; Tveter, T S; Ulery, J; Ullaland, K; Ulrich, J; Uras, A; Urciuoli, G M; Usai, G L; Vajzer, M; Vala, M; Valencia Palomo, L; Vande Vyvre, P; Vannucci, L; Van Hoorne, J W; van Leeuwen, M; Vargas, A; Varma, R; Vasileiou, M; Vasiliev, A; Vechernin, V; Veldhoen, M; Venaruzzo, M; Vercellin, E; Vergara, S; Vernet, R; Verweij, M; Vickovic, L; Viesti, G; Viinikainen, J; Vilakazi, Z; Villalobos Baillie, O; Vinogradov, A; Vinogradov, L; Vinogradov, Y; Virgili, T; Viyogi, Y P; Vodopyanov, A; Völkl, M A; Voloshin, S; Voloshin, K; Volpe, G; von Haller, B; Vorobyev, I; Vranic, D; Vrláková, J; Vulpescu, B; Vyushin, A; Wagner, B; Wagner, V; Wagner, J; Wang, Y; Wang, Y; Wang, M; Watanabe, D; Watanabe, K; Weber, M; Wessels, J P; Westerhoff, U; Wiechula, J; Wikne, J; Wilde, M; Wilk, G; Wilkinson, J; Williams, M C S; Windelband, B; Winn, M; Xiang, C; Yaldo, C G; Yamaguchi, Y; Yang, H; Yang, P; Yang, S; Yano, S; Yasnopolskiy, S; Yi, J; Yin, Z; Yoo, I-K; Yushmanov, I; Zaccolo, V; Zach, C; Zampolli, C; Zaporozhets, S; Zarochentsev, A; Závada, P; Zaviyalov, N; Zbroszczyk, H; Zelnicek, P; Zgura, I S; Zhalov, M; Zhang, F; Zhang, Y; Zhang, H; Zhang, X; Zhou, D; Zhou, Y; Zhou, F; Zhu, X; Zhu, J; Zhu, J; Zhu, H; Zichichi, A; Zimmermann, M B; Zimmermann, A; Zinovjev, G; Zoccarato, Y; Zynovyev, M; Zyzak, M

Differential cross sections of charged particles in inelastic pp collisions as a function of p T have been measured at [Formula: see text] at the LHC. The p T spectra are compared to NLO-pQCD calculations. Though the differential cross section for an individual [Formula: see text] cannot be described by NLO-pQCD, the relative increase of cross section with [Formula: see text] is in agreement with NLO-pQCD. Based on these measurements and observations, procedures are discussed to construct pp reference spectra at [Formula: see text] up to p T =50 GeV/ c as required for the calculation of the nuclear modification factor in nucleus-nucleus and proton-nucleus collisions.

Endoplasmic Reticulum Stress Induces Myostatin High Molecular Weight Aggregates and Impairs Mature Myostatin Secretion.

PubMed

Sachdev, Rishibha; Kappes-Horn, Karin; Paulsen, Lydia; Duernberger, Yvonne; Pleschka, Catharina; Denner, Philip; Kundu, Bishwajit; Reimann, Jens; Vorberg, Ina

2018-03-15

Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line. We find that increased MsntPP protein levels induce ER stress. MstnPP metabolites were predominantly retained within the endoplasmic reticulum (ER), also evident in sIBM histology. MstnPP cleavage products formed insoluble high molecular weight aggregates, a process that was aggravated by experimental ER stress. Importantly, ER stress also impaired secretion of mature myostatin. Reduced secretion and aggregation of MstnPP metabolites were not simply caused by overexpression, as both events were also observed in wildtype cells under ER stress. It is tempting to speculate that reduced circulating myostatin growth factor could be one explanation for the poor clinical efficacy of drugs targeting the myostatin pathway in sIBM.

Effects of body composition, pre- and postpartum energy intake and stage of production of energy utilization by beef cows.

PubMed

Houghton, P L; Lemenager, R P; Hendrix, K S; Moss, G E; Stewart, T S

1990-05-01

Mature Charolais x Angus cows (n = 128) were adjusted to a body condition score (BCS) of 3 (1 = very thin, 3 = moderate, 5 = very fat) between 130 and 190 d of gestation. When cows averaged 190 d of gestation, they were assigned randomly to a maintenance energy diet (ME) or to a diet very low in energy (LE). Cows were allotted within these prepartum (PRP) diets to a high-energy (HE) or LE diet at parturition. At 30 d postpartum (PP), cows were allotted to four treatments: a) slaughter at 0 (n = 32) or b) 48 h after calf removal (n = 32), c) cows whose calves were early weaned at 30 d PP (n = 32) or d) normally weaned at 205 d PP (n = 32). Low energy PRP intake reduced (P less than .01) BCS, cow weight, total empty body lipid (TEBL), body energy (BE) and daily predicted maintenance energy (PME)/W.75 by parturition. Pre- and postpartum energy intake combined to affect (P less than .10) these same factors in a similar manner at 30 d PP. From 30 to 60 d PP, early weaning reduced (P less than .05) PME/W.75. Cow BCS at 190 d of gestation had little effect (P greater than .10) on PME/W.75 or PME/Mcal of BE. Body condition score at parturition, however, affected (P less than .05) delta BCS, delta BE and PME/Mcal of BE by 30 and 60 d PP, with thinner cows losing less condition and requiring more PME/Mcal of BE. Cow BCS had a similar effect from 30 to 60 d PP. Total daily PME was greater for the fat cows during both the PRP and PP periods. Body composition, PRP and PP energy intake and early weaning affect energy requirements and energetic efficiency of beef cows.

Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1.

PubMed

Tellier, Géraldine; Lenne, Astrid; Cailliau-Maggio, Katia; Cabezas-Cruz, Alejandro; Valdés, James J; Martoriati, Alain; Aliouat, El M; Gosset, Pierre; Delaire, Baptiste; Fréville, Aline; Pierrot, Christine; Khalife, Jamal

2016-01-01

Protein phosphatase 1 (PP1c) is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. Here, we report that eukaryotic initiation factor 2β of Plasmodium falciparum (PfeIF2β) is an interactor of PfPP1c. Sequence analysis of PfeIF2β revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to PfPP1 ((29)FGEKKK(34), (103)KVAW(106)). As expected, we showed that PfeIF2β binds PfeIF2γ and PfeIF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfeIF2β-PfPP1 interaction using wild-type, single and double mutated versions of PfeIF2β revealed that both binding motifs are critical. We next showed that PfeIF2β is able to induce Germinal Vesicle Break Down (GVBD) when expressed in Xenopus oocytes, an indicator of its capacity to regulate PP1. Only combined mutations of both binding motifs abolished the interaction with PP1 and the induction of GVBD. In P. falciparum, although the locus is accessible for genetic manipulation, PfeIF2β seems to play an essential role in intraerythrocytic cycle as no viable knockout parasites were detectable. Interestingly, as for PfPP1, the subcellular fractionation of P. falciparum localized PfeIF2β in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of PfeIf2β in the nucleus. Hence, the role played by PfeIF2β in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1.

Strong binding and shrinkage of single and double nuclear systems (K−pp, K−ppn, K−K−p and K−K−pp) predicted by Faddeev-Yakubovsky calculations

PubMed Central

MAEDA, Shuji; AKAISHI, Yoshinori; YAMAZAKI, Toshimitsu

2013-01-01

Non-relativistic Faddeev and Faddeev-Yakubovsky calculations were made for K−pp, K−ppn, K−K−p and K−K−pp kaonic nuclear clusters, where the quasi bound states were treated as bound states by employing real separable potential models for the K−-K− and the K−-nucleon interactions as well as for the nucleon-nucleon interaction. The binding energies and spatial shrinkages of these states, obtained for various values of the interaction, were found to increase rapidly with the interaction strength. Their behaviors are shown in a reference diagram, where possible changes by varying the interaction in the dense nuclear medium are given. Using the Λ(1405) ansatz with a PDG mass of 1405 MeV/c2 for K−p, the following ground-state binding energies together with the wave functions were obtained: 51.5 MeV (K−pp), 69 MeV (K−ppn), 30.4 MeV (K−K−p) and 93 MeV (K−K−pp), which are in good agreement with previous results of variational calculation based on the Akaishi-Yamazaki coupled-channel potential. The K−K−pp state has a significantly increased density where the two nucleons are located very close to each other, in spite of the inner NN repulsion. Relativistic corrections on the calculated non-relativistic results indicate substantial lowering of the bound-state masses, especially of K−K−pp, toward the kaon condensation regime. The fact that the recently observed binding energy of K−pp is much larger (by a factor of 2) than the originally predicted one may infer an enhancement of the interaction in dense nuclei by about 25% possibly due to chiral symmetry restoration. In this respect some qualitative accounts are given based on “clearing QCD vacuum” model of Brown, Kubodera and Rho. PMID:24213206

[Granulocyte- colony stimulating factor (G-CSF) use in clinical practice in patients receiving chemotherapy for breast cancer: The Opaline Study].

PubMed

Jacot, William; Antoine, Eric-Charles; Hacini, Maya; Giron, Cathy; Rivière, Alain; Moureau-Zabotto, Laurence; Cassin, Daniel; Yazbek, Gabriel; Orfeuvre, Hubert; Sakek, Nacera; Diab, Rafik; Bastit, Laurent; Mille, Dominique; Azria, David

2015-12-01

To describe the French routine use of G-CSF in patients treated for breast cancer as per the EORTC recommendations. A prospective multicenter observational study conducted between February 2008 and September 2009 in 869 breast cancer patients treated by chemotherapy (CT) and for whom G-CSF treatment will be delivered in primary (PP) or secondary prophylaxis. The mean age was 55 years. A total of 80.3% of CT was in neoadjuvant/adjuvant setting (NAS). PP was delivered in 78.9% of the NAS patients and 67.5% in metastatic situation. Of the 702 evaluable patients, incidences of severe (SN) and febrile neutropenias (FN) in patients who received PP were 9.3% and 4.2%, respectively. In patients who did not received G-CSF at first cycle, SN and FN were 12.4% and 7.3%, respectively. The use of PP was mainly driven by the type of CT for patients treated in the NAS and by patient or disease related risk factors in the locally advanced/metastatic setting. This study has shown that the use of G-CSF was in accordance with the 2010 updates of the EORTC recommendations. However, G-CSF appears more widely used in the routine practice. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Measurements of charmonium production in p+p, p+Au, and Au+Au collisions at s NN = 200  GeV with the STAR experiment

DOE PAGES

Todoroki, Takahito

2017-09-25

Here, we present the first results from the STAR MTD of mid-rapidity charmonium measurements via the di-muon decay channel in p+p, p+Au, and Au+Au collisions at √S NN = 200 GeV at RHIC. The inclusive J/Ψ production cross section in p+p collisions can be described by the Non-Relativistic QCD (NRQCD) formalism coupled with the color glass condensate e ective theory (CGC) at low transverse momentum (p T) and next-to-leading order NRQCD at high p T. The nuclear modification factor in p+Au collisions for inclusive J/Ψ is below unity at low p T and consistent with unity at high p T,more » which can be described by calculations including both nuclear PDF and nuclear absorption e ects. The double ratio of inclusive J/Ψ and Ψ(2S) production rates for 0 < p T < 10 GeV/c at mid-rapidity between p+p and p+Au collisions is measured to be 1.37 0.42 0.19. The nuclear modification factor in Au+Au collisions for inclusive J/Ψ shows significant J/Ψ suppression at high p T in central collisions and can be qualitatively described by transport models including dissociation and regeneration contributions.« less

Measurements of charmonium production in p+p, p+Au, and Au+Au collisions at s NN = 200  GeV with the STAR experiment

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

Todoroki, Takahito

Here, we present the first results from the STAR MTD of mid-rapidity charmonium measurements via the di-muon decay channel in p+p, p+Au, and Au+Au collisions at √S NN = 200 GeV at RHIC. The inclusive J/Ψ production cross section in p+p collisions can be described by the Non-Relativistic QCD (NRQCD) formalism coupled with the color glass condensate e ective theory (CGC) at low transverse momentum (p T) and next-to-leading order NRQCD at high p T. The nuclear modification factor in p+Au collisions for inclusive J/Ψ is below unity at low p T and consistent with unity at high p T,more » which can be described by calculations including both nuclear PDF and nuclear absorption e ects. The double ratio of inclusive J/Ψ and Ψ(2S) production rates for 0 < p T < 10 GeV/c at mid-rapidity between p+p and p+Au collisions is measured to be 1.37 0.42 0.19. The nuclear modification factor in Au+Au collisions for inclusive J/Ψ shows significant J/Ψ suppression at high p T in central collisions and can be qualitatively described by transport models including dissociation and regeneration contributions.« less

D0-D¯0 mixing parameter y in the factorization-assisted topological-amplitude approach

NASA Astrophysics Data System (ADS)

Jiang, Hua-Yu; Yu, Fu-Sheng; Qin, Qin; Li, Hsiang-nan; Lü, Cai-Dian

2018-05-01

We calculate the {{{D}}}0{-}{\\overline{{{D}}}}0 mixing parameter y in the factorization-assisted topological-amplitude (FAT) approach, considering contributions from {{{D}}}0\\to {PP}, PV, and VV modes, where P (V) stands for a pseudoscalar (vector) meson. The {{{D}}}0\\to {PP} and PV decay amplitudes are extracted in the FAT approach, and the {{{D}}}0\\to {VV} decay amplitudes with final states in the longitudinal polarization are estimated via the parameter set for {{{D}}}0\\to {PV}. It is found that the VV contribution to y, being of order of 10‑4, is negligible, and that the PP and PV contributions amount only up to {y}{{PP+PV}}=(0.21+/- 0.07) % , a prediction more precise than those previously obtained in the literature, and much lower than the experimental data {y}{{\\exp }}=(0.61+/- 0.08) % . We conclude that D0 meson decays into other two-body and multi-particle final states are relevant to the evaluation of y, so it is difficult to understand it fully in an exclusive approach. Supported by National Natural Science Foundation of China (11347027, 11505083, 11375208, 11521505, 1162113100, 11235005, U1732101), Ministry of Science and Technology of R.O.C. (MOST-104-2112-M-001-037-MY3) and DFG Forschergruppe FOR 1873 “Quark Flavour Physics and Effective Field Theories”

Conserved regulatory mechanism controls the development of cells with rooting functions in land plants.

PubMed

Tam, Thomas Ho Yuen; Catarino, Bruno; Dolan, Liam

2015-07-21

Land plants develop filamentous cells-root hairs, rhizoids, and caulonemata-at the interface with the soil. Members of the group XI basic helix-loop-helix (bHLH) transcription factors encoded by LOTUS JAPONICUS ROOTHAIRLESS1-LIKE (LRL) genes positively regulate the development of root hairs in the angiosperms Lotus japonicus, Arabidopsis thaliana, and rice (Oryza sativa). Here we show that auxin promotes rhizoid and caulonema development by positively regulating the expression of PpLRL1 and PpLRL2, the two LRL genes in the Physcomitrella patens genome. Although the group VIII bHLH proteins, AtROOT HAIR DEFECTIVE6 and AtROOT HAIR DEFECTIVE SIX-LIKE1, promote root-hair development by positively regulating the expression of AtLRL3 in A. thaliana, LRL genes promote rhizoid development independently of PpROOT HAIR DEFECTIVE SIX-LIKE1 and PpROOT HAIR DEFECITVE SIX-LIKE2 (PpRSL1 and PpRSL2) gene function in P. patens. Together, these data demonstrate that both LRL and RSL genes are components of an ancient auxin-regulated gene network that controls the development of tip-growing cells with rooting functions among most extant land plants. Although this network has diverged in the moss and the angiosperm lineages, our data demonstrate that the core network acted in the last common ancestor of the mosses and angiosperms that existed sometime before 420 million years ago.

Conserved regulatory mechanism controls the development of cells with rooting functions in land plants

PubMed Central

Tam, Thomas Ho Yuen; Catarino, Bruno; Dolan, Liam

2015-01-01

Land plants develop filamentous cells—root hairs, rhizoids, and caulonemata—at the interface with the soil. Members of the group XI basic helix–loop–helix (bHLH) transcription factors encoded by LOTUS JAPONICUS ROOTHAIRLESS1-LIKE (LRL) genes positively regulate the development of root hairs in the angiosperms Lotus japonicus, Arabidopsis thaliana, and rice (Oryza sativa). Here we show that auxin promotes rhizoid and caulonema development by positively regulating the expression of PpLRL1 and PpLRL2, the two LRL genes in the Physcomitrella patens genome. Although the group VIII bHLH proteins, AtROOT HAIR DEFECTIVE6 and AtROOT HAIR DEFECTIVE SIX-LIKE1, promote root-hair development by positively regulating the expression of AtLRL3 in A. thaliana, LRL genes promote rhizoid development independently of PpROOT HAIR DEFECTIVE SIX-LIKE1 and PpROOT HAIR DEFECITVE SIX-LIKE2 (PpRSL1 and PpRSL2) gene function in P. patens. Together, these data demonstrate that both LRL and RSL genes are components of an ancient auxin-regulated gene network that controls the development of tip-growing cells with rooting functions among most extant land plants. Although this network has diverged in the moss and the angiosperm lineages, our data demonstrate that the core network acted in the last common ancestor of the mosses and angiosperms that existed sometime before 420 million years ago. PMID:26150509

27-Hydroxycholesterol increases Myc protein stability via suppressing PP2A, SCP1 and FBW7 transcription in MCF-7 breast cancer cells

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

Ma, Li-Ming; Liang, Zi-Rui; Zhou, Ke-Ren

27-hydroxycholesterol (27-HC), the most abundant metabolite of cholesterol, is a risk factor for breast cancer. It can increase the proliferation of breast cancer cells and promote the metastasis of breast tumours in mouse models. Myc is a critical oncoprotein overexpressed in breast cancer. However, whether 27-HC affects Myc expression has not been reported. In the current study, we aimed to investigate the effects of 27-HC on Myc and the underlying mechanisms in MCF-7 breast cancer cells. Our data demonstrated that 27-HC activated Myc via increasing its protein stability. Three key negative modulators of Myc protein stability, PP2A, SCP1 and FBW7,more » were suppressed by 27-HC at the transcriptional level. We performed a data-mining analysis of the chromatin immunoprecipitation with next-generation DNA sequencing (ChIP-Seq) data in the ChIPBase, and discovered that a number of putative transcription factors (TFs), including Myc itself, were involved in the transcriptional regulation of PP2A, SCP1 and FBW7. Our results provide a novel mechanistic insight into the activation of Myc by 27-HC via transcriptional repression of PP2A, SCP1 and FBW7 to increase Myc protein stability in breast cancer cells. - Highlights: • 27-Hydroxycholesterol (27-HC) activates Myc via increasing its protein stability. • 27-HC inhibits PP2A and SCP1 transcription to block pS62-Myc dephosphorylation. • 27-HC suppresses FBW7 transcription to prevent pT58-Myc degradation.« less

Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice

PubMed Central

Almenar Cubells, D; Bosch Roig, C; Jiménez Orozco, E; Álvarez, R; Cuervo, JM; Díaz Fernández, N; Sánchez Heras, AB; Galán Brotons, A; Giner Marco, V; Codes M De Villena, M

2013-01-01

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004–2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2–11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1–8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7–5.4) and higher response rate (OR: 2.1, 95%CI: 1.2–3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice. PMID:23331323

The Ebola Virus Nucleoprotein Recruits the Host PP2A-B56 Phosphatase to Activate Transcriptional Support Activity of VP30.

PubMed

Kruse, Thomas; Biedenkopf, Nadine; Hertz, Emil Peter Thrane; Dietzel, Erik; Stalmann, Gertrud; López-Méndez, Blanca; Davey, Norman E; Nilsson, Jakob; Becker, Stephan

2018-01-04

Transcription of the Ebola virus genome depends on the viral transcription factor VP30 in its unphosphorylated form, but the underlying molecular mechanism of VP30 dephosphorylation is unknown. Here we show that the Ebola virus nucleoprotein (NP) recruits the host PP2A-B56 protein phosphatase through a B56-binding LxxIxE motif and that this motif is essential for VP30 dephosphorylation and viral transcription. The LxxIxE motif and the binding site of VP30 in NP are in close proximity, and both binding sites are required for the dephosphorylation of VP30. We generate a specific inhibitor of PP2A-B56 and show that it suppresses Ebola virus transcription and infection. This work dissects the molecular mechanism of VP30 dephosphorylation by PP2A-B56, and it pinpoints this phosphatase as a potential target for therapeutic intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

[Association of mineral and bone disorder with increasing PWV in CKD 1-5 patients].

PubMed

Shiota, Jun; Watanabe, Mitsuhiro

2007-01-01

The association between pulse wave velocity(PWV) and chronic kidney disease mineral and bone disorder(CKD-MBD) was investigated in CKD 1-5 patients without dialysis. Pulse pressure(PP), PWV, serum Cr, non-HDL-cholesterol, Alb, Ca, Pi, calcitriol, intact-PTH and BAP were measured in sixty patients not receiving a phosphate binder or vitamin D. Using the relationship between age and baPWV in healthy subjects, we determined delta baPWV(measured baPWV-calculated baPWV) as an index for the effect of CKD-related factors. delta baPWV was significantly higher in diabetic patients (p < 0.00001). Simple regression analysis revealed that delta baPWV was positively correlated with PP (p < 0.05) and Log(intact-PTH) (p < 0.01), but negatively correlated with Log(estimated GFR) and Log(calcitriol) (p < 0.01). Multiple regression analysis revealed that delta baPWV was significantly associated with PP and calcitriol, or PP and intact-PTH. These results suggest a relationship between PWV and CKD-MBD.

Measurement of Υ(1S + 2S +3S) production in p + p and Au + Au collisions at \\(\\sqrt{s_{\\mathrm{NN}}}=200\\) GeV

DOE PAGES

Adare, A.; Afanasiev, S.; Aidala, C.; ...

2015-02-24

Measurements of bottomonium production in heavy-ion and p+p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three Υ states, Υ(1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au+Au and p+p collisions at \\(\\sqrt{s_{\\mathrm{NN}}}=200\\) GeV. The Υ(1S + 2S + 3S) → e⁺e⁻ differential cross section at midrapidity was found to be B eedσ/dy = 108 ± 38 (stat) ± 15 (syst) ± 11 (luminosity) pb in p+p collisions. The nuclear modification factor in the 30% most central Au+Au collisions indicates a suppression ofmore » the total Υ state yield relative to the extrapolation from p+p collision data. Thus, the suppression is consistent with measurements at higher energies by the CMS experiment at the Large Hadron Collider.« less

Mania triggered by sleep loss and risk of postpartum psychosis in women with bipolar disorder.

PubMed

Lewis, Katie J S; Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Perry, Amy; Craddock, Nick; Jones, Lisa; Jones, Ian

2018-01-01

Women with bipolar disorder are at high risk of affective psychoses following childbirth (i.e. "postpartum psychosis", PP) and there is a need to identify which factors underlie this increased risk. Vulnerability to mood dysregulation following sleep loss may influence risk of PP, as childbirth is typified by sleep disruption. We investigated whether a history of mood episodes triggered by sleep loss was associated with PP in women with bipolar disorder (BD). Participants were 870 parous women with BD recruited to the Bipolar Disorder Research Network. Lifetime diagnoses of BD and perinatal episodes were identified via interview and case notes. Information on whether mood episodes had been triggered by sleep loss was derived at interview. Rates of PP were compared between women who did and did not report mood episodes following sleep loss. Women who reported sleep loss triggering episodes of mania were twice as likely to have experienced an episode of PP (OR = 2.09, 95% CI = 1.47-2.97, p < 0.001) compared to women who did not report this. There was no significant association between depression triggered by sleep loss and PP (p = 0.526). Data were cross-sectional therefore may be subject to recall bias. We also did not have objective data on sleep disruption that had occurred during the postpartum period or prior to mood episodes. In clinical practice, a history of mania following sleep loss could be a marker of increased vulnerability to PP, and should be discussed with BD women who are pregnant or planning to conceive. Copyright © 2017. Published by Elsevier B.V.

δ-aminolevulinic acid–induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy

PubMed Central

Valdés, Pablo A.; Kim, Anthony; Brantsch, Marco; Niu, Carolyn; Moses, Ziev B.; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2011-01-01

Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery. PMID:21798847

Differences in characteristics among new pediatric neurology patients: the effect of a newly established private pediatric neurology practice.

PubMed

Van Cleave, Jeanne; Woodruff, Brian; Freed, Gary L

2008-01-01

To investigate changes in volume and characteristics of new patients referred when a private pediatric neurology practice (PP) opened in 2004 in an area served primarily by an academic medical center's (AMC) pediatric neurology practice. Retrospective analysis of medical and billing records to examine changes in volume, diagnosis, and sociodemographic factors of new patients at the AMC from July 2004 to June 2005; the PP during the same period; and the AMC during the year before. One year after the PP opened, 40% more new pediatric neurology patients were seen in this area than the year before. Compared with the AMC, PP saw a greater proportion of seizures (34% vs 26%, P < .05) and headaches (32% vs 17%, P < .001), and a lesser proportion of developmental delay/musculoskeletal disorders (12% vs 19%, P < .001) and congenital/metabolic disorders (<1% vs 2%, P < .001). Fewer PP patients lived >20 miles from the practice (32% vs 64%, P < .001), and fewer had public insurance (4% vs 33%, P < .001). The establishment of the PP dramatically increased the volume of new pediatric neurology patients in this area. After the PP opened, the AMC continued to care for most patients with rare diseases and fewer financial resources. Future research should examine whether the increase in volume reflects relief of pent-up demand or increased referral rates due to eased access, and should elucidate how differences in patient populations at academic and private subspecialty practices relate to access to subspecialty care and financial well-being of academic practices.

A novel scoring system for predicting adherent placenta in women with placenta previa.

PubMed

Tanimura, Kenji; Morizane, Mayumi; Deguchi, Masashi; Ebina, Yasuhiko; Tanaka, Utaru; Ueno, Yoshiko; Kitajima, Kazuhiro; Maeda, Tetsuo; Sugimura, Kazuro; Yamada, Hideto

2018-04-01

Placenta previa (PP) is one of the most significant risk factors for adherent placenta (AP). The aim of this study was to evaluate the diagnostic efficacy of a novel scoring system for predicting AP in pregnant women with PP. This prospective cohort study enrolled 175 women with PP. The placenta previa with adherent placenta score (PPAP score) is composed of 2 categories: (1) past history of cesarean section (CS), surgical abortion, and/or uterine surgery; and (2) ultrasonography and magnetic resonance imaging findings. Each category is graded as 0, 1, 2, or 4 points, yielding a total score between 0 and 24. When women with PP had PPAP score ≥8, they were considered to be at a high risk for AP and received placement of preoperative internal iliac artery occlusion balloon catheters. If they were found to have AP during CS, they underwent hysterectomy or placenta removal using advanced bipolar with balloon catheter occlusion. The predictive accuracy of PPAP score was evaluated. In total, 23 of the 175 women with PP were diagnosed as having AP, histopathologically or clinically. Twenty-one of 24 women with PPAP score ≥8 had AP, whereas two of 151 women with PPAP score <8 had AP. The scoring system yielded 91.3% sensitivity, 98.0% specificity, 87.5% positive predictive value, and 98.7% negative predictive value for predicting AP in women with PP. This prospective study demonstrated that PPAP scoring system may be useful for predicting AP in women with PP. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Sense of 1PP-Location Contributes to Shaping the Perceived Self-location Together with the Sense of Body-Location

PubMed Central

Huang, Hsu-Chia; Lee, Yen-Tung; Chen, Wen-Yeo; Liang, Caleb

2017-01-01

Self-location—the sense of where I am in space—provides an experiential anchor for one's interaction with the environment. In the studies of full-body illusions, many researchers have defined self-location solely in terms of body-location—the subjective feeling of where my body is. Although this view is useful, there is an issue regarding whether it can fully accommodate the role of 1PP-location—the sense of where my first-person perspective is located in space. In this study, we investigate self-location by comparing body-location and 1PP-location: using a head-mounted display (HMD) and a stereo camera, the subjects watched their own body standing in front of them and received tactile stimulations. We manipulated their senses of body-location and 1PP-location in three different conditions: the participants standing still (Basic condition), asking them to move forward (Walking condition), and swiftly moving the stereo camera away from their body (Visual condition). In the Walking condition, the participants watched their body moving away from their 1PP. In the Visual condition, the scene seen via the HMD was systematically receding. Our data show that, under different manipulations of movement, the spatial unity between 1PP-location and body-location can be temporarily interrupted. Interestingly, we also observed a “double-body effect.” We further suggest that it is better to consider body-location and 1PP-location as interrelated but distinct factors that jointly support the sense of self-location. PMID:28352241

The Sense of 1PP-Location Contributes to Shaping the Perceived Self-location Together with the Sense of Body-Location.

PubMed

Huang, Hsu-Chia; Lee, Yen-Tung; Chen, Wen-Yeo; Liang, Caleb

2017-01-01

Self-location -the sense of where I am in space-provides an experiential anchor for one's interaction with the environment. In the studies of full-body illusions, many researchers have defined self-location solely in terms of body-location -the subjective feeling of where my body is. Although this view is useful, there is an issue regarding whether it can fully accommodate the role of 1PP-location -the sense of where my first-person perspective is located in space. In this study, we investigate self-location by comparing body-location and 1PP-location: using a head-mounted display (HMD) and a stereo camera, the subjects watched their own body standing in front of them and received tactile stimulations. We manipulated their senses of body-location and 1PP-location in three different conditions: the participants standing still (Basic condition), asking them to move forward (Walking condition), and swiftly moving the stereo camera away from their body (Visual condition). In the Walking condition, the participants watched their body moving away from their 1PP. In the Visual condition, the scene seen via the HMD was systematically receding. Our data show that, under different manipulations of movement, the spatial unity between 1PP-location and body-location can be temporarily interrupted. Interestingly, we also observed a "double-body effect." We further suggest that it is better to consider body-location and 1PP-location as interrelated but distinct factors that jointly support the sense of self-location.

Transcriptional control of stem cell fate by E2Fs and pocket proteins

PubMed Central

Julian, Lisa M.; Blais, Alexandre

2015-01-01

E2F transcription factors and their regulatory partners, the pocket proteins (PPs), have emerged as essential regulators of stem cell fate control in a number of lineages. In mammals, this role extends from both pluripotent stem cells to those encompassing all embryonic germ layers, as well as extra-embryonic lineages. E2F/PP-mediated regulation of stem cell decisions is highly evolutionarily conserved, and is likely a pivotal biological mechanism underlying stem cell homeostasis. This has immense implications for organismal development, tissue maintenance, and regeneration. In this article, we discuss the roles of E2F factors and PPs in stem cell populations, focusing on mammalian systems. We discuss emerging findings that position the E2F and PP families as widespread and dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on the ever expanding landscape of E2F/PP target genes, and explore the possibility that E2Fs are not simply regulators of general ‘multi-purpose’ cell fate genes but can execute tissue- and cell type-specific gene regulatory programs. PMID:25972892

Measurement of the B ± Meson Nuclear Modification Factor in Pb-Pb Collisions at s N N = 5.02 TeV

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

Sirunyan, A. M.; Tumasyan, A.; Adam, W.

The differential production cross sections of B± mesons are measured via the exclusive decay channels B ± → J/ψK ± → μ +μ -K ± as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy √ sNN = 5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb -1 (351 μb -1). The measurement is performed in the B ± meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematicmore » range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. Finally, these results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.« less

Measurement of the B ± Meson Nuclear Modification Factor in Pb-Pb Collisions at s N N = 5.02 TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2017-10-13

The differential production cross sections of B± mesons are measured via the exclusive decay channels B ± → J/ψK ± → μ +μ -K ± as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy √ sNN = 5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb -1 (351 μb -1). The measurement is performed in the B ± meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematicmore » range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. Finally, these results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.« less

Malignant transformation of oral lichen planus and oral lichenoid lesions: A meta-analysis of 20095 patient data.

PubMed

Aghbari, Sana Maher Hasan; Abushouk, Abdelrahman Ibrahim; Attia, Attia; Elmaraezy, Ahmed; Menshawy, Amr; Ahmed, Mohamed Shehata; Elsaadany, Basma Abdelaleem; Ahmed, Eman Magdy

2017-05-01

For over a century, a heated debate existed over the possibility of malignant transformation of oral lichen planus (OLP). We performed this meta-analysis to evaluate the malignant potential of OLP and oral lichenoid lesions (OLL) and investigate the possible risk factors for OLP malignant transformation into oral squamous cell carcinoma (OSCC). We searched Medline, Scopus, and Web of Knowledge for relevant observational studies. Data on OLP malignant transformation were calculated as a pooled proportion (PP), using the Der-Simonian Liard method. We performed subgroup analyses by OLP diagnostic criteria, site, and clinical type, using Open Meta[Analyst] software. Data on possible risk factors for malignant transformation were pooled as odds ratios (ORs), using Comprehensive Meta-Analysis software. Pooling data for OLP malignant transformation from 57 studies (19,676 patients) resulted in an overall PP of 1.1% [95% CI: 0.9%, 1.4%], while pooling data from 14 recent studies that used the World Health Organization-2003 diagnostic criteria resulted in an overall-PP of 0.9% [95% CI: 0.5%, 1.3%]. The risk of malignant transformation was higher (PP=2.5%, 95% CI [1%, 4%]) in OLL patients (419 patients). A significant increase of malignant transformation risk was noted among smokers (OR=2, 95% CI [1.25, 3.22]), alcoholics (OR=3.52, 95% CI [1.54, 8.03]), and HCV-infected patients (OR=5, 95% CI [1.56, 16.07]), compared to patients without these risk factors. A small subset of OLP patients (1.1%) develop OSCC; therefore, regular follow-up for these patients is recommended. A higher incidence of malignant transformation was found among smokers, alcoholics, and HCV-infected patients; however, these associations should be further investigated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigating interfacial phenomena in polypropylene/glass fiber composites

NASA Astrophysics Data System (ADS)

Toke, Jeffrey Michael

The adhesion in polypropylene (PP)/glass composites is low due to the non-polar, non-reactive characteristics of PP. When maleated PP (mPP) is added to the matrix, adhesion is improved. Understanding the mechanisms of this phenomenon is critical in maximizing the adhesion in PP/glass composites. The strength of adhesion in PP/glass composites was investigated using glass bead composites. A Near-IR spectroscopic technique was used to evaluate the chemical reactions in the interphase. Twelve different commercial grades of maleated PP (mPP) were tested. The range of maleic anydride (MAH) content was from 0.3 weight percent (wt%) to 2.4 wt%, with one sample at 10 wt%. These mPPs were blended with a commercial PP from Huntsman, P4C5Z-027 (PP), a 20 MFI (melt flow index) polymer with minimal additives, in concentrations ranging from 0 to 20 wt%. Bead composites of non-coated (NON) and gamma-APS-coated beads (APS) were made to compare the strength of the interphase in the composite systems. The bead volume fraction used was 25 volume percent (vol%). Three polymers with different MAH content and different viscosities were tested at 1, 5, 10 and 20 wt%. All of the mPPs were tested at 5 wt%. In general, the mPP composites all exhibited higher strength compared to the PP. Pukanszky's model for tensile strength was applied that included the strength of the unfilled matrix and the volume percent of the beads in a single factor, B. Comparison of all of the polymers at 5 wt% showed that there were four groupings of the mPPs. The polymers with MAH content greater than 1.5 wt% showed the strongest adhesion with B values of ˜2.5. All of these polymers had viscosities less than 100 Pa-s (180°C, 1 Hz angular frequency). The next group of polymers, with B ˜ 2, had MAH contents ranging from 0.8 to 1.2 wt%, with viscosities ranging from the 21 Pa-s to greater than 2300 Pa-s (180°C, 1 Hz angular frequency). The following group, with B ˜ 0.9, had anhydride concentrations of 0.6 and 0.7 wt%, and viscosities of 127 and 3800 Pa-s, respectively. Finally, there were several polymers with B ˜ 0.6 that were not significantly different than the unmodified PP. Viscosity and anhydride concentration showed competing effects in the mPP samples. Overall, increasing the concentration of anhydride increased adhesion, but viscosity is reduced in high MAH content mPPs. When the anhydride content was below 1.5 wt%, increased viscosity showed greater adhesion. (Abstract shortened by UMI.)

Establishing Criteria for Assigning Personnel to Air Force Jobs Requiring Heavy Work

DTIC Science & Technology

1978-07-01

loads (for example, carrying meat at the slaughterhouse , carrying of sacks, loading wood by hand) wood cutting in the forest by hand tools, agricultural...8217 factor history. Medical Service Digest (United States Air Force), 27(2), 1976, pp. 14-16. 186 Trimeloni, Col. B.D. The Role of Women in the Air Force...Rahden. Effect of training on maximum oxygen intake and on anaerobic metabolism in man. Int. Z. Angew Physiol., 24(2), 1967, pp. 102-110. 188 Wyndham, C.H

Investigation of Gear Dynamics Signal Analysis

DTIC Science & Technology

1975-01-01

TEETH, PART 1, The Engineer, pp. 187-190, August 9, 1957. 37. Trbojevic , M. D ., LOAD DISTRIBUTION ON HELICAL GEAR TEETH, PART 2, The Engineer, pp...used in this study, load distribution factors were found to be negligible. A number of investigators, e.g., Poritsky et al,,34 Weber,35 Trbojevic ... D o o •8 aS < D O taO $3 •H £ o GO -P 00 -P W 0 EH 0) •H ptn 32 Figure 15. Generator Loading System. 33 . * t. Figure 17

Older Workers in the Market for Part-Time Employment. Appendices to PP 396.

DTIC Science & Technology

1983-09-01

Ehrenberg, R.G., Fringe Benefits and Overtime Behavior. Lexington, 1971. Levis, H. G., "Interes del Employeador en las Horas de Tobajo del Empleado...34 "The Employer Interest in Employees’ Hours of Work," Cuadernos de Economia , 18 (1969), pp. 38-54, summarized in Rosen, Harvey, reference below. Owen...just tangential to the g(h) function. The next question is: Which factors shift the optimum combination of h and c? C-I D * .k=* ~ .... LA A U..~..’ 4 g

Charged-particle nuclear modification factors in PbPb and pPb collisions at $$ \\sqrt{s_{\\mathrm{NN}}}=5.02 $$ TeV

DOE PAGES

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

2016-04-07

The spectra of charged particles produced within the pseudorapidity windowmore » $$| \\eta | < $$ 1 at $$\\sqrt{s_{\\mathrm{NN}}}= $$ 5.02 TeV are measured using 404 $$ \\mu $$b$$^{-1}$$ of PbPb and 27.4 pb$$^{-1}$$ of pp data collected by the CMS detector at the LHC in 2015. The spectra are presented over the transverse momentum ranges spanning 0.5 $$ < p_{\\mathrm{T}} < $$ 400 GeV in pp and 0.7 $$ < p_{\\mathrm{T}} < $$ 400 GeV in PbPb collisions. The corresponding nuclear modification factor, $${R_\\mathrm{AA}} $$, is measured in bins of collision centrality. The $${R_\\mathrm{AA}} $$ in the 5% most central collisions shows a maximal suppression by a factor of 7-8 in the $$p_{\\mathrm{T}}$$ region of 6-9 GeV. This dip is followed by an increase, which continues up to the highest $$ p_{\\mathrm{T}}$$ measured, and approaches unity in the vicinity of $$p_{\\mathrm{T}}= $$ 200 GeV. The $${R_\\mathrm{AA}} $$ is compared to theoretical predictions and earlier experimental results at lower collision energies. Here, the newly measured pp spectrum is combined with the pPb spectrum previously published by the CMS Collaboration to construct the pPb nuclear modification factor, $${R_{\\mathrm{ p }\\mathrm{A}}} $$, up to 120 GeV. For $$ p_{\\mathrm{T}} > $$ 20 GeV, $${R_{\\mathrm{ p }\\mathrm{A}}} $$ exhibits weak momentum dependence and shows a moderate enhancement above unity.« less

Breakthrough in current-in-plane tunneling measurement precision by application of multi-variable fitting algorithm.

PubMed

Cagliani, Alberto; Østerberg, Frederik W; Hansen, Ole; Shiv, Lior; Nielsen, Peter F; Petersen, Dirch H

2017-09-01

We present a breakthrough in micro-four-point probe (M4PP) metrology to substantially improve precision of transmission line (transfer length) type measurements by application of advanced electrode position correction. In particular, we demonstrate this methodology for the M4PP current-in-plane tunneling (CIPT) technique. The CIPT method has been a crucial tool in the development of magnetic tunnel junction (MTJ) stacks suitable for magnetic random-access memories for more than a decade. On two MTJ stacks, the measurement precision of resistance-area product and tunneling magnetoresistance was improved by up to a factor of 3.5 and the measurement reproducibility by up to a factor of 17, thanks to our improved position correction technique.

Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study.

PubMed

Larstorp, Anne Cecilie K; Ariansen, Inger; Gjesdal, Knut; Olsen, Michael H; Ibsen, Hans; Devereux, Richard B; Okin, Peter M; Dahlöf, Björn; Kjeldsen, Sverre E; Wachtell, Kristian

2012-08-01

Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota coding of electrocardiograms confirmed new-onset AF in 353 patients (4.0%) during mean 4.9 years of follow-up. In multivariate Cox regression analyses, baseline and in-treatment PP and baseline and in-treatment systolic blood pressure predicted new-onset AF, independent of baseline age, height, weight, and Framingham Risk Score; sex, race, and treatment allocation; and in-treatment heart rate and Cornell product. PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the -2 Log likelihood statistic, in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new-onset AF, independent of other risk factors.

Measurements of the nuclear modification factor for jets in Pb + Pb collisions at s NN = 2.76 TeV with the ATLAS detector

DOE PAGES

Aad, G.

2015-02-20

The measurements of inclusive jet production are performed in pp and Pb+Pb collisions at √ sNN = 2.76 TeV with the ATLAS detector at the LHC, corresponding to integrated luminosities of 4.0 and 0.14 nb -1, respectively. The jets are identified with the anti-kt algorithm with R = 0.4, and the spectra are measured over the kinematic range of jet transverse momentum 32T<500 GeV and absolute rapidity |y|<2.1 and as a function of collision centrality. The nuclear modification factor R AA is evaluated, and jets are found to be suppressed by approximately a factor of 2 in central collisions comparedmore » to pp collisions. The R AA shows a slight increase with p T and no significant variation with rapidity.« less

Measurements of the Nuclear Modification Factor for Jets in Pb+Pb Collisions at √(s)NN]=2.76  TeV with the ATLAS detector.

PubMed

Aad, G; Abbott, B; Abdallah, J; Abdel Khalek, S; Abdinov, O; Aben, R; Abi, B; Abolins, M; AbouZeid, O S; Abramowicz, H; Abreu, H; Abreu, R; Abulaiti, Y; Acharya, B S; Adamczyk, L; Adams, D L; Adelman, J; Adomeit, S; Adye, T; Agatonovic-Jovin, T; Aguilar-Saavedra, J A; Agustoni, M; Ahlen, S P; Ahmadov, F; Aielli, G; Akerstedt, H; Åkesson, T P A; Akimoto, G; Akimov, A V; Alberghi, G L; Albert, J; Albrand, S; Alconada Verzini, M J; Aleksa, M; Aleksandrov, I N; Alexa, C; Alexander, G; Alexandre, G; Alexopoulos, T; Alhroob, M; Alimonti, G; Alio, L; Alison, J; Allbrooke, B M M; Allison, L J; Allport, P P; Almond, J; Aloisio, A; Alonso, A; Alonso, F; Alpigiani, C; Altheimer, A; Alvarez Gonzalez, B; Alviggi, M G; Amako, K; Amaral Coutinho, Y; Amelung, C; Amidei, D; Amor Dos Santos, S P; Amorim, A; Amoroso, S; Amram, N; Amundsen, G; Anastopoulos, C; Ancu, L S; Andari, N; Andeen, T; Anders, C F; Anders, G; Anderson, K J; Andreazza, A; Andrei, V; Anduaga, X S; Angelidakis, S; Angelozzi, I; Anger, P; Angerami, A; Anghinolfi, F; Anisenkov, A V; Anjos, N; Annovi, A; Antonaki, A; Antonelli, M; Antonov, A; Antos, J; Anulli, F; Aoki, M; Aperio Bella, L; Apolle, R; Arabidze, G; Aracena, I; Arai, Y; Araque, J P; Arce, A T H; Arguin, J-F; Argyropoulos, S; Arik, M; Armbruster, A J; Arnaez, O; Arnal, V; Arnold, H; Arratia, M; Arslan, O; Artamonov, A; Artoni, G; Asai, S; Asbah, N; Ashkenazi, A; Åsman, B; Asquith, L; Assamagan, K; Astalos, R; Atkinson, M; Atlay, N B; Auerbach, B; Augsten, K; Aurousseau, M; Avolio, G; Azuelos, G; Azuma, Y; Baak, M A; Baas, A E; Bacci, C; Bachacou, H; Bachas, K; Backes, M; Backhaus, M; Backus Mayes, J; Badescu, E; Bagiacchi, P; Bagnaia, P; Bai, Y; Bain, T; Baines, J T; Baker, O K; Balek, P; Balli, F; Banas, E; Banerjee, Sw; Bannoura, A A E; Bansal, V; Bansil, H S; Barak, L; Baranov, S P; Barberio, E L; Barberis, D; Barbero, M; Barillari, T; Barisonzi, M; Barklow, T; Barlow, N; Barnett, B M; Barnett, R M; Barnovska, Z; Baroncelli, A; Barone, G; Barr, A J; Barreiro, F; Barreiro Guimarães da Costa, J; Bartoldus, R; Barton, A E; Bartos, P; Bartsch, V; Bassalat, A; Basye, A; Bates, R L; Batley, J R; Battaglia, M; Battistin, M; Bauer, F; Bawa, H S; Beattie, M D; Beau, T; Beauchemin, P H; Beccherle, R; Bechtle, P; Beck, H P; Becker, K; Becker, S; Beckingham, M; Becot, C; Beddall, A J; Beddall, A; Bedikian, S; Bednyakov, V A; Bee, C P; Beemster, L J; Beermann, T A; Begel, M; Behr, K; Belanger-Champagne, C; Bell, P J; Bell, W H; Bella, G; Bellagamba, L; Bellerive, A; Bellomo, M; Belotskiy, K; Beltramello, O; Benary, O; Benchekroun, D; Bendtz, K; Benekos, N; Benhammou, Y; Benhar Noccioli, E; Benitez Garcia, J A; Benjamin, D P; Bensinger, J R; Benslama, K; Bentvelsen, S; Berge, D; Bergeaas Kuutmann, E; Berger, N; Berghaus, F; Beringer, J; Bernard, C; Bernat, P; Bernius, C; Bernlochner, F U; Berry, T; Berta, P; Bertella, C; Bertoli, G; Bertolucci, F; Bertsche, C; Bertsche, D; Besana, M I; Besjes, G J; Bessidskaia Bylund, O; Bessner, M; Besson, N; Betancourt, C; Bethke, S; Bhimji, W; Bianchi, R M; Bianchini, L; Bianco, M; Biebel, O; Bieniek, S P; Bierwagen, K; Biesiada, J; Biglietti, M; Bilbao De Mendizabal, J; Bilokon, H; Bindi, M; Binet, S; Bingul, A; Bini, C; Black, C W; Black, J E; Black, K M; Blackburn, D; Blair, R E; Blanchard, J-B; Blazek, T; Bloch, I; Blocker, C; Blum, W; Blumenschein, U; Bobbink, G J; Bobrovnikov, V S; Bocchetta, S S; Bocci, A; Bock, C; Boddy, C R; Boehler, M; Boek, T T; Bogaerts, J A; Bogdanchikov, A G; Bogouch, A; Bohm, C; Bohm, J; Boisvert, V; Bold, T; Boldea, V; Boldyrev, A S; Bomben, M; Bona, M; Boonekamp, M; Borisov, A; Borissov, G; Borri, M; Borroni, S; Bortfeldt, J; Bortolotto, V; Bos, K; Boscherini, D; Bosman, M; Boterenbrood, H; Boudreau, J; Bouffard, J; Bouhova-Thacker, E V; Boumediene, D; Bourdarios, C; Bousson, N; Boutouil, S; Boveia, A; Boyd, J; Boyko, I R; Bracinik, J; Brandt, A; Brandt, G; Brandt, O; Bratzler, U; Brau, B; Brau, J E; Braun, H M; Brazzale, S F; Brelier, B; Brendlinger, K; Brennan, A J; Brenner, R; Bressler, S; Bristow, K; Bristow, T M; Britton, D; Brochu, F M; Brock, I; Brock, R; Bromberg, C; Bronner, J; Brooijmans, G; Brooks, T; Brooks, W K; Brosamer, J; Brost, E; Brown, J; Bruckman de Renstrom, P A; Bruncko, D; Bruneliere, R; Brunet, S; Bruni, A; Bruni, G; Bruschi, M; Bryngemark, L; Buanes, T; Buat, Q; Bucci, F; Buchholz, P; Buckingham, R M; Buckley, A G; Buda, S I; Budagov, I A; Buehrer, F; Bugge, L; Bugge, M K; Bulekov, O; Bundock, A C; Burckhart, H; Burdin, S; Burghgrave, B; Burke, S; Burmeister, I; Busato, E; Büscher, D; Büscher, V; Bussey, P; Buszello, C P; Butler, B; Butler, J M; Butt, A I; Buttar, C M; Butterworth, J M; Butti, P; Buttinger, W; Buzatu, A; Byszewski, M; Cabrera Urbán, S; Caforio, D; Cakir, O; Calafiura, P; Calandri, A; Calderini, G; Calfayan, P; Calkins, R; Caloba, L P; Calvet, D; Calvet, S; Camacho Toro, R; Camarda, S; Cameron, D; Caminada, L M; Caminal Armadans, R; Campana, S; Campanelli, M; Campoverde, A; Canale, V; Canepa, A; Cano Bret, M; Cantero, J; Cantrill, R; Cao, T; Capeans Garrido, M D M; Caprini, I; Caprini, M; Capua, M; Caputo, R; Cardarelli, R; Carli, T; Carlino, G; Carminati, L; Caron, S; Carquin, E; Carrillo-Montoya, G D; Carter, J R; Carvalho, J; Casadei, D; Casado, M P; Casolino, M; Castaneda-Miranda, E; Castelli, A; Castillo Gimenez, V; Castro, N F; Catastini, P; Catinaccio, A; Catmore, J R; Cattai, A; Cattani, G; Caughron, S; Cavaliere, V; Cavalli, D; Cavalli-Sforza, M; Cavasinni, V; Ceradini, F; Cerio, B C; Cerny, K; Cerqueira, A S; Cerri, A; Cerrito, L; Cerutti, F; Cerv, M; Cervelli, A; Cetin, S A; Chafaq, A; Chakraborty, D; Chalupkova, I; Chang, P; Chapleau, B; Chapman, J D; Charfeddine, D; Charlton, D G; Chau, C C; Chavez Barajas, C A; Cheatham, S; Chegwidden, A; Chekanov, S; Chekulaev, S V; Chelkov, G A; Chelstowska, M A; Chen, C; Chen, H; Chen, K; Chen, L; Chen, S; Chen, X; Chen, Y; Chen, Y; Cheng, H C; Cheng, Y; Cheplakov, A; Cherkaoui El Moursli, R; Chernyatin, V; Cheu, E; Chevalier, L; Chiarella, V; Chiefari, G; Childers, J T; Chilingarov, A; Chiodini, G; Chisholm, A S; Chislett, R T; Chitan, A; Chizhov, M V; Chouridou, S; Chow, B K B; Chromek-Burckhart, D; Chu, M L; Chudoba, J; Chwastowski, J J; Chytka, L; Ciapetti, G; Ciftci, A K; Ciftci, R; Cinca, D; Cindro, V; Ciocio, A; Cirkovic, P; Citron, Z H; Citterio, M; Ciubancan, M; Clark, A; Clark, P J; Clarke, R N; Cleland, W; Clemens, J C; Clement, C; Coadou, Y; Cobal, M; Coccaro, A; Cochran, J; Coffey, L; Cogan, J G; Coggeshall, J; Cole, B; Cole, S; Colijn, A P; Collot, J; Colombo, T; Colon, G; Compostella, G; Conde Muiño, P; Coniavitis, E; Conidi, M C; Connell, S H; Connelly, I A; Consonni, S M; Consorti, V; Constantinescu, S; Conta, C; Conti, G; Conventi, F; Cooke, M; Cooper, B D; Cooper-Sarkar, A M; Cooper-Smith, N J; Copic, K; Cornelissen, T; Corradi, M; Corriveau, F; Corso-Radu, A; Cortes-Gonzalez, A; Cortiana, G; Costa, G; Costa, M J; Costanzo, D; Côté, D; Cottin, G; Cowan, G; Cox, B E; Cranmer, K; Cree, G; Crépé-Renaudin, S; Crescioli, F; Cribbs, W A; Crispin Ortuzar, M; Cristinziani, M; Croft, V; Crosetti, G; Cuciuc, C-M; Cuhadar Donszelmann, T; Cummings, J; Curatolo, M; Cuthbert, C; Czirr, H; Czodrowski, P; Czyczula, Z; D'Auria, S; D'Onofrio, M; Da Cunha Sargedas De Sousa, M J; Da Via, C; Dabrowski, W; Dafinca, A; Dai, T; Dale, O; Dallaire, F; Dallapiccola, C; Dam, M; Daniells, A C; Dano Hoffmann, M; Dao, V; Darbo, G; Darmora, S; Dassoulas, J A; Dattagupta, A; Davey, W; David, C; Davidek, T; Davies, E; Davies, M; Davignon, O; Davison, A R; Davison, P; Davygora, Y; Dawe, E; Dawson, I; Daya-Ishmukhametova, R K; De, K; de Asmundis, R; De Castro, S; De Cecco, S; De Groot, N; de Jong, P; De la Torre, H; De Lorenzi, F; De Nooij, L; De Pedis, D; De Salvo, A; De Sanctis, U; De Santo, A; De Vivie De Regie, J B; Dearnaley, W J; Debbe, R; Debenedetti, C; Dechenaux, B; Dedovich, D V; Deigaard, I; Del Peso, J; Del Prete, T; Deliot, F; Delitzsch, C M; Deliyergiyev, M; Dell'Acqua, A; Dell'Asta, L; Dell'Orso, M; Della Pietra, M; Della Volpe, D; 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2015-02-20

Measurements of inclusive jet production are performed in pp and Pb+Pb collisions at √(s)NN=2.76  TeV with the ATLAS detector at the LHC, corresponding to integrated luminosities of 4.0 and 0.14  nb(-1), respectively. The jets are identified with the anti-k(t) algorithm with R=0.4, and the spectra are measured over the kinematic range of jet transverse momentum 32

Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

PubMed

Younis, T; Rayson, D; Jovanovic, S; Skedgel, C

2016-10-01

The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold.

Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated with Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy

PubMed Central

Montoya, Jessica L.; Iudicello, Jennifer; Fazeli, Pariya L.; Hong, Suzi; Potter, Michael; Ellis, Ronald J.; Grant, Igor; Letendre, Scott L.; Moore, David J.

2016-01-01

Background HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening, and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. Methods To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+; n = 72) and HIV-seronegative (HIV-; n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (i.e., angiopoietin 2, Tie-2, and vascular endothelial growth factor; VEGF) were collected. Results HIV+ and HIV- participants had similar levels of plasma Ang-2 (p = .48), Tie-2 (p = .27), VEGF (p = .18), and PP (p = .98). In a multivariable regression model, HIV interacted with Tie-2 (β = .41, p < .01) and VEGF (β = −.43, p = .01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = .31, p < .01). In turn, PP demonstrated a quadratic association with neurocognitive function (β = −.33, p = .01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. Conclusions These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function. PMID:27828873

Telomere Length and Pulse Pressure in Newly Diagnosed, Antipsychotic-Naive Patients With Nonaffective Psychosis

PubMed Central

Fernandez-Egea, Emilio; Bernardo, Miguel; Heaphy, Christopher M.; Griffith, Jeffrey K.; Parellada, Eduard; Esmatjes, Enric; Conget, Ignacio; Nguyen, Linh; George, Varghese; Stöppler, Hubert; Kirkpatrick, Brian

2009-01-01

Introduction: Recent studies suggest that in addition to factors such as treatment side effects, suicide, and poor health habits, people with schizophrenia may have an increased risk of diabetes prior to antipsychotic treatment. Diabetes is associated with an increased pulse pressure (PP) and a shortened telomere. We tested the hypothesis that prior to antipsychotic treatment, schizophrenia and related disorders are associated with a shortened telomere, as well as an increased PP. Methods: Telomere content (which is highly correlated with telomere length) and PP were measured in newly diagnosed, antipsychotic-naive patients with schizophrenia and related disorders on first clinical contact and in matched control subjects. Both groups were also administered an oral glucose tolerance test. Results: Compared with control subjects, the patients with psychosis had decreased telomere content and an increased PP. As previously reported, they also had increased glucose concentrations at 2 hours. These differences could not be attributed to differences in age, ethnicity, smoking, gender, body mass index, neighborhood of residence, socioeconomic status, aerobic conditioning, or an increased cortisol concentration in the psychotic subjects. Discussion: These results suggest that prior to antipsychotic use, nonaffective psychosis is associated with reduced telomere content and increased PP, indices that have been linked to an increased risk of diabetes and hypertension. PMID:19279086

Gender dependent association between perinatal morbidity and estrogen receptor-alpha Pvull polymorphism.

PubMed

Derzbach, László; Treszl, András; Balogh, Adám; Vásárhelyi, Barna; Tulassay, Tivadar; Rigó J, János

2005-01-01

Assuming the importance of estrogen in perinatal physiology, we tested the association of an estrogen receptor-alpha (ER-alpha) gene Pvull pP polymorphism with perinatal morbidity in premature infants. The ER-alpha Pp genotype was determined in 69 low-birth weight (LBW) boys and 72 LBW girls, 86 term boys and 81 term girls. The association between risk factors, genotype, gender and perinatal morbidity was tested with binary logistic regression analysis. Boys carrying "p" allele were at lower risk for necrotizing enterocolitis (OR [95% Cl]: 0.24 [0.07-0.83]) and patent ductus arteriosus (OR [95% Cl]: 0.24 [0.05-0.97]). The carrier state of the "p" allele was associated with a 34-h shorter period of oxygen supplementation on average (P=0.0018). Boys with pp genotype were at greater risk for intraventricular hemorrhage (OR [95% Cl]: 4.39 [1.15-16.82]). No association between ER-alpha Pvull polymorphism and morbidity was present in girls. Since homozygocity for any Pvull alleles (i.e. having PP or pp genotype) increases the risk for at least one of the most common perinatal complications, it is likely that the heterozygous carrier state of Pvull genotypes has a protective effect, which is gender-dependent.

Enterococcus faecalis Prophage Dynamics and Contributions to Pathogenic Traits

PubMed Central

Matos, Renata C.; Lapaque, Nicolas; Rigottier-Gois, Lionel; Debarbieux, Laurent; Meylheuc, Thierry; Gonzalez-Zorn, Bruno; Repoila, Francis; Lopes, Maria de Fatima; Serror, Pascale

2013-01-01

Polylysogeny is frequently considered to be the result of an adaptive evolutionary process in which prophages confer fitness and/or virulence factors, thus making them important for evolution of both bacterial populations and infectious diseases. The Enterococcus faecalis V583 isolate belongs to the high-risk clonal complex 2 that is particularly well adapted to the hospital environment. Its genome carries 7 prophage-like elements (V583-pp1 to -pp7), one of which is ubiquitous in the species. In this study, we investigated the activity of the V583 prophages and their contribution to E. faecalis biological traits. We systematically analyzed the ability of each prophage to excise from the bacterial chromosome, to replicate and to package its DNA. We also created a set of E. faecalis isogenic strains that lack from one to all six non-ubiquitous prophages by mimicking natural excision. Our work reveals that prophages of E. faecalis V583 excise from the bacterial chromosome in the presence of a fluoroquinolone, and are able to produce active phage progeny. Intricate interactions between V583 prophages were also unveiled: i) pp7, coined EfCIV583 for E. faecalis chromosomal island of V583, hijacks capsids from helper phage 1, leading to the formation of distinct virions, and ii) pp1, pp3 and pp5 inhibit excision of pp4 and pp6. The hijacking exerted by EfCIV583 on helper phage 1 capsids is the first example of molecular piracy in Gram positive bacteria other than staphylococci. Furthermore, prophages encoding platelet-binding-like proteins were found to be involved in adhesion to human platelets, considered as a first step towards the development of infective endocarditis. Our findings reveal not only a role of E. faecalis V583 prophages in pathogenicity, but also provide an explanation for the correlation between antibiotic usage and E. faecalis success as a nosocomial pathogen, as fluoriquinolone may provoke release of prophages and promote gene dissemination among isolates. PMID:23754962

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition

PubMed Central

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-01-01

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a (pp2a) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing atherosclerotic process by blocking the proliferation of VSMCs. PMID:29186909

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition.

PubMed

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-11-27

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a ( pp2a ) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing atherosclerotic process by blocking the proliferation of VSMCs.

RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium.

PubMed

Knoop, Kathryn A; Kumar, Nachiket; Butler, Betsy R; Sakthivel, Senthilkumar K; Taylor, Rebekah T; Nochi, Tomonori; Akiba, Hisaya; Yagita, Hideo; Kiyono, Hiroshi; Williams, Ifor R

2009-11-01

Microfold cells (M cells) are specialized epithelial cells situated over Peyer's patches (PP) and other organized mucosal lymphoid tissues that transport commensal bacteria and other particulate Ags into intraepithelial pockets accessed by APCs. The TNF superfamily member receptor activator of NF-kappaB ligand (RANKL) is selectively expressed by subepithelial stromal cells in PP domes. We found that RANKL null mice have <2% of wild-type levels of PP M cells and markedly diminished uptake of 200 nm diameter fluorescent beads. Ab-mediated neutralization of RANKL in adult wild-type mice also eliminated most PP M cells. The M cell deficit in RANKL null mice was corrected by systemic administration of exogenous RANKL. Treatment with RANKL also induced the differentiation of villous M cells on all small intestinal villi with the capacity for avid uptake of Salmonella and Yersinia organisms and fluorescent beads. The RANK receptor for RANKL is expressed by epithelial cells throughout the small intestine. We conclude that availability of RANKL is the critical factor controlling the differentiation of M cells from RANK-expressing intestinal epithelial precursor cells.

The Navy Enlistment Field Marketing Experiment. Volume 7. The Wharton Administered Navy Tracking Survey: A Segmentation Approach

DTIC Science & Technology

1982-10-15

the two may interact. L1 *1 -35- REFERENCES [1] Arnold, Stephen J. (1979), "A Test for Clusters," Journal of Marketing Research , November, pp 545-551...of Marketing Research , August, pp 405-412. APPENDIX A RESULTS OF FACTOR ANALYSIS OF LIFE GOALS . . . . . -37- Ft-M AnSIS CF FEq. LIFE GOALS GM"L...Volume 5, Pre-intervention Recruiting Environ- ment, 1981. [9] Wind, Yoram (1978), "Issues and Advances in Segmentation Research," Journal of Marketing

The Effect of Load Factor on Aircraft Handling Qualities.

DTIC Science & Technology

1984-08-10

sideslip, rudder and aileron deflection are calculated in the AMAT and BMAT program using data frcon this program and solving the side force, yawing and...0 PP = 0 RI = I NY = 8 GOTO 4530 4520 00 = 0 PP = 0 :RI = 8 NY = 8 4538 REM CHANGES EXISTING ELEMENTS OF AMAT & BMAT FOR CO NT AUG - ON & OFF 4540...IN POUNDS ;E 5670 A(9,9) = L4 * A(3,9) - L5 * ZD(5) - 16 5680 GOSUB 5716 5696 GOTO 5590 5706 RETURN 5710 REM SUBROUTINE FOR STORING AMAT & BMAT TO

Neutral meson production and correlation with charged hadrons in pp and Pb-Pb collisions with the ALICE experiment at the LHC

NASA Astrophysics Data System (ADS)

Vauthier, Astrid; Alice Collaboration

2017-11-01

Among the probes used to investigate the properties of the Quark-Gluon Plasma, the measurement of the energy loss of high-energy partons can be used to put constraints on energy-loss models and to ultimately access medium characteristics, such as the energy density or the temperature. The study of two-particle correlations allows us to obtain very different constraints compared to the nuclear modification factor. In particular, the correlation of charged hadrons with high energy π0 or direct photons is believed to give a measurement of the parton energy loss and insights into the medium-induced modification of the fragmentation process. High energy neutral pions are reconstructed using the ALICE electromagnetic calorimeters EMCal and PHOS, and the charged particles are detected by the main tracking detectors ITS and TPC. In these proceedings, the measurement of neutral mesons at √{ s} = 2.76TeV in pp collisions are presented, as well as the measurements of azimuthal π0-hadron correlations in pp and Pb-Pb collisions at √{ s} = 2.76TeV, and the extracted per-trigger yield modification factor (IAA). Comparisons with theoretical model calculations are also added.

Measurements of the charm jet cross section and nuclear modification factor in pPb collisions at s NN = 5.02   TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2017-06-23

The CMS Collaboration presents the first measurement of the differential cross section of jets from charm quarks produced in proton-lead (pPb) collisions at a nucleon-nucleon center-of-mass energy ofmore » $$\\sqrt{s{NN}}$$ = 5.02 TeV, as well as results from charm quark jets in proton-proton (pp) collisions at $$\\sqrt{s}$$= 2.76 and 5.02 TeV. By comparing the yields of the pPb and pp collision systems at the same energy, a nuclear modification factor for charm jets in pPb collisions at $$\\sqrt{s{NN}}$$ = 5.02 TeV of $$R_{pA}$$ = 0.92 +/- 0.07 (stat) +/- 0.11 (syst) is obtained. This is consistent with an absence of final-state energy loss for charm quarks in pPb collisions. In addition, the fraction of jets coming from charm quarks is found to be consistent with that predicted by PYTHIA 6 for pp collisions at $$\\sqrt{s}$$= 2.76 and 5.02 TeV, and is independent of the jet transverse momentum from 55 to 400 GeV.« less

Measurement of the B^{±} Meson Nuclear Modification Factor in Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV.

PubMed

Sirunyan, A M; Tumasyan, A; Adam, W; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Hörmann, N; Hrubec, J; Jeitler, M; König, A; Krätschmer, I; Liko, D; Matsushita, T; Mikulec, I; Rabady, D; Rad, N; Rohringer, H; Schieck, J; Strauss, J; Waltenberger, W; Wulz, C-E; Chekhovsky, V; Mossolov, V; Suarez Gonzalez, J; Shumeiko, N; Alderweireldt, S; De Wolf, E A; Janssen, X; Lauwers, J; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Abu Zeid, S; Blekman, F; D'Hondt, J; De Bruyn, I; De Clercq, J; Deroover, K; Lowette, S; Moortgat, S; Moreels, L; Olbrechts, A; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Karapostoli, G; Lenzi, T; Luetic, J; Maerschalk, T; Marinov, A; Randle-Conde, A; Seva, T; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Zhang, F; Cimmino, A; Cornelis, T; Dobur, D; Fagot, A; Gul, M; Khvastunov, I; Poyraz, D; Salva, S; Schöfbeck, R; Tytgat, M; Van Driessche, W; Verbeke, W; Zaganidis, N; Bakhshiansohi, H; Bondu, O; Brochet, S; Bruno, G; Caudron, A; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Jafari, A; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Piotrzkowski, K; Quertenmont, L; Vidal Marono, M; Wertz, S; Beliy, N; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Mora Herrera, C; Mundim, L; Nogima, H; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Torres Da Silva De Araujo, F; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Fernandez Perez Tomei, T R; Gregores, E M; Mercadante, P G; Moon, C S; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Rodozov, M; Stoykova, S; Sultanov, G; Vutova, M; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Fang, W; Gao, X; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Jiang, C H; Leggat, D; Liu, Z; Romeo, F; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Yazgan, E; Zhang, H; Zhao, J; Ban, Y; Chen, G; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; González Hernández, C F; Ruiz Alvarez, J D; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Susa, T; Ather, M W; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Finger, M; Finger, M; Carrera Jarrin, E; Assran, Y; Mahmoud, M A; Mahrous, A; Dewanjee, R K; Kadastik, M; Perrini, L; Raidal, M; Tiko, A; Veelken, C; Eerola, P; Pekkanen, J; Voutilainen, M; Härkönen, J; Järvinen, T; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Tuominen, E; Tuominiemi, J; Tuovinen, E; Talvitie, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Faure, J L; Ferri, F; Ganjour, S; Ghosh, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Kucher, I; Locci, E; Machet, M; Malcles, J; Rander, J; Rosowsky, A; Sahin, M Ö; Titov, M; Abdulsalam, A; Antropov, I; Baffioni, S; Beaudette, F; Busson, P; Cadamuro, L; Chapon, E; Charlot, C; Davignon, O; Granier de Cassagnac, R; Jo, M; Lisniak, S; Lobanov, A; Miné, P; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Pigard, P; Regnard, S; Salerno, R; Sirois, Y; Stahl Leiton, A G; Strebler, T; Yilmaz, Y; Zabi, A; Agram, J-L; Andrea, J; Bloch, D; Brom, J-M; Buttignol, M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Coubez, X; Fontaine, J-C; Gelé, D; Goerlach, U; Le Bihan, A-C; Van Hove, P; Gadrat, S; Beauceron, S; Bernet, C; Boudoul, G; Chierici, R; Contardo, D; Courbon, B; Depasse, P; El Mamouni, H; Fay, J; Finco, L; Gascon, S; Gouzevitch, M; Grenier, G; Ille, B; Lagarde, F; Laktineh, I B; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Popov, A; Sordini, V; Vander Donckt, M; Viret, S; Khvedelidze, A; Tsamalaidze, Z; Autermann, C; Beranek, S; Feld, L; Kiesel, M K; Klein, K; Lipinski, M; Preuten, M; Schomakers, C; Schulz, J; Verlage, T; Albert, A; Brodski, M; Dietz-Laursonn, E; Duchardt, D; Endres, M; Erdmann, M; Erdweg, S; Esch, T; Fischer, R; Güth, A; Hamer, M; Hebbeker, T; Heidemann, C; Hoepfner, K; Knutzen, S; Merschmeyer, M; Meyer, A; Millet, P; Mukherjee, S; Olschewski, M; Padeken, K; Pook, T; Radziej, M; Reithler, H; Rieger, M; Scheuch, F; Sonnenschein, L; Teyssier, D; Thüer, S; Flügge, G; Kargoll, B; Kress, T; Künsken, A; Lingemann, J; Müller, T; Nehrkorn, A; Nowack, A; Pistone, C; Pooth, O; Stahl, A; Aldaya Martin, M; Arndt, T; Asawatangtrakuldee, C; Beernaert, K; Behnke, O; Behrens, U; Bin Anuar, A A; Borras, K; Botta, V; Campbell, A; Connor, P; Contreras-Campana, C; Costanza, F; Diez Pardos, C; Eckerlin, G; Eckstein, D; Eichhorn, T; Eren, E; Gallo, E; Garay Garcia, J; Geiser, A; Gizhko, A; Grados Luyando, J M; Grohsjean, A; Gunnellini, P; Harb, A; Hauk, J; Hempel, M; Jung, H; Kalogeropoulos, A; Kasemann, M; Keaveney, J; Kleinwort, C; Korol, I; Krücker, D; Lange, W; Lelek, A; Lenz, T; Leonard, J; Lipka, K; Lohmann, W; Mankel, R; Melzer-Pellmann, I-A; Meyer, A B; Mittag, G; Mnich, J; Mussgiller, A; Ntomari, E; Pitzl, D; Placakyte, R; Raspereza, A; Roland, B; Savitskyi, M; Saxena, P; Shevchenko, R; Spannagel, S; Stefaniuk, N; Van Onsem, G P; Walsh, R; Wen, Y; Wichmann, K; Wissing, C; Bein, S; Blobel, V; Centis Vignali, M; Draeger, A R; Dreyer, T; Garutti, E; Gonzalez, D; Haller, J; Hoffmann, M; Junkes, A; Klanner, R; Kogler, R; Kovalchuk, N; Kurz, S; Lapsien, T; Marchesini, I; Marconi, D; Meyer, M; Niedziela, M; Nowatschin, D; Pantaleo, F; Peiffer, T; Perieanu, A; Scharf, C; Schleper, P; Schmidt, A; Schumann, S; Schwandt, J; Sonneveld, J; Stadie, H; Steinbrück, G; Stober, F M; Stöver, M; Tholen, H; Troendle, D; Usai, E; Vanelderen, L; Vanhoefer, A; Vormwald, B; Akbiyik, M; Barth, C; Baur, S; Baus, C; Berger, J; Butz, E; Caspart, R; Chwalek, T; Colombo, F; De Boer, W; Dierlamm, A; Freund, B; Friese, R; Giffels, M; Gilbert, A; Haitz, D; Hartmann, F; Heindl, S M; Husemann, U; Kassel, F; Kudella, S; Mildner, H; Mozer, M U; Müller, Th; Plagge, M; Quast, G; Rabbertz, K; Schröder, M; Shvetsov, I; Sieber, G; Simonis, H J; Ulrich, R; Wayand, S; Weber, M; Weiler, T; Williamson, S; Wöhrmann, C; Wolf, R; Anagnostou, G; Daskalakis, G; Geralis, T; Giakoumopoulou, V A; Kyriakis, A; Loukas, D; Topsis-Giotis, I; Kesisoglou, S; Panagiotou, A; Saoulidou, N; Evangelou, I; Flouris, G; Foudas, C; Kokkas, P; Manthos, N; Papadopoulos, I; Paradas, E; Strologas, J; Triantis, F A; Csanad, M; Filipovic, N; Pasztor, G; Bencze, G; Hajdu, C; Horvath, D; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Karancsi, J; Makovec, A; Molnar, J; Szillasi, Z; Bartók, M; Raics, P; Trocsanyi, Z L; Ujvari, B; Choudhury, S; Komaragiri, J R; Bahinipati, S; Bhowmik, S; Mal, P; Mandal, K; Nayak, A; Sahoo, D K; Sahoo, N; Swain, S K; Bansal, S; Beri, S B; Bhatnagar, V; Chawla, R; Dhingra, N; Bhawandeep, U; Kalsi, A K; Kaur, A; Kaur, M; Kumar, R; Kumari, P; Mehta, A; Mittal, M; Singh, J B; Walia, G; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A; Chauhan, S; Choudhary, B C; Garg, R B; Keshri, S; Malhotra, S; Naimuddin, M; Ranjan, K; Sharma, R; Sharma, V; Bhardwaj, R; Bhattacharya, R; Bhattacharya, S; Dey, S; Dutt, S; Dutta, S; Ghosh, S; Majumdar, N; Modak, A; Mondal, K; Mukhopadhyay, S; Nandan, S; Purohit, A; Roy, A; Roy, D; Roy Chowdhury, S; Sarkar, S; Sharan, M; Thakur, S; Behera, P K; Chudasama, R; Dutta, D; Jha, V; Kumar, V; Mohanty, A K; Netrakanti, P K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Dugad, S; Mahakud, B; Mitra, S; Mohanty, G B; Parida, B; Sur, N; Sutar, B; Banerjee, S; Bhattacharya, S; 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Castle, J; Khalil, S; Kropivnitskaya, A; Majumder, D; Mcbrayer, W; Murray, M; Royon, C; Sanders, S; Stringer, R; Tapia Takaki, J D; Wang, Q; Ivanov, A; Kaadze, K; Maravin, Y; Mohammadi, A; Saini, L K; Skhirtladze, N; Toda, S; Rebassoo, F; Wright, D; Anelli, C; Baden, A; Baron, O; Belloni, A; Calvert, B; Eno, S C; Ferraioli, C; Hadley, N J; Jabeen, S; Jeng, G Y; Kellogg, R G; Kunkle, J; Mignerey, A C; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonwar, S C; Abercrombie, D; Allen, B; Azzolini, V; Barbieri, R; Baty, A; Bi, R; Bierwagen, K; Brandt, S; Busza, W; Cali, I A; D'Alfonso, M; Demiragli, Z; Gomez Ceballos, G; Goncharov, M; Hsu, D; Iiyama, Y; Innocenti, G M; Klute, M; Kovalskyi, D; Lai, Y S; Lee, Y-J; Levin, A; Luckey, P D; Maier, B; Marini, A C; Mcginn, C; Mironov, C; Narayanan, S; Niu, X; Paus, C; Roland, C; Roland, G; Salfeld-Nebgen, J; Stephans, G S F; Tatar, K; Turner, A; Velicanu, D; Wang, J; Wang, T W; Wyslouch, B; Benvenuti, A C; Chatterjee, R M; Evans, A; Hansen, P; Kalafut, S; Kao, S C; Kubota, Y; Lesko, Z; Mans, J; Nourbakhsh, S; Ruckstuhl, N; Rusack, R; Tambe, N; Turkewitz, J; Acosta, J G; Oliveros, S; Avdeeva, E; Bloom, K; Claes, D R; Fangmeier, C; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Monroy, J; Siado, J E; Snow, G R; Stieger, B; Alyari, M; Dolen, J; Godshalk, A; Harrington, C; Iashvili, I; Kharchilava, A; Parker, A; Rappoccio, S; Roozbahani, B; Alverson, G; Barberis, E; Hortiangtham, A; Massironi, A; Morse, D M; Nash, D; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wang, R-J; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Mucia, N; Odell, N; Pollack, B; Schmitt, M H; Sung, K; Trovato, M; Velasco, M; Dev, N; Hildreth, M; Hurtado Anampa, K; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Loukas, N; Marinelli, N; Meng, F; Mueller, C; Musienko, Y; Planer, M; Reinsvold, A; Ruchti, R; Rupprecht, N; Smith, G; Taroni, S; Wayne, M; Wolf, M; Woodard, A; Alimena, J; Antonelli, L; Bylsma, B; Durkin, L S; Flowers, S; Francis, B; Hart, A; Hill, C; Ji, W; Liu, B; Luo, W; Puigh, D; Winer, B L; Wulsin, H W; Benaglia, A; Cooperstein, S; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Lange, D; Luo, J; Marlow, D; Mei, K; Ojalvo, I; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Svyatkovskiy, A; Tully, C; Malik, S; Norberg, S; Barker, A; Barnes, V E; Folgueras, S; Gutay, L; Jha, M K; Jones, M; Jung, A W; Khatiwada, A; Miller, D H; Neumeister, N; Schulte, J F; Sun, J; Wang, F; Xie, W; Cheng, T; Parashar, N; Stupak, J; Adair, A; Akgun, B; Chen, Z; Ecklund, K M; Geurts, F J M; Guilbaud, M; Li, W; Michlin, B; Northup, M; Padley, B P; Roberts, J; Rorie, J; Tu, Z; Zabel, J; Betchart, B; Bodek, A; de Barbaro, P; Demina, R; Duh, Y T; Ferbel, T; Galanti, M; Garcia-Bellido, A; Han, J; Hindrichs, O; Khukhunaishvili, A; Lo, K H; Tan, P; Verzetti, M; Ciesielski, R; Goulianos, K; Mesropian, C; Agapitos, A; Chou, J P; Gershtein, Y; Gómez Espinosa, T A; Halkiadakis, E; Heindl, M; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Kyriacou, S; Lath, A; Montalvo, R; Nash, K; Osherson, M; Saka, H; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Foerster, M; Heideman, J; Riley, G; Rose, K; Spanier, S; Thapa, K; Bouhali, O; Castaneda Hernandez, A; Celik, A; Dalchenko, M; De Mattia, M; Delgado, A; Dildick, S; Eusebi, R; Gilmore, J; Huang, T; Kamon, T; Mueller, R; Pakhotin, Y; Patel, R; Perloff, A; Perniè, L; Rathjens, D; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Damgov, J; De Guio, F; Dragoiu, C; Dudero, P R; Faulkner, J; Gurpinar, E; Kunori, S; Lamichhane, K; Lee, S W; Libeiro, T; Peltola, T; Undleeb, S; Volobouev, I; Wang, Z; Greene, S; Gurrola, A; Janjam, R; Johns, W; Maguire, C; Melo, A; Ni, H; Sheldon, P; Tuo, S; Velkovska, J; Xu, Q; Arenton, M W; Barria, P; Cox, B; Hirosky, R; Ledovskoy, A; Li, H; Neu, C; Sinthuprasith, T; Sun, X; Wang, Y; Wolfe, E; Xia, F; Clarke, C; Harr, R; Karchin, P E; Sturdy, J; Zaleski, S; Belknap, D A; Buchanan, J; Caillol, C; Dasu, S; Dodd, L; Duric, S; Gomber, B; Grothe, M; Herndon, M; Hervé, A; Hussain, U; Klabbers, P; Lanaro, A; Levine, A; Long, K; Loveless, R; Pierro, G A; Polese, G; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

2017-10-13

The differential production cross sections of B^{±} mesons are measured via the exclusive decay channels B^{±}→J/ψK^{±}→μ^{+}μ^{-}K^{±} as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02  TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0  pb^{-1} (351  μb^{-1}). The measurement is performed in the B^{±} meson transverse momentum range of 7 to 50  GeV/c, in the rapidity interval |y|<2.4. In this kinematic range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. These results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.

Tissue response to collagen containing polypropylene meshes in an ovine vaginal repair model.

PubMed

Darzi, Saeedeh; Urbankova, Iva; Su, Kai; White, Jacinta; Lo, Camden; Alexander, David; Werkmeister, Jerome A; Gargett, Caroline E; Deprest, Jan

2016-07-15

Pelvic Organ Prolapse (POP) is the herniation of pelvic organs into the vagina. Despite broad acceptance of mesh use in POP surgical repair, the complication rate is unacceptable. We hypothesized that collagen-containing polypropylene (PP) mesh types could modulate mesh-tissue integration and reduce long-term inflammation, thereby reducing mesh-associated complications. This study compared the long-term tissue response to an unmodified PP mesh and two collagen containing meshes in an ovine model which has similar pelvic anatomy and vaginal size to human. Three commercially available macroporous PP meshes, uncoated PP mesh (Avaulta Solo) (PP), the same textile PP mesh layered with a sheet of cross-linked porcine acellular matrix (Avaulta Plus) (PP-ACM) and a different yet also macroporous PP (Sofradim) mesh coated with solubilized atelocollagen (Ugytex) (PP-sCOL) were implanted in the ovine vagina and tissue explanted after 60 and 180days. The macrophage phenotype and response to implanted meshes, and vascularity were quantified by immunostaining and morphometry. We quantified changes in extracellular matrix composition biochemically and collagen organisation and percentage area around the interface of the mesh implants by Sirius Red birefringence and morphometry. PP-ACM induced a more sustained inflammatory response, indicated by similar CD45(+) leukocytes but reduced CD163(+) M2 macrophages at 60days (P<0.05). PP-sCOL increased Von Willebrand Factor (vWF)-immunoreactive vessel profiles after 60days. At the micro-molecular level, collagen birefringence quantification revealed significantly fewer mature collagen fibrils (red, thick fibrils) at the mesh-tissue interface than control tissue for all mesh types (P<0.001) but still significantly greater than the proportion of immature (green thin fibrils) at 60days (P<0.05). The proportion of mature collagen fibrils increased with time around the mesh filaments, particularly those containing collagen. The total collagen percent area at the mesh interface was greatest around the PP-ACM mesh at 60days (P<0.05). By 180days the total mature and immature collagen fibres at the interface of the mesh filaments resembled that of native tissue. In particular, these results suggest that both meshes containing collagen evoke different types of tissue responses at different times during the healing response yet both ultimately lead to physiological tissue formation approaching that of normal tissue. Pelvic organ prolapse (POP) is the descent of the pelvic organs to the vagina. POP affects more than 25% of all women and the lifetime risk of undergoing POP surgery is 19%. Although synthetic polypropylene (PP) meshes have improved the outcome of the surgical treatment for POP, there was an unacceptable rate of adverse events including mesh exposure and contracture. It is hypothesized that coating the PP meshes with collagen would provide a protective effect by preventing severe mesh adhesions to the wound, resulting in a better controlled initial inflammatory response, and diminished risk of exposure. In this study we assessed the effect of two collagen-containing PP meshes on the long-term vaginal tissue response using new techniques to quantify these tissue responses. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Evaluation and Refinement of the Environment Stress Index (ESI) for Different Climatic Conditions

DTIC Science & Technology

2002-06-01

generally determined through meteorological parameters that enable one to estimate the influence of several environmental factors on thermal comfort and...pp 1-20 Gun RT, Budd GM (1995) Effects of thermal, personal and behavioral factors on the physiological strain, thermal comfort and productivity of

Interactions of ABA signaling core components (SlPYLs, SlPP2Cs, and SlSnRK2s) in tomato (Solanum lycopersicon).

PubMed

Chen, Pei; Sun, Yu-Fei; Kai, Wen-Bin; Liang, Bin; Zhang, Yu-Shu; Zhai, Xia-Wan; Jiang, Li; Du, Yang-Wei; Leng, Ping

2016-10-20

Abscisic acid (ABA) regulates fruit development and ripening via its signaling. However, the exact role of ABA signaling core components in fruit have not yet been clarified. In this study, we investigated the potential interactions of tomato (Solanum lycopersicon) ABA signaling core components using yeast two-hybrid analysis, with or without ABA at different concentrations. The results showed that among 12 PYR/PYL/RCAR ABA receptors (SlPYLs), SlPYL1, SlPYL2, SlPYL4, SlPYL5, SlPYL 7, SlPYL8, SlPYL9, SlPYL10, SlPYL11, and SlPYL13 were ABA-dependent receptors, while SlPYL3 and SlPYL12 were ABA-independent receptors. Among five SlPP2Cs (type 2C protein phosphatases) and seven SlSnRK2s (subfamily 2 of SNF1-related kinases), all SlSnRK2s could interact with SlPP2C2, while SlSnRK2.8 also interacted with SlPP2C3. SlSnRK2.5 could interact with SlABF2/4 (ABA-responsive element binding factors). Expressions of SlPYL1, SlPYL2, SlPYL8, and SlPYL10 were upregulated under exogenous ABA but downregulated under nordihydroguaiaretic acid (NDGA) at the mature green stage of fruit ripening. The expressions of SlPP2C1, SlPP2C2, SlPP2C3, and SlPP2C5 were upregulated in ABA-treated fruit, but downregulated in NDGA-treated fruit at the mature green stage. The expressions of SlSnRK2.4, SlSnRK2.5, SlSnRK2.6, and SlSnRK2.7 were upregulated by ABA, but downregulated by NDGA. However, SlSnRK2.2 was down regulated by ABA. Expression of SlABF2/3/4 was enhanced by ABA but decreased by NDGA. Based on these results, we concluded that the majority of ABA receptor PYLs interact with SlPP2Cs in an ABA-dependent manner. SlPP2C2 and SlPP2C3 can interact with SlSnRK2s. SlSnRK2.5 could interact with SlABF2/4. Most ABA signaling core components respond to exogenous ABA. Copyright © 2016 Elsevier GmbH. All rights reserved.

Exclusive photoproduction of J/ψ and ψ(2S) in pp and AA collisions

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

Cisek, Anna; Schäfer, Wolfgang; Szczurek, Antoni

2015-04-10

The amplitude for γp → J/ψp(γp → ψ'p) is calculated in a pQCD k{sub ⊥}-factorization approach. The total cross section for this process is calculated for different unintegrated gluon distributions and compared with the HERA data and the data extracted recently by the LHCb collaboration. The amplitude for γp → J/ψp(γp → ψ'p) is used to predict the cross section for exclusive photoproduction of the J/ψ(ψ') meson in proton-proton and nucleus-nucleus collisions. In the pp case, compared to earlier calculations we include both Dirac and Pauli electromagnetic form factors. We also discuss the dependence of nuclear shadowing on the charmoniummore » state.« less

Prospective phase II study evaluating the efficacy of swallow ability screening tests and pneumonia prevention using a team approach for elderly patients with gastric cancer.

PubMed

Miki, Yuichiro; Makuuchi, Rie; Honda, Shinsaku; Tokunaga, Masanori; Tanizawa, Yutaka; Bando, Etsuro; Kawamura, Taiichi; Yurikusa, Takashi; Tanuma, Akira; Terashima, Masanori

2018-03-01

Aging partly impairs swallowing function, which is considered a risk factor for postoperative pneumonia (PP). We evaluated the efficacy of a new team-based strategy to reduce the incidence of PP in elderly patients with gastric cancer. This single-center, prospective phase II study included elderly patients (≥75 years old) with gastric cancer undergoing gastric surgery. The primary endpoint was the incidence of Clavien-Dindo grade II or higher PP. Patients were initially screened using three swallowing function screening tests: a symptom questionnaire, the modified water swallow test (MSWT), and the repetitive saliva swallowing test (RSST). All patients were provided standard preoperative oral checks and care and simple neck muscle training. For patients who screened positive, a videofluorographic swallowing study was performed; if an abnormality was found, the patient was given intensive swallowing rehabilitation both pre- and postoperatively. Of 86 eligible patients enrolled, PP developed in 3 (3.5%). The 60% confidence interval of 1.8-6.3% had an upper limit below the prespecified threshold of 7.8%. Positive screening results were found for 19 patients (22.1%) on the symptom questionnaire, 3 (3.5%) on the MSWT, and 1 (1.2%) on the RSST. PP was not observed in any patients who screened positive. In conclusion, although the screening tests we adopted here were not sufficient to identify patients at high risk of aspiration pneumonia, perioperative interventions using a team approach might be effective in reducing the incidence of PP in elderly patients with gastric cancer.

Three Pseudomonas putida FNR Family Proteins with Different Sensitivities to O2.

PubMed

Ibrahim, Susan A; Crack, Jason C; Rolfe, Matthew D; Borrero-de Acuña, José Manuel; Thomson, Andrew J; Le Brun, Nick E; Schobert, Max; Stapleton, Melanie R; Green, Jeffrey

2015-07-03

The Escherichia coli fumarate-nitrate reduction regulator (FNR) protein is the paradigm for bacterial O2-sensing transcription factors. However, unlike E. coli, some bacterial species possess multiple FNR proteins that presumably have evolved to fulfill distinct roles. Here, three FNR proteins (ANR, PP_3233, and PP_3287) from a single bacterial species, Pseudomonas putida KT2440, have been analyzed. Under anaerobic conditions, all three proteins had spectral properties resembling those of [4Fe-4S] proteins. The reactivity of the ANR [4Fe-4S] cluster with O2 was similar to that of E. coli FNR, and during conversion to the apo-protein, via a [2Fe-2S] intermediate, cluster sulfur was retained. Like ANR, reconstituted PP_3233 and PP_3287 were converted to [2Fe-2S] forms when exposed to O2, but their [4Fe-4S] clusters reacted more slowly. Transcription from an FNR-dependent promoter with a consensus FNR-binding site in P. putida and E. coli strains expressing only one FNR protein was consistent with the in vitro responses to O2. Taken together, the experimental results suggest that the local environments of the iron-sulfur clusters in the different P. putida FNR proteins influence their reactivity with O2, such that ANR resembles E. coli FNR and is highly responsive to low concentrations of O2, whereas PP_3233 and PP_3287 have evolved to be less sensitive to O2. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Primitive-path statistics of entangled polymers: mapping multi-chain simulations onto single-chain mean-field models

NASA Astrophysics Data System (ADS)

Steenbakkers, Rudi J. A.; Tzoumanekas, Christos; Li, Ying; Liu, Wing Kam; Kröger, Martin; Schieber, Jay D.

2014-01-01

We present a method to map the full equilibrium distribution of the primitive-path (PP) length, obtained from multi-chain simulations of polymer melts, onto a single-chain mean-field ‘target’ model. Most previous works used the Doi-Edwards tube model as a target. However, the average number of monomers per PP segment, obtained from multi-chain PP networks, has consistently shown a discrepancy of a factor of two with respect to tube-model estimates. Part of the problem is that the tube model neglects fluctuations in the lengths of PP segments, the number of entanglements per chain and the distribution of monomers among PP segments, while all these fluctuations are observed in multi-chain simulations. Here we use a recently proposed slip-link model, which includes fluctuations in all these variables as well as in the spatial positions of the entanglements. This turns out to be essential to obtain qualitative and quantitative agreement with the equilibrium PP-length distribution obtained from multi-chain simulations. By fitting this distribution, we are able to determine two of the three parameters of the model, which govern its equilibrium properties. This mapping is executed for four different linear polymers and for different molecular weights. The two parameters are found to depend on chemistry, but not on molecular weight. The model predicts a constant plateau modulus minus a correction inversely proportional to molecular weight. The value for well-entangled chains, with the parameters determined ab initio, lies in the range of experimental data for the materials investigated.

Idiopathic normal pressure hydrocephalus: analysis of factors related to cerebrospinal fluid dynamics determining functional prognosis.

PubMed

Bárcena, A; Mestre, C; Cañizal, J M; Rivero, B; Lobato, R D

1997-01-01

This investigation has been undertaken to analyze the findings with both the cerebrospinal fluid (CSF) pressure (Pcsf) and CSF pulse pressure (PP) in order to predict the outcome of patients with the syndrome of idiopathic normal pressure hydrocephalus (NPH). Accordingly, a prospective clinical study was planned in which two groups of patients with NPH, having analogous prevalence of several matched clinical and radiological parameters, were separated on the basis of their positive or negative response to shunting. Both the resting Pcsf and CSF PP profiles were compared in these two groups, and between them and normal controls. CSF PP amplitude and CSF PP latency correlated directly in conditions associated with either normal or high compliance (controls and patients with Alzheimer-like disorders), whereas this correlation was inverse in states of low compliance (NPH). On the other hand, shunt-responders showed a resting Pcsf significantly higher than both non-responders and controls. The following conclusions were obtained: 1) CSF PP is a high-amplitude and relative low-latency wave in NPH when compared with controls: 2) CSF PP amplitude and latency correlate directly in normal subjects and in those with primary cerebral atrophy; 3) a non-reversible stage of NPH could be conceived in contradistinction to the reversible one, in both of which an inverse correlation between the amplitude and the latency takes place, the main difference between them being the resting Pcsf, which is significantly lower in the former than in the latter, depending on the degree of atrophic changes developed.

A prospective observational study comparing a non-operator dependent automatic PWV analyser to pulse pressure, in assessing arterial stiffness in hemodialysis.

PubMed

Salvadé, Igor; Schätti-Stählin, Sibylle; Violetti, Eleonora; Schönholzer, Carlo; Cereghetti, Claudio; Zwahlen, Hugo; Berwert, Lorenzo; Burnier, Michel; Gabutti, Luca

2015-04-23

Chronic kidney disease (CKD) accelerates vascular stiffening related to age. Arterial stiffness may be evaluated measuring the carotid-femoral pulse wave velocity (PWV) or more simply, as recommended by KDOQI, monitoring pulse pressure (PP). Both correlate to survival and incidence of cardiovascular disease. PWV can also be estimated on the brachial artery using a Mobil-O-Graph; a non-operator dependent automatic device. The aim was to analyse whether, in a dialysis population, PWV obtained by Mobil-O-Graph (MogPWV) is more sensitive for vascular aging than PP. A cohort of 143 patients from 4 dialysis units has been followed measuring MogPWV and PP every 3 to 6 months and compared to a control group with the same risk factors but an eGFR > 30 ml/min. MogPWV contrarily to PP did discriminate the dialysis population from the control group. The mean difference translated in age between the two populations was 8.4 years. The increase in MogPWV, as a function of age, was more rapid in the dialysis group. 13.3% of the dialysis patients but only 3.0% of the control group were outliers for MogPWV. The mortality rate (16 out of 143) was similar in outliers and inliers (7.4 and 8.0%/year). Stratifying patients according to MogPWV, a significant difference in survival was seen. A high parathormone (PTH) and to be dialysed for a hypertensive nephropathy were associated to a higher baseline MogPWV. Assessing PWV on the brachial artery using a Mobil-O-Graph is a valid and simple alternative, which, in the dialysis population, is more sensitive for vascular aging than PP. As demonstrated in previous studies PWV correlates to mortality. Among specific CKD risk factors only PTH is associated with a higher baseline PWV. ClinicalTrials.gov Identifier: NCT02327962.

Encapsulated VEGF-secreting cells enhance proliferation of neuronal progenitors in the hippocampus of AβPP/Ps1 mice.

PubMed

Antequera, Desiree; Portero, Aitziber; Bolos, Marta; Orive, Gorka; Hernández, Rosa M Rm A; Pedraz, José Luis; Carro, Eva

2012-01-01

Vascular endothelial growth factor (VEGF) promotes neurogenesis in the adult hippocampus, but the way in which this process occurs in the Alzheimer's disease (AD) brain is still unknown. We examined the proliferation of neuronal precursors with an ex vivo approach, using encapsulated VEGF secreting cells, in AβPP/PS1 mice, a mouse model of AD. Overexpression of VEGF and VEGF receptor flk-1 was observed in the cerebral cortex from VEGF microcapsules-treated AβPP/PS1 mice at 1, 3 and 6 months after VEGF-microcapsule implantation. Stereological counting of 5-bromodeoxyuridine positive cells revealed that encapsulated VEGF secreting cells significantly enhanced cellular proliferation in the hippocampal dentate gyrus (DG). The number of neuronal precursors in VEGF microcapsules-treated AβPP/PS1 mice was also greater, and this effect remains after 6 months. We also confirmed that encapsulated VEGF secreting cells also stimulated angiogenesis in the cerebral cortex and hippocampal dentate gyrus. In addition, we found that VEGF-microcapsule treatment was associated with a depressed expression and activity of acetylcholinesterase in the hippocampus of AβPP/PS1 mice, a similar pattern as first-line medications for the treatment of AD. We conclude that stereologically-implanted VEGF-microcapsules exert an acute and long-standing neurotrophic effects, and could be utilized to improve potential therapies to control the progression of AD.

Strange hadron production in pp, pPb, and PbPb collisions at LHC energies

NASA Astrophysics Data System (ADS)

Ni, Hong

2018-02-01

Identified particle spectra provide an important tool for understanding the particle production mechanism and the dynamical evolution of the medium created in relativistic heavy ion collisions. Studies involving strange and multi-strange hadrons, such as K0S, Λ, and Ξ-, carry additional information since there is no net strangeness content in the initial colliding system. Strangeness enhancement in AA collisions with respect to pp and pA collisions has long been considered as one of the signatures for quark-gluon plasma (QGP) formation. Recent observations of collective effects in high-multiplicity pp and pA collisions raise the question of whether QGP can also be formed in the smaller systems. Systematic studies of strange particle abundance, particle ratios, and nuclear modification factors can shed light on this issue. The CMS experiment has excellent strange-particle reconstruction capabilities over a broad kinematic range, and dedicated high-multiplicity triggers in pp and pPb collisions. The spectra of K0S, Λ, and Ξ- hadrons have been measured in various multiplicity and rapidity regions as a function of pT in pp, pPb, and PbPb collisions for several collision energies. The spectral shapes and particle ratios are compared in the different collision systems for events that have the same multiplicity and interpreted in the context of hydrodynamics models.

Anti-biofilm activity of Pseudoalteromonas flavipulchra SktPp1 against Serratia marcescens SMJ-11

NASA Astrophysics Data System (ADS)

Iqbal, Faiq; Usup, Gires; Ahmad, Asmat

2015-09-01

This study aimed to examine the anti-biofilm activity of Pseudoalteromonas flavipulchra SktPp1 crude extract against the biofilm producer, Serratia marcescens. The crude extract of P. flavipulchra SktPp1 was extracted with ethyl acetate. The sub-minimum inhibitory concentration (MIC), 0.1 mg/ml, has been used in this study. The anti-biofilm activity of P. flavipulchra SktPp1 crude extract was assessed against the biofilm of S. marcescens using the crystal violet assay. The growth curve has been used as the indicator of the effect of crude extracts to bacterial growth. The sub-MIC crude extract was tested against two of S. marcescens virulence factors, including the swarming ability and production of prodigiosin using the swarming assay and prodigiosin assay. The growth curves of S. marcescens indicated that the sub-MIC concentration of crude extract did not affect the growth of S. marcescens. The production of prodigiosin was reduced by 44%. The diameter of the swarming area was reduced from 8.7 cm to 0.8 cm. The sub-MIC crude extract inhibits 26.9% of the biofilm production in S. marcescens. This crude extract lost its activity at 50°C and above. In conclusion, crude extract of P. flavipulchra SktPp1 has the ability to inhibit S. marcescens SMJ-11 biofilm formation.

[Physical performance of older adults living in rural areas at sea level and at high altitude in Peru].

PubMed

Estela-Ayamamani, David; Espinoza-Figueroa, Jossué; Columbus-Morales, Mauricio; Runzer-Colmenares, Fernando; Parodi, José F; Mayta-Tristán, Percy

2015-01-01

Living at high altitudes requires the inhabitants to adapt biologically and socially to the environment. The objective of this study was to determine the difference in physical performance (PP) in rural populations at sea level and at high altitude. A cross-sectional study was conducted in rural communities in Ancash, Peru, located at 3.345 meters above sea level (m.a.s.l.) and also in communities located in coastal areas at 6m.a.s.l. PP was measured by the Short Physical Performance Battery (SPPB) and other associated factors. Adjusted prevalence ratios (aPR) were calculated. A total of 130 older adults were assessed in the high altitude communities and 129 on the coast. The median age was 71.4 years, and 55.6% were female. Low physical performance (SPPB ≤ 6) was 10.0% at high altitude and 19.4% on the coast (p<0.05). Factors associated with low physical performance were residing at the coast (aPR: 2.10, 95% CI 1.02 to 4.33), self-reported poor health (aPR: 2.48, 95% CI 1.21 -5.08), hypertension (aPR: 1.73, 95% CI 1.01 to 2.98), and age (aPR: 1.04, 95% CI 1.01 to 1.07), while being a farmer (aPR: 0.49, 95% CI 0.25 to 0.97), and being independent (aPR: 0.37, 95% CI 0,20-, 072) were found to be protective factors. It was also found that the inhabitants of the coast have a mean of 0.86 points lower total SPPB than the high altitude ones (p=0.004). There is an association between altitude of residence and PP in older adults. The prevalence of a low PP in older adults in rural areas at sea level is twice as high compared to those living in high altitude rural communities. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana

PubMed Central

Wu, Yuzhou; Hou, Jiexi; Yu, Fen; Nguyen, Suong T. T.; McCurdy, David W.

2018-01-01

Transfer cells (TCs) play important roles in facilitating enhanced rates of nutrient transport at key apoplasmic/symplasmic junctions along the nutrient acquisition and transport pathways in plants. TCs achieve this capacity by developing elaborate wall ingrowth networks which serve to increase plasma membrane surface area thus increasing the cell's surface area-to-volume ratio to achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma (PP) cells of Arabidopsis leaf veins trans-differentiate to become PP TCs which likely function in a two-step phloem loading mechanism by facilitating unloading of photoassimilates into the apoplasm for subsequent energy-dependent uptake into the sieve element/companion cell (SE/CC) complex. We are using PP TCs in Arabidopsis as a genetic model to identify transcription factors involved in coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo-Schiff propidium iodide-stained tissue revealed different profiles of temporal development of wall ingrowth deposition across maturing cotyledons and juvenile leaves, and a basipetal gradient of deposition across mature adult leaves. RNA-Seq analysis was undertaken to identify differentially expressed genes common to these three different profiles of wall ingrowth deposition. This analysis identified 68 transcription factors up-regulated two-fold or more in at least two of the three experimental comparisons, with six of these transcription factors belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC genes using insertional mutants revealed significant reductions in levels of wall ingrowth deposition, particularly in a double mutant of NAC056 and NAC018, as well as compromised sucrose-dependent root growth, indicating impaired capacity for phloem loading. Collectively, these results support the proposition that Clade III members of the NAC-domain family in Arabidopsis play important roles in regulating wall ingrowth deposition in PP TCs. PMID:29599795

Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana.

PubMed

Wu, Yuzhou; Hou, Jiexi; Yu, Fen; Nguyen, Suong T T; McCurdy, David W

2018-01-01

Transfer cells (TCs) play important roles in facilitating enhanced rates of nutrient transport at key apoplasmic/symplasmic junctions along the nutrient acquisition and transport pathways in plants. TCs achieve this capacity by developing elaborate wall ingrowth networks which serve to increase plasma membrane surface area thus increasing the cell's surface area-to-volume ratio to achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma (PP) cells of Arabidopsis leaf veins trans -differentiate to become PP TCs which likely function in a two-step phloem loading mechanism by facilitating unloading of photoassimilates into the apoplasm for subsequent energy-dependent uptake into the sieve element/companion cell (SE/CC) complex. We are using PP TCs in Arabidopsis as a genetic model to identify transcription factors involved in coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo-Schiff propidium iodide-stained tissue revealed different profiles of temporal development of wall ingrowth deposition across maturing cotyledons and juvenile leaves, and a basipetal gradient of deposition across mature adult leaves. RNA-Seq analysis was undertaken to identify differentially expressed genes common to these three different profiles of wall ingrowth deposition. This analysis identified 68 transcription factors up-regulated two-fold or more in at least two of the three experimental comparisons, with six of these transcription factors belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC genes using insertional mutants revealed significant reductions in levels of wall ingrowth deposition, particularly in a double mutant of NAC056 and NAC018 , as well as compromised sucrose-dependent root growth, indicating impaired capacity for phloem loading. Collectively, these results support the proposition that Clade III members of the NAC-domain family in Arabidopsis play important roles in regulating wall ingrowth deposition in PP TCs.

Factors affecting the frequency of infection by the sigma virus in experimental populations of Drosophila melanogaster.

PubMed

Fleuriet, A

1982-01-01

The experiments reported in this paper deal with the maintenance of the non contagious, hereditary virus sigma in populations of its host, Drosophila melanogaster. Evidence was previously provided of the existence of two viral Types I and II, depending on their sensitivity to the ref(2)Pp allele (the ref(2)P locus interferes with the multiplication of the virus in the fly). The viral Type I which is the most sensitive to the ref(2)Pp allele, is eliminated in the presence of this allele, even when most of the flies were originally infected in the population. On the contrary, the presence of the ref(2)Pp allele does not prevent a viral Type II, introduced in a population, from infecting most of the flies. The possibility that a change has occurred recently in French natural populations of Drosophila melanogaster is discussed.

Pancreatic Polypeptide Cell Proliferation in the Pancreas and Duodenum Coexisting in a Patient With Pancreatic Adenocarcinoma Treated With a GLP-1 Analog.

PubMed

Talmon, Geoffrey A; Wren, J David; Nguyen, Christophe L; Pour, Parviz M

2017-07-01

A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells. Among the etiological factors, the possible long-lasting effects of the GLP-1 analog, with which the patient was treated, are discussed. This is the first report in the literature of both the coexistence of a pancreatic adenocarcinoma and invasive PPoma and the occurrence of PP and insulin cells in human duodenal mucosa.

[Dynamics of tooth decay prevalence in children receiving long-term preventive program in school dental facilities].

PubMed

Avraamova, O G; Kulazhenko, T V; Gabitova, K F

2016-01-01

The paper presents the assessment of tooth decay prevalence in clinically homogenous groups of children receiving long-term preventive program (PP) in school dental facilities. Five-years PP were introduced in clinical practice in 2 Moscow schools. Preventive treatment was performed by dental hygienist. The results show that systematic preventive treatment in school dental offices starting from elementary school allows reducing dental caries incidence 46-53% and stabilize the incidence of caries complications. It should be mentioned though that analysis of individualized outcomes proves heterogeneity of study results despite of equal conditions of PP. Potentially significant hence is early diagnostics and treatment of initial caries forms as demineralization foci, especially in children with intensive tooth decay. Optimization of pediatric dentist and dental hygienist activity in school dental facilities is the main factor of caries prevention efficiency.

Measurements of J/ψ Production and Polarization in p+p and p+Au Collisions at s NN = 200 GeV with the STAR Experiment

NASA Astrophysics Data System (ADS)

Liu, Zhen

We present the measurements of J/ψ production at mid-rapidity via the di-muon decay channel in p+p and p+Au collisions at s NN = 200 GeV by the STAR experiment at RHIC. In p+p collisions, the measured inclusive J/ψ cross section can be qualitatively described by model calculations. The J/ψ polarization parameters, λ𝜃, λϕ as well as the frame-invariant quantity λinv, are presented as a function of transverse momentum in both the helicity and Collins-Soper frames. No significant polarization is observed. In addition, the nuclear modification factor for inclusive J/ψ in p+Au collisions is similar to that measured in d+Au collisions and favors an additional nuclear absorption effect on top of the nuclear PDF effect.

Measurement of the transition form factor of {eta} meson with WASA-at-COSY

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

Bhatt, H.

2011-10-24

Reaction {eta}{yields}e{sup +}e{sup -}{gamma} is used to investigate the transition form factor of {eta} meson with WASA detector at COSY. Where the {eta} meson is produced in pp collision at 1.4 GeV. We present the analysis techniques and preliminary results of {eta} Dalitz decays.

Medical Student Response to a Class Lipid-Screening Project.

ERIC Educational Resources Information Center

Lum, Gifford; And Others

1982-01-01

Medical students at the State University of New York's Downstate Medical Center initiated and carried out a voluntary project to screen lipids (cholesterol) to identify known coronary risk factors. The incidence of coronary disease factors among these students and the response of students with high cholesterol levels are reported. (Authors/PP)

Executive Self-Assessment and Development in the United States Air Force

DTIC Science & Technology

1989-05-01

34 (Harvard Business Review, January-February 1988, pp.45-53) 056 Drucker , P. " Management and the World’s Work." (Harvard Business Review, September...professional military factors, general leadership and management factors, and functional/technical factors. The study also includes a critical review and...maintaining a comprehensive executive self-assessment and development system. The study concludes with specific recommendations for management action

Andrographolide Enhances Nuclear Factor-κB Subunit p65 Ser536 Dephosphorylation through Activation of Protein Phosphatase 2A in Vascular Smooth Muscle Cells*

PubMed Central

Hsieh, Cheng Y.; Hsu, Ming J.; Hsiao, George; Wang, Yi H.; Huang, Chi W.; Chen, Shiuan W.; Jayakumar, Thanasekaran; Chiu, Pei T.; Chiu, Yi H.; Sheu, Joen R.

2011-01-01

Recent studies have demonstrated that transcription factor nuclear factor (NF)-κB inhibition may contribute to the protective anti-inflammatory actions of andrographolide, an abundant component of plants of the genus Andrographis. However, the precise mechanism by which andrographolide inhibits NF-κB signaling remains unclear. We thus investigated the mechanism involved in andrographolide suppression of NF-κB signaling in rat vascular smooth muscle cells (VSMCs) exposed to proinflammatory stimuli, LPS, and IFN-γ. Andrographolide was shown to suppress LPS/IFN-γ-induced inducible nitric-oxide synthase and matrix metalloprotease 9 expression in rat VSMCs. Andrographolide also inhibited LPS/IFN-γ-induced p65 nuclear translocation, DNA binding activity, p65 Ser536 phosphorylation, and NF-κB reporter activity. However, IKK phosphorylation and downstream inhibitory κBα phosphorylation and degradation were not altered by the presence of andrographolide in LPS/IFN-γ-stimulated VSMCs. These andrographolide inhibitory actions could be prevented by selective inhibition of neutral sphingomyelinase and protein phosphatase 2A (PP2A). Furthermore, andrographolide was demonstrated to increase ceramide formation and PP2A activity in VSMCs and to inhibit neointimal formation in rat carotid injury models. These results suggest that andrographolide caused neutral sphingomyelinase-mediated ceramide formation and PP2A activation to dephosphorylate p65 Ser536, leading to NF-κB inactivation and subsequent inducible nitric-oxide synthase down-regulation in rat VSMCs stimulated by LPS and IFN-γ. PMID:21169355

Exposure to mass media and interpersonal counseling has additive effects on exclusive breastfeeding and its psychosocial determinants among Vietnamese mothers

PubMed Central

Kim, Sunny S.; Nguyen, Tuan T.; Hajeebhoy, Nemat; Tran, Lan M.; Alayon, Silvia; Ruel, Marie T.; Rawat, Rahul; Frongillo, Edward A.; Menon, Purnima

2016-01-01

Abstract The pathways through which behavior change interventions impact breastfeeding practices have not been well studied. This study aimed to examine: (1) the effects of exposure to mass media and interpersonal counseling on exclusive breastfeeding (EBF) and hypothesized psychosocial determinants (i.e. knowledge, intention, beliefs, social norms, and self‐efficacy); and (2) the pathways through which exposure to mass media and interpersonal counseling are associated with EBF. We used survey data from mothers with children < 2 year (n = 2045) from the 2013 process evaluation of Alive & Thrive's program in Viet Nam. Multiple linear regression analyses and structural equation modeling were used to estimate effects. Exposure to mass media only, interpersonal counseling only, both or neither was 51%, 5%, 19% and 25%, respectively. Exposure to both mass media and interpersonal counseling had additive effects on EBF as well as on related psychosocial factors, compared with no exposure. For example, EBF prevalence was 26.1 percentage points (pp) higher in the group that received interpersonal counseling only, 3.9 pp higher in the mass media group and 31.8 pp higher in the group that received both interventions. As hypothesized, more than 90% of the total effect of the two interventions on EBF was explained by the psychosocial factors measured. Our findings suggest that combining different behavior change interventions leads to greater changes in psychosocial factors, which in turn positively affects breastfeeding behaviors. PMID:27334544

Effect of conjugated linoleic acid on proliferation and cytokine expression of bovine peripheral blood mononuclear cells and splenocytes ex vivo.

PubMed

Renner, Lydia; von Soosten, Dirk; Sipka, Anja; Döll, Susanne; Beineke, Andreas; Schuberth, Hans-Joachim; Dänicke, Sven

2012-04-01

Twenty-five primiparous Holstein cows were divided into five experimental groups (five animals per group) by different feeding (control fat preparation [CON] or conjugated linoleic acid [CLA] supplement) and slaughtering times. The daily consumption of CLA was 6.0 g of the trans-10, cis-12 CLA-isomer and 5.7 g cis-9, trans-11 CLA isomer. An initial group (IG) was slaughtered one day post partum (pp) and the remaining 20 animals after 42 and 105 days pp, respectively. Blood for peripheral blood mononuclear cells (PBMC) separation was taken seven days ante partum and immediately before slaughter. The spleen was removed during dissection for isolation of splenocytes and samples for histopathological examination. Cell viability and Concanavalin A-stimulated proliferation was analysed by MTT and Alamar Blue assay. Basal expression of cytokines (interleukin [IL]-4, IL-10, IL-12, tumour necrosis factor alpha [TNF-alpha] and interferon gamma [IFN-gamma]) was measured by quantitative real time polymerase chain reaction (qRT-PCR) in unstimulated PMBC and splenocytes. With PBMC, stimulation indices increased from 1 day pp to 105 days pp with no differences between CLA and CON groups. With splenocytes, the stimulation index of the CLA group was lower compared to CON group 105 days pp. Baseline expression of cytokines was not effected by CLA feeding comparing similar time points. Also, no differences occurred in the expression of IL-4 in PBMC and IL-10 as well as TNF-alpha in both cell populations, when comparing the feeding groups separately with IG. IL-4 was more frequently expressed in CLA group 42 days pp in splenocytes. IFN-gamma expression was increased 105 days pp in CLA group in splenocytes and PBMC. IL-12 was higher expressed 105 days (PBMC) or 42 days pp (splenocytes) when compared to IG. There was no effect of CLA feeding or slaughter time on histopathology of the spleen. In conclusion, the present results demonstrate an inhibiting effect of CLA on the mitogen-induced activation of splenocytes.

Preventing Unintended Pregnancy and HIV Transmission: Effects of the HIV Treatment Cascade on Contraceptive Use and Choice in Rural KwaZulu-Natal

PubMed Central

Raifman, Julia; Chetty, Terusha; Tanser, Frank; Mutevedzi, Tinofa; Matthews, Philippa; Herbst, Kobus; Pillay, Deenan

2014-01-01

Background: For women living with HIV, contraception using condoms is recommended because it prevents not only unintended pregnancy but also acquisition of other sexually transmitted infections and onward transmission of HIV. Dual-method dual-protection contraception (condoms with other contraceptive methods) is preferable over single-method dual-protection contraception (condoms alone) because of its higher contraceptive effectiveness. We estimate the effect of progression through the HIV treatment cascade on contraceptive use and choice among HIV-infected women in rural South Africa. Methods: We linked population-based surveillance data on contraception collected by the Wellcome Trust Africa Centre for Health and Population Studies to data from the local antiretroviral treatment (ART) program in Hlabisa subdistrict, KwaZulu-Natal. In bivariate probit regression, we estimated the effects of progressing through the cascade on contraceptive choice among HIV-infected sexually active women aged 15–49 years (N = 3169), controlling for a wide range of potential confounders. Findings: Contraception use increased across the cascade from <40% among HIV-infected women who did not know their status to >70% among women who have been on ART for 4–7 years. Holding other factors equal (1) awareness of HIV status, (2) ART initiation, and (3) being on ART for 4–7 years increased the likelihood of single-method/dual-method dual protection by the following percentage points (pp), compared with women who were unaware of their HIV status: (1) 4.6 pp (P = 0.030)/3.5 pp (P = 0.001), (2) 10.3 pp (P = 0.003)/5.2 pp (P = 0.007), and (3) 21.6 pp (P < 0.001)/11.2 pp (P < 0.001). Conclusions: Progression through the HIV treatment cascade significantly increased the likelihood of contraception in general and contraception with condoms in particular. ART programs are likely to contribute to HIV prevention through the behavioral pathway of changing contraception use and choice. PMID:25436821

Preventing unintended pregnancy and HIV transmission: effects of the HIV treatment cascade on contraceptive use and choice in rural KwaZulu-Natal.

PubMed

Raifman, Julia; Chetty, Terusha; Tanser, Frank; Mutevedzi, Tinofa; Matthews, Philippa; Herbst, Kobus; Pillay, Deenan; Bärnighausen, Till

2014-12-01

For women living with HIV, contraception using condoms is recommended because it prevents not only unintended pregnancy but also acquisition of other sexually transmitted infections and onward transmission of HIV. Dual-method dual-protection contraception (condoms with other contraceptive methods) is preferable over single-method dual-protection contraception (condoms alone) because of its higher contraceptive effectiveness. We estimate the effect of progression through the HIV treatment cascade on contraceptive use and choice among HIV-infected women in rural South Africa. We linked population-based surveillance data on contraception collected by the Wellcome Trust Africa Centre for Health and Population Studies to data from the local antiretroviral treatment (ART) program in Hlabisa subdistrict, KwaZulu-Natal. In bivariate probit regression, we estimated the effects of progressing through the cascade on contraceptive choice among HIV-infected sexually active women aged 15-49 years (N = 3169), controlling for a wide range of potential confounders. Contraception use increased across the cascade from <40% among HIV-infected women who did not know their status to >70% among women who have been on ART for 4-7 years. Holding other factors equal (1) awareness of HIV status, (2) ART initiation, and (3) being on ART for 4-7 years increased the likelihood of single-method/dual-method dual protection by the following percentage points (pp), compared with women who were unaware of their HIV status: (1) 4.6 pp (P = 0.030)/3.5 pp (P = 0.001), (2) 10.3 pp (P = 0.003)/5.2 pp (P = 0.007), and (3) 21.6 pp (P < 0.001)/11.2 pp (P < 0.001). Progression through the HIV treatment cascade significantly increased the likelihood of contraception in general and contraception with condoms in particular. ART programs are likely to contribute to HIV prevention through the behavioral pathway of changing contraception use and choice.

New values anthropometry for classification of nutritional status in the elderly.

PubMed

Silva Rodrigues, R A; Martinez Espinosa, M; Duarte Melo, C; Rodrigues Perracini, M; Rezende Fett, W C; Fett, C A

2014-07-01

Anthropometry provides information on the physical status of the individual and can be associated with aspects of health including nutritional status. Currently, the stratification of the arm and calf circumferences is classified into only two situations: "malnourished" and "well-nourished". A total of 513 interviews were conducted, and 391 elderly people (≥ 65 years) completed the assessment using the Mini Nutritional Assessment (MNA) and anthropometry of selected samples of the population of Cuiabá-MT. The body mass index (BMI, kg/m2) was calculated for the elderly people, establishing five new reference values for circumferences, arm relaxed (RAC), abdomen (AC), and calf (CC) in centimeters (cm). The median age was 71 years (64% women and 36% men) and was correlated to the RAC (r=-0.180, p<0.001) and CC (r=-0.202, pp<0.001). The BMI obtained the median of 27 (15% malnourished, risk of malnutrition 13%, eutrophic 24%; overweight 33%, obese 16%), and it was correlated to the RAC (r=0.798, pp<0.001), AC (r=0.823 p p<0.001) and CC (r=0.605, pp<0.001). The MNA was 26 (malnourished 13.8%, risk of malnutrition 12.3%, well-nourished, 73.9%). The BMI stratification by morbidity vs no morbidity was 27.50 (n=287) and 24.4 (n=104) to total sample respectively (pp<0,05). The RAC x AC (r=0.798, pp<0.001), RAC x CC (r=0.648, pp<0.001), and CC x AC (r=0.496, pp<0.001) were correlated between themselves. The eutrophic classification by circumference for both genders: RAC=27.1-29.00 cm, AC=88.1-95.00 cm, CC=32.60-33.00 cm. There are more overweight and obese than malnourished, which is a risk factor for morbidity and MNA only identifies malnutrition. Circumferences showed good association with BMI and are easy to apply. Therefore, the proposal of the circumferences can simplify and expand the nutritional assessment.

Diabetes mellitus affects biomechanical properties of the optic nerve head in the rat.

PubMed

Terai, Naim; Spoerl, Eberhard; Haustein, Michael; Hornykewycz, Karin; Haentzschel, Janek; Pillunat, Lutz E

2012-01-01

To investigate the effect of diabetes on the biomechanical behavior of the optic nerve head (ONH) and the peripapillary sclera (ppSc) in streptozocine-induced diabetic rats. Diabetes mellitus was induced in 20 Wistar rats using streptozocine. Twenty-five nondiabetic rats served as controls. Eyes were enucleated after 12 weeks and 2 strips of one eye were prepared containing ONH or ppSc. The stress-strain relation was measured in the stress range of 0.05-10 MPa using a biomaterial tester. At 5% strain the stress of the ONH in diabetic rats was 897±295 kPa and in the control group it was 671±246 kPa; there was a significant difference between both groups (p=0.011). The stress of the diabetic ppSc (574±185 kPa) increased compared to that of the nondiabetic ppSc (477±171 kPa), but this did not reach statistical significance (p=0.174). The calculated tangent modulus at 5% strain was 11.79 MPa in the diabetic ONH and 8.77 MPa in the nondiabetic ONH; there was a significant difference between both groups (p=0.006). The calculated tangent modulus at 5% strain was 7.17 MPa in the diabetic ppSc and 6.12 MPa in the nondiabetic ppSc, without a statistically significant difference (p=0.09). In contrast to the ppSc, the ONH of diabetic rats showed a significant increase in stiffness compared to nondiabetic rats, which might be explained by nonenzymatic collagen cross-linking mediated by advanced glycation end products due to high blood glucose levels in diabetes. Further studies are needed to investigate if these biomechanical changes represent a detrimental risk factor for intraocular pressure regulation in diabetic glaucoma patients. Copyright © 2011 S. Karger AG, Basel.

Organic amendments enhance Pb tolerance and accumulation during micropropagation of Daphne jasminea.

PubMed

Wiszniewska, Alina; Muszyńska, Ewa; Hanus-Fajerska, Ewa; Smoleń, Sylwester; Dziurka, Michał; Dziurka, Kinga

2017-01-01

The study investigated the effects of organic amendments: pineapple pulp (PP) and agar hydrolyzate (AH), on micropropagation and Pb bioaccumulation and tolerance in a woody shrub Daphne jasminea cultured in vitro. The amendments were analyzed for their content of carbohydrates, phenolic acids, and phytohormones and added at a dose of 10 mL L -1 to the medium containing 1.0 mM lead nitrate. Micropropagation coefficient increased by 10.2-16.6 % in PP and AH variants, respectively. Growth tolerance index increased by 22.9-31.8 % for the shoots and by 60.1-82.4 % for the roots. In the absence of Pb, the additives inhibited multiplication and growth of microplantlets. PP and AH facilitated Pb accumulation in plant organs, especially in the roots. PP enhanced bioconcentration factor and AH improved Pb translocation to the shoots. Adaptation to Pb was associated with increased accumulation of phenolics and higher radical scavenging activity. Medium supplementation, particularly with AH, enhanced antiradical activity of Pb-adapted lines but reduced the content of phenolic compounds. The study results indicated that supplementation with organic amendments may be beneficial in in vitro selection against lead toxicity.

Biodistribution and photodynamic effect of protoporphyrin IX in rat urinary bladders after intravesical instillation of 5-aminolaevulinic acid

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Bown, Stephen G.

1995-03-01

Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Complications such as scarring of the detrusor muscle and prolonged cutaneous photosensitivity may be reduced by using the new photosensitizer precursor, 5- aminolaevulinic acid (ALA). After instillation of ALA, the concentration, pH, and time of bladder retention of ALA solution were found to be the key factors to a satisfactory PpIX buildup in the mucosa. The optimum PpIX fluorescence intensity ratio between mucosa and muscle layer is 10 to 1 with a pH 5.5, 1% ALA solution retained for 5 hours. Higher concentration resulted in more mucosal PpIX formation, but less selectivity. Unbuffered ALA was unsuitable for bladder instillation. Two days after laser treatment with 25 J/cm2 at 630 nm with optimal sensitization, typical histological findings were urothelial sloughing and lamina propria edema without obvious muscle damage. After 7 days, recovery of the urothelium was almost complete and fibroblast infiltration was minimal. ALA induced PpIX after bladder instillation may be an appropriate photosensitizer for future management of superficial bladder cancer.

Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres

PubMed Central

Tanno, Yuji; Kitajima, Tomoya S.; Honda, Takashi; Ando, Yasuto; Ishiguro, Kei-ichiro; Watanabe, Yoshinori

2010-01-01

Shugoshin (Sgo) is a conserved centromeric protein. Mammalian Sgo1 collaborates with protein phosphatase 2A (PP2A) to protect mitotic cohesin from the prophase dissociation pathway. Although another shugoshin-like protein, Sgo2, is required for the centromeric protection of cohesion in germ cells, its precise molecular function remains largely elusive. We demonstrate that hSgo2 plays a dual role in chromosome congression and centromeric protection of cohesion in HeLa cells, while the latter function is exposed only in perturbed mitosis. These functions partly overlap with those of Aurora B, a kinase setting faithful chromosome segregation. Accordingly, we identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK, factors required for centromeric protection and chromosome congression, respectively. Furthermore, these phosphorylations are essential for localizing PP2A and MCAK to centromeres. This mechanism seems applicable to germ cells as well. Thus, our study identifies Sgo2 as a hitherto unknown crucial cellular substrate of Aurora B in mammalian cells. PMID:20889715

Nuclear-cytoplasmic shuttling protein PP2AB56 contributes to mTORC1-dependent dephosphorylation of FOXK1.

PubMed

Nakatsumi, Hirokazu; Oka, Takeru; Higa, Tsunaki; Shirane, Michiko; Nakayama, Keiichi I

2018-05-29

Mammalian target of rapamycin complex 1 (mTORC1) kinase is a master regulator of the cellular response to nutrition-related signals such as insulin and amino acids. mTORC1 is activated on the lysosomal membrane and induces phosphorylation of a variety of downstream molecules. We previously showed that activated mTORC1 induces protein phosphatase 2A (PP2A)-mediated dephosphorylation of the transcription factor forkhead box K1 (FOXK1). The mechanism underlying the signal transduction from the cytoplasmic mTORC1 to the nuclear FOXK1 has remained unclear, however, we now show that a nuclear-cytoplasmic transport system is necessary for the mTORC1-FOXK1 signal transduction. This reaction is mediated by a shuttling protein B56, which is a regulatory subunit of PP2A and plays an essential role in the mTORC1-dependent dephosphorylation of FOXK1. These results suggest that PP2A B56 phosphatase contributes to the signaling for mTORC1-dependent transcriptional regulation. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Revolution from a F.A.R. The Cuban Armed Forces in Africa and the Middle East

DTIC Science & Technology

1977-09-01

UsalmatŘp. s1974, (Ps*tb Sloloff, Peter H.. "User’s Guide for Gurreralteed "Iaro. C.L IXrard 4Mak, 3,l, Bp. Ar Saae 97)A 8 Factor Analysis program...8217Economnic Analysis of the [atrocity DI5ilooedo of Itisinnus. Seesaw D., "Raid Diflompaw ta HowCriminal Activity,’ 30 pp.. Jusn 1974, (Presented atN re t...34ocieessdRteinof P13 Aulpoata. Joseph, "A Crmitiqu of Costl Analysis ,’ ui 49th Annual Conference, Western Economic Astocia AD A 007 912 pp.. Jut 1973, AD

Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice.

PubMed

Ma, Dezun; Gao, Pengfei; Qian, Lili; Wang, Qingqing; Cai, Chunbo; Jiang, Shengwang; Xiao, Gaojun; Cui, Wentao

2015-08-24

Myostatin, a transforming growth factor-β family member, is a negative regulator of skeletal muscle development and growth. Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle. Myostatin propeptide is an inhibitor of myostatin activity and is considered a potential agent to stimulate muscle growth in livestock. In this study, we generated transgenic mice overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type porcine myostatin propeptide (ppMS), respectively, to examine their effects on muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS transgenic female mice and also in ppMS transgenic male mice. However, there was no enhanced muscle growth observed in pmMS transgenic male mice. To explore why there is such a big difference in muscle growth between pmMS and ppMS transgenic male mice, the expression level of androgen receptor (AR) mutant AR45 was measured by Western blot. Results indicated that AR45 expression significantly increased in pmMS transgenic male mice while it decreased dramatically in ppMS transgenic male mice. Our data demonstrate that both pmMS and ppMS act as myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS in male mice is reversed by an increased AR45 expression. These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model

NASA Astrophysics Data System (ADS)

Maytin, Edward; Anand, Sanjay; Sato, Nobuyuki; Mack, Judith; Ortel, Bernhard

2005-04-01

During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within cells. We discovered a novel way to increase the conversion of ALA to PpIX, by administering agents that can drive terminal differentiation (i.e., accelerate cellular maturation). Terminally-differentiated epithelial cells show higher levels of intracellular PpIX, apparently via increased levels of a rate-limiting enzyme, coproporphyrinogen oxidase (CPO). To study these mechanisms in a three-dimensional tissue, we developed an organotypic model that mimics true epidermal physiology in a majority of respects. A line of rat epidermal keratinocytes (REKs), when grown in raft cultures, displays all the features of a fully-differentiated epidermis. Addition of ALA to the culture medium results in ALA uptake and PpIX synthesis, with subsequent death of keratinocytes upon exposure to blue light. Using this model, we can manipulate cellular differentiation via three different approaches. (1) Vitamin D, a hormone that enhances keratinocyte differentiation; (2) Hoxb13, a nuclear transcription factor that affects the genetically-controlled differentiation program of stratifying cells (3) Hyaluronan, an abundant extracellular matrix molecule that regulates epidermal differentiation. Because the raft cultures contain only a single cell type (no blood, fibroblasts, etc.) the effects of terminal differentiation upon CPO, PpIX, and keratinocyte cell death can be specifically defined.

Evolution of Abscisic Acid Synthesis and Signaling Mechanisms

PubMed Central

Hauser, Felix; Waadt, Rainer; Schroeder, Julian I.

2011-01-01

The plant hormone abscisic acid (ABA) mediates seed dormancy, controls seedling development and triggers tolerance to abiotic stresses, including drought. Core ABA signaling components consist of a recently identified group of ABA receptor proteins of the PYRABACTIN RESISTANCE (PYR)/REGULATORY COMPONENT OF ABA RECEPTOR (RCAR) family that act as negative regulators of members of the PROTEIN PHOSPHATASE 2C (PP2C) family. Inhibition of PP2C activity enables activation of SNF1-RELATED KINASE 2 (SnRK2) protein kinases, which target downstream components, including transcription factors, ion channels and NADPH oxidases. These and other components form a complex ABA signaling network. Here, an in depth analysis of the evolution of components in this ABA signaling network shows that (i) PYR/RCAR ABA receptor and ABF-type transcription factor families arose during land colonization of plants and are not found in algae and other species, (ii) ABA biosynthesis enzymes have evolved to plant- and fungal-specific forms, leading to different ABA synthesis pathways, (iii) existing stress signaling components, including PP2C phosphatases and SnRK kinases, were adapted for novel roles in this plant-specific network to respond to water limitation. In addition, evolutionarily conserved secondary structures in the PYR/RCAR ABA receptor family are visualized. PMID:21549957

The association between smoking and blood pressure in men: a cross-sectional study.

PubMed

Li, Guoju; Wang, Hailing; Wang, Ke; Wang, Wenrui; Dong, Fen; Qian, Yonggang; Gong, Haiying; Hui, Chunxia; Xu, Guodong; Li, Yanlong; Pan, Li; Zhang, Biao; Shan, Guangliang

2017-10-10

Cigarette smoking is a known risk factor for cardiovascular disease (CVD), but the association between smoking and blood pressure is unclear. Thus, the current study examined the association between cigarette smoking and blood pressure in men. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were examined using digital blood pressure measuring device, and smoking status was determined with China National Health Survey. The ANCOVA showed that the adjusted DBP and MAP were lower in current smokers versus nonsmokers and the adjusted SBP was lower in current smokers versus former smokers (P < 0.05). Additionally, the adjusted PP tend to be decreased steadily as the pack·years increased in current smokers. In a fully adjusted logistic regression model, former smokers had increased ORs (95% CI) of 1.48 (1.01, 2.18) of hypertension and current smokers had not increased ORs (95% CI) of 0.83 (0.61, 1.12), compared with never smokers. The findings revealed that the adjusted blood pressure were lower in current smokers versus nonsmokers and former smokers. No significant dose-dependent effect of current smoking on blood pressure indices except PP was observed. Smoking cessation was significantly associated with an increased risk of hypertension. However, current smoking was not a risk factor of hypertension.

PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65

PubMed Central

Zhang, Tiejun; Park, Kyeong Ah; Li, Yuwen; Byun, Hee Sun; Jeon, Juhee; Lee, Yoonjung; Hong, Jang Hee; Kim, Jin Man; Huang, Song-Mei; Choi, Seung-Won; Kim, Sun-Hwan; Sohn, Kyung-Cheol; Ro, Hyunju; Lee, Ji Hoon; Lu, Tao; Stark, George R.; Shen, Han-Ming; Liu, Zheng-gang; Park, Jongsun; Hur, Gang Min

2014-01-01

Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that plant homeodomain finger protein 20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In plant homeodomain finger protein 20-overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between plant homeodomain finger protein 20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that plant homeodomain finger protein 20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies plant homeodomain finger protein 20 as a novel regulator of NF-κB activation and suggests that elevated expression of plant homeodomain finger protein 20 may drive constitutive NF-κB activation in some cancers. PMID:23797602

Hope and Adaptation to Old Age: Their Relationship with Individual-Demographic Factors

ERIC Educational Resources Information Center

Moraitou, Despina; Kolovou, Chrysa; Papasozomenou, Chrysa; Paschoula, Catherine

2006-01-01

This study examined the relationship between hope as disposition, adaptation to old age, and individual-demographic factors. One hundred and fifty older adults, aged 60-93 years old, completed the Adult Dispositional Hope Scale developed by Snyder et AL. [1991, Journal of Personality and Social Psychology, 60, pp. 570-585], and the Adaptation to…

Elevated maternal placental protein 13 serum levels at term of pregnancy in postpartum major hemorrhage (>1000 mLs). A prospective cohort study.

PubMed

Farina, Antonio; Bernabini, Dalila; Zucchini, Cinzia; De Sanctis, Paola; Quezada, Maria Soledad; Mattioli, Mara; Rizzo, Nicola

2017-09-01

To compare placental protein 13 (PP13) levels in the serum of women with primary postpartum hemorrhage (PPH) with a control population. A prospective cohort study was conducted between May 2014 and May 2016 and included 435 pregnant women at term (38 weeks gestation) without any known risk factor and with normal labor. Multiples of median (MoM) were used to evaluate differences of the PP13 values between cases and controls. PP13 concentrations were adjusted for maternal and neonatal weight. Multivariable analysis was used to detect independent contribution of predictors of PPH. Fifteen had a major PPH >1000 mLs and represented the cases of the study. They were matched with 399 controls. Twenty-one patients who had a minor PPH (500-1000 mLs) were excluded. The mean observed rank in the PPH group was higher than that of controls (28.5 vs 13.5, P-value=.01). PP13 MoM values adjusted for maternal weight were higher than expected being 1.44±0.45 in PPH cases and 1.00±0.59 in controls (P-value .008). This difference was still significant even after adjustment for neonatal weight that represented a confounding variable. Higher PP13 levels are independently associated with major PPH >1000 mLs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pathogen exploitation of an abscisic acid- and jasmonate-inducible MAPK phosphatase and its interception by Arabidopsis immunity.

PubMed

Mine, Akira; Berens, Matthias L; Nobori, Tatsuya; Anver, Shajahan; Fukumoto, Kaori; Winkelmüller, Thomas M; Takeda, Atsushi; Becker, Dieter; Tsuda, Kenichi

2017-07-11

Phytopathogens promote virulence by, for example, exploiting signaling pathways mediated by phytohormones such as abscisic acid (ABA) and jasmonate (JA). Some plants can counteract pathogen virulence by invoking a potent form of immunity called effector-triggered immunity (ETI). Here, we report that ABA and JA mediate inactivation of the immune-associated MAP kinases (MAPKs), MPK3 and MPK6, in Arabidopsis thaliana ABA induced expression of genes encoding the protein phosphatases 2C (PP2Cs), HAI1 , HAI2 , and HAI3 through ABF/AREB transcription factors. These three HAI PP2Cs interacted with MPK3 and MPK6 and were required for ABA-mediated MPK3/MPK6 inactivation and immune suppression. The bacterial pathogen Pseudomonas syringae pv. tomato ( Pto ) DC3000 activates ABA signaling and produces a JA-mimicking phytotoxin, coronatine (COR), that promotes virulence. We found that Pto DC3000 induces HAI1 through COR-mediated activation of MYC2, a master transcription factor in JA signaling. HAI1 dephosphorylated MPK3 and MPK6 in vitro and was necessary for COR-mediated suppression of MPK3/MPK6 activation and immunity. Intriguingly, upon ETI activation, A. thaliana plants overcame the HAI1-dependent virulence of COR by blocking JA signaling. Finally, we showed conservation of induction of HAI PP2Cs by ABA and JA in other Brassicaceae species. Taken together, these results suggest that ABA and JA signaling pathways, which are hijacked by the bacterial pathogen, converge on the HAI PP2Cs that suppress activation of the immune-associated MAPKs. Also, our data unveil interception of JA-signaling activation as a host counterstrategy against the bacterial suppression of MAPKs during ETI.

A role for protein phosphatase-2A in p38 mitogen-activated protein kinase-mediated regulation of the c-Jun NH(2)-terminal kinase pathway in human neutrophils.

PubMed

Avdi, Natalie J; Malcolm, Kenneth C; Nick, Jerry A; Worthen, G Scott

2002-10-25

Human neutrophil accumulation in inflammatory foci is essential for the effective control of microbial infections. Although exposure of neutrophils to cytokines such as tumor necrosis factor-alpha (TNFalpha), generated at sites of inflammation, leads to activation of MAPK pathways, mechanisms responsible for the fine regulation of specific MAPK modules remain unknown. We have previously demonstrated activation of a TNFalpha-mediated JNK pathway module, leading to apoptosis in adherent human neutrophils (Avdi, N. J., Nick, J. A., Whitlock, B. B., Billstrom, M. A., Henson, P. M., Johnson, G. L., and Worthen, G. S. (2001) J. Biol. Chem. 276, 2189-2199). Herein, evidence is presented linking regulation of the JNK pathway to p38 MAPK and the Ser/Thr protein phosphatase-2A (PP2A). Inhibition of p38 MAPK by SB 203580 and M 39 resulted in significant augmentation of TNFalpha-induced JNK and MKK4 (but not MKK7 or MEKK1) activation, whereas prior exposure to a p38-activating agent (platelet-activating factor) diminished the TNFalpha-induced JNK response. TNFalpha-induced apoptosis was also greatly enhanced upon p38 inhibition. Studies with a reconstituted cell-free system indicated the absence of a direct inhibitory effect of p38 MAPK on the JNK module. Neutrophil exposure to the Ser/Thr phosphatase inhibitors okadaic acid and calyculin A induced JNK activation. Increased phosphatase activity following TNFalpha stimulation was shown to be PP2A-associated and p38-dependent. Furthermore, PP2A-induced dephosphorylation of MKK4 resulted in its inactivation. Thus, in neutrophils, p38 MAPK, through a PP2A-mediated mechanism, regulates the JNK pathway, thus determining the extent and nature of subsequent responses such as apoptosis.

Can poly-parameter linear-free energy relationships (pp-LFERs) improve modelling bioaccumulation in fish?

PubMed

Zhao, Shizhen; Jones, Kevin C; Sweetman, Andrew J

2018-01-01

A wide range of studies have characterized different types of biosorbent, with regard to their interactions with chemicals. This has resulted in the development of poly-parameter linear free energy relationships (pp-LFERs) for the estimation of partitioning of neutral organic compounds to biological phases (e.g., storage lipids, phospholipids and serum albumins). The aims of this study were to explore and evaluate the influence of implementing pp-LFERs both into a one-compartment fish model and a multi-compartment physiologically based toxicokinetic (PBTK) fish model and the associated implications for chemical risk assessment. For this purpose, fish was used as reference biota, due to their important role in aquatic food chains and dietary exposure to humans. The bioconcentration factor (BCF) was utilized as the evaluation metric. Overall, our results indicated that models incorporating pp-LFERs (R 2  = 0.75) slightly outperformed the single parameter (sp) LFERs approach in the one-compartmental fish model (R 2  = 0.72). A pronounced enhancement was achieved for compounds with log K OW between 4 and 5 with increased R 2 from 0.52 to 0.71. The minimal improvement was caused by the overestimation of lipid contribution and underestimation of protein contribution by the sp-approach, which cancelled each other out. Meanwhile, a greater improvement was observed for multi-compartmental PBTK models with consideration of metabolism, making all predictions fall within a factor of 10 compared with measured data. For screening purposes, the K OW -based (sp-LFERs) approach should be sufficient to quantify the main partitioning characteristics. Further developments are required for the consideration of ionization and more accurate quantification of biotransformation in biota. Copyright © 2017 Elsevier Ltd. All rights reserved.

Correlates of VA mental health treatment utilization among OEF/OIF/OND veterans: Resilience, stigma, social support, personality, and beliefs about treatment.

PubMed

DeViva, Jason C; Sheerin, Christina M; Southwick, Steven M; Roy, Alicia M; Pietrzak, Robert H; Harpaz-Rotem, Ilan

2016-05-01

Veterans of Operations Iraqi Freedom/Enduring Freedom/New Dawn (OEF/OIF/OND) tend not to engage in mental health care. Identifying modifiable factors related to mental health service utilization could facilitate development of interventions to increase utilization. The current study examined the relationship between mental health care utilization and measures of PTSD symptoms, resilience, stigma, beliefs about mental health care, perceived barriers to mental health care, posttraumatic growth and meaning, social support, and personality factors in a sample of 100 OEF/OIF/OND veterans with PTSD symptoms referred to VA mental health care. Participants who received psychotherapy and pharmacotherapy (PP) scored higher on measures of PTSD symptoms, stigma, and adaptive beliefs about mental health treatment, and lower on measures of resilience, postdeployment social support, emotional stability, and conscientiousness, than participants who received no treatment (NT). Participants who received psychotherapy only (PT) scored higher on a measure of PTSD symptoms than NT participants. PT participants scored higher on an emotional stability measure and lower on measures of PTSD symptoms and stigma than PP participants. Multinomial logistic regression including all variables significantly related to treatment utilization indicated that PTSD symptoms and adaptive beliefs about psychotherapy and pharmacotherapy were higher in the PT and PP groups than in the NT group, and concerns about discrimination were higher in the PP group than the NT group. Interventions targeting beliefs about mental health care could increase mental health treatment utilization among OEF/OIF/OND veterans. Concerns about stigma may affect the utilization process differently at different decision points. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Secondary Amenorrhea among Female Athletes. Current Understandings.

ERIC Educational Resources Information Center

Sasiene, Gwen Hagenbuch

1983-01-01

Research pertaining to female athletes' problems with secondary amenorrhea is reviewed. Studies point to stress, weight loss, anorexia nervosa, obesity, arduous athletic training, and age of onset of training as factors which may contribute to this disorder. (PP)

Measurements of the electric form factor of the neutron up to Q2=3.4 GeV2 using the reaction 3He(e,e'n)pp.

PubMed

Riordan, S; Abrahamyan, S; Craver, B; Kelleher, A; Kolarkar, A; Miller, J; Cates, G D; Liyanage, N; Wojtsekhowski, B; Acha, A; Allada, K; Anderson, B; Aniol, K A; Annand, J R M; Arrington, J; Averett, T; Beck, A; Bellis, M; Boeglin, W; Breuer, H; Calarco, J R; Camsonne, A; Chen, J P; Chudakov, E; Coman, L; Crowe, B; Cusanno, F; Day, D; Degtyarenko, P; Dolph, P A M; Dutta, C; Ferdi, C; Fernández-Ramírez, C; Feuerbach, R; Fraile, L M; Franklin, G; Frullani, S; Fuchs, S; Garibaldi, F; Gevorgyan, N; Gilman, R; Glamazdin, A; Gomez, J; Grimm, K; Hansen, J-O; Herraiz, J L; Higinbotham, D W; Holmes, R; Holmstrom, T; Howell, D; de Jager, C W; Jiang, X; Jones, M K; Katich, J; Kaufman, L J; Khandaker, M; Kelly, J J; Kiselev, D; Korsch, W; LeRose, J; Lindgren, R; Markowitz, P; Margaziotis, D J; Beck, S May-Tal; Mayilyan, S; McCormick, K; Meziani, Z-E; Michaels, R; Moffit, B; Nanda, S; Nelyubin, V; Ngo, T; Nikolenko, D M; Norum, B; Pentchev, L; Perdrisat, C F; Piasetzky, E; Pomatsalyuk, R; Protopopescu, D; Puckett, A J R; Punjabi, V A; Qian, X; Qiang, Y; Quinn, B; Rachek, I; Ransome, R D; Reimer, P E; Reitz, B; Roche, J; Ron, G; Rondon, O; Rosner, G; Saha, A; Sargsian, M M; Sawatzky, B; Segal, J; Shabestari, M; Shahinyan, A; Shestakov, Yu; Singh, J; Sirca, S; Souder, P; Stepanyan, S; Stibunov, V; Sulkosky, V; Tajima, S; Tobias, W A; Udias, J M; Urciuoli, G M; Vlahovic, B; Voskanyan, H; Wang, K; Wesselmann, F R; Vignote, J R; Wood, S A; Wright, J; Yao, H; Zhu, X

2010-12-31

The electric form factor of the neutron was determined from studies of the reaction 3He(e,e'n)pp in quasielastic kinematics in Hall A at Jefferson Lab. Longitudinally polarized electrons were scattered off a polarized target in which the nuclear polarization was oriented perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons that were registered in a large-solid-angle detector. More than doubling the Q2 range over which it is known, we find G(E)(n)=0.0236±0.0017(stat)±0.0026(syst), 0.0208±0.0024±0.0019, and 0.0147±0.0020±0.0014 for Q(2)=1.72, 2.48, and 3.41 GeV2, respectively.

Measurement of the neutron electric to magnetic form factor ratio at Q2=1.58  GeV2 using the reaction 3He[over →](e[over →],e'n)pp.

PubMed

Schlimme, B S; Achenbach, P; Ayerbe Gayoso, C A; Bernauer, J C; Böhm, R; Bosnar, D; Challand, Th; Distler, M O; Doria, L; Fellenberger, F; Fonvieille, H; Gómez Rodríguez, M; Grabmayr, P; Hehl, T; Heil, W; Kiselev, D; Krimmer, J; Makek, M; Merkel, H; Middleton, D G; Müller, U; Nungesser, L; Ott, B A; Pochodzalla, J; Potokar, M; Sánchez Majos, S; Sargsian, M M; Sick, I; Sirca, S; Weinriefer, M; Wendel, M; Yoon, C J

2013-09-27

A measurement of beam helicity asymmetries in the reaction 3He[over →](e[over →],e'n)pp is performed at the Mainz Microtron in quasielastic kinematics to determine the electric to magnetic form factor ratio of the neutron GEn/GMn at a four-momentum transfer Q2=1.58  GeV2. Longitudinally polarized electrons are scattered on a highly polarized 3He gas target. The scattered electrons are detected with a high-resolution magnetic spectrometer, and the ejected neutrons are detected with a dedicated neutron detector composed of scintillator bars. To reduce systematic errors, data are taken for four different target polarization orientations allowing the determination of GEn/GMn from a double ratio. We find μnGEn/GMn=0.250±0.058(stat)±0.017(syst).

A comparative study of the effects of cone-plate and parallel-plate geometries on rheological properties under oscillatory shear flow

NASA Astrophysics Data System (ADS)

Song, Hyeong Yong; Salehiyan, Reza; Li, Xiaolei; Lee, Seung Hak; Hyun, Kyu

2017-11-01

In this study, the effects of cone-plate (C/P) and parallel-plate (P/P) geometries were investigated on the rheological properties of various complex fluids, e.g. single-phase (polymer melts and solutions) and multiphase systems (polymer blend and nanocomposite, and suspension). Small amplitude oscillatory shear (SAOS) tests were carried out to compare linear rheological responses while nonlinear responses were compared using large amplitude oscillatory shear (LAOS) tests at different frequencies. Moreover, Fourier-transform (FT)-rheology method was used to analyze the nonlinear responses under LAOS flow. Experimental results were compared with predictions obtained by single-point correction and shear rate correction. For all systems, SAOS data measured by C/P and P/P coincide with each other, but results showed discordance between C/P and P/P measurements in the nonlinear regime. For all systems except xanthan gum solutions, first-harmonic moduli were corrected using a single horizontal shift factor, whereas FT rheology-based nonlinear parameters ( I 3/1, I 5/1, Q 3, and Q 5) were corrected using vertical shift factors that are well predicted by single-point correction. Xanthan gum solutions exhibited anomalous corrections. Their first-harmonic Fourier moduli were superposed using a horizontal shift factor predicted by shear rate correction applicable to highly shear thinning fluids. The distinguished corrections were observed for FT rheology-based nonlinear parameters. I 3/1 and I 5/1 were superposed by horizontal shifts, while the other systems displayed vertical shifts of I 3/1 and I 5/1. Q 3 and Q 5 of xanthan gum solutions were corrected using both horizontal and vertical shift factors. In particular, the obtained vertical shift factors for Q 3 and Q 5 were twice as large as predictions made by single-point correction. Such larger values are rationalized by the definitions of Q 3 and Q 5. These results highlight the significance of horizontal shift corrections in nonlinear oscillatory shear data.

Ethnic Differences in Effects of Maternal Pre-Pregnancy and Pregnancy Adiposity on Offspring Size and Adiposity

PubMed Central

Lin, Xinyi; Aris, Izzuddin M.; Tint, Mya Thway; Soh, Shu E.; Godfrey, Keith M.; Yeo, George Seow-Heong; Kwek, Kenneth; Chan, Jerry Kok-Yen; Gluckman, Peter D.; Chong, Yap Seng; Yap, Fabian; Holbrook, Joanna D.

2015-01-01

Context: Maternal adiposity and overnutrition, both before and during pregnancy, plays a key role in the subsequent development of obesity and metabolic outcomes in offspring. Objective: We explored the hypothesis that maternal adiposity (pre-pregnancy and at 26–28 weeks' gestation) and mid-pregnancy gestational weight gain (GWG) are independently associated with offspring size and adiposity in early childhood, and determined whether these effects are ethnicity dependent. Design: In a prospective mother-offspring cohort study (N = 976, 56% Chinese, 26% Malay, and 18% Indian), we assessed the associations of offspring size (weight, length) and adiposity (subscapular and triceps skinfolds), measured at birth and age 6, 12, 18, and 24 mo, with maternal pre-pregnancy body mass index (ppBMI), mid-pregnancy GWG, and mid-pregnancy four-site skinfold thicknesses (triceps, biceps, subscapular, suprailiac). Results: ppBMI and mid-pregnancy GWG were independently associated with postnatal weight up to 2 y and skinfold thickness at birth. Weight and subscapular and triceps skinfolds at birth increased by 2.56% (95% confidence interval, 1.68–3.45%), 3.85% (2.16–5.57%), and 2.14% (0.54–3.75%), respectively for every SD increase in ppBMI. Similarly, a one-SD increase in GWG increased weight and subscapular and triceps skinfolds at birth by 2.44% (1.66–3.23%), 3.28% (1.75–4.84%), and 3.23% (1.65–4.84%), respectively. ppBMI and mid-pregnancy suprailiac skinfold independently predicted postnatal skinfold adiposity up to 2 years of age, whereas only GWG predicted postnatal length. The associations of GWG with postnatal weight and length were present only among Chinese and Indians, but not Malays (P < .05 for interaction). Conclusions: ppBMI and GWG are independent modifiable factors for child size and adiposity up to 2 years of age. The associations are ethnic-dependent, and underscore the importance of ethnic specific studies before generalizing the applicability of risk factors reported in other populations. PMID:26200236

A simple and highly selective molecular imprinting polymer-based methodology for propylparaben monitoring in personal care products and industrial waste waters.

PubMed

Vicario, Ana; Aragón, Leslie; Wang, Chien C; Bertolino, Franco; Gomez, María R

2018-02-05

In this work, a novel molecularly imprinted polymer (MIP) proposed as solid phase extraction sorbent was developed for the determination of propylparaben (PP) in diverse cosmetic samples. The use of parabens (PAs) is authorized by regulatory agencies as microbiological preservative; however, recently several studies claim that large-scale use of these preservatives can be a potential health risk and harmful to the environment. Diverse factors that influence on polymer synthesis were studied, including template, functional monomer, porogen and crosslinker used. Morphological characterization of the MIP was performed using SEM and BET analysis. Parameters affecting the molecularly imprinted solid phase extraction (MISPE) and elution efficiency of PP were evaluated. After sample clean-up, the analyte was analyzed by high performance liquid chromatography (HPLC). The whole procedure was validated, showing satisfactory analytical parameters. After applying the MISPE methodology, the extraction recoveries were always better than 86.15%; the obtained precision expressed as RSD% was always lower than 2.19 for the corrected peak areas. Good linear relationship was obtained within the range 8-500ngmL -1 of PP, r 2 =0.99985. Lower limits of detection and quantification after MISPE procedure of 2.4 and 8ngmL -1 , respectively were reached, in comparison with previously reported methodologies. The development of MISPE-HPLC methodology provided a simple an economic way for accomplishing a clean-up/preconcentration step and the subsequent determination of PP in a complex matrix. The performance of the proposed method was compared against C-18 and silica solid phase extraction (SPE) cartridges. The recovery factors obtained after applying extraction methods were 96.6, 64.8 and 0.79 for MISPE, C18-SPE and silica-SPE procedures, respectively. The proposed methodology improves the retention capability of SPE material plus robustness and possibility of reutilization, enabling it to be used for PP routine monitoring in diverse personal care products (PCP) and environmental samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of secretin stimulated pancreatic secretion by pancreatic polypeptide.

PubMed

Adrian, T E; Besterman, H S; Mallinson, C N; Greenberg, G R; Bloom, S R

1979-01-01

The effect of PP on secretin-stimulated pancreatic secretion was assessed in five healthy subjects. During an intravenous infusion of BPP at a dose which produced plasma levels similar to those seen after meals in healthy young adults the volume and bicarbonate content of duodenal juice was reduced by 25% (p less than 0.05) and 24% (p less than 0.05) respectively, while protein and bilirubin concentrations were more markedly reduced by 68% (p less than 0.0005) and 67% (p less than 0.0005) respectively. PP, thus, may be an important inhibitory factor in the control of bilirubin and pancreatic enzyme secretion in man.

Inhibition of secretin stimulated pancreatic secretion by pancreatic polypeptide.

PubMed Central

Adrian, T E; Besterman, H S; Mallinson, C N; Greenberg, G R; Bloom, S R

1979-01-01

The effect of PP on secretin-stimulated pancreatic secretion was assessed in five healthy subjects. During an intravenous infusion of BPP at a dose which produced plasma levels similar to those seen after meals in healthy young adults the volume and bicarbonate content of duodenal juice was reduced by 25% (p less than 0.05) and 24% (p less than 0.05) respectively, while protein and bilirubin concentrations were more markedly reduced by 68% (p less than 0.0005) and 67% (p less than 0.0005) respectively. PP, thus, may be an important inhibitory factor in the control of bilirubin and pancreatic enzyme secretion in man. PMID:761835

Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents; unique intracellular disintegration of SMA micelles.

PubMed

Nakamura, Hideaki; Fang, Jun; Gahininath, Bharate; Tsukigawa, Kenji; Maeda, Hiroshi

2011-11-07

SMA-ZnPP and PEG-ZnPP are micellar drugs, encapsulating zinc protoporphyrin IX (ZnPP) with styrene maleic acid copolymer (SMA) and covalent conjugate of ZnPP with polyethylene glycol (PEG) respectively. Their intracellular uptake rate and subcellular localization were investigated. We found SMA-ZnPP showed higher and more efficient (about 2.5 times) intracellular uptake rate than PEG-ZnPP, although both SMA-ZnPP and PEG-ZnPP micelles were localized at endoplasmic reticulum (ER) and inhibited the target enzyme heme oxygenase 1 (HO-1) similarly. Both micellar ZnPP were taken up into the tumor cells by endocytosis. Furthermore SMA-ZnPP and PEG-ZnPP were examined for their drug releasing mechanisms. Liberation of ZnPP from the SMA micelle appears to depend on cellular amphiphilic components such as lecithin, while that for PEG-ZnPP depends on hydrolytic cleavage. These results indicate that these micelle formulations make water insoluble ZnPP to water soluble practical anticancer agents. Copyright © 2011 Elsevier B.V. All rights reserved.

A THz plasmonics perfect absorber and Fabry-Perot cavity mechanism (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhou, Jiangfeng; Bhattarai, Khagendra; Silva, Sinhara; Jeon, Jiyeon; Kim, Junoh; Lee, Sang Jun; Ku, Zahyun

2016-10-01

The plasmonic metamaterial perfect absorber (MPA) is a recently developed branch of metamaterial which exhibits nearly unity absorption within certain frequency range.[1-6] The optically thin MPA possesses characteristic features of angular-independence, high Q-factor and strong field localization that have inspired a wide range of applications including electromagnetic wave absorption,[3, 7, 8] spatial[6] and spectral[5] modulation of light,[9] selective thermal emission,[9] thermal detecting[10] and refractive index sensing for gas[11] and liquid[12, 13] targets. In this work, we demonstrate a MPA working at terahertz (THz) regime and characterize it using an ultrafast THz time-domain spectroscopy (THz-TDS). Our study reveal an ultra-thin Fabry-Perot cavity mechanism compared to the impedance matching mechanism widely adopted in previous study [1-6]. Our results also shows higher-order resonances when the cavities length increases. These higher order modes exhibits much larger Q-factor that can benefit potential sensing and imaging applications. [1] C. M. Watts, X. L. Liu, and W. J. Padilla, "Metamaterial Electromagnetic Wave Absorbers," Advanced Materials, vol. 24, pp. 98-120, Jun 19 2012. [2] M. Hedayati, F. Faupel, and M. Elbahri, "Review of Plasmonic Nanocomposite Metamaterial Absorber," Materials, vol. 7, pp. 1221-1248, 2014. [3] N. I. Landy, S. Sajuyigbe, J. J. Mock, D. R. Smith, and W. J. Padilla, "Perfect metamaterial absorber," Physical Review Letters, vol. 100, p. 207402, May 23 2008. [4] H. R. Seren, G. R. Keiser, L. Cao, J. Zhang, A. C. Strikwerda, K. Fan, et al., "Optically Modulated Multiband Terahertz Perfect Absorber," Advanced Optical Materials, vol. 2, pp. 1221-1226, 2014. [5] D. Shrekenhamer, J. Montoya, S. Krishna, and W. J. Padilla, "Four-Color Metamaterial Absorber THz Spatial Light Modulator," Advanced Optical Materials, vol. 1, pp. 905-909, 2013. [6] S. Savo, D. Shrekenhamer, and W. J. Padilla, "Liquid Crystal Metamaterial Absorber Spatial Light Modulator for THz Applications," Advanced Optical Materials, vol. 2, pp. 275-279, 2014. [7] H. Tao, N. I. Landy, C. M. Bingham, X. Zhang, R. D. Averitt, and W. J. Padilla, "A metamaterial absorber for the terahertz regime: Design, fabrication and characterization," Optics Express, vol. 16, pp. 7181-7188, May 12 2008. [8] J. Hao, J. Wang, X. Liu, W. J. Padilla, L. Zhou, and M. Qiu, "High performance optical absorber based on a plasmonic metamaterial," Applied Physics Letters, vol. 96, p. 251104, 2010. [9] X. Liu, T. Tyler, T. Starr, A. F. Starr, N. M. Jokerst, and W. J. Padilla, "Taming the Blackbody with Infrared Metamaterials as Selective Thermal Emitters," Physical Review Letters, vol. 107, p. 045901, 07/18/ 2011. [10] T. Maier and H. Brückl, "Wavelength-tunable microbolometers with metamaterial absorbers," Optics Letters, vol. 34, pp. 3012-3014, 2009/10/01 2009. [11] A. Tittl, P. Mai, R. Taubert, D. Dregely, N. Liu, and H. Giessen, "Palladium-Based Plasmonic Perfect Absorber in the Visible Wavelength Range and Its Application to Hydrogen Sensing," Nano Letters, vol. 11, pp. 4366-4369, 2011/10/12 2011. [12] N. Liu, M. Mesch, T. Weiss, M. Hentschel, and H. Giessen, "Infrared Perfect Absorber and Its Application As Plasmonic Sensor," Nano Letters, vol. 10, pp. 2342-2348, Jul 2010. [13] G. H. Li, X. S. Chen, O. P. Li, C. X. Shao, Y. Jiang, L. J. Huang, et al., "A novel plasmonic resonance sensor based on an infrared perfect absorber," Journal of Physics D-Applied Physics, vol. 45, p. 205102, May 23 2012.

Exposure to mass media and interpersonal counseling has additive effects on exclusive breastfeeding and its psychosocial determinants among Vietnamese mothers.

PubMed

Nguyen, Phuong H; Kim, Sunny S; Nguyen, Tuan T; Hajeebhoy, Nemat; Tran, Lan M; Alayon, Silvia; Ruel, Marie T; Rawat, Rahul; Frongillo, Edward A; Menon, Purnima

2016-10-01

The pathways through which behavior change interventions impact breastfeeding practices have not been well studied. This study aimed to examine: (1) the effects of exposure to mass media and interpersonal counseling on exclusive breastfeeding (EBF) and hypothesized psychosocial determinants (i.e. knowledge, intention, beliefs, social norms, and self-efficacy); and (2) the pathways through which exposure to mass media and interpersonal counseling are associated with EBF. We used survey data from mothers with children < 2 year (n = 2045) from the 2013 process evaluation of Alive & Thrive's program in Viet Nam. Multiple linear regression analyses and structural equation modeling were used to estimate effects. Exposure to mass media only, interpersonal counseling only, both or neither was 51%, 5%, 19% and 25%, respectively. Exposure to both mass media and interpersonal counseling had additive effects on EBF as well as on related psychosocial factors, compared with no exposure. For example, EBF prevalence was 26.1 percentage points (pp) higher in the group that received interpersonal counseling only, 3.9 pp higher in the mass media group and 31.8 pp higher in the group that received both interventions. As hypothesized, more than 90% of the total effect of the two interventions on EBF was explained by the psychosocial factors measured. Our findings suggest that combining different behavior change interventions leads to greater changes in psychosocial factors, which in turn positively affects breastfeeding behaviors. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

Testing hydrodynamic descriptions of p+p collisions at $$\\sqrt{s}=7$$ TeV

DOE PAGES

Habich, M.; Miller, G. A.; Romatschke, Paul; ...

2016-07-19

In high-energy collisions of heavy ions, experimental findings of collective flow are customarily associated with the presence of a thermalized medium expanding according to the laws of hydrodynamics. Recently, the ATLAS, CMS, and ALICE experiments found signals of the same type and magnitude in ultrarelativistic proton-proton collisions. In this study, the state-of-the-art hydrodynamic model SONIC is used to simulate the systems created in p+p collisions. By varying the size of the second-order transport coefficients, the range of applicability of hydrodynamics itself to the systems created in p+p collisions is quantified. It is found that hydrodynamics can give quantitatively reliable resultsmore » for the particle spectra and the elliptic momentum anisotropy coefficient v 2. As a result, using a simple geometric model of the proton based on the elastic form factor leads to results of similar type and magnitude to those found in experiment when allowing for a small bulk viscosity coefficient.« less

Production of D0 meson in pp and PbPb Collisions at √SNN = 5.02 TeV with CMS

NASA Astrophysics Data System (ADS)

Lee, Yen-Jie

2018-02-01

Heavy flavour mesons are used as powerful tools for the study of the strongly interacting medium in heavy ion collisions as heavy quarks are sensitive to the transport properties of the medium. In these proceedings, D0 nuclear modification factors, comparing the yields in PbPb and pp collisions, and azimuthal anisotropies in PbPb collisions are reported. Prompt D0 mesons and their antiparticles have been measured with the CMS detector via the hadronic decay channels D0 → K-π+ and D0 → K+π- in PbPb and pp collisions at a centre-of-mass energy of 5.02 TeV. Nonprompt D0 from b quark decays are subtracted. The D0 results are compared to inclusive charged particles, non-prompt J/ψ mesons from b decays and B+ mesons in order to reveal possible meson mass dependence of the observables.

Gadd34 Requirement for Normal Hemoglobin Synthesis

PubMed Central

Patterson, Andrew D.; Hollander, M. Christine; Miller, Georgina F.; Fornace, Albert J.

2006-01-01

The protein encoded by growth arrest and DNA damage-inducible transcript 34 (Gadd34) is associated with translation initiation regulation following certain stress responses. Through interaction with the protein phosphatase 1 catalytic subunit (PP1c), Gadd34 recruits PP1c for the removal of an inhibitory phosphate group on the α subunit of elongation initiation factor 2, thereby reversing the shutoff of protein synthesis initiated by stress-inducible kinases. In the absence of stress, the physiologic consequences of Gadd34 function are not known. Initial analysis of Gadd34-null mice revealed several significant findings, including hypersplenism, decreased erythrocyte volume, increased numbers of circulating erythrocytes, and decreased hemoglobin content, resembling some thalassemia syndromes. Biochemical analysis of the hemoglobin-producing reticulocyte (an erythrocyte precursor) revealed that the decreased hemoglobin content in the Gadd34-null erythrocyte is due to the reduced initiation of the globin translation machinery. We propose that an equilibrium state exists between Gadd34/PP1c and the opposing heme-regulated inhibitor kinase during hemoglobin synthesis in the reticulocyte. PMID:16478986

Impact of kerosene heater usage on indoor NO/sub 2/ exposures in 50 East Tennessee homes

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

Dudney, C.S.; Hawthorne, A.R.; Monar, K.P.

1988-01-01

As part of a study of indoor air quality in 300 houses in Roane County, Tennessee, a special study was made on kerosene heater usage and indoor pollutant levels, with emphasis on NO/sub 2/. Owners of 45 homes with kerosene heaters deployed pairs of passive NO/sub 2/ monitors on a weekly basis for ten weeks and recorded the weekly amount of heater use. Without correcting for house-specific factors, such as air exchange rate, indoor NO/sub 2/ levels were found to increase about 0.3 ppB per h/week of homeowner-reported heater use. In the absence of heater use, NO/sub 2/ levels weremore » about 10 ppB in houses with and without kerosene heaters. In four houses with kerosene heaters and one house without, continuous measurements were made of NO, NO/sub x/, SO/sub 2/, and CO. CO and SO/sub 2/ levels increased threefold and tenfold, respectively, when the heater was operated compared to when it was off. Mean SO/sub 2/ levels during heater operation were 57, 46, and 110 ppB in three houses with radiant heaters and 13.5 ppB in one house with a convective heater. 5 refs., 8 figs., 3 tabs.« less

Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis

PubMed Central

Douglas, Pauline; Ye, Ruiqiong; Morrice, Nicholas; Britton, Sébastien; Trinkle-Mulcahy, Laura

2015-01-01

Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis. PMID:25986610

Multicentre, Prospective Observational Study of Pegfilgrastim Primary Prophylaxis in Patients at High Risk of Febrile Neutropenia in Poland: PROFIL Study

PubMed Central

Jurczak, Wojciech; Kalinka-Warzocha, Ewa; Chmielowska, Ewa; Duchnowska, Renata; Wojciechowska-Lampka, Elzbieta

2015-01-01

Aim of the study PROFIL was a prospective observational study conducted to investigate physicians’ evaluation of febrile neutropenia (FN) risk and reasons for giving pegfilgrastim primary prophylaxis (PP) in routine clinical practice in Poland. Material and methods Adult cancer patients treated with chemotherapy (CT), assessed by investigators as having high overall FN risk, and who received pegfilgrastim in cycle 1 were enrolled between 03/2009 and 09/2010. Investigators assessed FN risk of the CT regimen, individual risk factors, and overall FN risk, and were asked to provide the most important reasons for providing pegfilgrastim PP. Investigator-assessed CT FN risk was compared with guideline classification. Results Data were analysed from 1006 breast, ovarian, and lung cancer, and non-Hodgkin (NHL) and Hodgkin lymphoma (HL) patients. The most important reasons for using pegfilgrastim PP were high CT FN risk and advanced disease; these were consistent across tumour types and treatment intent. The investigators generally assessed high CT FN risk in agreement with guideline classification. Febrile neutropenia occurred in 4% of patients, most commonly in HL, NHL, and patients with advanced disease. Conclusions High CT FN risk and advanced stage of disease were found to be the most important reasons for providing pegfilgrastim PP by physicians in Poland. PMID:26557762

Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

NASA Technical Reports Server (NTRS)

Swingle, Mark R.; Ciszak, Ewa M.; Honkanen, Richard E.

2004-01-01

Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

Identification and elucidation of in vivo function of two alanine racemases from Pseudomonas putida KT2440.

PubMed

Duque, Estrella; Daddaoua, Abdelali; Cordero, Baldo F; De la Torre, Jesús; Antonia Molina-Henares, Maria; Ramos, Juan-Luis

2017-10-01

The genome of Pseudomonas putida KT2440 contains two open reading frames (ORFs), PP_3722 and PP_5269, that encode proteins with a Pyridoxal phosphate binding motif and a high similarity to alanine racemases. Alanine racemases play a key role in the biosynthesis of D-alanine, a crucial amino acid in the peptidoglycan layer. For these ORFs, we generated single and double mutants and found that inactivation of PP_5269 resulted in D-alanine auxotrophy, while inactivation of PP_3722 did not. Furthermore, as expected, the PP_3722/PP_5269 double mutant was a strict auxotroph for D-alanine. These results indicate that PP_5269 is an alr allele and that it is the essential alanine racemase in P. putida. We observed that the PP_5269 mutant grew very slowly, while the double PP_5269/PP_3722 mutant did not grow at all. This suggests that PP_3722 may replace PP_5269 in vivo. In fact, when the ORF encoding PP_3772 was cloned into a wide host range expression vector, ORF PP_3722 successfully complemented P. putida PP_5269 mutants. We purified both proteins to homogeneity and while they exhibit similar K M values, the V max of PP_5269 is fourfold higher than that of PP_3722. Here, we propose that PP_5269 and PP_3722 encode functional alanine racemases and that these genes be named alr-1 and alr-2 respectively. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

The small-x gluon distribution in centrality biased pA and pp collisions

NASA Astrophysics Data System (ADS)

Dumitru, Adrian; Kapilevich, Gary; Skokov, Vladimir

2018-06-01

The nuclear modification factor RpA (pT) provides information on the small-x gluon distribution of a nucleus at hadron colliders. Several experiments have recently measured the nuclear modification factor not only in minimum bias but also for central pA collisions. In this paper we analyze the bias on the configurations of soft gluon fields introduced by a centrality selection via the number of hard particles. Such bias can be viewed as reweighting of configurations of small-x gluons. We find that the biased nuclear modification factor QpA (pT) for central collisions is above RpA (pT) for minimum bias events, and that it may redevelop a "Cronin peak" even at small x. The magnitude of the peak is predicted to increase approximately like 1 /A⊥ ν, ν ∼ 0.6 ± 0.1, if one is able to select more compact configurations of the projectile proton where its gluons occupy a smaller transverse area A⊥. We predict an enhanced Qpp (pT) - 1 ∼ 1 /(pT2) ν and a Cronin peak even for central pp collisions.

The Persian Gulf and the National Interest.

DTIC Science & Technology

1982-02-01

with Unique Solution,v 20 pp., Jun 1970, 234-253) AD A055 536 AD A038 535 PP 223 PP 213 "angel, Marc, "S1tochastic Mechanics of MlulolOf Mlouldl Mengel ...Theory," 54 pp.. Jun 1978. AD A058 540 PP 216 - Clasified PP 229 Mengel , Marc, "Diffusion Theory 04 Asection Rates. li pp 219 Formulation and Elnstein...CEtisetion." 60 pp., Ap 78, AD A054 422 PP 230 PP 220 Mengel . Marc, "Diffusion The"r of Reaction Rate. 11 Mowrer, Donald E., "Diegonalfaction by amop Mtrices

β-Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α-PP2A-Mediated Dephosphorylation.

PubMed

Weeks, Kate L; Ranieri, Antonella; Karaś, Agnieszka; Bernardo, Bianca C; Ashcroft, Alexandra S; Molenaar, Chris; McMullen, Julie R; Avkiran, Metin

2017-03-25

Class IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal-responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor-2. β-Adrenoceptor (β-AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation-independent nuclear export and phosphorylation-dependent nuclear accumulation of cardiomyocyte HDAC5. The relative importance of phosphorylation at Ser259/Ser498 versus Ser279 in HDAC5 regulation is also controversial. We aimed to determine the impact of β-AR stimulation on the phosphorylation, localization, and function of cardiomyocyte HDAC5 and delineate underlying molecular mechanisms. A novel 3-dimensional confocal microscopy method that objectively quantifies the whole-cell nuclear/cytoplasmic distribution of green fluorescent protein tagged HDAC5 revealed the β-AR agonist isoproterenol to induce β 1 -AR-mediated and protein kinase A-dependent HDAC5 nuclear accumulation in adult rat cardiomyocytes, which was accompanied by dephosphorylation at Ser259/279/498. Mutation of Ser259/Ser498 to Ala promoted HDAC5 nuclear accumulation and myocyte enhancer factor-2 inhibition, whereas Ser279 ablation had no such effect and did not block isoproterenol-induced nuclear accumulation. Inhibition of the Ser/Thr phosphatase PP2A blocked isoproterenol-induced HDAC5 dephosphorylation. Co-immunoprecipitation revealed a specific interaction of HDAC5 with the PP2A targeting subunit B55α, as well as catalytic and scaffolding subunits, which increased >3-fold with isoproterenol. Knockdown of B55α in neonatal cardiomyocytes attenuated isoproterenol-induced HDAC5 dephosphorylation. β-AR stimulation induces HDAC5 nuclear accumulation in cardiomyocytes by a mechanism that is protein kinase A-dependent but requires B55α-PP2A-mediated dephosphorylation of Ser259/Ser498 rather than protein kinase A-mediated phosphorylation of Ser279. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures.

PubMed

Juhász, Tamás; Matta, Csaba; Somogyi, Csilla; Katona, Éva; Takács, Roland; Soha, Rudolf Ferenc; Szabó, István A; Cserháti, Csaba; Sződy, Róbert; Karácsonyi, Zoltán; Bakó, Eva; Gergely, Pál; Zákány, Róza

2014-03-01

Biomechanical stimuli play important roles in the formation of articular cartilage during early foetal life, and optimal mechanical load is a crucial regulatory factor of adult chondrocyte metabolism and function. In this study, we undertook to analyse mechanotransduction pathways during in vitro chondrogenesis. Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were cultivated as high density cell cultures for 6 days. Mechanical stimulation was carried out by a self-designed bioreactor that exerted uniaxial intermittent cyclic load transmitted by the culture medium as hydrostatic pressure and fluid shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min) was applied on culturing days 2 and 3, when final commitment and differentiation of chondroprogenitor cells occurred in this model. The applied mechanical load significantly augmented cartilage matrix production and elevated mRNA expression of several cartilage matrix constituents, including collagen type II and aggrecan core protein, as well as matrix-producing hyaluronan synthases through enhanced expression, phosphorylation and nuclear signals of the main chondrogenic transcription factor Sox9. Along with increased cAMP levels, a significantly enhanced protein kinase A (PKA) activity was also detected and CREB, the archetypal downstream transcription factor of PKA signalling, exhibited elevated phosphorylation levels and stronger nuclear signals in response to mechanical stimuli. All the above effects were diminished by the PKA-inhibitor H89. Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 resulted in enhanced cartilage formation, which was additive to that of the mechanical stimulation, implying that the chondrogenesis-promoting effect of mechanical load was independent of Epac. At the same time, PP2A activity was reduced following mechanical load and treatments with the PP2A-inhibitor okadaic acid were able to mimic the effects of the intervention. Our results indicate that proper mechanical stimuli augment in vitro cartilage formation via promoting both differentiation and matrix production of chondrogenic cells, and the opposing regulation of the PKA/CREB-Sox9 and the PP2A signalling pathways is crucial in this phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

K * ( 892 ) 0 and Φ ( 1020 ) meson production at high transverse momentum in p p and Pb-Pb collisions at s NN = 2.76 TeV

DOE PAGES

Adam, J.; Adamová, D.; Aggarwal, M. M.; ...

2017-06-12

Tmore » he production of K*(892) 0 and φ(1020) mesons in proton-proton (pp) and lead-lead (Pb-Pb) collisions at s NN =2.76eV has been analyzed using a high luminosity data sample accumulated in 2011 with the ALICE detector at the Large Hadron Collider (LHC). he transverse momentum (p ) spectra have been measured for K*(892) 0 and φ(1020) mesons via their hadronic decay channels for p up to 20 GeV/c. he measurements in pp collisions have been compared to model calculations and used to determine the nuclear modification factor and particle ratios. he K*(892) 0/K ratio exhibits significant reduction from pp to central Pb-Pb collisions, consistent with the suppression of the K*(892) 0 yield at low p due to rescattering of its decay products in the hadronic phase. In central Pb-Pb collisions the p dependent φ(1020)/π and K*(892) 0/π ratios show an enhancement over pp collisions for p ≈ 3 GeV/c, consistent with previous observations of strong radial flow. At high p , particle ratios in Pb-Pb collisions are similar to those measured in pp collisions. In central Pb-Pb collisions, the production of K*(892) 0 and φ(1020) mesons is suppressed for p > 8 GeV/c. his suppression is similar to that of charged pions, kaons, and protons, indicating that the suppression does not depend on particle mass or flavor in the light quark sector.« less

K * ( 892 ) 0 and Φ ( 1020 ) meson production at high transverse momentum in p p and Pb-Pb collisions at s NN = 2.76 TeV

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

Adam, J.; Adamová, D.; Aggarwal, M. M.

Tmore » he production of K*(892) 0 and φ(1020) mesons in proton-proton (pp) and lead-lead (Pb-Pb) collisions at s NN =2.76eV has been analyzed using a high luminosity data sample accumulated in 2011 with the ALICE detector at the Large Hadron Collider (LHC). he transverse momentum (p ) spectra have been measured for K*(892) 0 and φ(1020) mesons via their hadronic decay channels for p up to 20 GeV/c. he measurements in pp collisions have been compared to model calculations and used to determine the nuclear modification factor and particle ratios. he K*(892) 0/K ratio exhibits significant reduction from pp to central Pb-Pb collisions, consistent with the suppression of the K*(892) 0 yield at low p due to rescattering of its decay products in the hadronic phase. In central Pb-Pb collisions the p dependent φ(1020)/π and K*(892) 0/π ratios show an enhancement over pp collisions for p ≈ 3 GeV/c, consistent with previous observations of strong radial flow. At high p , particle ratios in Pb-Pb collisions are similar to those measured in pp collisions. In central Pb-Pb collisions, the production of K*(892) 0 and φ(1020) mesons is suppressed for p > 8 GeV/c. his suppression is similar to that of charged pions, kaons, and protons, indicating that the suppression does not depend on particle mass or flavor in the light quark sector.« less

Multilevel Control of Arabidopsis 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase by Protein Phosphatase 2A[W

PubMed Central

Leivar, Pablo; Antolín-Llovera, Meritxell; Ferrero, Sergi; Closa, Marta; Arró, Montserrat; Ferrer, Albert; Boronat, Albert; Campos, Narciso

2011-01-01

Plants synthesize a myriad of isoprenoid products that are required both for essential constitutive processes and for adaptive responses to the environment. The enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyzes a key regulatory step of the mevalonate pathway for isoprenoid biosynthesis and is modulated by many endogenous and external stimuli. In spite of that, no protein factor interacting with and regulating plant HMGR in vivo has been described so far. Here, we report the identification of two B′′ regulatory subunits of protein phosphatase 2A (PP2A), designated B′′α and B′′β, that interact with HMGR1S and HMGR1L, the major isoforms of Arabidopsis thaliana HMGR. B′′α and B′′β are Ca2+ binding proteins of the EF-hand type. We show that HMGR transcript, protein, and activity levels are modulated by PP2A in Arabidopsis. When seedlings are transferred to salt-containing medium, B′′α and PP2A mediate the decrease and subsequent increase of HMGR activity, which results from a steady rise of HMGR1-encoding transcript levels and an initial sharper reduction of HMGR protein level. In unchallenged plants, PP2A is a posttranslational negative regulator of HMGR activity with the participation of B′′β. Our data indicate that PP2A exerts multilevel control on HMGR through the five-member B′′ protein family during normal development and in response to a variety of stress conditions. PMID:21478440

Piezoelectricity and ferroelectricity of cellular polypropylene electrets films characterized by piezoresponse force microscopy

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

Miao, Hongchen; Sun, Yao; Zhou, Xilong

Cellular electrets polymer is a new ferroelectret material exhibiting large piezoelectricity and has attracted considerable attentions in researches and industries. Property characterization is very important for this material and current investigations are mostly on macroscopic properties. In this work, we conduct nanoscale piezoelectric and ferroelectric characterizations of cellular polypropylene (PP) films using piezoresponse force microscopy (PFM). First, both the single-frequency PFM and dual-frequency resonance-tracking PFM testings were conducted on the cellular PP film. The localized piezoelectric constant d{sub 33} is estimated to be 7–11pC/N by correcting the resonance magnification with quality factor and it is about one order lower thanmore » the macroscopic value. Next, using the switching spectroscopy PFM (SS-PFM), we studied polarization switching behavior of the cellular PP films. Results show that it exhibits the typical ferroelectric-like phase hysteresis loops and butterfly-shaped amplitude loops, which is similar to that of a poly(vinylidene fluoride) (PVDF) ferroelectric polymer film. However, both the phase and amplitude loops of the PP film are intensively asymmetric, which is thought to be caused by the nonzero remnant polarization after poling. Then, the D-E hysteresis loops of both the cellular PP film and PVDF film were measured by using the same wave form as that used in the SS-PFM, and the results show significant differences. Finally, we suggest that the ferroelectric-like behavior of cellular electrets films should be distinguished from that of typical ferroelectrics, both macroscopically and microscopically.« less

Physicians in Postgraduate Training Characteristics and Support of Palliative Sedation for Existential Distress.

PubMed

Cripe, Larry D; Perkins, Susan M; Cottingham, Ann; Tong, Yan; Kozak, Mary Ann; Mehta, Rakesh

2017-09-01

Palliative sedation for refractory existential distress (PS-ED) is ethically troubling but potentially critical to quality end-of-life (EOL) care. Physicians' in postgraduate training support toward PS-ED is unknown nor is it known how empathy, hope, optimism, or intrinsic religious motivation (IRM) affect their support. These knowledge gaps hinder efforts to support physicians who struggle with patients' EOL care preferences. One hundred thirty-four postgraduate physicians rated their support of PS for refractory physical pain (PS-PP) or PS-ED, ranked the importance of patient preferences in ethically challenging situations, and completed measures of empathy, hope, optimism, and IRM. Predictors of PS-ED and PS-PP support were examined using binary and multinomial logistic regression. Only 22.7% of residents were very supportive of PS-ED, and 82.0% were very supportive of PS-PP. Support for PS-PP or PS-ED did not correlate with levels of empathy, hope, optimism, or IRM; however, for residents with lower IRM, greater optimism was associated with greater PS-ED support. In contrast, among residents with higher IRM, optimism was not associated with PS-ED support. Comparing current results to published surveys, a similar proportion of residents and practicing physicians support PS-ED and PS-PP. In contrast to practicing physicians, however, IRM does not directly influence residents' supportiveness. The interaction between optimism and IRM suggests residents' beliefs and characteristics are salient to their EOL decisions. End-of-life curricula should provide physicians opportunities to reflect on the personal and ethical factors that influence their support for PS-ED.

Family history of diabetes modifies the effect of blood pressure for incident diabetes in Middle Eastern women: Tehran Lipid and Glucose Study.

PubMed

Hatami, M; Hadaegh, F; Khalili, D; Sheikholeslami, F; Azizi, F

2012-02-01

Elevated blood pressure (BP) may lead to incident diabetes. However, data about the effect of different BP components on incident diabetes in Middle Eastern women is lacking. We evaluated systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP) as independent predictors of diabetes in Iranian women. We performed a population-based prospective study among 3028 non-diabetic women, aged ≥20 years. Odds ratios (ORs) of diabetes were calculated for every 1 s.d. increase in SBP, DBP, PP and MAP. During ≈6 years of follow-up, 220 women developed diabetes. There were significant interactions between family history of diabetes and SBP, PP and MAP (P≤0.01) in predicting incident diabetes. In women without a family history of diabetes, all BP components were significantly associated with diabetes in the age-adjusted model; the risk factor-adjusted ORs were significant (P<0.05) for SBP, PP and MAP (1.30, 1.34 and 1.27, respectively) with similar predictive ability (area under the receiver operating characteristic curve ≈83%). In women with family history of diabetes, in the age-adjusted model, SBP, DBP and MAP were associated with diabetes; in multivariable model, they were not independent predictors of diabetes. In conclusion, in women without family history of diabetes, SBP, PP and MAP, were independent predictors of diabetes with almost similar predictive ability; hence, in the evaluation of the risk of BP components for prediction of diabetes, the presence of family history of diabetes should be considered.

Cellular pH and PI3K signaling as determinants of Protoporphyrin IX conversion and ALA PDT response

NASA Astrophysics Data System (ADS)

Anderson, Michael; El-Hamidi, Hamid; Celli, Jonathan

2018-02-01

ALA PDT is a FDA approved cancer treatment. The general model is that excess exogenous ALA is eventually converted to the active photosensitizer, PpIX, and accumulates PpIX to concentrations well above baseline. This accumulation, however, varies considerable from person to person and even intra-tumorally due to a high number of factors that are involved. Due to this there is an increasing desire to pair ALA PDT with other treatments to enhance the efficacy of PDT. This idea itself isn't new as the labs of Bin Chen and Edward Maytin have a long history of using biology to enhance PpIX accumulation. The PI3K pathway is a long-studied cancer treatment target due to it being one of the most ubiquitous over expressed pathways in cancer and that many treatments have demonstrated enhanced efficacy upon PI3K inhibition. In this paper we show that the PI3K pathway inhibitor, LY294002, alters PpIX accumulation in cells (decreased for A431 and increases for Panc-1 and Panc-1 OR) and significantly increases the efficacy of ALA PDT in every case for both monolayer and spheroid cultures. Additionally, we show that PDT treatments using the nonendogenous photosensitizer, verteporfin, also have enhanced efficacy upon PI3K inhibition. Beyond the treatment synergy of PI3K inhibition and PDT, this work presents a cell pairing model that is perfect to study the previously, to our knowledge, undocumented connection between the PI3K pathway and PpIX accumulation.

NOTE: Calibration of low-energy electron beams from a mobile linear accelerator with plane-parallel chambers using both TG-51 and TG-21 protocols

NASA Astrophysics Data System (ADS)

Beddar, A. S.; Tailor, R. C.

2004-04-01

A new approach to intraoperative radiation therapy led to the development of mobile linear electron accelerators that provide lower electron energy beams than the usual conventional accelerators commonly encountered in radiotherapy. Such mobile electron accelerators produce electron beams that have nominal energies of 4, 6, 9 and 12 MeV. This work compares the absorbed dose output calibrations using both the AAPM TG-51 and TG-21 dose calibration protocols for two types of ion chambers: a plane-parallel (PP) ionization chamber and a cylindrical ionization chamber. Our results indicate that the use of a 'Markus' PP chamber causes 2 3% overestimation in dose output determination if accredited dosimetry-calibration laboratory based chamber factors \\big(N_{{\\rm D},{\\rm w}}^{{}^{60}{\\rm Co}}, N_x\\big) are used. However, if the ionization chamber factors are derived using a cross-comparison at a high-energy electron beam, then a good agreement is obtained (within 1%) with a calibrated cylindrical chamber over the entire energy range down to 4 MeV. Furthermore, even though the TG-51 does not recommend using cylindrical chambers at the low energies, our results show that the cylindrical chamber has a good agreement with the PP chamber not only at 6 MeV but also down to 4 MeV electron beams.

Suppression of (Υ1S), Υ(2S), and Υ(3S) quarkonium states in PbPb collisions at s NN = 2.76 TeV

DOE PAGES

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

2017-04-19

The production yields of Υ(1S), Υ(2S), and Υ(3S) quarkonium states are measured through their decays into muon pairs in the CMS detector, in PbPb and pp collisions at the centre-of-mass energy per nucleon pair of 2.76 TeV. The data correspond to integrated luminosities of 166μb –1 and 5.4pb –1 for PbPb and pp collisions, respectively. Differential production cross sections are reported as functions of Υ rapidity y up to 2.4, and transverse momentum p T up to 20GeV/c. A strong centrality-dependent suppression is observed in PbPb relative to pp collisions, by factors of up to ≈2 and 8, for themore » Υ(1S) and Υ(2S) states, respectively. No significant dependence of this suppression is observed as a function of y or p T. The Υ(3S) state is not observed in PbPb collisions, which corresponds to a suppression for the centrality-integrated data by at least a factor of ≈7 at a 95% confidence level. As a result, the observed suppression is in agreement with theoretical scenarios modeling the sequential melting of quarkonium states in a quark gluon plasma.« less

Error analysis for intrinsic quality factor measurement in superconducting radio frequency resonators

DOE PAGES

Melnychuk, O.; Grassellino, A.; Romanenko, A.

2014-12-19

In this paper, we discuss error analysis for intrinsic quality factor (Q₀) and accelerating gradient (E acc ) measurements in superconducting radio frequency (SRF) resonators. The analysis is applicable for cavity performance tests that are routinely performed at SRF facilities worldwide. We review the sources of uncertainties along with the assumptions on their correlations and present uncertainty calculations with a more complete procedure for treatment of correlations than in previous publications [T. Powers, in Proceedings of the 12th Workshop on RF Superconductivity, SuP02 (Elsevier, 2005), pp. 24–27]. Applying this approach to cavity data collected at Vertical Test Stand facility atmore » Fermilab, we estimated total uncertainty for both Q₀ and E acc to be at the level of approximately 4% for input coupler coupling parameter β₁ in the [0.5, 2.5] range. Above 2.5 (below 0.5) Q₀ uncertainty increases (decreases) with β₁ whereas E acc uncertainty, in contrast with results in Powers [in Proceedings of the 12th Workshop on RF Superconductivity, SuP02 (Elsevier, 2005), pp. 24–27], is independent of β₁. Overall, our estimated Q₀ uncertainty is approximately half as large as that in Powers [in Proceedings of the 12th Workshop on RF Superconductivity, SuP02 (Elsevier, 2005), pp. 24–27].« less

Platelet-derived-growth-factor-induced signalling in human platelets: phosphoinositide-3-kinase-dependent inhibition of platelet activation.

PubMed Central

Selheim, F; Fukami, M H; Holmsen, H; Vassbotn, F S

2000-01-01

Human platelets release platelet-derived growth factor (PDGF) from alpha-granules during platelet activation. We have previously shown that platelets have PDGF alpha-receptors, a transmembrane tyrosine kinase that takes part in negative feedback regulation during platelet activation. Here we have described a study of PDGF-induced tyrosine phosphorylation of platelet substrates and phosphoinositide 3-kinase (PI-3K) activity in collagen-stimulated platelets. By immunoblotting with phosphotyrosine antibodies of collagen-activated platelets we found that PDGF increased the phosphorylation of several platelet substrates, e.g. pp140, pp120 and pp85. PDGF inhibited collagen-induced platelet activation in the presence of inhibitors of autocrine stimulation, thus blocking the pure collagen-induced signal transduction. PDGF enhanced the collagen-induced formation of PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) as measured by HPLC. Wortmannin and LY294002, two unrelated inhibitors of PI-3K, were used to investigate the role of PI-3K in PDGF-induced platelet signalling. Incubation of platelets with wortmannin and LY294002 blocked the formation of three phosphorylated inositides as well as the inhibitory effect of PDGF on collagen-induced platelet activation. We conclude that the inhibitory effect of PDGF on platelet activation is PI-3K dependent. This is the first demonstration of a negative regulatory function of 3-phosphorylated inositides in platelets. PMID:10947961

Platelet-derived-growth-factor-induced signalling in human platelets: phosphoinositide-3-kinase-dependent inhibition of platelet activation.

PubMed

Selheim, F; Fukami, M H; Holmsen, H; Vassbotn, F S

2000-09-01

Human platelets release platelet-derived growth factor (PDGF) from alpha-granules during platelet activation. We have previously shown that platelets have PDGF alpha-receptors, a transmembrane tyrosine kinase that takes part in negative feedback regulation during platelet activation. Here we have described a study of PDGF-induced tyrosine phosphorylation of platelet substrates and phosphoinositide 3-kinase (PI-3K) activity in collagen-stimulated platelets. By immunoblotting with phosphotyrosine antibodies of collagen-activated platelets we found that PDGF increased the phosphorylation of several platelet substrates, e.g. pp140, pp120 and pp85. PDGF inhibited collagen-induced platelet activation in the presence of inhibitors of autocrine stimulation, thus blocking the pure collagen-induced signal transduction. PDGF enhanced the collagen-induced formation of PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) as measured by HPLC. Wortmannin and LY294002, two unrelated inhibitors of PI-3K, were used to investigate the role of PI-3K in PDGF-induced platelet signalling. Incubation of platelets with wortmannin and LY294002 blocked the formation of three phosphorylated inositides as well as the inhibitory effect of PDGF on collagen-induced platelet activation. We conclude that the inhibitory effect of PDGF on platelet activation is PI-3K dependent. This is the first demonstration of a negative regulatory function of 3-phosphorylated inositides in platelets.

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis.

PubMed

Elborn, J Stuart; Ramsey, Bonnie W; Boyle, Michael P; Konstan, Michael W; Huang, Xiaohong; Marigowda, Gautham; Waltz, David; Wainwright, Claire E

2016-08-01

Lumacaftor/ivacaftor combination therapy has shown clinical benefits in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation; however, pretreatment lung function is a confounding factor that potentially affects the efficacy and safety of this therapy. We aimed to assess the efficacy and safety of lumacaftor/ivacaftor therapy in these patients, defined by specific categories of lung function. Both trials (TRAFFIC and TRANSPORT) included in this pooled analysis were multinational, randomised, double-blind, placebo-controlled, parallel-group, phase 3 studies. Eligible patients from 187 participating centres in North America, Australia, and the European Union (both trials) were aged 12 years or older with a confirmed diagnosis of cystic fibrosis, homozygous for the Phe508del CFTR mutation, and with a percent predicted FEV1 (ppFEV1) of 40-90 at the time of screening. Patients were randomly assigned with an interactive web response system (1:1:1) to receive placebo, lumacaftor (600 mg once daily) plus ivacaftor (250 mg every 12 h), or lumacaftor (400 mg every 12 h) plus ivacaftor (250 mg every 12 h) for 24 weeks. Prespecified subgroup analyses of pooled efficacy and safety data by lung function, as measured by ppFEV1, were done for patients with baseline ppFEV1 (<40 and ≥40) and screening ppFEV1 (<70 and ≥70). The primary endpoint was the absolute change from baseline in ppFEV1 at week 24 analysed in all randomised patients who received at least one dose of study drug. Both trials are registered with ClinicalTrials.gov (TRAFFIC: NCT01807923; TRANSPORT: NCT01807949). Both trials were done between April, 2013, and April, 2014. Of the 1108 patients included in the efficacy analysis, 81 patients had a ppFEV1 that decreased to lower than 40 between screening and baseline and 1016 had a ppFEV1 of 40 or higher at baseline. At screening, 730 had a ppFEV1 of less than 70, and 342 had a ppFEV1 of 70 or higher. Improvements in the absolute change from baseline at week 24 in ppFEV1 were observed with both lumacaftor/ivacaftor doses in the subgroup with baseline ppFEV1 levels lower than 40 (least-squares mean difference vs placebo was 3·7 percentage points [95% CI 0·5-6·9; p=0·024] in the lumacaftor [600 mg/day]-ivacaftor group and 3·3 percentage points [0·2-6·4; p=0·036] in the lumacaftor [400 mg/12 h]-ivacaftor group). Improvements in ppFEV1 compared with placebo were also reported in the subgroup with baseline ppFEV1 levels of 40 or higher (3·3 percentage points [2·3-4·4; p<0·0001] in the lumacaftor [600 mg per day]-ivacaftor group and 2·8 percentage points [1·7-3·8; p<0·0001] in the lumacaftor [400 mg/12 h]-ivacaftor group). Similar absolute improvements in ppFEV1 compared with placebo were observed in subgroups with screening ppFEV1 levels lower than 70 and ppFEV1 levels of 70 or higher. Increases in body-mass index and reduction in number of pulmonary exacerbation events were observed in both lumacaftor/ivacaftor dose groups compared with placebo across all lung function subgroups. Treatment was generally well tolerated, although the incidence of some respiratory adverse events was higher with lumacaftor/ivacaftor than with placebo in all subgroups. In patients with baseline ppFEV1 levels lower than 40, these adverse events included cough, dyspnoea, and abnormal respiration. These analyses confirm that lumacaftor/ivacaftor combination therapy benefits patients with cystic fibrosis homozygous for Phe508del CFTR who have varying degrees of lung function impairment. Vertex Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Degradation Paradigm of the Gut Hormone, Pancreatic Polypeptide, by Hepatic and Renal Peptidases

PubMed Central

Minnion, James; Tan, Tricia; Scott, Rebecca; Germain, Natacha; Ling, Yiin; Chen, Rong; Ghatei, Mohammad; Bloom, Stephen

2017-01-01

Pancreatic polypeptide (PP) is a gut hormone that acts on Y4 receptors to reduce appetite. Obese humans display a reduced postprandial increase in PP and remain fully sensitive to the anorectic effects of exogenous PP. The utility of PP as an anti-obesity treatment is limited by its short circulating half-life. Insight into the mechanisms by which PP is degraded could aid in the design of long-acting PP analogs. We investigated the role of peptidases in PP degradation to determine whether inhibition of these enzymes enhanced PP plasma levels and bioactivity in vivo. Dipeptidyl peptidase IV (DPPIV) and neprilysin (NEP) were two peptidase found to cleave PP. Limiting the effect of both peptidases improved the in vivo anorectic effect of PP and PP-based analogs. These findings suggest that inhibiting the degradation of PP using specific inhibitors and/or the design of analogs resistant to cleavage by DPPIV and NEP might be useful in the development of PP as an anti-obesity pharmacotherapy. PMID:28323997

Characterization of Phlebotomus papatasi peritrophins, and the role of PpPer1 in Leishmania major survival in its natural vector.

PubMed

Coutinho-Abreu, Iliano V; Sharma, Narinder K; Robles-Murguia, Maricela; Ramalho-Ortigao, Marcelo

2013-01-01

The peritrophic matrix (PM) plays a key role in compartmentalization of the blood meal and as barrier to pathogens in many disease vectors. To establish an infection in sand flies, Leishmania must escape from the endoperitrophic space to prevent excretion with remnants of the blood meal digestion. In spite of the role played regarding Leishmania survival, little is known about sand fly PM molecular components and structural organization. We characterized three peritrophins (PpPer1, PpPer2, and PpPer3) from Phlebotomus papatasi. PpPer1 and PpPer2 display, respectively, four and one chitin-binding domains (CBDs). PpPer3 on the other hand has two CBDs, one mucin-like domain, and a putative domain with hallmarks of a CBD, but with changes in key amino acids. Temporal and spatial expression analyses show that PpPer1 is expressed specifically in the female midgut after blood feeding. PpPer2 and PpPer3 mRNAs were constitutively expressed in midgut and hindgut, with PpPer3 also being expressed in Malpighian tubules. PpPer2 was the only gene expressed in developmental stages. Interestingly, PpPer1 and PpPer3 expression are regulated by Le. major infection. Recombinant PpPer1, PpPer2 and PpPer3 were obtained and shown to display similar biochemical profiles as the native; we also show that PpPer1 and PpPer2 are able to bind chitin. Knockdown of PpPer1 led to a 44% reduction in protein, which in spite of producing an effect on the percentage of infected sand flies, resulted in a 39% increase of parasite load at 48 h. Our data suggest that PpPer1 is a component for the P. papatasi PM and likely involved in the PM role as barrier against Le. major infection.

The relative hydrolytic reactivities of pyrophosphites and pyrophosphates.

PubMed

Mistry, Dharmit; Powles, Nicholas

2013-09-14

The pH-rate profiles for the hydrolysis of pyrophosphate (PP(V)) and pyrophosphite (PP(III), pyro-di-H-phosphonate) are a complex function of pH, reflecting the different ionic species and their relative reactivities. PP(III) is more reactive than PP(V) at all pHs and only PP(III) shows a hydroxide-ion reaction at high pH, so it is 10(10)-fold more reactive than PP(V) in 0.1 M NaOH. The pK(a2) of PP(III) ~0.44, so the dominant species at pH's > 1 is the di-anion PP(III)(2-). Although there is no observable (NMR or ITC) binding of Mg(2+) to the PP(III) di-anion there is a modest increase in the rate of hydrolysis of PP(III) by Mg(2+). PP(III) is neither a substrate nor an inhibitor of pyrophosphatase, the enzyme that efficiently catalyses the hydrolysis of PP(V).

Human Factors Research in Aircrew Performance and Training

DTIC Science & Technology

1989-08-01

and development called instructional design (Gagn6, Briggs , & Wager, 1988). Developments in computer-based instruction promise to increase training...Handbook of human factors (pp. 976-1011). New York: Wiley & Sons. Gagn6, R. M., Briggs , L. J., & Wager, W. W. (1988). Principles of instructional...SERVICE: SUPPORT TO MULTITRACK TESTING Dr. D. Michael McAnulty, Mr. Gary Coker, Ms. Cassandra Hocutt, Ms. Stephanie Noland, and Mr. Kenneth Persin

An apple rootstock overexpressing a peach CBF gene alters growth and flowering in the scion but does not impact cold hardiness or dormancy

USDA-ARS?s Scientific Manuscript database

The C-repeat Binding Factor (CBF) transcription factor is involved in responses to low temperature and water deficit in many plant species. Overexpression of CBF genes leads to enhanced freezing tolerance and growth inhibition in many species. The overexpression of a peach CBF (PpCBF1) gene in a t...

Comparative transcriptome analysis provides insights into molecular mechanisms for parthenocarpic fruit development in eggplant (Solanum melongena L.).

PubMed

Chen, Xia; Zhang, Min; Tan, Jie; Huang, Shuping; Wang, Chunli; Zhang, Hongyuan; Tan, Taiming

2017-01-01

Genetic control of parthenocarpy, a desirable trait in edible fruit with hard seeds, has been extensively studied. However, the molecular mechanism of parthenocarpic fruit development in eggplant (Solanum melongena L.) is still unclear. To provide insights into eggplant parthenocarpy, the transcriptomic profiles of a natural parthenocarpic (PP05) and two non-parthenocarpic (PnP05 and GnP05) eggplant lines were analyzed using RNA-sequencing (RNA-seq) technology. These sequences were assembled into 38925 unigenes, of which 22683 had an annotated function and 3419 were predicted as novel genes or from alternative splicing. 4864 and 1592 unigenes that were identified as DEGs between comparison groups PP05 vs PnP05 and PP05 vs GnP05, respectively. 506 common DEGs were found contained in both comparison groups, including 258 up-regulated and 248 down-regulated genes. Functional enrichment analyses identified many common or specific biological processes and gene set potentially associated with plant development. The most pronounced findings are that differentially regulated genes potentially-related with auxin signaling between parthenocarpic and non-parthenocarpic eggplants, e.g. calcium-binding protein PBP1 and transcription factor E2FB, which mediate the auxin distribution and auxin-dependent cell division, respectively, are up-regulated in the PP05; whereas homologs of GH3.1 and AUX/IAA, which are involved in inactivation of IAA and interference of auxin signaling, respectively, are down-regulated in PP05. Furthermore, gibberellin and cytokinin signaling genes and genes related to flower development were found differentially regulated between these eggplant lines. The present study provides comprehensive transcriptomic profiles of eggplants with or without parthenocarpic capacity. The information will deepen our understanding of the molecular mechanisms of eggplant parthenocarpy. The DEGs, especially these filtered from PP05 vs PnP05 + GnP05, will be valuable for further investigation of key genes involved in the parthenocarpic fruit development and genomics-assisted breeding.

PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis.

PubMed

Grinthal, Alison; Adamovic, Ivana; Weiner, Beth; Karplus, Martin; Kleckner, Nancy

2010-02-09

PR65 is the two-layered (alpha-alpha solenoid) HEAT-repeat (Huntingtin, elongation factor 3, a subunit of protein phosphatase 2A, PI3 kinase target of rapamycin 1) scaffold of protein phosphatase PP2A. Molecular dynamics simulations predict that, at forces expected in living systems, PR65 undergoes (visco-)elastic deformations in response to pulling/pushing on its ends. At lower forces, smooth global flexural and torsional changes occur via even redistribution of stress along the hydrophobic core of the molecule. At intermediate forces, helix-helix separation along one layer ("fracturing") leads to global relaxation plus loss of contact in the other layer to unstack the affected units. Fracture sites are determined by unusual sequences in contiguous interhelix turns. Normal mode analysis of the heterotrimeric PP2A enzyme reveals that its ambient conformational fluctuations are dominated by elastic deformations of PR65, which introduce a mechanical linkage between the separately bound regulatory and catalytic subunits. PR65-dominated fluctuations of PP2A have the effect of opening and closing the enzyme's substrate binding/catalysis interface, as well as altering the positions of certain catalytic residues. These results suggest that substrate binding/catalysis are sensitive to mechanical force. Force could be imposed from the outside (e.g., in PP2A's response to spindle tension) or arise spontaneously (e.g., in PP2A's interaction with unstructured proteins such as Tau, a microtubule-associated Alzheimer's-implicated protein). The presented example supports the view that conformation and function of protein complexes can be modulated by mechanical energy inputs, as well as by chemical energy inputs from ligand binding. Given that helical-repeat proteins are involved in many cellular processes, the findings also encourage the view that mechanical forces may be of widespread importance.

PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis

PubMed Central

Grinthal, Alison; Adamovic, Ivana; Weiner, Beth; Karplus, Martin; Kleckner, Nancy

2010-01-01

PR65 is the two-layered (α-α solenoid) HEAT-repeat (Huntingtin, elongation factor 3, a subunit of protein phosphatase 2A, PI3 kinase target of rapamycin 1) scaffold of protein phosphatase PP2A. Molecular dynamics simulations predict that, at forces expected in living systems, PR65 undergoes (visco-)elastic deformations in response to pulling/pushing on its ends. At lower forces, smooth global flexural and torsional changes occur via even redistribution of stress along the hydrophobic core of the molecule. At intermediate forces, helix–helix separation along one layer (“fracturing”) leads to global relaxation plus loss of contact in the other layer to unstack the affected units. Fracture sites are determined by unusual sequences in contiguous interhelix turns. Normal mode analysis of the heterotrimeric PP2A enzyme reveals that its ambient conformational fluctuations are dominated by elastic deformations of PR65, which introduce a mechanical linkage between the separately bound regulatory and catalytic subunits. PR65-dominated fluctuations of PP2A have the effect of opening and closing the enzyme’s substrate binding/catalysis interface, as well as altering the positions of certain catalytic residues. These results suggest that substrate binding/catalysis are sensitive to mechanical force. Force could be imposed from the outside (e.g., in PP2A’s response to spindle tension) or arise spontaneously (e.g., in PP2A’s interaction with unstructured proteins such as Tau, a microtubule-associated Alzheimer’s-implicated protein). The presented example supports the view that conformation and function of protein complexes can be modulated by mechanical energy inputs, as well as by chemical energy inputs from ligand binding. Given that helical-repeat proteins are involved in many cellular processes, the findings also encourage the view that mechanical forces may be of widespread importance. PMID:20133745

The neural correlates of biomechanical constraints in hand laterality judgment task performed from other person's perspective: A near-infrared spectroscopy study.

PubMed

Meng, Shuang; Oi, Misato; Saito, Godai; Saito, Hirofumi

2017-01-01

Previous studies, mainly using a first-person perspective (1PP), have shown that the judgments of the hand laterality judgment (HLJ) task are dependent on biomechanical constraints (BC). Specifically, differing reaction times (RT) for hand pictures rotated medially or laterally around the mid sagittal plane are attributed to the BC effect on motor imagery. In contrast, we investigated whether the HLJ task is also subject to BC when performed from a third-person perspective (3PP) as well as 1PP using near-infrared spectroscopy (NIRS) to measure the brain activity of prefrontal cortex (PFC) in right-handed participants assigned to 1PP or 3PP groups. The 1PP group judged whether a presented hand was their own left or right hand, and the 3PP group whether it was the other's left or right hand. Using their HLJ task error rates, the 1PP and 3PP groups were subdivided into an Error Group (EG) and No Error Group (NEG). For the 1PP group, both EG and NEG showed a significant Hand Laterality × Orientation interaction for RT, indicating the BC effect on motor imagery. For the 3PP group, however, neither EG nor NEG showed the interaction, even though EG showed a significantly longer RT than NEG. These results suggest that the 3PP EG appropriately followed the 3PP task instruction, while the NEG might have taken 1PP. However, the 3PP EG NIRS profile of left PFC showed a significant Hand Laterality × Orientation interaction, while the 1PP EG did not. More noteworthy is that the left PFC activation of EG showed an interaction between the 1PP and 3PP groups when the left hand was presented. Furthermore, in the NEG, the PFC activation was not influenced by the BC in either the 1PP or 3PP condition. These results indicate that BC interferes with the HLJ task performed from the 1PP and 3PP.

Lateralized dual task interference in left-handers: initial value differences do not affect the outcome.

PubMed

McBride, D M; Cherry, B J; Kee, D W; Neale, P L

1995-07-01

The study was conducted to clarify factors involved in dual-task finger-tapping interference. Left-handers, as assessed by hand-writing preference and left-hand baseline tapping advantage, tapped both alone and while solving anagrams. Even though the left-hand baseline tapping advantage was experimentally removed on some (adjusted) trials, greater left- than right-hand tapping interference was observed during concurrent task performance. This result coupled with previous findings for right-handed subjects [Kee and Cherry, Neuropsychologia, Vol. 28, pp. 313-316, 1990] indicates that lateralized interference effects are not merely due to initial baseline tapping differences as proposed by Willis and Goodwin [Neuropsychologia, Vol. 25, pp. 719-724, 1987].

Fabrication of borassus fruit lignocellulose fiber/PP composites and comparison with jute, sisal and coir fibers.

PubMed

Sudhakara, P; Jagadeesh, Dani; Wang, YiQi; Prasad, C Venkata; Devi, A P Kamala; Balakrishnan, G; Kim, B S; Song, J I

2013-10-15

Novel composites based on borassus fruit fine fiber (BFF) and polypropylene (PP) were fabricated with variable fiber composition (5, 10, 15 and 20 wt%) by injection molding. Maleated PP (MAPP) was also used as compatibilizer at 5 wt% for effective fiber-matrix adhesion. FTIR analysis confirms the evidence of a chemical bonding between the fiber and polymeric matrix through esterification in presence of MAPP. The tensile and flexural properties were found to increase with 15 and 10 wt% fiber loadings respectively, and decreased thereafter. Coir, jute and sisal fiber composites were also fabricated with 15 wt% fiber loading under the same conditions as used for BFF/PP composites. It was found that the mechanical properties of BFF (15 wt%)/PP composites were equivalent to jute/PP, sisal/PP and superior to coir/PP composites. Jute/PP and sisal/PP composites showed higher water absorption than BFF/PP and coir/PP composites. These results have demonstrated that the BFF/PP composites can also be an alternative material for composites applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

A SABATH Methyltransferase from the moss Physcomitrella patens catalyzes

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

Zhao, Nan; Ferrer, Jean-Luc; Moon, Hong S

2012-01-01

Known SABATH methyltransferases, all of which were identified from seed plants, catalyze methylation of either the carboxyl group of a variety of low molecular weight metabolites or the nitrogen moiety of precursors of caffeine. In this study, the SABATH family from the bryophyte Physcomitrella patens was identified and characterized. Four SABATH-like sequences (PpSABATH1, PpSABATH2, PpSABATH3, and PpSABATH4) were identified from the P. patens genome. Only PpSABATH1 and PpSABATH2 showed expression in the leafy gametophyte of P. patens. Full-length cDNAs of PpSABATH1 and PpSABATH2 were cloned and expressed in soluble form in Escherichia coli. Recombinant PpSABATH1 and PpSABATH2 were tested formore » methyltransferase activity with a total of 75 compounds. While showing no activity with carboxylic acids or nitrogen-containing compounds, PpSABATH1 displayed methyltransferase activity with a number of thiols. PpSABATH2 did not show activity with any of the compounds tested. Among the thiols analyzed, PpSABATH1 showed the highest level of activity with thiobenzoic acid with an apparent Km value of 95.5 lM, which is comparable to those of known SABATHs. Using thiobenzoic acid as substrate, GC MS analysis indicated that the methylation catalyzed by PpSABATH1 is on the sulfur atom. The mechanism for S-methylation of thiols catalyzed by PpSABATH1 was partially revealed by homology-based structural modeling. The expression of PpSABATH1 was induced by the treatment of thiobenzoic acid. Further transgenic studies showed that tobacco plants overexpressing PpSABATH1 exhibited enhanced tolerance to thiobenzoic acid, suggesting that PpSABATH1 have a role in the detoxification of xenobiotic thiols.« less

PP2A activity is controlled by methylation and regulates oncoprotein expression in melanoma cells: a mechanism which participates in growth inhibition induced by chloroethylnitrosourea treatment.

PubMed

Guénin, Samuel; Schwartz, Laurent; Morvan, Daniel; Steyaert, Jean Marc; Poignet, Amandine; Madelmont, Jean Claude; Demidem, Aicha

2008-01-01

Protein phosphatase 2A (PP2A), an Akt pathway inhibitor, is considered to be activated by methylation of its catalytic subunit. Also PP2A downregulation was proposed to take part in carcinogenesis. Recently, PP2A activation was shown to be activated in response to DNA damage. To obtain further information on the role of PP2A in tumors and response to DNA damage, we investigated the relationship between PP2A methylation and activity, cell proliferation, Akt activation, c-Myc expression and PTEN activity in B16 melanoma cells untreated and after chloroethylnitrosourea (CENU) treatment. In untreated cells, okadaic acid, an antagonist of PP2A methylation, inhibited PP2A activity, stimulated cell proliferation, increased Akt activation and c-Myc expression. Xylulose-5-phosphate, an agonist of PP2A methylation, increased PP2A activity, decreased cell proliferation, Akt activation and c-Myc expression. However, both PP2A methylation modulators increased PTEN activity. During the response to CENU treatment, PP2A methylation and activity were strongly increased, Akt activation and c-Myc expression were decreased. However PTEN activity was increased. After tumor cell growth recovery, these modifications were moderately decreased. PP2A methylation was quantified and correlated positively with PP2A activity, and negatively with criteria for cell aggressiveness (cell proliferation, Akt activation, c-Myc expression). Based on these data, PP2A methylation status controls PP2A activity and oncoproteins expression and PP2A is strongly activated after CENU treatment thus partly explaining the growth inhibition in response to this agent. It follows that PP2A promethylating agents are potential candidates for anticancer drugs.

PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

PubMed Central

Than, Nandor Gabor; Romero, Roberto; Meiri, Hamutal; Erez, Offer; Xu, Yi; Tarquini, Federica; Barna, Laszlo; Szilagyi, Andras; Ackerman, Ron; Sammar, Marei; Fule, Tibor; Karaszi, Katalin; Kovalszky, Ilona; Dong, Zhong; Kim, Chong Jai; Zavodszky, Peter; Papp, Zoltan; Gonen, Ron

2011-01-01

Background Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood. Methods and Findings We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13 - blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR. Conclusions ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test. PMID:21799738

The Association Between Serum Activin A Levels and Hypertension in the Elderly: A Cross-Sectional Analysis From I-Lan Longitudinal Aging Study.

PubMed

Tsai, Yi-Lin; Chang, Chun-Chin; Liu, Li-Kuo; Huang, Po-Hsun; Chen, Liang-Kung; Lin, Shing-Jong

2018-02-09

Hypertension is an important risk factor for cardiovascular disease. Activin A, a member of the transforming growth factor-β cytokine family, has been shown to regulate blood pressure through the renin-angiotensin system. However, the relationship between activin A and blood pressure remains uncertain. The objective of this study was to determine whether serum activin A levels are associated with blood pressure. A total of 470 participants of I-Lan longitudinal Aging Study (ILAS) were eligible for this study. Serum levels of activin A were assessed by enzyme-linked immunosorbent assay. Cross-sectional analyses were performed, including comparisons of demographic characteristics, hypertensive status, and activin A levels. Among the study participants (50% men, mean age, 69 years), 236 (50.2%) were hypertensive and 234 (49.8%) were normotensive. Hypertensive patients had significantly higher serum activin A levels than normotensives (normotensive vs. hypertensive: 507 ± 169 vs. 554 ± 176 pg/ml, mean ± SD, P < 0.001). All subjects were divided into 3 tertiles on the basis of serum activin A levels. Increasing tertiles of activin A were associated with higher systolic blood pressure (SBP), diastolic blood pressure and pulse pressure (PP) (all P < 0.001). After adjusting for all the potential confounding factors, serum activin A concentration was still significantly associated with SBP (P = 0.02) and PP (P = 0.03). Serum activin A level was associated with SBP and PP. Further studies are required to assess their causal relationship and the clinical relevance. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Blood Pressure and Cerebral White Matter Share Common Genetic Factors in Mexican-Americans

PubMed Central

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2010-01-01

Elevated arterial pulse pressure (PP) and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially due to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy (FA) of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican-Americans. The patterns of whole-brain and regional genetic overlap between BP and FA were interpreted in the context the pulse-wave encephalopathy (PWE) theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7×1.7×3mm, 55 directions) diffusion tensor imaging (DTI) data were analyzed for 332 (202 females; mean age=47.9±13.3years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements [PP, systolic (SBP) and diastolic (DBP)] and FA (whole-brain and regional values). Intersubject variance in PP and SBP exhibited a significant genetic overlap with variance in whole-brain FA values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=−.75, p=0.01). The pattern of genetic overlap between BP and WM integrity was generally in-agreement with the PWE theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development suggesting a possible role for genotype-by-age interactions. PMID:21135356

Deriving a clinical prediction rule to target sexual healthcare to women attending British General Practices.

PubMed

Edelman, N L; Cassell, J A; Mercer, C H; Bremner, S A; Jones, C I; Gersten, A; deVisser, R O

2018-07-01

Some women attending General Practices (GPs) are at higher risk of unintended pregnancy (RUIP) and sexually transmitted infections (STI) than others. A clinical prediction rule (CPR) may help target resources using psychosocial questions as an acceptable, effective means of assessment. The aim was to derive a CPR that discriminates women who would benefit from sexual health discussion and intervention. Participants were recruited to a cross-sectional survey from six GPs in a city in South-East England in 2016. On arrival, female patients aged 16-44 years were invited to complete a questionnaire that addressed psychosocial factors, and the following self-reported outcomes: 2+ sexual partners in the last year (2PP) and RUIP. For each sexual risk, psychosocial questions were retained from logistic regression modelling which best discriminated women at risk using the C-statistic. Sensitivity and specificity were established in consultation with GP staff. The final sample comprised N = 1238 women. 2PP was predicted by 11 questions including age, binge-drinking weekly, ever having a partner who insulted you often, current smoking, and not cohabiting (C-statistic = 0.83, sensitivity = 73% and specificity = 77%). RUIP was predicted by 5 questions including sexual debut <16 years, and emergency contraception use in the last 6 months (C-statistic = 0.70, sensitivity = 69% and specificity = 57%). 2PP was better discriminated than RUIP but neither to a clinically-useful degree. The finding that different psychosocial factors predicted each outcome has implications for prevention strategies. Further research should investigate causal links between psychosocial factors and sexual risk. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Measurement of K 0 S and K *0 in p+p, d+Au, and Cu+Cu collisions at sqrt S NN = 200 GeV

DOE PAGES

Adare, A.; Aidala, C.

2014-11-01

The PHENIX experiment at the Relativistic Heavy Ion Collider has performed a systematic study of K 0 S and K *0 meson production at midrapidity in p+p, d+Au, and Cu+Cu collisions at sqrt S NN = 200 GeV. The K 0 S and K *0 mesons are reconstructed via their K 0 S and π 0(→γγ)π 0 (→γγ) and K *0 → K ± π ± decay modes, respectively. The measured transverse-momentum spectra are used to determine the nuclear modification factor of K 0 S and K *0 mesons in d+Au and Cu+Cu collisions at different centralities. In the d+Aumore » collisions, the nuclear modification factor of K 0 S and K *0 mesons is almost constant as a function of transverse momentum and is consistent with unity showing that cold-nuclear-matter effects do not play a significant role in the measured kinematic range. In Cu+Cu collisions, within the uncertainties no nuclear modification is registered in peripheral collisions. In central collisions, both mesons show suppression relative to the expectations from the p+p yield scaled by the number of binary nucleon-nucleon collisions in the Cu+Cu system. In the p T range 2–5 GeV/c, the strange mesons ( K 0 S, K *0) similarly to the Φ meson with hidden strangeness, show an intermediate suppression between the more suppressed light quark mesons (π 0) and the nonsuppressed baryons (p, p-bar). At higher transverse momentum, p T > 5 GeV/c, production of all particles is similarly suppressed by a factor of ≈2. (auth)« less

Branching fractions for {chi}{sub cJ{yields}}pp{pi}{sup 0}, pp{eta}, and pp{omega}

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

Onyisi, P. U. E.; Rosner, J. L.; Alexander, J. P.

2010-07-01

Using a sample of 25.9x10{sup 6} {psi}(2S) decays acquired with the CLEO-c detector at the CESR e{sup +}e{sup -} collider, we report branching fractions for the decays {chi}{sub cJ{yields}}pp{pi}{sup 0}, pp{eta}, and pp{omega}, with J=0, 1, 2. Our results for B({chi}{sub cJ{yields}}pp{pi}{sup 0}) and B({chi}{sub cJ{yields}}pp{eta}) are consistent with, but more precise than, previous measurements. Furthermore, we include the first measurement of B({chi}{sub cJ{yields}}pp{omega}).

Isolation of lactobacillus reuteri from Peyer's patches and their effects on sIgA production and gut microbiota diversity.

PubMed

Wang, Panpan; Li, Ya; Xiao, Hang; Shi, Yonghui; Le, Guo-Wei; Sun, Jin

2016-09-01

We previously reported that specific Lactobacillus reuteri colonized within mouse Peyer's patches (PP) effectively prevented high fat diet induced obesity and low-grade chronic inflammation. We further investigated the role of PP Lactobacillus reuteri on sIgA production in rats in this study. Lactobacilli were isolated from rat PP. All isolates were L. reuteri and belonged to three phenotypes according to amplified fragment length polymorphism analysis. Typical strains of two main clusters, PP1 and PP2, were used to treat control and vitamin A deficient (VAD) rats, respectively. The feeding of PP1 and PP2 affected sIgA and Lactobacillus diversity by strain-specific manner. Free sIgA was significantly increased by PP1 (p = 0.069) and PP2 (p < 0.05) in the control rats but not in the VAD rats. Only PP1 significantly changed PP Lactobacillus diversity in the control rats (p < 0.05). However, PP2 specifically changed ileal Lactobacillus diversity in both control and VAD rats. Fecal sIgA was correlated with PP Lactobacillus diversity (R(2) = 0.7958, p = 0.011). Modulation of sIgA production by PP L. reuteri of rat is dependent on vitamin A and change of Lactobacillus diversity in PP. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Taking a Regional Healthcare Coalition Approach to Mitigating Surge Capacity Needs of Mass Casualty or Pandemic Events

DTIC Science & Technology

2012-06-01

participation needs of a coalition—active involvement. In the book Work and the Nature of Man, Frederick Hertzberg details his “ two - factor theory ” in...gaining motivation for employees or, as exemplified in this case, coalition participants.59 The theory posits that there are two factors that...59 Frederick Hertzberg; Work and the Nature of Man; 1973; Mentor Books, New York; Two - factor Theory Pp. 149-158 60 Hertzberg’s

The melt-recrystallization behavior of highly oriented α-iPP fibers embedded in a HIPS matrix.

PubMed

Ye, Liwei; Li, Huihui; Qiu, Zhaobin; Yan, Shouke

2015-03-21

The melt-recrystallization behavior of α-iPP fibers embedded in an amorphous HIPS matrix has been studied by means of optical microscopy. The amorphous HIPS serving as a supporter of iPP fibers does not become involved in the nucleation and crystallization process of the molten highly oriented iPP fibers. It also does not provide any birefringence under the optical microscope with crossed polarizers. This enables the study of orientation-induced β-iPP crystallization through a control of the melting status of the fibers. Through melting the fibers at different temperatures above 175 °C and subsequent recrystallization, some β-iPP crystals were always produced. The content of the β-iPP crystal depends strongly on the melting temperature and melting time of the iPP fibers. It was confirmed that melting the iPP fibers at relatively lower temperature, e.g. 176 °C, less amount of β-iPP crystals were observed. The content of β-iPP crystal enhances first with increasing melting temperature and then decreases with further increase of the fiber melting temperature. The β-iPP crystallization is found to be most favorable upon melting the fibers at 178 °C for 2 min. This demonstrates the requirement of a certain chain or chain segment orientation for generating β-iPP crystallization on the one hand, while higher orientation of the iPP chains or chain segments encourages the growth of iPP crystals in the α-form on the other hand. This has been further confirmed by varying the melting time of the fiber at different temperatures, since relaxation of the iPP molecular chains at a fixed temperature is time dependent. Moreover, the complete transformation of α-iPP fibers in some local places into β-iPP crystals implies that the αβ-transition may not be required for the orientation-induced β-iPP crystallization.

Tg-SwDI Transgenic Mice Exhibit Novel Alterations in AβPP Processing, Aβ Degradation, and Resilient Amyloid Angiopathy

PubMed Central

Van Vickle, Gregory D.; Esh, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Kalback, Walter M.; Patton, R. Lyle; Luehrs, Dean C.; Walker, Douglas G.; Lue, Lih-Fen; Beach, Thomas G.; Davis, Judianne; Van Nostrand, William E.; Castaño, Eduardo M.; Roher, Alex E.

2008-01-01

Alzheimer’s disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-β (Aβ) peptides. We characterized the chemical composition of the Aβ peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse Aβ accumulation. The processing of the N- and C-terminal regions of mutant AβPP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low AβPP transgene expression levels, suggests that inefficient Aβ proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic AβPP processing and fundamental insights into the faulty degradation and clearance of Aβ in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents. PMID:18599612

ABSCISIC ACID INSENSITIVE3 Is Involved in Cold Response and Freezing Tolerance Regulation in Physcomitrella patens.

PubMed

Tan, Tinghong; Sun, Yanni; Peng, Xingji; Wu, Guochun; Bao, Fang; He, Yikun; Zhou, Huapeng; Lin, Honghui

2017-01-01

  Synopsis This work demonstrates that PpABI3 contributes to freezing tolerance regulation in Physcomitrella patens. Transcription factor ABSCISIC ACID INSENSITIVE3 (ABI3) is known to play a major role in regulating seed dormancy, germination, seedling development as well as stress responses. ABI3 is conserved among land plants; however, its roles in non-seed plants under stress conditions have not been well characterized. In this study, we report that ABI3 is involved in freezing tolerance regulation during cold acclimation at least in part through ABA signaling pathway in moss Physcomitrella patens ( P. patens ). Deletion of PpABI3 (Δ abi3-1 ) compromises the induction of genes related to cold response and antioxidative protection, resulting in reduced accumulation of cryoprotectants and antioxidants. In addition, photosystem II (PSII) activity is repressed in Δ abi3-1 during cold acclimation partially due to alternations of photosynthetic protein complexes compositions. The gametophyte of Δ abi3-1 displays severe growth inhibition and developmental deficiency under low temperature condition, while two independent complementary lines display phenotypes similar to that of wild-type P. patens (WT). Furthermore, the freezing tolerance of Δ abi3-1 was significantly affected by deletion of PpABI3 . These data revealed that PpABI3 plays an important role in low temperature response and freezing tolerance in P. patens .

The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.

PubMed

Kokkoris, Kyriakos; Gallo Castro, Daniela; Martin, Sophie G

2014-05-01

Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.

Influence of RpoS, cAMP-receptor protein, and ppGpp on expression of the opgGH operon and osmoregulated periplasmic glucan content of Salmonella enterica serovar Typhimurium.

PubMed

Costa, Cristina S; Pizarro, Ramón A; Antón, Dora N

2009-11-01

A transcriptional fusion (opgG1::MudJ) to the opgGH operon of Salmonella enterica serovar Typhimurium (S. Typhimurium) LT2, isolated by resistance to mecillinam, was used to study the influence of global regulators RpoS, ppGpp, and cAMP/cAMP-receptor protein (CRP) on expression of the opgGH operon and osmoregulated periplasmic glucan (OPG) content. Neither high growth medium osmolarity nor absence of ppGpp or CRP had important effects on opgG1::MudJ expression in exponential cultures. However, under the same conditions, OPG content was strongly decreased by high osmolarity or cAMP/CRP defectiveness, and reduced to a half by lack of ppGpp. In stationary cultures, high osmolarity as well as CRP loss caused significant descents in opgG1::MudJ expression that were compensated by inactivation of RpoS sigma factor. No effect of RpoS inactivation on OPG content was observed. It is concluded that opgGH expression in S. Typhimurium is only slightly affected by high osmolarity, but is inversely modulated by RpoS level. On the other hand, osmolarity and the cAMP/CRP global regulatory system appear to control OPG content, either directly or indirectly, mainly at the post-transcriptional level.

White light-informed optical properties improve ultrasound-guided fluorescence tomography of photoactive protoporphyrin IX

NASA Astrophysics Data System (ADS)

Flynn, Brendan P.; DSouza, Alisha V.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

2013-04-01

Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025 μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations.

Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis.

PubMed

Douglas, Pauline; Ye, Ruiqiong; Morrice, Nicholas; Britton, Sébastien; Trinkle-Mulcahy, Laura; Lees-Miller, Susan P

2015-08-01

Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Mechanism for Angular Deformation of L-shaped Specimens —Influence of Filling Material and Shrinkage Factor—

NASA Astrophysics Data System (ADS)

Furuhashi, Hiroshi; Aoki, Takerou; Okabe, Sayaka; Arai, Tsuyoshi; Seto, Masahiro; Yamabe, Masashi

L-shape is the important and fundamental shape for injection molded parts. Therefore to reveal the corner angular deformation mechanism of this shape is also valuable for understanding the warpage mechanism of injection molded parts. In this study, we investigated the influence of the filling materials (fiber, talc and not filled) and two kinds of anisotropic shrinkage factors, solidification shrinkage and shrinkage caused by thermal expansion coefficient during cooling, to the angular deformation of L-shaped specimens and the following conclusions were obtained 1) The anisotropic solidification shrinkage of MD/TD and the anisotropic thermal expansion coefficient of MD/TD are considered to cause the angular deformation of L-shaped specimens. But the contribution ratios of these two anisotropies depend on the filling material for plastics. 2) The angular deformation of PP and PBT filled with glass fiber is mainly caused by the anisotropic thermal expansion coefficient and on the other hand, that of PP and PBT without filling material is caused by anisotropic solidification shrinkage. However both anisotropies cause the angular deformation of PP filled with talc. 3) The plate thickness dependence of the angular deformation of PP filled with talc is the singular peculiar phenomenon. The plate thickness dependence of anisotropic solidification shrinkage of this material (it is also singular) is considered to have an important influence on this phenomenon.

Measurements of electrons from semi-leptonic heavy flavor decays in p+p and Au+Au collisions at √{sNN } = 200 GeV at STAR

NASA Astrophysics Data System (ADS)

Wang, Yaping; STAR Collaboration

2017-08-01

In these proceedings, we present recent results on electrons from semi-leptonic decays of open heavy-flavor hadrons (eHF) with the STAR detector at the Relativistic Heavy Ion Collider. We report the updated measurements of eHF production in p+p collisions at √{ s } = 200 GeV with significantly improved precision and wider kinematic coverage than previous measurements. With this new p+p reference, we obtain the nuclear modification factor (RAA) for eHF in Au+Au collisions at √{sNN } = 200 GeV using 2010 data. The RAA shows significant suppression at high pT in most central Au+Au collisions, while the suppression reduces gradually towards more peripheral collisions. We compare eHFRAA in central Au+Au collisions to that in central U+U collisions at √{sNN } = 193 GeV and find that they are consistent within uncertainties. We also show the results of B-hadron contribution to eHF extracted from azimuthal correlations between eHF and charged hadrons in p+p collisions. Finally we report the measurements of eHF from open bottom hadron decays and discuss the prospect of measuring eHF from open bottom and charm hadron decays separately utilizing the Heavy Flavor Tracker in Au+Au collisions.

Associations of Dairy Intake with Arterial Stiffness in Brazilian Adults: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Ribeiro, Amanda Gomes; Mill, José Geraldo; Cade, Nágela Valadão; Velasquez-Melendez, Gustavo; Matos, Sheila Maria Alvim; Molina, Maria Del Carmen Bisi

2018-05-31

Recent studies have suggested the possible effect of dairy product intake on cardiovascular risk markers, including arterial stiffness. Our aim was to investigate whether dairy food intake is associated with arterial stiffness, which we assessed by carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP) in a cross-sectional analysis of baseline data (2008⁻2010; n = 12,892) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Dairy consumption was evaluated with a validated food-frequency questionnaire (FFQ) by computing servings per day for total and subgroups of dairy products. Dairy consumption was described in four categories (≤1 serving/day to >4 servings/day). Covariance analysis (ANCOVA) was used to compare cfPWV across increasing intake of dairy food, adjusting for confounding factors, including non-dairy food groups. The intake of total dairy was inversely associated with cfPWV and PP (-0.13 m/s and -1.3 mmHg, from the lowest and to the highest category of dairy intake). Low-fat dairy, fermented dairy and cheese showed an inverse relationship with cfPWV and PP. These findings suggest a beneficial effect of dairy consumption to reduce arterial stiffness. However, further evidence from longitudinal studies or long-term intervention is needed to support reduction of cfPWV and PP mediating the beneficial effects of dairy products on cardiovascular health.

Investigations on photolon-and porphyrin-doped sol-gel fiberoptic coatings for laser-assisted applications in medicine

NASA Astrophysics Data System (ADS)

Bindig, U.; Ulatowska-Jarza, A.; Kopaczynska, M.; Müller, G.; Podbielska, H.

2008-01-01

In view of laser-assisted medical applications, the construction of silica-based sol-gel fiberoptic sensors based on photolon (Ph) and protoporphyrin IX (PP IX) is discussed. Electron microscopy and AFM were used to characterize the silica sol-gel coatings. AFM measurements indicate a change in the surface porosity. The PP IX-based sensors were constructed as a one-layer optode as well as a multilayered structure. An additional hybrid sensor made up of alternate layers of PP IX-and Ph-doped sol-gel was also constructed and examined. Sol-gel matrices were prepared from silicate precursor tetraethylorthosilicate (TEOS) mixed with ethanol in acid-catalyzed hydrolysis. The carrier matrices of photosensitive dyes were produced with factor R = 20, where R denotes the ratio of solvent moles (ethanol) to the number of TEOS moles. A multilayered coating was built up using the reverse-dipping technique. The overall coating thickness was determined by electron microscopy. Doped sol-gels with different PP IX concentrations were used to produce fiberoptic coatings. The film optodes with a different number of layers were examined by fluorescence spectroscopy. It was found that photolon and protoporphyrin IX entrapped in sol-gel preserve their chemical reactivity and have contact with the external environment. The hybrid sensor demonstrated clear fluorescence and a reversible behavior in gaseous environments.

Breast Self-Examination in the Personal Health Course.

ERIC Educational Resources Information Center

Young, Michael

1983-01-01

Female college students were surveyed regarding their acceptance of a film format for teaching breast self-examination. Factors that distinguished college women who regularly examined their breasts included: (1) conservatism; (2) confidence; (3) previous instruction; and (4) perception of the threat of cancer. (Author/PP)

Complacency: A Threat to Homeland Security

DTIC Science & Technology

2014-06-01

dangerous drugs; assuring the safety of bridges and dams; using pesticides in agriculture; and, less dramatically, distributing electric power. (LaPorte...mind (pp. 235–255). Oxford: Basil Blackwell. 79 Stramler, J. H. Jr. (1993). The dictionary for human factors/ergonomics. Boca Raton, FL: CRC Press

Quantitative Robust Control Engineering: Theory and Applications

DTIC Science & Technology

2006-09-01

30]. Gutman, PO., Baril , C. Neuman, L. (1994), An algorithm for computing value sets of uncertain transfer functions in factored real form...linear compensation design for saturating unstable uncertain plants. Int. J. Control, Vol. 44, pp. 1137-1146. [90]. Oldak S., Baril C. and Gutman

The Children of Working Parents.

ERIC Educational Resources Information Center

Crouter, Ann C.

1983-01-01

The fact that a mother works has no universally predictable effect on a child, according to recent research. Factors which do matter include: (1) child's age and sex; (2) family's social position; and (3) nature of the mother's work. Improved child care and working conditions are needed. (PP)

Molecular cloning, expression and single nucleotide polymorphisms of protein phosphatase 1 (PP1) in mandarin fish (Siniperca chuatsi).

PubMed

Cheng, Xiao-Yan; He, Shan; Liang, Xu-Fang; Song, Yi; Yuan, Xiao-Chen; Li, Ling; Wen, Zheng-Yong; Cai, Wen-Jing; Tao, Ya-Xiong

2015-11-01

In the wild, mandarin fish (Siniperca chuatsi) only feed on live prey fish, refusing dead prey. When reared in ponds, training will result in some mandarin fish accepting artificial diets. However, little is currently known about the molecular mechanism of the individual difference. Serine/threonine protein phosphatase 1 (PP1) is a suppressor of learning and long-term memory (LTM) in mammals. In the present study, the relationship between PP1 and the individual difference in acceptance of artificial diets in mandarin fish was investigated. The complete CDS (coding sequence) of four PP1 isoforms (PP1caa, PP1cab, PP1cb and PP1cc) were cloned in mandarin fish. The amino acid sequences of these PP1 isoforms are highly conserved in different species. The mRNA expressions of PP1caa and PP1cb in brain of artificial diet feeders were significantly higher than those in nonfeeders, suggesting the deficiency in the maintenance of long-term memory of its natural food habit (live prey fish). The SNP loci in PP1caa and PP1cb were also found to be associated with the individual difference in acceptance of artificial diets in mandarin fish. These SNPs of PP1caa and PP1cb genes could be useful markers for gene-associated breeding of mandarin fish, which could accept artificial diets. In conclusion, different mRNA expression and SNPs of PP1caa and PP1cb genes in feeders and nonfeeders of artificial diets might contribute to understanding the molecular mechanism of individual difference in acceptance of artificial diets in mandarin fish. Copyright © 2015 Elsevier Inc. All rights reserved.

Protein Phosphatase 1-α Regulates AS160 Ser588 and Thr642 Dephosphorylation in Skeletal Muscle.

PubMed

Sharma, Pragya; Arias, Edward B; Cartee, Gregory D

2016-09-01

Akt substrate of 160 kDa (AS160) phosphorylation on Thr(642) and Ser(588) by Akt is essential for insulin's full effect on glucose transport. However, protein phosphorylation is determined by the balance of actions by kinases and phosphatases, and the specific phosphatase(s) controlling AS160 dephosphorylation is (are) unknown. Accordingly, we assessed roles of highly expressed skeletal muscle serine/threonine phosphatases (PP1, PP2A, PP2B, and PP2C) on AS160 dephosphorylation. Preliminary screening of candidate phosphatases used an AS160 dephosphorylation assay. Lysates from insulin-stimulated skeletal muscle were treated with pharmacological phosphatase inhibitors and assessed for AS160 Ser(588) and Thr(642) dephosphorylation. AS160 dephosphorylation on both phosphorylation sites was unaltered by PP2B or PP2C inhibitors. Okadaic acid (low dose inhibits PP2A; high dose inhibits PP1) delayed AS160 Ser(588) (both doses) and Thr(642) (high dose only) dephosphorylation concomitant with greater Akt phosphorylation (both doses). AS160 was coimmunoprecipitated with PP1-α but not with PP1-β, PP1-γ1, or PP2A. Recombinant inhibitor-2 protein (a selective PP1 inhibitor) delayed AS160 dephosphorylation on both phosphorylation sites without altering Akt phosphorylation. Furthermore, knockdown of PP1-α but not PP1-β or PP1-γ1 by small interfering RNA caused greater AS160 Ser(588) and Thr(642) phosphorylation concomitant with unaltered Akt phosphorylation. Together, these results identified PP1-α as a regulator of AS160 Thr(642) and Ser(588) dephosphorylation in skeletal muscle. © 2016 by the American Diabetes Association.

Modified pectic polysaccharide from turmeric (Curcuma longa): A potent dietary component against gastric ulcer.

PubMed

Harsha, Mysore R; Chandra Prakash, Serkad V; Dharmesh, Shylaja M

2016-03-15

Native, intact (TrPP) and modified, low-molecular-weight (MTrPP) forms of pectic polysaccharides isolated from turmeric were evaluated for ulcer-preventive potentials in in vitro and in vivo models. Data indicated that MTrPP possessed significantly better ulcer-preventive property than TrPP; inhibiting ulcer scores up to 85%. Results were substantiated by effective muco-protection, H(+),K(+)-ATPase down-regulation, inhibition of H. pylori growth/adherence, higher antioxidant/cytoprotective mechanisms. Structural data indicated TrPP and MTrPP differ in their molecular weights and structural characteristics with different sugar compositions and side chain ratios. MTrPP was rich in galacturonic acid (687mg/g; TrPP-544mg/g) and galactose (52.9%; TrPP-21.7%). Results were substantiated by NMR/FTIR data indicating the presence of homogalacturonan and rhamnogalacturonam-I containing galactans. By virtue of binding to inflammatory marker (galectin-3), galactans may reduce inflammation induced ulcerations. The low molecular weight of MTrPP (155kDa; TrPP-13kDa) may increase its bioavailability than TrPP, thus MTrPP may possess higher antiulcer potential. Copyright © 2015 Elsevier Ltd. All rights reserved.

Energy contribution of NOVA food groups and sociodemographic determinants of ultra-processed food consumption in the Mexican population.

PubMed

Marrón-Ponce, Joaquín A; Sánchez-Pimienta, Tania G; Louzada, Maria Laura da Costa; Batis, Carolina

2018-01-01

To identify the energy contributions of NOVA food groups in the Mexican diet and the associations between individual sociodemographic characteristics and the energy contribution of ultra-processed foods (UPF). We classified foods and beverages reported in a 24 h recall according to the NOVA food framework into: (i) unprocessed or minimally processed foods; (ii) processed culinary ingredients; (iii) processed foods; and (iv) UPF. We estimated the energy contribution of each food group and ran a multiple linear regression to identify the associations between sociodemographic characteristics and UPF energy contribution. Mexican National Health and Nutrition Survey 2012. Individuals ≥1 years old (n 10 087). Unprocessed or minimally processed foods had the highest dietary energy contribution (54·0 % of energy), followed by UPF (29·8 %), processed culinary ingredients (10·2 %) and processed foods (6·0 %). The energy contribution of UPF was higher in: pre-school-aged children v. other age groups (3·8 to 12·5 percentage points difference (pp)); urban areas v. rural (5·6 pp); the Central and North regions v. the South (2·7 and 8·4 pp, respectively); medium and high socio-economic status v. low (4·5 pp, in both); and with higher head of household educational level v. without education (3·4 to 7·8 pp). In 2012, about 30 % of energy in the Mexican diet came from UPF. Our results showed that younger ages, urbanization, living in the North region, high socio-economic status and high head of household educational level are sociodemographic factors related to higher consumption of UPF in Mexico.

The Arabian Sea as a high-nutrient, low-chlorophyll region during the late Southwest Monsoon

NASA Astrophysics Data System (ADS)

Naqvi, S. W. A.; Moffett, J. W.; Gauns, M. U.; Narvekar, P. V.; Pratihary, A. K.; Naik, H.; Shenoy, D. M.; Jayakumar, D. A.; Goepfert, T. J.; Patra, P. K.; Al-Azri, A.; Ahmed, S. I.

2010-07-01

Extensive observations were made during the late Southwest Monsoon of 2004 over the Indian and Omani shelves, and along a transect that extended from the southern coast of Oman to the central west coast of India, tracking the southern leg of the US JGOFS expedition (1994-1995) in the west. The data are used, in conjunction with satellite-derived data, to investigate long-term trends in chlorophyll and sea surface temperature, indicators of upwelling intensity, and to understand factors that control primary production (PP) in the Arabian Sea, focussing on the role of iron. Our results do not support an intensification of upwelling in the western Arabian Sea, reported to have been caused by the decline in the winter/spring Eurasian snow cover since 1997. We also noticed, for the first time, an unexpected development of high-nutrient, low-chlorophyll condition off the southern Omani coast. This feature, coupled with other characteristics of the system, such as a narrow shelf and relatively low iron concentrations in surface waters, suggest a close similarity between the Omani upwelling system and the Peruvian and California upwelling systems, where PP is limited by iron. Iron limitation of PP may complicate simple relationship between upwelling and PP assumed by previous workers, and contribute to the anomalous offshore occurrence of the most severe oxygen (O2) depletion in the region. Over the much wider Indian shelf, which experiences large-scale bottom water O2-depletion in summer, adequate iron supply from reducing bottom-waters and sediments seems to support moderately high PP; however, such production is restricted to the thin, oxygenated surface layer, probably because of the unsuitability of the O2-depleted environment for the growth of oxygenic photosynthesizers.

Psychological interventions to reduce suicidality in high-risk patients with major depression: a randomized controlled trial.

PubMed

Celano, C M; Beale, E E; Mastromauro, C A; Stewart, J G; Millstein, R A; Auerbach, R P; Bedoya, C A; Huffman, J C

2017-04-01

Positive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior. A total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment. Compared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = -3.15, 95% confidence interval -6.18 to -0.12, effect size = -0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks. Contrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk.

Psychological interventions to reduce suicidality in high-risk patients with major depression: a randomized controlled trial

PubMed Central

Celano, C. M.; Beale, E. E.; Mastromauro, C. A.; Stewart, J. G.; Millstein, R. A.; Auerbach, R. P.; Bedoya, C. A.; Huffman, J. C.

2016-01-01

Background Positive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior. Method A total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment. Results Compared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = −3.15, 95% confidence interval −6.18 to −0.12, effect size = −0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks. Conclusions Contrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk. PMID:27876105

Non-motor parkinsonian pathology in aging A53T α-synuclein mice is associated with progressive synucleinopathy and altered enzymatic function.

PubMed

Farrell, Kaitlin F; Krishnamachari, Sesha; Villanueva, Ernesto; Lou, Haiyan; Alerte, Tshianda N M; Peet, Eloise; Drolet, Robert E; Perez, Ruth G

2014-02-01

Aging, the main risk factor for Parkinson's disease (PD), is associated with increased α-synuclein levels in substantia nigra pars compacta (SNc). Excess α-synuclein spurs Lewy-like pathology and dysregulates the activity of protein phosphatase 2A (PP2A). PP2A dephosphorylates many neuroproteins, including the catecholamine rate-limiting enzyme, tyrosine hydroxylase (TH). A loss of nigral dopaminergic neurons induces PD movement problems, but before those abnormalities occur, behaviors such as olfactory loss, anxiety, and constipation often manifest. Identifying mouse models with early PD behavioral changes could provide a model in which to test emerging therapeutic compounds. To this end, we evaluated mice expressing A53T mutant human (A53T) α-synuclein for behavior and α-synuclein pathology in olfactory bulb, adrenal gland, and gut. Aging A53T mice exhibited olfactory loss and anxiety that paralleled olfactory and adrenal α-synuclein aggregation. PP2A activity was also diminished in olfactory and adrenal tissues harboring insoluble α-synuclein. Low adrenal PP2A activity co-occurred with TH hyperactivity, making this the first study to link adrenal synucleinopathy to anxiety and catecholamine dysregulation. Aggregated A53T α-synuclein recombinant protein also had impaired stimulatory effects on soluble recombinant PP2A. Collectively, the data identify an excellent model in which to screen compounds for their ability to block the spread of α-synuclein pathology associated with pre-motor stages of PD. © 2013 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

Prevalence of lung cancer in Isfahan Province, Iran.

PubMed

Tolou Ghamari, Zahra

2018-06-01

To describe for the first time period prevalence (PP) and incidence rate (Ir) for patients with lung cancer in Isfahan Province/Iran. Data associated to the Surveillance, Epidemiology, and End Results; (SEER) was collected from the Isfahan Cancer Registry from March 2011 to March 2015. Lung cancer was distinguished by the related established topography code. PP and Ir were calculated and expressed per 100,000 persons. In all, 548 females and 1399 males were identified. For the total population the PP was calculated as 39.1 (distinguished as: 30.7 for bronchus and lung, 7.9 for larynx and 0.5 for trachea). This value corresponded to a PP of 55.3 for males and 22.3 for females (p < 0.001). Irs versus mortality rates were calculated for each year, i.e. 2011-2012, 2012-2013, 2013-2014, and 2014-2015, as 9.3 vs 6.3, 10.1 vs 6.6, 9.9 vs 6.3, 9.6 vs 6.4, respectively. The mean (SD, range) age of the patients was 65.8 (14.7, 1-103) years. In relation to the age of study population, lung cancer occurred in 94% of patients aged between 40 and 90 years. The PP for lung cancer in male population was 2.5 times higher than females. There was a 3.2% increase in the Irs over the study period. To facilitate early diagnosis for better management associated to pharmacotherapy or surgical care, our findings emphasized the advantage of further research and greater effort toward environmental, job related exposure, genetic and geographical factors in Isfahan Province/Iran. Copyright © 2018 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Preliminary study of prevalence for bladder cancer in Isfahan Province, Iran.

PubMed

Mazdak, Hamid; Tolou-Ghamari, Zahra

2018-06-01

To clarify period prevalence (PP), incidence rate (Ir), and reported mortality for patients with bladder cancer (BC) in Isfahan Province/Iran, as BC is the most common cancer of the urinary tract in Iran and other parts of the world. Data from 21 March 2011 to 3 March 2015 was obtained from the Isfahan Cancer Registry. BC was distinguished by the related established topography code (C67). Ir and PP were calculated and expressed per 100 000 persons. In all, 279 females and 1376 males were identified. For the total population the PP was calculated as 33.2. This value corresponded to a PP of 54.4 for males and 11.4 for females ( P  < 0.001). Histologically, 63% of patients had invasive BC. Irs versus mortality rates were calculated for each year, i.e. 2011-2012, 2012-2013, 2013-2014, and 2014-2015, as 7.7 vs 0.56, 8.1 vs 0.74, 7.4 vs 0.98, and 9.9 vs 0.84, respectively. The mean (SD, range) age of the patients was 65.2 (13.9, 3-100) years. In relation to the age of the study population, BC occurred in 12% of patients aged <50 years and in 15% of those aged ≥80 years. The PP for BC in the male population was 4.8-times higher than females. There was a 28.6% increase in the Ir over the study period. Further study concerning environmental exposure, genetic factors, job-related exposure to various chemical carcinogens, and geographical distribution in Isfahan and its' rural provinces would seem to be valuable.

Human cytomegalovirus tegument protein pp150 acts as a cyclin A2-CDK-dependent sensor of the host cell cycle and differentiation state.

PubMed

Bogdanow, Boris; Weisbach, Henry; von Einem, Jens; Straschewski, Sarah; Voigt, Sebastian; Winkler, Michael; Hagemeier, Christian; Wiebusch, Lüder

2013-10-22

Upon cell entry, herpesviruses deliver a multitude of premade virion proteins to their hosts. The interplay between these incoming proteins and cell-specific regulatory factors dictates the outcome of infections at the cellular level. Here, we report a unique type of virion-host cell interaction that is essential for the cell cycle and differentiation state-dependent onset of human cytomegalovirus (HCMV) lytic gene expression. The major tegument 150-kDa phosphoprotein (pp150) of HCMV binds to cyclin A2 via a functional RXL/Cy motif resulting in its cyclin A2-dependent phosphorylation. Alanine substitution of the RXL/Cy motif prevents this interaction and allows the virus to fully escape the cyclin-dependent kinase (CDK)-mediated block of immediate early (IE) gene expression in S/G2 phase that normally restricts the onset of the HCMV replication cycle to G0/G1. Furthermore, the cyclin A2-CDK-pp150 axis is also involved in the establishment of HCMV quiescence in NTera2 cells, showing the importance of this molecular switch for differentiation state-dependent regulation of IE gene expression. Consistent with the known nucleocapsid-binding function of pp150, its RXL/Cy-dependent phosphorylation affects gene expression of the parental virion only, suggesting a cis-acting, virus particle-associated mechanism of control. The pp150 homologs of other primate and mammalian CMVs lack an RXL/Cy motif and accordingly even the nearest relative of HCMV, chimpanzee CMV, starts its lytic cycle in a cell cycle-independent manner. Thus, HCMV has evolved a molecular sensor for cyclin A2-CDK activity to restrict its IE gene expression program as a unique level of self-limitation and adaptation to its human host.

Suppression of pro-inflammatory T-cell responses by human mesothelial cells.

PubMed

Lin, Chan-Yu; Kift-Morgan, Ann; Moser, Bernhard; Topley, Nicholas; Eberl, Matthias

2013-07-01

Human γδ T cells reactive to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) contribute to acute inflammatory responses. We have previously shown that peritoneal dialysis (PD)-associated infections with HMB-PP producing bacteria are characterized by locally elevated γδ T-cell frequencies and poorer clinical outcome compared with HMB-PP negative infections, implying that γδ T cells may be of diagnostic, prognostic and therapeutic value in acute disease. The regulation by local tissue cells of these potentially detrimental γδ T-cell responses remains to be investigated. Freshly isolated γδ or αβ T cells were cultured with primary mesothelial cells derived from omental tissue, or with mesothelial cell-conditioned medium. Stimulation of cytokine production and proliferation by peripheral T cells in response to HMB-PP or CD3/CD28 beads was assessed by flow cytometry. Resting mesothelial cells were potent suppressors of pro-inflammatory γδ T cells as well as CD4+ and CD8+ αβ T cells. The suppression of γδ T-cell responses was mediated through soluble factors released by primary mesothelial cells and could be counteracted by SB-431542, a selective inhibitor of TGF-β and activin signalling. Recombinant TGF-β1 but not activin-A mimicked the mesothelial cell-mediated suppression of γδ T-cell responses to HMB-PP. The present findings indicate an important regulatory function of mesothelial cells in the peritoneal cavity by dampening pro-inflammatory T-cell responses, which may help preserve the tissue integrity of the peritoneal membrane in the steady state and possibly during the resolution of acute inflammation.

Association of pulse wave velocity and pulse pressure with decline in kidney function.

PubMed

Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2014-05-01

The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

Cholera Toxin Production during Anaerobic Trimethylamine N-Oxide Respiration Is Mediated by Stringent Response in Vibrio cholerae*

PubMed Central

Oh, Young Taek; Park, Yongjin; Yoon, Mi Young; Bari, Wasimul; Go, Junhyeok; Min, Kyung Bae; Raskin, David M.; Lee, Kang-Mu; Yoon, Sang Sun

2014-01-01

As a facultative anaerobe, Vibrio cholerae can grow by anaerobic respiration. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly promoted during anaerobic growth using trimethylamine N-oxide (TMAO) as an alternative electron acceptor. Here, we investigated the molecular mechanisms of TMAO-stimulated CT production and uncovered the crucial involvement of stringent response in this process. V. cholerae 7th pandemic strain N16961 produced a significantly elevated level of ppGpp, the bacterial stringent response alarmone, during anaerobic TMAO respiration. Bacterial viability was impaired, and DNA replication was also affected under the same growth condition, further suggesting that stringent response is induced. A ΔrelA ΔspoT ppGpp overproducer strain produced an enhanced level of CT, whereas anaerobic growth via TMAO respiration was severely inhibited. In contrast, a ppGpp-null strain (ΔrelA ΔspoT ΔrelV) grew substantially better, but produced no CT, suggesting that CT production and bacterial growth are inversely regulated in response to ppGpp accumulation. Bacterial capability to produce CT was completely lost when the dksA gene, which encodes a protein that works cooperatively with ppGpp, was deleted. In the ΔdksA mutant, stringent response growth inhibition was alleviated, further supporting the inverse regulation of CT production and anaerobic growth. In vivo virulence of ΔrelA ΔspoT ΔrelV or ΔdksA mutants was significantly attenuated. The ΔrelA ΔspoT mutant maintained virulence when infected with exogenous TMAO despite its defective growth. Together, our results reveal that stringent response is activated under TMAO-stimulated anaerobic growth, and it regulates CT production in a growth-dependent manner in V. cholerae. PMID:24648517

USSR and Eastern Europe Scientific Abstracts, Biomedical and Behavioral Sciences, Number 94.

DTIC Science & Technology

1978-09-14

support the hypothesis that the earlier appearance of fungi toxic products resulting from phenol oxidation may be a factor in the resistance of Vyatka rye...Mironovka Research Institute of Wheat Breeding and Grain Production [Abstract] In order to determine factors which influence sprouting and germination of...2, 1978 pp 105-122 BEDO, Sandor, Chinoin Pharmaceuticals and Chemical Products Factory, Budapest [Abstract] The following subjects are discussed

Pictorial Display Design to Enhance Spatial Awareness of Operators in Unmanned Aviation

DTIC Science & Technology

2007-03-01

Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY...and the ability to forecast the factors affecting the aircraft at any moment in time” ( Moroze & Snow, 1999). Endsley (1988) provided a first...disorientation in aviation (pp. 379-449). Reston, VA : American Institute of aeronautics and astronautics, Inc. Gawron, V. (2004). Psychological factors

Molecular mechanism of serine/threonine protein phosphatase 1 (PP1cα-PP1r7) in spermatogenesis of Toxocara canis.

PubMed

Ma, Guang Xu; Zhou, Rong Qiong; Song, Zhen Hui; Zhu, Hong Hong; Zhou, Zuo Yong; Zeng, Yuan Qin

2015-09-01

Toxocariasis is one of the most important, but neglected, zoonoses, which is mainly caused by Toxocara canis. To better understand the role of serine/threonine protein phosphatase 1 (PP1) in reproductive processes of male adult T. canis, differential expression analysis was used to reveal the profiles of PP1 catalytic subunit α (PP1cα) gene Tc-stp-1 and PP1 regulatory subunit 7 (PP1r7) gene TcM-1309. Indirect fluorescence immunocytochemistry was carried out to determine the subcellular distribution of PP1cα. Double-stranded RNA interference (RNAi) assays were employed to illustrate the function and mechanism of PP1cα in male adult reproduction. Real-time quantitative PCR (qPCR) showed transcriptional consistency of Tc-stp-1 and TcM-1309 in sperm-producing germline tissues and localization research showed cytoplasmic distribution of PP1cα in sf9 cells, which indicated relevant involvements of PP1cα and PP1r7 in spermatogenesis. Moreover, spatiotemporal transcriptional differences of Tc-stp-1 were determined by gene knockdown analysis, which revealed abnormal morphologies and blocked meiotic divisions of spermatocytes by phenotypic aberration scanning, thereby highlighting the crucial involvement of PP1cα in spermatogenesis. These results revealed a PP1cα-PP1r7 mechanism by which PP1 regulates kinetochore-microtubule interactions in spermatogenesis and provided important clues to identify novel drug or vaccine targets for toxocariasis control. Copyright © 2015 Elsevier B.V. All rights reserved.

Postoperative Diabetes Insipidus and Hyponatremia in Children after Transsphenoidal Surgery for Adrenocorticotropin Hormone and Growth Hormone Secreting Adenomas.

PubMed

Saldarriaga, Carolina; Lyssikatos, Charlampos; Belyavskaya, Elena; Keil, Margaret; Chittiboina, Prashant; Sinaii, Ninet; Stratakis, Constantine A; Lodish, Maya

2018-04-01

To define the incidence and risk factors of postoperative sodium alterations in pediatric patients undergoing transsphenoidal surgery (TSS) for adrenocorticotropic hormone and growth hormone secreting pituitary adenomas. We retrospectively reviewed 160 patients ≤18 years of age who had TSS for pituitary adenomas at our institution from 1999 to 2017. Variables included daily serum sodium through postoperative day 10, urine specific gravity, and medications administered. We examined associations between sex, repeat surgery, manipulation of the posterior pituitary (PP), tumor invasion into the PP, tumor type and size, cerebrospinal fluid (CSF) leak, lumbar drain insertion, body mass index, puberty, and development of diabetes insipidus (DI) or syndrome of inappropriate antidiuretic hormone secretion (SIADH). Mean age was 12.9 ± 3.4 years (female = 81). Patients had adrenocorticotropic hormone (150/160) and growth hormone (10/160) producing adenomas. Forty-two (26%) patients developed DI. Among the 37 of 160 who required desmopressin acutely, 13 of 37 required it long term. Risk of long-term need for desmopressin was significantly higher in patients who had CSF leak 9 of 48 (P = .003), lumbar drain 6 of 30 (P = .019), manipulation 11 of 50 (P < .001), or invasion 4 of 15 (P = .022) of the PP. Sixty patients developed hyponatremia, 19 because of SIADH, 39 to hypotonic fluids and 2 to cerebral salt wasting syndrome. Patients with SIADH were placed on fluid restriction; 1 received salt tablets. Among 160 children who underwent TSS for pituitary adenomas, the incidence of DI and SIADH after TSS was 26% and 14%, respectively. Combined risk factors for DI and/or SIADH include female sex, manipulation of and/or tumor invasion into the PP, and CSF leak or lumbar drain. ClinicalTrials.gov: NCT00001595 and NCT00060541. Published by Elsevier Inc.

Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion.

PubMed

Nuche-Berenguer, Bernardo; Ramos-Álvarez, Irene; Jensen, R T

2016-06-01

In pancreatic acinar cells, the Src family of kinases (SFK) is involved in the activation of several signaling cascades that are implicated in mediating cellular processes (growth, cytoskeletal changes, apoptosis). However, the role of SFKs in various physiological responses such as enzyme secretion or in pathophysiological processes such as acute pancreatitis is either controversial, unknown, or incompletely understood. To address this, in this study, we investigated the role/mechanisms of SFKs in acute pancreatitis and enzyme release. Enzyme secretion was studied in rat dispersed pancreatic acini, in vitro acute-pancreatitis-like changes induced by supramaximal COOH-terminal octapeptide of cholecystokinin (CCK). SFK involvement assessed using the chemical SFK inhibitor (PP2) with its inactive control, 4-amino-7-phenylpyrazol[3,4-d]pyrimidine (PP3), under experimental conditions, markedly inhibiting SFK activation. In CCK-stimulated pancreatic acinar cells, activation occurred of trypsinogen, various MAP kinases (p42/44, JNK), transcription factors (signal transducer and activator of transcription-3, nuclear factor-κB, activator protein-1), caspases (3, 8, and 9) inducing apoptosis, LDH release reflective of necrosis, and various chemokines secreted (monocyte chemotactic protein-1, macrophage inflammatory protein-1α, regulated on activation, normal T cell expressed and secreted). All were inhibited by PP2, not by PP3, except caspase activation leading to apoptosis, which was increased, and trypsin activation, which was unaffected, as was CCK-induced amylase release. These results demonstrate SFK activation is playing a dual role in acute pancreatitis, inhibiting apoptosis and promoting necrosis as well as chemokine/cytokine release inducing inflammation, leading to more severe disease, as well as not affecting secretion. Thus, our studies indicate that SFK is a key mediator of inflammation and pancreatic acinar cell death in acute pancreatitis, suggesting it could be a potential therapeutic target in acute pancreatitis. Copyright © 2016 the American Physiological Society.

The PP1 binding code: a molecular-lego strategy that governs specificity.

PubMed

Heroes, Ewald; Lesage, Bart; Görnemann, Janina; Beullens, Monique; Van Meervelt, Luc; Bollen, Mathieu

2013-01-01

Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly 200 validated interactors in vertebrates. PP1-interacting proteins (PIPs) are ubiquitously expressed but show an exceptional diversity in brain, testis and white blood cells. The binding of PIPs is mainly mediated by short motifs that dock to surface grooves of PP1. Although PIPs often contain variants of the same PP1 binding motifs, they differ in the number and combination of docking sites. This molecular-lego strategy for binding to PP1 creates holoenzymes with unique properties. The PP1 binding code can be described as specific, universal, degenerate, nonexclusive and dynamic. PIPs control associated PP1 by interference with substrate recruitment or access to the active site. In addition, some PIPs have a subcellular targeting domain that promotes dephosphorylation by increasing the local concentration of PP1. The diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo. © 2012 The Authors Journal compilation © 2012 FEBS.

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

Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.

The tegument phosphoprotein pp65 (UL83) is the most abundant virion protein in human cytomegalovirus (HCMV). Since pp65 is immunodominant in persistently infected individuals, subunit vaccines against HCMV often include pp65 as T cell stimulatory component. Although HCMV pp65 is non-essential for viral growth in vitro it is thought to have an important role in primary and persistent infection since pp65 displays multiple immunomodulatory functions. To determine whether pp65 is required for infection and to evaluate its role in natural and vaccination-induced immunity we generated a rhesus CMV lacking both homologues, pp65a (Rh111) and pp65b (Rh112). Lack of pp65 resulted inmore » a slight growth defect in vitro and an increase of defective particle formation. However, most pp65-deleted virions in the supernatant were phenotypically normal and proteomics analysis revealed that the ratios of the remaining viral proteins were largely unchanged. RhCMV Δpp65ab was able to persistently infect CMV-negative rhesus macaques (RM) and to super-infect RM previously infected with CMV. To determine whether T cells against pp65 are essential for protection against CMV, we challenged Δpp65ab-infected animals with RhCMV ΔUS2-11, a viral recombinant that lacks inhibitors of MHC-I antigen presentation and is thus unable to overcome CMV-specific T cell immunity. Despite a complete lack of pp65-specific T cells, Δpp65ab protected against ΔUS2-11 challenge suggesting that pp65-specific T cells are not essential for T cell immunity against CMV. Using the same approach we further demonstrate that pp65b-specific T cells, induced by heterologous prime/boost vaccination, are not sufficient to protect against ΔUS2-11 challenge. Our data provides a new approach to test the efficacy of subunit vaccine candidates and suggest that pp65 vaccines are insufficient to induce a T cell response that recapitulates the protective effect of natural infection.« less

Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5)·extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1.

PubMed

Mazalouskas, Matthew D; Godoy-Ruiz, Raquel; Weber, David J; Zimmer, Danna B; Honkanen, Richard E; Wadzinski, Brian E

2014-02-14

Serine/threonine protein phosphatase 5 (PP5, PPP5C) is known to interact with the chaperonin heat shock protein 90 (HSP90) and is involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, such as cell growth, differentiation, proliferation, motility, and apoptosis. Here, we identify PP5 in stable complexes with extracellular signal-regulated kinases (ERKs). Studies using mutant proteins reveal that the formation of PP5·ERK1 and PP5·ERK2 complexes partially depends on HSP90 binding to PP5 but does not require PP5 or ERK1/2 activity. However, PP5 and ERK activity regulates the phosphorylation state of Raf1 kinase, an upstream activator of ERK signaling. Whereas expression of constitutively active Rac1 promotes the assembly of PP5·ERK1/2 complexes, acute activation of ERK1/2 fails to influence the phosphatase-kinase interaction. Introduction of oncogenic HRas (HRas(V12)) has no effect on PP5-ERK1 binding but selectively decreases the interaction of PP5 with ERK2, in a manner that is independent of PP5 and MAPK/ERK kinase (MEK) activity, yet paradoxically requires ERK2 activity. Additional studies conducted with oncogenic variants of KRas4B reveal that KRas(L61), but not KRas(V12), also decreases the PP5-ERK2 interaction. The expression of wild type HRas or KRas proteins fails to reduce PP5-ERK2 binding, indicating that the effect is specific to HRas(V12) and KRas(L61) gain-of-function mutations. These findings reveal a novel, differential responsiveness of PP5-ERK1 and PP5-ERK2 interactions to select oncogenic Ras variants and also support a role for PP5·ERK complexes in regulating the feedback phosphorylation of PP5-associated Raf1.

Constitutive neuropeptide Y Y4 receptor expression in human colonic adenocarcinoma cell lines

PubMed Central

Cox, Helen M; Tough, Iain R; Zandvliet, Dorothea W J; Holliday, Nicholas D

2001-01-01

Three human adenocarcinoma cell lines, Colony-24 (Col-24), Col-6 and Col-1 have been studied as confluent epithelial layers able to transport ions vectorially in response to basolateral vasoactive intestinal polypeptide (VIP) and pancreatic polypeptides (PP). Different species PP stimulated responses in Col-24 with Y4-like pharmacology. Bovine (b)PP, human (h)PP and porcine (p)PP were equipotent (EC50 values 3.0 – 5.0 nM) while rat (r)PP, avian (a)PP and [Leu31, Pro34]PYY (Pro34PYY) were significantly less potent. PYY was inactive. The PP pharmacology in Col-1 was comparable with Col-24. However, Col-6 cells were different; pPP had an EC50 intermediate (22.0 nM) between that of bPP (3.0 nM) and hPP (173.2 nM), with aPP and rPP being at least a further fold less potent. Deamidation of Tyr36 in bPP (by O-methylation or hydroxylation) or removal of the residue resulted in significant loss of activity in Col-24. GR231118 (1 μM) had no PP-like effects. In Col-24 and Col-1, GR231118 significantly attenuated bPP (30 nM) or hPP (100 nM) responses, but it did not alter bPP responses in Col-6. BIBP3226 and GR231118 both inhibited Y1-mediated responses which were only present in Col-6. RT – PCR analysis confirmed the presence of hY4 receptor mRNA in Col-24 and Col-1 epithelia but a barely visible hY4 product was observed in Col-6 and we suggest that an atypical Y4 receptor is expressed in this cell line. PMID:11156595

Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth

PubMed Central

Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken’ichi; Mitsukawa, Norihiro; Ohto, Chikara

2014-01-01

In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass. PMID:25038254

Praedicere Possumus: An Italian web-based application for predictive microbiology to ensure food safety.

PubMed

Polese, Pierluigi; Torre, Manuela Del; Stecchini, Mara Lucia

2018-03-31

The use of predictive modelling tools, which mainly describe the response of microorganisms to a particular set of environmental conditions, may contribute to a better understanding of microbial behaviour in foods. In this paper, a tertiary model, in the form of a readily available and userfriendly web-based application Praedicere Possumus (PP) is presented with research examples from our laboratories. Through the PP application, users have access to different modules, which apply a set of published models considered reliable for determining the compliance of a food product with EU safety criteria and for optimising processing throughout the identification of critical control points. The application pivots around a growth/no-growth boundary model, coupled with a growth model, and includes thermal and non-thermal inactivation models. Integrated functionalities, such as the fractional contribution of each inhibitory factor to growth probability (f) and the time evolution of the growth probability (P t ), have also been included. The PP application is expected to assist food industry and food safety authorities in their common commitment towards the improvement of food safety.

CO2 Washout Testing of NASA Space Suits

NASA Technical Reports Server (NTRS)

Norcross, Jason

2012-01-01

During the presentation "CO2 Washout Testing of NASA Spacesuits," Jason Norcross discussed the results of recent carbon dioxide CO2 washout testing of NASA spacesuits including the Rear Entry I-suit (REI), Enhanced Mobility Advanced Crew Escape Suit (EM-ACES), and possibly the ACES and Z-1 EVA prototype. When a spacesuit is used during ground testing, adequate CO2 washout must be provided for the suited subject. Symptoms of acute CO2 exposure depend on the partial pressure of CO2 (ppCO2) available to enter the lungs during respiration. The primary factors during ground-based testing that influence the ppCO2 level in the oronasal area include the metabolic rate of the subject and air flow through the suit. These tests were done to characterize inspired oronasal ppCO2 for a range of workloads and flow rates for which ground testing is nominally performed. During this presentation, Norcross provided descriptions of the spacesuits, test hardware, methodology, and results, as well as implications for future ground testing and verification of flight requirements.

B′-protein phosphatase 2A is a functional binding partner of delta-retroviral integrase

PubMed Central

Maertens, Goedele N.

2016-01-01

To establish infection, a retrovirus must insert a DNA copy of its RNA genome into host chromatin. This reaction is catalysed by the virally encoded enzyme integrase (IN) and is facilitated by viral genus-specific host factors. Herein, cellular serine/threonine protein phosphatase 2A (PP2A) is identified as a functional IN binding partner exclusive to δ-retroviruses, including human T cell lymphotropic virus type 1 and 2 (HTLV-1 and HTLV-2) and bovine leukaemia virus (BLV). PP2A is a heterotrimer composed of a scaffold, catalytic and one of any of four families of regulatory subunits, and the interaction is specific to the B′ family of the regulatory subunits. B′-PP2A and HTLV-1 IN display nuclear co-localization, and the B′ subunit stimulates concerted strand transfer activity of δ-retroviral INs in vitro. The protein–protein interaction interface maps to a patch of highly conserved residues on B′, which when mutated render B′ incapable of binding to and stimulating HTLV-1 and -2 IN strand transfer activity. PMID:26657642

A genetic fuzzy analytical hierarchy process based projection pursuit method for selecting schemes of water transportation projects

NASA Astrophysics Data System (ADS)

Jin, Juliang; Li, Lei; Wang, Wensheng; Zhang, Ming

2006-10-01

The optimal selection of schemes of water transportation projects is a process of choosing a relatively optimal scheme from a number of schemes of water transportation programming and management projects, which is of importance in both theory and practice in water resource systems engineering. In order to achieve consistency and eliminate the dimensions of fuzzy qualitative and fuzzy quantitative evaluation indexes, to determine the weights of the indexes objectively, and to increase the differences among the comprehensive evaluation index values of water transportation project schemes, a projection pursuit method, named FPRM-PP for short, was developed in this work for selecting the optimal water transportation project scheme based on the fuzzy preference relation matrix. The research results show that FPRM-PP is intuitive and practical, the correction range of the fuzzy preference relation matrix A it produces is relatively small, and the result obtained is both stable and accurate; therefore FPRM-PP can be widely used in the optimal selection of different multi-factor decision-making schemes.

Additive effects of fibroblast growth factor 23 neutralization and dietary phytase on chick calcium and phosphorus metabolism.

PubMed

Ren, Z Z; Bütz, D E; Wahhab, A N; Piepenburg, A J; Cook, M E

2017-05-01

Phytase hydrolyzes phytate rendering phosphorus available for intestinal absorption, while systemic neutralization of fibroblast growth factor 23 (FGF-23), using anti-FGF-23 antibody, has been shown to increase phosphate retention. Hence, neutralization of FGF-23 should be additive with phytase in reducing dietary non-phytate phosphorus (nPP) needs in chickens fed plant-based diets rich in phytic acid. This study was designed to test the additive effects of maternally derived anti-FGF-23 antibody and dietary phytase on the performance of chicks fed a low nPP diet from one to 14 d. Single Comb White Leghorn laying hens were vaccinated with either an adjuvant control or a synthetic FGF-23 peptide (GMNPPPYS). Chicks from vaccinated hens with control or anti-FGF-23 maternal antibodies were fed either a diet containing 0.2% nPP and 0.9% calcium with or without 500 unit phytase per kg of diet (2 × 2 factorial with main effects of antibody type and phytase addition, n = 15 pens of chicks/treatment). A significant interaction between dietary phytase and maternally derived anti-FGF-23 antibody on growth and feed efficiency was observed (P ≤ 0.05), in which chicks receiving either phytase or maternally derived anti-FGF-23 antibody had improved body weight gain (21 or 15%, respectively) and feed efficiency (16 or 18%, respectively) as compared to chicks with control antibody and not fed phytase. Both phytase and maternally derived anti-FGF-23 antibody independently increased (P ≤ 0.05) plasma phosphate (11 and 11%, respectively) and percent tibiotarsus ash (13 and 11%, respectively). Significant main effects and the lack of an interaction supported an additive effect of phytase and anti-FGF-23 antibody on plasma phosphate and percent tibiotarsus ash. Feeding phytase to chicks fed 0.2% nPP increased plasma FGF-23 levels by 22% (P ≤ 0.05); however, no effects of anti-FGF-23 antibody on plasma FGF-23 levels were observed. In conclusion, dietary phytase and presence of anti-FGF-23 antibody have an additive effect on plasma phosphate and tibiotarsus ash in chicks fed low nPP diets. Data support that phytase and anti-FGF-23 antibody increase phosphate utilization by different mechanisms. © 2016 Poultry Science Association Inc.

Toxicology of oxides of nitrogen. I. Toxic concentrations

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

La Towsky, L.W.; MacQuiddy, E.L.; Tollman, J.P.

1941-01-01

One hundred twelve rabbits, cats, guinea pigs, rats, and mice were exposed to 30 to 1000 ppM NO/sub 2/. Average time to produce death was: 30 ppM - none in 3 hr, 100 ppM - 318 min, 150 ppM - 90 min, 400 ppM - 58 min, 600 ppM - 32 min, 800 ppM - 29 min, 1000 ppM - 19 min. Rats and mice were more sensitive, sometimes exhibiting delayed effects (e.g., 2 to 3 hr at 55 ppM). Cats were most sensitive in that they thrash excitedly, thus breathing more. Methemoglobin was frequently seen in blood during exposure.more » Death was from edema (most common), asphyxia, or pneumonitis (secondary).« less

Phosphorylated Nuclear Receptor CAR Forms a Homodimer To Repress Its Constitutive Activity for Ligand Activation

PubMed Central

Shizu, Ryota; Osabe, Makoto; Perera, Lalith; Moore, Rick; Sueyoshi, Tatsuya

2017-01-01

ABSTRACT The nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and the development of diseases, including diabetes and tumors. CAR inactivates its constitutive activity by phosphorylation at threonine 38. Utilizing receptor for protein kinase 1 (RACK1) as the regulatory subunit, protein phosphatase 2A (PP2A) dephosphorylates threonine 38 to activate CAR. Here we demonstrate that CAR undergoes homodimer-monomer conversion to regulate this dephosphorylation. By coexpression of two differently tagged CAR proteins in Huh-7 cells, mouse primary hepatocytes, and mouse livers, coimmunoprecipitation and two-dimensional gel electrophoresis revealed that CAR can form a homodimer in a configuration in which the PP2A/RACK1 binding site is buried within its dimer interface. Epidermal growth factor (EGF) was found to stimulate CAR homodimerization, thus constraining CAR in its inactive form. The agonistic ligand CITCO binds directly to the CAR homodimer and dissociates phosphorylated CAR into its monomers, exposing the PP2A/RACK1 binding site for dephosphorylation. Phenobarbital, which is not a CAR ligand, binds the EGF receptor, reversing the EGF signal to monomerize CAR for its indirect activation. Thus, the homodimer-monomer conversion is the underlying molecular mechanism that regulates CAR activation, by placing phosphorylated threonine 38 as the common target for both direct and indirect activation of CAR. PMID:28265001

Feedback Regulation of ABA Signaling and Biosynthesis by a bZIP Transcription Factor Targets Drought-Resistance-Related Genes1[OPEN

PubMed Central

Tang, Ning; Yang, Jun; Peng, Lei; Ma, Siqi; Xu, Yan; Li, Guoliang

2016-01-01

The OsbZIP23 transcription factor has been characterized for its essential role in drought resistance in rice (Oryza sativa), but the mechanism is unknown. In this study, we first investigated the transcriptional activation of OsbZIP23. A homolog of SnRK2 protein kinase (SAPK2) was found to interact with and phosphorylate OsbZIP23 for its transcriptional activation. SAPK2 also interacted with OsPP2C49, an ABI1 homolog, which deactivated the SAPK2 to inhibit the transcriptional activation activity of OsbZIP23. Next, we performed genome-wide identification of OsbZIP23 targets by immunoprecipitation sequencing and RNA sequencing analyses in the OsbZIP23-overexpression, osbzip23 mutant, and wild-type rice under normal and drought stress conditions. OsbZIP23 directly regulates a large number of reported genes that function in stress response, hormone signaling, and developmental processes. Among these targets, we found that OsbZIP23 could positively regulate OsPP2C49, and overexpression of OsPP2C49 in rice resulted in significantly decreased sensitivity of the abscisic acid (ABA) response and rapid dehydration. Moreover, OsNCED4 (9-cis-epoxycarotenoid dioxygenase4), a key gene in ABA biosynthesis, was also positively regulated by OsbZIP23. Together, our results suggest that OsbZIP23 acts as a central regulator in ABA signaling and biosynthesis, and drought resistance in rice. PMID:27325665

RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells.

PubMed

Hesbacher, Sonja; Pfitzer, Lisa; Wiedorfer, Katharina; Angermeyer, Sabrina; Borst, Andreas; Haferkamp, Sebastian; Scholz, Claus-Jürgen; Wobser, Marion; Schrama, David; Houben, Roland

2016-05-31

The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells.

Abscisic Acid (ABA ) Promotes the Induction and Maintenance of Pear (Pyrus pyrifolia White Pear Group) Flower Bud Endodormancy

PubMed Central

Li, Jianzhao; Xu, Ying; Niu, Qingfeng; He, Lufang; Teng, Yuanwen; Bai, Songling

2018-01-01

Dormancy is an adaptive mechanism that allows temperate deciduous plants to survive unfavorable winter conditions. In the present work, we investigated the possible function of abscisic acid (ABA) on the endodormancy process in pear. The ABA content increased during pear flower bud endodormancy establishment and decreased towards endodormancy release. In total, 39 putative genes related to ABA metabolism and signal transductions were identified from pear genome. During the para- to endodormancy transition, PpNCED-2 and PpNCED-3 had high expression levels, while PpCYP707As expression levels were low. However, during endodormancy, the expression of PpCYP707A-3 sharply increased with increasing cold accumulation. At the same time, the ABA content of pear buds declined, and the percentage of bud breaks rapidly increased. On the other hand, the expression levels of PpPYLs, PpPP2Cs, PpSnRK2s, and PpABI4/ABI5s were also changed during the pear flower bud dormancy cycle. Furthermore, exogenous ABA application to para-dormant buds significantly reduced the bud breaks and accelerated the transition to endodormancy. During the whole treatment time, the expression level of PpPP2C-12 decreased to a greater extent in ABA-treated buds than in control. However, the expression levels of PpSnRK2-1, PpSnRK2-4, and PpABI5-1 were higher in ABA-treated buds. Our results indicated that PpCYP707A-3 and PpNCEDs play pivotal roles on the regulation of endodormancy release, while ABA signal transduction pathway also appears to be involved in the process. The present work provided the basic information about the function of ABA-related genes during pear flower bud dormancy process. PMID:29361708

Enhanced Induction of T Cell Immunity Using Dendritic Cells Pulsed with HIV Tat and HCMV-pp65 Fusion Protein In Vitro

PubMed Central

Park, Jung-Sun; Park, Soo-Young; Cho, Hyun-Il; Sohn, Hyun-Jung

2011-01-01

Background Cytotoxic T lymphocytes (CTLs) appear to play an important role in the control and prevention of human cytomegalovirus (HCMV) infection. The pp65 antigen is a structural protein, which has been defined as a potential target for effective immunity against HCMV infection. Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (Tat) into protein facilitates rapid, efficient entry into cells. Methods To establish a strategy for the generation of HCMV-specific CTLs in vitro, recombinant truncated N- and C-terminal pp65 protein (pp65 N&C) and N- and C-terminal pp65 protein fused with Tat (Tat/pp65 N&C) was produced in E.coli system. Peripheral blood mononuclear cells were stimulated with dendritic cells (DCs) pulsed with pp65 N&C or Tat/pp65 N&C protein and immune responses induced was examined using IFN-γ ELISPOT assay, cytotoxicity assay and tetramer staining. Results DCs pulsed with Tat/pp65N&C protein could induce higher T-cell responses in vitro compared with pp65N&C. Moreover, the DCs pulsed with Tat/pp65 N&C could stimulate both of CD8+ and CD4+ T-cell responses. The T cells induced by DCs pulsed with Tat/pp65 N&C showed higher cytotoxicity than that of pp65-pulsed DCs against autologous lymphoblastoid B-cell line (LCL) expressing the HCMV-pp65 antigen. Conclusion Our results suggest that DCs pulsed with Tat/pp65 N&C protein effectively induced pp65-specific CTL in vitro. Tat fusion recombinant protein may be useful for the development of adoptive T-cell immunotherapy and DC-based vaccines. PMID:21860612

Improved murine glioma detection following modified diet and photobleaching of skin PpIX fluorescence

NASA Astrophysics Data System (ADS)

Gibbs, Summer L.; O'Hara, Julia A.; Hoopes, P. Jack; Pogue, Brian W.

2007-02-01

The Aminolevulinic Acid (ALA) - Protoporphyrin IX (PpIX) system is unique in the world of photosensitizers in that the prodrug ALA is enzymatically transformed via the tissue of interest into fluorescently detectable levels of PpIX. This system can be used to monitor cellular metabolism of tumor tissue for applications such as therapy monitoring. Detecting PpIX fluorescence noninvasively has proven difficult due to the high levels of PpIX produced in the skin compared to other tissue both with and without ALA administration. In the current study, methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration have been examined. Use of a purified diet is found to decrease both skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration, while addition of a broad spectrum antibiotic to the water shows little effect. Following ALA administration, improved brain tumor detection is seen when skin PpIX fluorescence is photobleached via blue light prior to transmission spectroscopic measurements of tumor bearing and control animals. Both of these methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration are shown to have a large effect on the ability to detect tumor tissue PpIX fluorescence noninvasively in vivo.

Variable liver fat concentration as a proxy for body fat mobilization postpartum has minor effects on insulin-induced changes in hepatic gene expression related to energy metabolism in dairy cows.

PubMed

Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Bruckmaier, R M; Röntgen, M; Kuhla, B; Hammon, H M

2017-02-01

The liver plays a central role in adaptation for energy requirements around calving, and changes in the effects of insulin on hepatic energy metabolism contribute to metabolic adaptation in dairy cows. Hepatic insulin effects may depend on body fat mobilization. The objective of this study was to investigate the effects of insulin on the hepatic gene expression of enzymes involved in energy metabolism and factors related to nutrition partitioning in cows with high and low total liver fat concentration (LFC) after calving. Holstein cows were retrospectively grouped according to their LFC after calving as a proxy for body fat mobilization. Cows were classified as low (LLFC; LFC <24% fat/dry matter; n = 9) and high (HLFC; LFC >24.4% fat/dry matter; n = 10) fat-mobilizing after calving. Euglycemic-hyperinsulinemic clamps [6 mU/(kg × min) of insulin for 6 h] were performed in wk 5 antepartum (ap) and wk 3 postpartum (pp). Before and at the end of the euglycemic-hyperinsulinemic clamps, liver biopsies were taken to measure the mRNA abundance of enzymes involved in carbohydrate and lipid metabolism, expression related to the somatotropic axis, and adrenergic and glucocorticoid receptors. The mRNA abundance of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK; PCK1), acyl-CoA-dehydrogenase very long chain (ACADVL), and hydroxyl-methyl-glutaryl-CoA-synthase 1 increased, but the mRNA abundance of solute carrier family 2 (SLC2A2 and SLC2A4), growth hormone receptor 1A (GHR1A), insulin-like growth factor 1 (IGF1), sterol regulatory element binding factor 1, adrenoceptor α 1A, and glucocorticoid receptor decreased from ap to pp. Insulin treatment was associated with decreased PCK1, mitochondrial PEPCK, glucose-6-phosphatase, propionyl-CoA-carboxylase α, carnitine-palmitoyl-transferase 1A, ACADVL, and insulin receptor mRNA, but increased IGF1 and SLC2A4 mRNA ap and pp and GHR1A mRNA pp. The mRNA abundance of SLC2A4 was greater, and the mRNA abundance of GHR1A and IGF1 tended to be lower in LLFC than in HLFC. Administration of insulin, albeit at a supraphysiological dose, was associated with inhibition of gene expression related to glucose production and β-oxidation, but we observed variable effects in the degree of insulin depression of individual genes. Insulin status is important for regulation of nutrient partitioning, but different LFC pp had very little influence on changes in hepatic gene expression following administration of insulin. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The ‘spiteful’ origins of human cooperation

PubMed Central

Marlowe, Frank W.; Berbesque, J. Colette; Barrett, Clark; Bolyanatz, Alexander; Gurven, Michael; Tracer, David

2011-01-01

We analyse generosity, second-party (‘spiteful’) punishment (2PP), and third-party (‘altruistic’) punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that ‘spiteful’ 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation. PMID:21159680

The 'spiteful' origins of human cooperation.

PubMed

Marlowe, Frank W; Berbesque, J Colette; Barrett, Clark; Bolyanatz, Alexander; Gurven, Michael; Tracer, David

2011-07-22

We analyse generosity, second-party ('spiteful') punishment (2PP), and third-party ('altruistic') punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that 'spiteful' 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation.

Technology to Augment Early Home Visitation for Child Maltreatment Prevention: A Pragmatic Randomized Trial.

PubMed

Ondersma, Steven J; Martin, Joanne; Fortson, Beverly; Whitaker, Daniel J; Self-Brown, Shannon; Beatty, Jessica; Loree, Amy; Bard, David; Chaffin, Mark

2017-11-01

Early home visitation (EHV) for child maltreatment prevention is widely adopted but has received inconsistent empirical support. Supplementation with interactive software may facilitate attention to major risk factors and use of evidence-based approaches. We developed eight 20-min computer-delivered modules for use by mothers during the course of EHV. These modules were tested in a randomized trial in which 413 mothers were assigned to software-supplemented e-Parenting Program ( ePP), services as usual (SAU), or community referral conditions, with evaluation at 6 and 12 months. Outcomes included satisfaction, working alliance, EHV retention, child maltreatment, and child maltreatment risk factors. The software was well-received overall. At the 6-month follow-up, working alliance ratings were higher in the ePP condition relative to the SAU condition (Cohen's d = .36, p < .01), with no differences at 12 months. There were no between-group differences in maltreatment or major risk factors at either time point. Despite good acceptability and feasibility, these findings provide limited support for use of this software within EHV. These findings contribute to the mixed results seen across different models of EHV for child maltreatment prevention.

Evaluation of Wearable Simulation Interface for Military Training

DTIC Science & Technology

2012-01-01

Lampton, 2005). This assumption was based on support from the identi- cal elements theory (Holding, 1965; Thorndike & Woodworth, 1901), which states that...Annual Meeting of the Human Fac- tors and Ergonomics Society (pp. 2014–2018). Santa Monica, CA: Human Factors and Ergonomics Society. Thorndike , E. L

Advanced Human Factors Engineering Tool Technologies.

DTIC Science & Technology

1988-03-01

charger/ AC adapter immersible probe air temperature probe surface temperature probe . * Sling psychrometer , MSA or Taylor 1328A * Aspirating... psychrometer , Model PP-100 or CP-147, Psychro-Dyne * Wet-bulb-heat-stress monitor, Model B&K 1219, Briel & Kjaer Transducer, Model B&K MM 0030 (3 each), Brijel

Study of the Hellenic Military Education Buying Process Using Trend Analysis to Identify Determinant Factors

DTIC Science & Technology

2007-06-01

objectives, and because of their 26 Kotler Philip and Keller Kevin Lane, Marketing Management 12e...pp. 143-156. Kotler , Philip and Keller, Kevin Lane. Marketing Management 12e, Prentice Hall, 2005. NPS Academic Catalog 2007. NPS Registrar Office

Aralkyl selenoglycosides and related selenosugars in acetylated form activate protein phosphatase-1 and -2A.

PubMed

Kónya, Zoltán; Bécsi, Bálint; Kiss, Andrea; Tamás, István; Lontay, Beáta; Szilágyi, László; Kövér, Katalin E; Erdődi, Ferenc

2018-05-01

Aralkyl and aryl selenoglycosides as well as glycosyl selenocarboxylate derivatives were assayed on the activity of protein phosphatase-1 (PP1) and -2A (PP2A) catalytic subunits (PP1c and PP2Ac) in search of compounds for PP1c and PP2Ac effectors. The majority of tested selenoglycosides activated both PP1c and PP2Ac by ∼2-4-fold in a phosphatase assay with phosphorylated myosin light chain substrate when the hydroxyl groups of the glycosyl moiety were acetylated, but they were without any effects in the non-acetylated forms. A peptide from the myosin phosphatase target subunit-1 (MYPT1 23-38 ) that included an RVxF PP1c-binding motif attenuated activation of PP1c by 2-Trifluoromethylbenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-d-glucopyranoside (TFM-BASG) and 4-Bromobenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-d-glucopyranoside (Br-BASG). MYPT1 23-38 stimulated PP2Ac and contributed to PP2Ac activation exerted by either Br-BASG or TFM-BASG. Br-BASG and TFM-BASG suppressed partially binding of PP1c to MYPT1 in surface plasmon resonance based binding experiments. Molecular docking predicted that the hydrophobic binding surfaces in PP1c for interaction with either the RVxF residues of PP1c-interactors or selenoglycosides are partially overlapped. Br-BASG and TFM-BASG caused a moderate increase in the phosphatase activity of HeLa cells in 1 h, and suppressed cell viability in 24 h incubations. In conclusion, our present study identified selenoglycosides as novel activators of PP1 and PP2A as well as provided insights into the structural background of their interactions establishing a molecular model for future design of more efficient phosphatase activator molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

PubMed

Chattopadhyay, Debasish; Swingle, Mark R; Salter, Edward A; Wood, Eric; D'Arcy, Brandon; Zivanov, Catherine; Abney, Kevin; Musiyenko, Alla; Rusin, Scott F; Kettenbach, Arminja; Yet, Larry; Schroeder, Chad E; Golden, Jennifer E; Dunham, Wade H; Gingras, Anne-Claude; Banerjee, Surajit; Forbes, David; Wierzbicki, Andrzej; Honkanen, Richard E

2016-06-01

Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptional regulation of genes encoding ABA metabolism enzymes during the fruit development and dehydration stress of pear 'Gold Nijisseiki'.

PubMed

Dai, Shengjie; Li, Ping; Chen, Pei; Li, Qian; Pei, Yuelin; He, Suihuan; Sun, Yufei; Wang, Ya; Kai, Wenbin; Zhao, Bo; Liao, Yalan; Leng, Ping

2014-09-01

To investigate the contribution of abscisic acid (ABA) in pear 'Gold Nijisseiki' during fruit ripening and under dehydration stress, two cDNAs (PpNCED1 and PpNCED2) which encode 9-cis-epoxycarotenoid dioxygenase (NCED) (a key enzyme in ABA biosynthesis), two cDNAs (PpCYP707A1 and PpCYP707A2) which encode 8'-hydroxylase (a key enzyme in the oxidative catabolism of ABA), one cDNA (PpACS3) which encodes 1-aminocyclopropane-1-carboxylic acid (ACC), and one cDNA (PpACO1) which encodes ACC oxidase involved in ethylene biosynthesis were cloned from 'Gold Nijisseiki' fruit. In the pulp, peel and seed, expressions of PpNCED1 and PpNCED2 rose in two stages which corresponded with the increase of ABA levels. The expression of PpCYP707A1 dramatically declined after 60-90 days after full bloom (DAFB) in contrast to the changes of ABA levels during this period, while PpCYP707A2 stayed low during the whole development of fruit. Application of exogenous ABA at 100 DAFB increased the soluble sugar content and the ethylene release but significantly decreased the titratable acid and chlorophyll contents in fruits. When fruits harvested at 100 DAFB were stored in the laboratory (25 °C, 50% relative humidity), the ABA content and the expressions of PpNCED1/2 and PpCYP707A1 in the pulp, peel and seed increased significantly, while ethylene reached its highest value after the maximum peak of ABA accompanied with the expressions of PpACS3 and PpACO1. In sum the endogenous ABA may play an important role in the fruit ripening and dehydration of pear 'Gold Nijisseiki' and the ABA level was regulated mainly by the dynamics of PpNCED1, PpNCED2 and PpCYP707A1 at the transcriptional level. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Postnatal development and lymphocyte production of jejunal and ileal Peyer's patches in normal and gnotobiotic pigs.

PubMed Central

Pabst, R; Geist, M; Rothkötter, H J; Fritz, F J

1988-01-01

The development of the number, size, structure and proliferative capacity of Peyer's patches (PP) in the jejunum and ileum has been studied during the early postnatal period of conventional and germ-free pigs. A mean of 15 discrete PP in the jejunum and upper ileum (jejPP) were counted at birth, and the number increased only gradually. A continuous PP is located in the terminal ileum (ileal PP). The length of both jejPP and ileal PP increased with age due to the increase in follicle size and in the number of follicles in the ileal PP. In older pigs, only the ileal PP regressed to small scattered follicles. In germ-free piglets at 39 and 59 days of age, longer PP were found than in normal new-born piglets, but they were significantly shorter than in age-matched controls. Lymphocyte production was studied by the metaphase-arrest technique using vincristine. Lymphocyte production in follicles increased dramatically with age, while in other compartments, such as the inter-follicular and dome area, a low age-independent production of lymphocytes was found. There were no differences in lymphocytopoiesis between jejPP and ileal PP. The present data show major differences in the development, structure and function of PP in pigs in comparison to other species. These species-specific aspects are important for future studies on the immunological function of PP. Images Figure 1 Figure 5 PMID:3410497

Search for Higgs boson production in dilepton and missing energy final states with 5.4 fb(-1) of pp collisions at square root(s) = 1.96 TeV.

PubMed

Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Ancu, L S; Aoki, M; Arnoud, Y; Arov, M; Askew, A; Asman, B; Atramentov, O; Avila, C; BackusMayes, J; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Barfuss, A-F; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Bu, X B; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Calfayan, P; Calpas, B; Calvet, S; Camacho-Pérez, E; Cammin, J; Carrasco-Lizarraga, M A; Carrera, E; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Cheu, E; Chevalier-Théry, S; Cho, D K; Cho, S W; Choi, S; Choudhary, B; Christoudias, T; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Cutts, D; Cwiok, M; Das, A; Davies, G; De, K; de Jong, S J; De la Cruz-Burelo, E; DeVaughan, K; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dorland, T; Dubey, A; Dudko, L V; Duflot, L; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fuess, S; Gadfort, T; Galea, C F; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Geng, W; Gerbaudo, D; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Golovanov, G; Gómez, B; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Haefner, P; Hagopian, S; Haley, J; Hall, I; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinson, A P; Heintz, U; Hensel, C; Heredia-De la Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hohlfeld, M; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Huske, N; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jamin, D; Jesik, R; Johns, K; Johnson, C; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Juste, A; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Khatidze, D; Kirby, M H; Kirsch, M; Kohli, J M; Kozelov, A V; Kraus, J; Kumar, A; Kupco, A; Kurca, T; Kuzmin, V A; Kvita, J; Lam, D; Lammers, S; Landsberg, G; Lebrun, P; Lee, H S; Lee, W M; Leflat, A; Lellouch, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Mackin, D; Mättig, P; Magaña-Villalba, R; Mal, P K; Malik, S; Malyshev, V L; Maravin, Y; Martínez-Ortega, J; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Mendoza, L; Menezes, D; Mercadante, P G; Merkin, M; Meyer, A; Meyer, J; Mondal, N K; Moulik, T; Muanza, G S; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nogima, H; Novaes, S F; Nunnemann, T; Obrant, G; Onoprienko, D; Orduna, J; Osman, N; Osta, J; Otec, R; Otero y Garzón, G J; Owen, M; Padilla, M; Padley, P; Pangilinan, M; Parashar, N; Parihar, V; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Penning, B; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pol, M-E; Polozov, P; Popov, A V; Prewitt, M; Price, D; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Ranjan, K; Ratoff, P N; Razumov, I; Renkel, P; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rominsky, M; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shary, V; Shchukin, A A; Shivpuri, R K; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Stolin, V; Stoyanova, D A; Strandberg, J; Strang, M A; Strauss, E; Strauss, M; Ströhmer, R; Strom, D; Stutte, L; Svoisky, P; Takahashi, M; Tanasijczuk, A; Taylor, W; Tiller, B; Titov, M; Tokmenin, V V; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; van den Berg, P J; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vilanova, D; Vint, P; Vokac, P; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Wetstein, M; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Xu, C; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, Z; Yin, H; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zeitnitz, C; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L; Zutshi, V; Zverev, E G

2010-02-12

A search for the standard model Higgs boson is presented using events with two charged leptons and large missing transverse energy selected from 5.4 fb(-1) of integrated luminosity in pp collisions at square root(s) = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron collider. No significant excess of events above background predictions is found, and observed (expected) upper limits at 95% confidence level on the rate of Higgs boson production are derived that are a factor of 1.55 (1.36) above the predicted standard model cross section at m(H) = 165 GeV.

Effects of electron beam radiation dose on the compatibilization behaviour in recycled polypropylene/microcrystalline cellulose composites

NASA Astrophysics Data System (ADS)

Samat, N.; Motsidi, S. N. R.; Lazim, N. H. M.

2018-01-01

The purpose of this research was to evaluate the influence of dose level of electron beam on the compatibilization behavior of recycled polypropylene (rPP) in rPP/microcrystalline cellulose (MCC) composites. Initially, the rPP was irradiated with various dose of electron beam (5 kGy up to 250 kGy) which then mixed with unirradiated rPP (u-rPP) at a ratio of 30:70 respectively. The composites were prepared by incorporating a series wt% of MCC fibers into rPP (u-rPP : i-rPP) using extruder and finally moulded with an injection moulding machine. The compatibility behavior of irradiated rPP (i-rPP) were analysed with mechanical tensile and thermal methods. The results of mechanical analysis showed great improvement in tensile modulus but an increase in radiation dosage gradually decreased this property. Nevertheless, the tensile strength exhibited a minor effect. The thermal stability of composites is lowered with increase in the absorbed dose, more significantly at higher content of MCC. Fracture surface observations reveal adhesion between the cellulose and rPP matrix.

Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth.

PubMed

Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken'ichi; Mitsukawa, Norihiro; Ohto, Chikara

2014-10-01

In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Drosophila Uri, a PP1α binding protein, is essential for viability, maintenance of DNA integrity and normal transcriptional activity

PubMed Central

Kirchner, Jasmin; Vissi, Emese; Gross, Sascha; Szoor, Balazs; Rudenko, Andrey; Alphey, Luke; White-Cooper, Helen

2008-01-01

Background Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1α and PP1β subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1α and PP1β. Results URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that Drosophila Uri binds PP1α with much higher affinity than PP1β, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a uri loss of function allele, and show that uri is essential for viability in Drosophila. uri mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei. Conclusion Uri is the first PP1α specific binding protein to be described in Drosophila. Uri protein plays a role in transcriptional regulation. Activity of uri is required to maintain DNA integrity and cell survival in normal development. PMID:18412953

Human Factors Influencing Decision Making

DTIC Science & Technology

1998-07-01

than General Grant. Van Fleet and Yukl 28 (1986): "A study of World War I veterans suggested that the presence of hunger , thirst, fatigue, ignorance of...Greenwood Press, New York, 1987, pp. 167-184. 27 Fishburne, F.J. " Neuropsychological applications in military settings." In Reuven Gal and A. David...suggested that the presence of hunger , thirst, fatigue, ignorance of plans and idleness increases the danger from fear. The most important factors in

Advances and Challenges in Super-Resolution

DTIC Science & Technology

2004-03-15

resolution in video. In: Proc. European Conf on Computer Vision (ECCV), May 2002, pp. 331–336. N. Sochen, R . Kimmel, R . Malladi . 1998. A general...2004a). 48 Vol. 14, 47–57 (2004) distinguish between a generic down-sampling operation (or CCD decimation by a factor r ) and the sampling...factor r often depends on the number of available low-resolution frames, the computational limitations (exponential in r ), and the accuracy of motion

Development of Fracture Mechanics Maps for Composite Materials. Volume 4.

DTIC Science & Technology

1985-12-01

CONSTITUENTS, ETC.) ON NOTCH SENSITIVITY. A LIST OF FRACTURE MODELS AUTHORS REF, ABBRV. CRITERION HOLE SLITS M.E. WADDOUPS J.R. EISENMANN 3 WEK LEFM / / B.E...fracture model) SCF Stress Concentration Factor SIF Stress Intensity Factor WEK Waddoups- Eisenmann -Kaminski (-fracture model) 9 WN Whitney-Nuismer...Technomic Pub. Co., Inc., Stamford, Conn., 1968, pp. 20-43. 3. M.E. Waddoups, J.R. Eisenmann and B.E. Kaminski, "Macroscopic Fracture Mechanics of

Novel (p)ppGpp Binding and Metabolizing Proteins of Escherichia coli.

PubMed

Zhang, Yong; Zborníková, Eva; Rejman, Dominik; Gerdes, Kenn

2018-03-06

The alarmone (p)ppGpp plays pivotal roles in basic bacterial stress responses by increasing tolerance of various nutritional limitations and chemical insults, including antibiotics. Despite intensive studies since (p)ppGpp was discovered over 4 decades ago, (p)ppGpp binding proteins have not been systematically identified in Escherichia coli We applied DRaCALA ( d ifferential ra dial c apillary a ction of l igand a ssay) to identify (p)ppGpp-protein interactions. We discovered 12 new (p)ppGpp targets in E. coli that, based on their physiological functions, could be classified into four major groups, involved in (i) purine nucleotide homeostasis (YgdH), (ii) ribosome biogenesis and translation (RsgA, Era, HflX, and LepA), (iii) maturation of dehydrogenases (HypB), and (iv) metabolism of (p)ppGpp (MutT, NudG, TrmE, NadR, PhoA, and UshA). We present a comprehensive and comparative biochemical and physiological characterization of these novel (p)ppGpp targets together with a comparative analysis of relevant, known (p)ppGpp binding proteins. Via this, primary targets of (p)ppGpp in E. coli are identified. The GTP salvage biosynthesis pathway and ribosome biogenesis and translation are confirmed as targets of (p)ppGpp that are highly conserved between E. coli and Firmicutes In addition, an alternative (p)ppGpp degradative pathway, involving NudG and MutT, was uncovered. This report thus significantly expands the known cohort of (p)ppGpp targets in E. coli IMPORTANCE Antibiotic resistance and tolerance exhibited by pathogenic bacteria have resulted in a global public health crisis. Remarkably, almost all bacterial pathogens require the alarmone (p)ppGpp to be virulent. Thus, (p)ppGpp not only induces tolerance of nutritional limitations and chemical insults, including antibiotics, but is also often required for induction of virulence genes. However, understanding of the molecular targets of (p)ppGpp and the mechanisms by which (p)ppGpp influences bacterial physiology is incomplete. In this study, a systematic approach was used to uncover novel targets of (p)ppGpp in E. coli , the best-studied model bacterium. Comprehensive comparative studies of the targets revealed conserved target pathways of (p)ppGpp in both Gram-positive and -negative bacteria and novel targets of (p)ppGpp, including an alternative degradative pathway of (p)ppGpp. Thus, our discoveries may help in understanding of how (p)ppGpp increases the stress resilience and multidrug tolerance not only of the model organism E. coli but also of the pathogenic organisms in which these targets are conserved. Copyright © 2018 Zhang et al.

Molecular Investigations of the Structure and Function of the Protein Phosphatase 1:Spinophilin:Inhibitor-2 Heterotrimeric Complex

PubMed Central

Dancheck, Barbara; Ragusa, Michael J.; Allaire, Marc; Nairn, Angus C.; Page, Rebecca; Peti, Wolfgang

2011-01-01

Regulation of the major ser/thr phosphatase Protein Phosphatase 1 (PP1) is controlled by a diverse array of targeting and inhibitor proteins. Though many PP1 regulatory proteins share at least one PP1 binding motif, usually the RVxF motif, it was recently discovered that certain pairs of targeting and inhibitor proteins bind PP1 simultaneously to form PP1 heterotrimeric complexes. To date, structural information for these heterotrimeric complexes, and, in turn, how they direct PP1 activity is entirely lacking. Using a combination of NMR spectroscopy, biochemistry and small angle X-ray scattering (SAXS), we show that major structural rearrangements in both spinophilin (targeting) and Inhibitor-2 (I-2, inhibitor) are essential for the formation of the heterotrimeric PP1:spinophilin:I-2 (PSI) complex. The RVxF motif of I-2 is released from PP1 during the formation of PSI, making the less prevalent SILK motif of I-2 essential for complex stability. The release of the I-2 RVxF motif allows for enhanced flexibility of both I-2 and spinophilin in the heterotrimeric complex. In addition, we used inductively coupled plasma atomic emission spectroscopy to show that PP1 contains two metals in both heterodimeric complexes (PP1:spinophilin and PP1:I2) and PSI, demonstrating that PSI retains the biochemical characteristics of the PP1:I2 holoenzyme. Finally, we combined the NMR and biochemical data with SAXS and molecular dynamics simulations to generate a structural model of the full heterotrimeric PSI complex. Collectively, these data reveal the molecular events that enable PP1 heterotrimeric complexes to exploit both the targeting and inhibitory features of the PP1-regulatory proteins to form multi-functional PP1 holoenzymes. PMID:21218781

Morale Maladies in American and Foreign Higher Education: The Faculty Flameout Diagnosis.

ERIC Educational Resources Information Center

Hunter, Mary; And Others

1983-01-01

Asked about morale at their institutions, faculty from across the United States and from several foreign countries reported that morale was low. Overwork, preference for teaching rather than research, and other factors were blamed for morale problems. Suggestions for improving faculty morale are given. (PP)

Assessing Potential Predisposition of Elementary School Children to Heart Disease.

ERIC Educational Resources Information Center

Crow, Thomas A.; And Others

1982-01-01

A health assessment battery was developed to screen elementary school children in Clovis (California) for factors that might lead to heart disease. Students' height, blood pressure, flexibility, weight, and body fatness (by skin-fold tests) were measured. Plans call for future development of longitudinal student profiles. (Authors/PP)

Development and Initial Validation of Public Domain Basic Interest Markers

ERIC Educational Resources Information Center

Liao, Hsin-Ya; Armstrong, Patrick Ian; Rounds, James

2008-01-01

Goldberg (Goldberg, L. R. (1999). "A broad-bandwidth, public-domain, personality inventory measuring the lower-level facets of several five-factor models." In: I. Mervielde, I. Deary, F. De Fruyt, & F. Ostendorf (Eds.), "Personality psychology in Europe" (Vol. 7, pp. 7-28). Tilburg, The Netherlands: Tilburg University…

Validation of Core Temperature Estimation Algorithm

DTIC Science & Technology

2016-01-20

thermoregulation that can affect heart rate. These factors include diet , caffeine, sleep, and psychological stress. Of the 47,549 data points that...O’Connor and R. Huggins, "Exertional Heat Stroke: New Concepts Regarding Cause and Care," Current Sports Medicine Reports, pp. 115–123, 2012. 3. B. Ely

Predeployment Motivation and Ambivalence Among Canadian Forces Augmentees: The Influence of Demographic Factors

DTIC Science & Technology

2003-12-01

consequences (pp. 361-386). Hillsdale, NJ: Erlbaum. 31. Conner, M., Sherlock , K., & Orbell, S. (1998). Psychosocial detreminant5s of ecstasy use in young...donate. Health Psychology, 5, 565-580. 35. Thompson, M. M. & Holmes , J. G., (1996). Ambivalence in Close Relationships: Conflicted cognitions as a

Remarks on Causative Verbs and Object Deletion in English

ERIC Educational Resources Information Center

Onozuka, Hiromi

2007-01-01

Rappaport Hovav and Levin [Rappaport Hovav, M., Levin, B., 1998. "Building verb meanings." In: Butt, M., Geuder, W. (Eds.), "The Projection of Arguments: Lexical and Compositional Factors." CSLI Publications, Stanford, pp. 97-134] contend that result verbs disallow object deletion because of their lexical semantic properties. Their point is that…

Teaching about Reversing the Arms Race.

ERIC Educational Resources Information Center

Melman, Seymour

1982-01-01

The scarcity of college courses dealing with disarmament is noted, and educators are urged to address the question of arms limitation. Military and economic factors which limit the ability of the United States to continue the arms race are listed, and plans for reversing the arms race are discussed. (PP)

Supplementation of Pork Patties with Bovine Plasma Protein Hydrolysates Augments Antioxidant Properties and Improves Quality.

PubMed

Seo, Hyun-Woo; Seo, Jin-Kyu; Yang, Han-Sul

2016-01-01

This study investigated the effects of bovine plasma protein (PP) hydrolysates on the antioxidant and quality properties of pork patties during storage. Pork patties were divided into 4 groups: without butylated hydroxytoluene (BHT) and PP hydrolysates (control), 0.02% BHT (T1), 1% PP hydrolysates (T2), and 2% PP hydrolysates (T3). Pork patty supplemented with PP hydrolysates had higher pH values and lower weight loss during cooking than the control patties. Results showed that lightness and hardness both decreased upon the addition of PP hydrolysates. All samples containing BHT and PP hydrolysates had reduced TBARS and peroxide values during storage. In particular, 2% PP hydrolysates were more effective in delaying lipid oxidation than were the other treatments. It was concluded that treatment with 2% PP hydrolysates can enhance the acceptance of pork patty.

Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone

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

Guo, Feng; Stanevich, Vitali; Wlodarchak, Nathan

Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central for the complex PP2A regulation and is crucial for broad aspects of cellular function. The crystal structure of PP2A bound to PP2A phosphatase activator (PTPA) and ATPγS reveals that PTPA makes broad contacts with the structural elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA-binding stabilizes the protein fold of apo-PP2A required for activation, and orients ATP phosphoryl groups to bind directly to the PP2A active site. This allows ATP to modulate the metal-binding preferences of the PP2A active site and utilize the PP2A activemore » site for ATP hydrolysis. In vitro, ATP selectively and drastically enhances binding of endogenous catalytic metal ions, which requires ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function in cell proliferation and survival. Our results suggest novel mechanisms of PTPA in PP2A activation with structural economy and a unique ATP-binding pocket that could potentially serve as a specific therapeutic target.« less

Relationship between compatibilizer and yield strength of PLA/PP Blend

NASA Astrophysics Data System (ADS)

Jariyakulsith, Pattanun; Puajindanetr, Somchai

2018-01-01

The aim of this research is to study the relationship between compatibilizer and yield strength of polylactic acid (PLA) and polypropylene (PP) blend. The PLA is blended with PP (PLA/PP) at the ratios of 70/30, 50/50 and 30/70. In addition, (1) polypropylene grafted maleic anhydride (PP-g-MAH) as a compatibilizer at 0.3 and 0.7 part per hundred of PLA/PP resin (phr) and (2) dicumyl peroxide (DCP) being an initiator at 0.03 and 0.07 phr are added in each composition. Yield strength is characterized to study the interaction between compatibilizer, initiator and yield strength by using experimental design of multilevel full factorial. The results show that (1) the yield strength of PLA/PP blend are increased after addition of compatibilizer. Because the adding of PP-g-MAH and DCP resulted in improving compatibility between PLA and PP. (2) there are interaction between PP-g-MAH and DCP that have affected the final properties of PLA/PP blend. The highest yield strength of 27.68 MPa is provided at the ratio of 70/30 blend by using the 0.3 phr of PP-g-MAH and 0.03 phr of DCP. Linear regression model is fitted and follow the assumptions of normal distribution.

Hyperphosphorylation of PP2A in colorectal cancer and the potential therapeutic value showed by its forskolin-induced dephosphorylation and activation.

PubMed

Cristóbal, Ion; Rincón, Raúl; Manso, Rebeca; Madoz-Gúrpide, Juan; Caramés, Cristina; del Puerto-Nevado, Laura; Rojo, Federico; García-Foncillas, Jesús

2014-09-01

The tumor suppressor protein phosphatase 2A (PP2A) is frequently inactivated in human cancer and phosphorylation of its catalytic subunit (p-PP2A-C) at tyrosine-307 (Y307) has been described to inhibit this phosphatase. However, its molecular and clinical relevance in colorectal cancer (CRC) remains unclear. p-PP2A-C Y307 was determined by immunoblotting in 7 CRC cell lines and 35 CRC patients. CRC cells were treated with the PP2A activator forskolin alone or combined with the PP2A inhibitor okadaic acid, 5-fluorouracil and oxaliplatin. We examined cell growth, colonosphere formation, caspase activity and AKT and ERK activation. PP2A-C was found hyperphosphorylated in CRC cell lines. Forskolin dephosphorylated and activated PP2A, impairing proliferation and colonosphere formation, and inducing activation of caspase 3/7 and changes in AKT and ERK phosphorylation. Moreover, forskolin showed additive effects with 5-fluorouracil and oxaliplatin treatments. Analysis of p-PP2A-C Y307 in primary tumors confirmed the presence of this alteration in a subgroup of CRC patients. Our data show that PP2A-C hyperphosphorylation is a frequent event that contributes to PP2A inhibition in CRC. Antitumoral effects of forskolin-mediated PP2A activation suggest that the analysis of p-PP2A-C Y307 status could be used to identify a subgroup of patients who would benefit from treatments based on PP2A activators. Copyright © 2014 Elsevier B.V. All rights reserved.

Phosphatidic acid (PA) binds PP2AA1 to regulate PP2A activity and PIN1 polar localization.

PubMed

Gao, Hong-Bo; Chu, Yu-Jia; Xue, Hong-Wei

2013-09-01

Phospholipase D (PLD) exerts broad biological functions in eukaryotes through regulating downstream effectors by its product, phosphatidic acid (PA). Protein kinases and phosphatases, such as mammalian target of rapamycin (mTOR), Protein Phosphatase 1 (PP1) and Protein Phosphatase 2C (PP2C), are PA-binding proteins that execute crucial regulatory functions in both animals and plants. PA participates in many signaling pathways by modulating the enzymatic activity and/or subcellular localization of bound proteins. In this study, we demonstrated that PLD-derived PA interacts with the scaffolding A1 subunit of Protein Phosphatase 2A (PP2A) and regulates PP2A-mediated PIN1 dephosphorylation in Arabidopsis. Genetic and pharmacological studies showed that both PA and PP2A participate in the regulation of auxin distribution. In addition, both the phosphorylation status and polar localization of PIN1 protein were affected by PLD inhibitors. Exogenous PA triggered the membrane accumulation of PP2AA1 and enhanced the PP2A activity at membrane, while PLD inhibition resulted in the reduced endosomal localization and perinuclear aggregation of PP2AA1. These results demonstrate the important role of PLD-derived PA in normal PP2A-mediated PIN dephosphorylation and reveal a novel mechanism, in which PA recruits PP2AA1 to the membrane system and regulates PP2A function on membrane-targeted proteins. As PA and PP2A are conserved among eukaryotes, other organisms might use similar mechanisms to mediate multiple biological processes.

Polypropylene/Short Glass Fibers Composites: Effects of Coupling Agents on Mechanical Properties, Thermal Behaviors, and Morphology

PubMed Central

Lin, Jia-Horng; Huang, Chien-Lin; Liu, Chi-Fan; Chen, Chih-Kuang; Lin, Zheng-Ian; Lou, Ching-Wen

2015-01-01

This study uses the melt compounding method to produce polypropylene (PP)/short glass fibers (SGF) composites. PP serves as matrix while SGF serves as reinforcement. Two coupling agents, maleic anhydride grafted polypropylene, (PP-g-MA) and maleic anhydride grafted styrene-ethylene-butylene-styrene block copolymer (SEBS-g-MA) are incorporated in the PP/SGF composites during the compounding process, in order to improve the interfacial adhesion and create diverse desired properties of the composites. According to the mechanical property evaluations, increasing PP-g-MA as a coupling agent provides the composites with higher tensile, flexural, and impact properties. In contrast, increasing SEBS-g-MA as a coupling agent provides the composites with decreasing tensile and flexural strengths, but also increasing impact strength. The DSC results indicate that using either PP-g-MA or SEBS-g-MA as the coupling agent increases the crystallization temperature. However, the melting temperature of PP barely changes. The spherulitic morphology results show that PP has a smaller spherulite size when it is processed with PP-g-MA or SEBS-g-MA as the coupling agent. The SEM results indicate that SGF is evenly distributed in PP matrices, but there are distinct voids between these two materials, indicating a poor interfacial adhesion. After PP-g-MA or SEBS-g-MA is incorporated, SGF can be encapsulated by PP, and the voids between them are fewer and indistinctive. This indicates that the coupling agents can effectively improve the interfacial compatibility between PP and SGF, and as a result improves the diverse properties of PP/SGF composites. PMID:28793710

Two ω-3 FADs Are Associated with Peach Fruit Volatile Formation

PubMed Central

Wang, Jiao-Jiao; Liu, Hong-Ru; Gao, Jie; Huang, Yu-Ji; Zhang, Bo; Chen, Kun-Song

2016-01-01

Aroma-related volatiles, together with sugars and acids, play an important role in determining fruit flavor quality. Characteristic volatiles of peach fruit are mainly derived from fatty acids such as linoleic acid (18:2) and linolenic acid (18:3). In the present study, six genes encoding fatty acid desaturases (FAD) were cloned, including two ω-6 FAD genes (PpFAD2, PpFAD6) and four ω-3 FAD genes (PpFAD3-1, PpFAD3-2, PpFAD7 and PpFAD8). Heterologous expression of peach FADs in tobacco plants showed that PpFAD3-1, and PpFAD3-2 significantly reduced contents of 18:2, and accumulated significant higher levels of 18:3. In the case of volatiles, transgenic plants produced lower concentrations of hexanal and higher levels of (E)-2-hexenal. Consequently, the ratio of the (E)-2-hexenal and hexanal was about 5- and 3-fold higher than that of wild type (WT) in PpFAD3-1 and PpFAD3-2 transformants, respectively. No significant changes in volatile profiles were observed in transgenic plants overexpressing the four other peach FAD genes. Real-time quantitative polymerase chain reaction (qPCR) analysis showed that ripe fruit had high PpFAD3-1 and low PpFAD3-2 transcript levels. In contrast, high PpFAD3-2 and low PpFAD3-1 transcript levels were observed in young fruit. These results indicate a temporal regulation of these two ω-3 FADs during development and ripening, influencing peach fruit volatile formation. PMID:27043529

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

Zissa, D.E.

The charged multiplicity cross sections of 50 GeV/c anti pp annihilation reactions are examined through the use of the corresponding anti pp - pp cross section differences. In addition, various four-constraint reactions such as the elastic reaction and the reaction anti pp ..-->.. anti pp ..pi../sup +/..pi../sup -/ are studied at the same incident anti p beam momentum. The source of the data is a film sample of 92,000 pictures of the 30-inch hydrogen bubble chamber exposed to an anti p enriched 50 GeV/c negative beam. There are 2.8 antiprotons per picture on the average. The proportional wire chambers allowmore » for precise measurement of beam and fast secondary charged particle trajectories. The average charged multiplicity of the difference distribution is larger than that of the anti pp sample as a whole. Although the anti pp - pp total cross section difference is approximately 12%, about 50% of the anti pp events with 14 charged particles appear in the difference. The difference distribution is in good agreement with a model by Eylon and Harari for anti pp annihilations. The model is based on simple counting rules for quark interaction diagrams. The form of the difference distribution has an energy dependence which may be interpreted as evidence for multiple cluster formation for anti pp annihilations above about 30 GeV. Alternatively, Koba-Nielsen-Olesen scaling describes the distribution over the entire range of existing data. Copius ..delta.. (1232) production and diffractive dissociation are exhibited in the reaction anti pp ..-->.. anti pp..pi../sup -/..pi../sup -/. The subchannel reaction anti pp ..-->.. anti ..delta../sup - -/..delta../sup - -/ is examined in terms of pion exchange. The cross sections for the reaction anti pp ..-->.. anti pp2..pi../sup -/2..pi../sup -/ is determined. No statistically significant amount of annihilation is found into two, four, and six charged pions without associated neutral particles.« less

AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

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

Liu, Xin, E-mail: fangfei6073@126.com; Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn; Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn

2012-06-15

Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, andmore » abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.« less

1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription

PubMed Central

Ammosova, Tatyana; Platonov, Maxim; Ivanov, Andrei; Kont, Yasemin Saygideğer; Kumari, Namita; Kehn-Hall, Kylene; Jerebtsova, Marina; Kulkarni, Amol A; Üren, Aykut; Kovalskyy, Dmytro; Nekhai, Sergei

2014-01-01

Background and Purpose HIV-1 transcription is activated by the Tat protein which recruits the cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. Tat binds to protein phosphatase-1 (PP1) through the Q35VCF38 sequence and translocates PP1 to the nucleus. PP1 dephosphorylates CDK9 and activates HIV-1 transcription. We have synthesized a low MW compound 1H4, that targets PP1 and prevents HIV-1 Tat interaction with PP1 and inhibits HIV-1 gene transcription. Here, we report our further work with the 1H4-derived compounds and analysis of their mechanism of action. Experimental Approach Using the 1H4-PP1 complex as a model, we iteratively designed and synthesized follow-up libraries that were analysed for the inhibition of HIV-1 transcription and toxicity. We also confirmed the mechanism of action of the PP1-targeting molecules by determining the affinity of binding of these molecules to PP1, by analysing their effects on PP1 activity, disruption of PP1 binding to Tat and shuttling of PP1 to the nucleus. Key Results We identified a tetrahydroquinoline derivative, compound 7, which disrupted the interaction of Tat with PP1. We further optimized compound 7 and obtained compound 7c, renamed 1E7-03, which inhibited HIV-1 with low IC50 (fivefold lower than the previously reported compound, 1H4), showed no cytotoxicity and displayed a plasma half-life greater than 8 h in mice. 1E7-03 bound to PP1 in vitro and prevented shuttling of PP1 into the nucleus. Conclusions and Implications Our study shows that low MW compounds that functionally mimic the PP1-binding RVxF peptide can inhibit HIV-1 transcription by deregulating PP1. PMID:25073485

Encapsulation efficacy of natural and synthetic photosensitizers by silica nanoparticles for photodynamic applications.

PubMed

Makhadmeh, Ghaseb Naser; Abdul Aziz, Azlan; Abdul Razak, Khairunisak; Abu Noqta, Osama

2015-12-01

This study analysed the physical effects of Cichorium Pumilum (CP), as a natural photosensitizer (PS), and Protoporphyrin IX (PpIX), as a synthetic PS, encapsulated with silica nanoparticles (SiNPs) in photodynamic therapy. The optimum concentrations of CP and PpIX, needed to destroy Red Blood Cells (RBC), were determined and the efficacy of encapsulated CP and PpIX were compared with naked CP and PpIX was verified. The results confirmed the applicability of CP and PpIX encapsulated in SiNPs on RBCs, and established a relationship between the encapsulated CP and PpIX concentration and the time required to rupture 50% of the RBCs (t50). The CP and PpIX encapsulated in SiNPs exhibited higher efficacy compared with that of naked CP and PpIX, respectively, and CP had less efficacy compared with PpIX.

Phase separation of DMDBS from iPP, and controlled crystalline orientation

NASA Astrophysics Data System (ADS)

Sreenivas, K.; Kumaraswamy, Guruswamy; Basargekar, R. S.

2012-02-01

We report an unexpected dependence of DMDBS phase separation temperature on the molecular weight of the matrix isotactic polypropylene (iPP). DMDBS crystallizes out at lower temperatures for iPP with decreasing molecular weight (and correspondingly lower tacticity). This molecular weight dependence is unique to iPP, and is not observed for either syndiotactic PP or for random ethylene-PP copolymers. We show that thermodynamic Flory-type arguments are unable to rationalize the observed results. We also results on extrusion film casting of iPP containing DMDBS and show that flow-alignment of DMDBS networks template the orientation of PP crystals. The modulus and yield strength increase on addition of DMDBS, relative to the neat iPP. Tensile modulus and yield stress of drawn films increase with the degree of orientation, and we are able to achieve a substantial increase even at relatively low draw ratios.

PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte.

PubMed

Tang, An; Shi, Peiliang; Song, Anying; Zou, Dayuan; Zhou, Yue; Gu, Pengyu; Huang, Zan; Wang, Qinghua; Lin, Zhaoyu; Gao, Xiang

2016-06-02

Studies using in vitro cultured oocytes have indicated that the protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, participates in multiple steps of meiosis. Details of oocyte maturation regulation by PP2A remain unclear and an in vivo model can provide more convincing information. Here, we inactivated PP2A by mutating genes encoding for its catalytic subunits (PP2Acs) in mouse oocytes. We found that eliminating both PP2Acs caused female infertility. Oocytes lacking PP2Acs failed to complete 1(st) meiotic division due to chromosome misalignment and abnormal spindle assembly. In mitosis, PP2A counteracts Aurora kinase B/C (AurkB/C) to facilitate correct kinetochore-microtubule (KT-MT) attachment. In meiosis I in oocyte, we found that PP2Ac deficiency destabilized KT-MT attachments. Chemical inhibition of AurkB/C in PP2Ac-null oocytes partly restored the formation of lateral/merotelic KT-MT attachments but not correct KT-MT attachments. Taken together, our findings demonstrate that PP2Acs are essential for chromosome alignments and regulate the formation of correct KT-MT attachments in meiosis I in oocytes.

Basal protein phosphatase 2A activity restrains cytokine expression: role for MAPKs and tristetraprolin.

PubMed

Rahman, Md Mostafizur; Rumzhum, Nowshin N; Morris, Jonathan C; Clark, Andrew R; Verrills, Nicole M; Ammit, Alaina J

2015-05-18

PP2A is a master controller of multiple inflammatory signaling pathways. It is a target in asthma; however the molecular mechanisms by which PP2A controls inflammation warrant further investigation. In A549 lung epithelial cells in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the anti-inflammatory protein - tristetraprolin (TTP), a destabilizing RNA binding protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition increases TTP mRNA expression, resultant TTP protein builds up in the hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro-inflammatory cytokines increase and anti-inflammatory proteins are rendered inactive. Importantly, these effects can be reversed by the PP2A activators FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression in cells stimulated with TNFα; as inhibition of PP2A with OA or PP2A-C siRNA results in significant increases in cytokine production. Collectively, these data reveal the molecular mechanisms of PP2A regulation and highlight the potential of boosting the power of endogenous phosphatases as novel anti-inflammatory strategies to combat asthmatic inflammation.

Human Neutrophil Clearance of Bacterial Pathogens Triggers Anti-Microbial γδ T Cell Responses in Early Infection

PubMed Central

Roberts, Gareth W.; Heuston, Sinéad; Brown, Amanda C.; Chess, James A.; Toleman, Mark A.; Gahan, Cormac G. M.; Hill, Colin; Parish, Tanya; Williams, John D.; Davies, Simon J.; Johnson, David W.; Topley, Nicholas; Moser, Bernhard; Eberl, Matthias

2011-01-01

Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early infection and suggest novel diagnostic and therapeutic approaches. PMID:21589907

Transcriptomic and physiological responses to fishmeal substitution with plant proteins in formulated feed in farmed Atlantic salmon (Salmo salar)

PubMed Central

2012-01-01

Background Aquaculture of piscivorous fish is in continual expansion resulting in a global requirement to reduce the dependence on wild caught fish for generation of fishmeal and fish oil. Plant proteins represent a suitable protein alternative to fish meal and are increasingly being used in fish feed. In this study, we examined the transcriptional response of Atlantic salmon (Salmo salar) to a high marine protein (MP) or low fishmeal, higher plant protein replacement diet (PP), formulated to the same nutritional specification within previously determined acceptable maximum levels of individual plant feed materials. Results After 77 days of feeding the fish in both groups doubled in weight, however neither growth performance, feed efficiency, condition factor nor organ indices were significantly different. Assessment of histopathological changes in the heart, intestine or liver did not reveal any negative effects of the PP diet. Transcriptomic analysis was performed in mid intestine, liver and skeletal muscle, using an Atlantic salmon oligonucleotide microarray (Salar_2, Agilent 4x44K). The dietary comparison revealed large alteration in gene expression in all the tissues studied between fish on the two diets. Gene ontology analysis showed, in the mid intestine of fish fed PP, higher expression of genes involved in enteritis, protein and energy metabolism, mitochondrial activity/kinases and transport, and a lower expression of genes involved in cell proliferation and apoptosis compared to fish fed MP. The liver of fish fed PP showed a lower expression of immune response genes but a higher expression of cell proliferation and apoptosis processes that may lead to cell reorganization in this tissue. The skeletal muscle of fish fed PP vs MP was characterized by a suppression of processes including immune response, energy and protein metabolism, cell proliferation and apoptosis which may reflect a more energy efficient tissue. Conclusions The PP diet resulted in significant effects on transcription in all the 3 tissues studied. Despite of these alterations, we demonstrated that high level of plant derived proteins in a salmon diet allowed fish to grow with equal efficiency as those on a high marine protein diet, and with no difference in biometric quality parameters. PMID:22853566

CO2 Washout Testing of the REI and EM-ACES Space Suits

NASA Technical Reports Server (NTRS)

Mitchell, Kathryn C.; Norcross, Jason

2012-01-01

When a space suit is used during ground testing, adequate carbon dioxide (CO2) washout must be provided for the suited subject. Symptoms of acute CO2 exposure depend on partial pressure of CO2 (ppCO2), metabolic rate of the subject, and other factors. This test was done to characterize inspired oronasal ppCO2 in the Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES) for a range of workloads and flow rates for which ground testing is nominally performed. Three subjects were tested in each suit. In all but one case, each subject performed the test twice. Suit pressure was maintained at 4.3 psid. Subjects wore the suit while resting, performing arm ergometry, and walking on a treadmill to generate metabolic workloads of about 500 to 3000 BTU/hr. Supply airflow was varied between 6, 5, and 4 actual cubic feet per minute (ACFM) at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored in real time by gas analyzers with sampling tubes connected to the mask. Metabolic rate was calculated from the total CO2 production measured by an additional gas analyzer at the suit air outlet. Real-time metabolic rate was used to adjust the arm ergometer or treadmill workload to meet target metabolic rates. In both suits, inspired CO2 was affected mainly by the metabolic rate of the subject: increased metabolic rate significantly (P < 0.05) increased inspired ppCO2. Decreased air flow caused small increases in inspired ppCO2. The effect of flow was more evident at metabolic rates . 2000 BTU/hr. CO2 washout values of the EM-ACES were slightly but not significantly better than those of the REI suit. Regression equations were developed for each suit to predict the mean inspired ppCO2 as a function of metabolic rate and suit flow rate. This paper provides detailed descriptions of the test hardware, methodology, and results as well as implications for future ground testing in the REI-suit and EM-ACES.

The modulation of the phosphorylation status of NKCC1 in organ cultured bovine lenses: Implications for the regulation of fiber cell and overall lens volume.

PubMed

Vorontsova, Irene; Donaldson, Paul J; Kong, Zhiying; Wickremesinghe, Chiharu; Lam, Leo; Lim, Julie C

2017-12-01

In previous work, we have shown the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to be a key effector of lens fiber cell volume regulation. Since others have shown that the activity of NKCC1 is regulated via its phosphorylation status, the purpose of this study was to investigate whether NKCC1 phosphorylation can be modulated in organ cultured bovine lenses, and to see how this relates to changes in lens wet weight. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level. Changes to NKCC1-P status were then assessed by organ culturing bovine lenses in either isotonic, hypertonic or hypotonic solutions in the presence or absence of the NKCC inhibitor, bumetanide, or phosphatase inhibitors okadaic acid and calyculin A. After 1-22 h of culturing, lenses were weighed, assessed for transparency and the cortical protein fractions analyzed by western blot using antibodies to detect total NKCC1 and NKCC1-P. NKCC1, NKCC1-P, SPAK, PP1 and PP2A were all detected in the membrane fraction of bovine lenses. Under hypertonic conditions, NKCC1 is phosphorylated and activated to mediate a regulatory volume increase. Finally, NKCC1-P signal increased in the presence of phosphatase inhibitors indicating that PP1/PP2A can dephosphorylate NKCC1. These results show that the phosphorylation status and hence activity of NKCC1 is dynamically regulated and that in response to hypertonic stress, NKCC1 activity is increased to effect a regulatory volume increase that limits cell shrinkage. These findings support the view that the lens dynamically regulates ion fluxes to maintain steady state lens volume, and suggest that dysfunction of this regulation maybe an initiating factor in the localized fiber cell swelling that is a characteristic of diabetic lens cataract. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transcriptomic and physiological responses to fishmeal substitution with plant proteins in formulated feed in farmed Atlantic salmon (Salmo salar).

PubMed

Tacchi, Luca; Secombes, Christopher J; Bickerdike, Ralph; Adler, Michael A; Venegas, Claudia; Takle, Harald; Martin, Samuel A M

2012-08-01

Aquaculture of piscivorous fish is in continual expansion resulting in a global requirement to reduce the dependence on wild caught fish for generation of fishmeal and fish oil. Plant proteins represent a suitable protein alternative to fish meal and are increasingly being used in fish feed. In this study, we examined the transcriptional response of Atlantic salmon (Salmo salar) to a high marine protein (MP) or low fishmeal, higher plant protein replacement diet (PP), formulated to the same nutritional specification within previously determined acceptable maximum levels of individual plant feed materials. After 77 days of feeding the fish in both groups doubled in weight, however neither growth performance, feed efficiency, condition factor nor organ indices were significantly different. Assessment of histopathological changes in the heart, intestine or liver did not reveal any negative effects of the PP diet. Transcriptomic analysis was performed in mid intestine, liver and skeletal muscle, using an Atlantic salmon oligonucleotide microarray (Salar_2, Agilent 4x44K). The dietary comparison revealed large alteration in gene expression in all the tissues studied between fish on the two diets. Gene ontology analysis showed, in the mid intestine of fish fed PP, higher expression of genes involved in enteritis, protein and energy metabolism, mitochondrial activity/kinases and transport, and a lower expression of genes involved in cell proliferation and apoptosis compared to fish fed MP. The liver of fish fed PP showed a lower expression of immune response genes but a higher expression of cell proliferation and apoptosis processes that may lead to cell reorganization in this tissue. The skeletal muscle of fish fed PP vs MP was characterized by a suppression of processes including immune response, energy and protein metabolism, cell proliferation and apoptosis which may reflect a more energy efficient tissue. The PP diet resulted in significant effects on transcription in all the 3 tissues studied. Despite of these alterations, we demonstrated that high level of plant derived proteins in a salmon diet allowed fish to grow with equal efficiency as those on a high marine protein diet, and with no difference in biometric quality parameters.

The homeodomain-leucine zipper (HD-Zip) class I transcription factors ATHB7 and ATHB12 modulate abscisic acid signalling by regulating protein phosphatase 2C and abscisic acid receptor gene activities.

PubMed

Valdés, Ana Elisa; Overnäs, Elin; Johansson, Henrik; Rada-Iglesias, Alvaro; Engström, Peter

2012-11-01

Plants perceiving drought activate multiple responses to improve survival, including large-scale alterations in gene expression. This article reports on the roles in the drought response of two Arabidopsis thaliana homeodomain-leucine zipper class I genes; ATHB7 and ATHB12, both strongly induced by water-deficit and abscisic acid (ABA). ABA-mediated transcriptional regulation of both genes is shown to depend on the activity of protein phosphatases type 2C (PP2C). ATHB7 and ATHB12 are, thus, targets of the ABA signalling mechanism defined by the PP2Cs and the PYR/PYL family of ABA receptors, with which the PP2C proteins interact. Our results from chromatin immunoprecipitation and gene expression analyses demonstrate that ATHB7 and ATHB12 act as positive transcriptional regulators of PP2C genes, and thereby as negative regulators of abscisic acid signalling. In support of this notion, our results also show that ATHB7 and ATHB12 act to repress the transcription of genes encoding the ABA receptors PYL5 and PYL8 in response to an ABA stimulus. In summary, we demonstrate that ATHB7 and ATHB12 have essential functions in the primary response to drought, as mediators of a negative feedback effect on ABA signalling in the plant response to water deficit.

Determination of phenylenediamine isomers in hair dyes by coal cinders micro-column extraction and MEKC.

PubMed

Wu, Yiwei; Jiang, Feng; Chen, Lin; Zheng, Jing; Deng, Zhenli; Tao, Qing; Zhang, Jing; Han, Lijuan; Wei, Xiaoshu; Yu, Aimin; Zhang, Haili

2011-06-01

A new micellar electrokinetic chromatography (MEKC) method using beta-cyclodextrins (β-CDs) and 1-butyl-3-methylimidazolium hexafluorophosphates (ionic liquids) as additives was successfully developed for determination of para-, meta-, and ortho-phenylenediamines isomers (p-P, m-P, and o-P) in hair dyes. To improve the sensitivity of the MEKC-UV, a simple and cheap flow injection (FI) technique using a micro-column packed with coal cinders (the by-products from combustion in a boiler) as solid-phase extractant was also investigated. In the presence of 20 mmol L(-1) phosphates at pH 5.5, addition of 12 mmol L(-1) ionic liquids and 8 mmol L(-1) β-CDs greatly improved the separation efficiency. The three analytes could be quantitatively adsorbed by coal cinders, and desorbed readily with 0.15 mL of 0.01 mol L(-1) NaOH. Under the optimum conditions, an enrichment factor (EF) of 33.3 was obtained, and determination limits of p-P, m-P, and o-P were 1.97 × 10(-7), 0.99 × 10(-7), and 0.61 × 10(-7) mol L(-1), respectively. The adsorption capacities of the coal cinders micro-column for p-P, m-P, and o-P were all 1.20 mg g(-1). The presented procedure was successfully applied to the determination of p-P, m-P, and o-P in hair dyes with satisfactory results.

Biosynthesis of allene oxides in Physcomitrella patens

PubMed Central

2012-01-01

Background The moss Physcomitrella patens contains C18- as well as C20-polyunsaturated fatty acids that can be metabolized by different enzymes to form oxylipins such as the cyclopentenone cis(+)-12-oxo phytodienoic acid. Mutants defective in the biosynthesis of cyclopentenones showed reduced fertility, aberrant sporophyte morphology and interrupted sporogenesis. The initial step in this biosynthetic route is the conversion of a fatty acid hydroperoxide to an allene oxide. This reaction is catalyzed by allene oxide synthase (AOS) belonging as hydroperoxide lyase (HPL) to the cytochrome P450 family Cyp74. In this study we characterized two AOS from P. patens, PpAOS1 and PpAOS2. Results Our results show that PpAOS1 is highly active with both C18 and C20-hydroperoxy-fatty acid substrates, whereas PpAOS2 is fully active only with C20-substrates, exhibiting trace activity (~1000-fold lower kcat/KM) with C18 substrates. Analysis of products of PpAOS1 and PpHPL further demonstrated that both enzymes have an inherent side activity mirroring the close inter-connection of AOS and HPL catalysis. By employing site directed mutagenesis we provide evidence that single amino acid residues in the active site are also determining the catalytic activity of a 9-/13-AOS – a finding that previously has only been reported for substrate specific 13-AOS. However, PpHPL cannot be converted into an AOS by exchanging the same determinant. Localization studies using YFP-labeled AOS showed that PpAOS2 is localized in the plastid while PpAOS1 may be found in the cytosol. Analysis of the wound-induced cis(+)-12-oxo phytodienoic acid accumulation in PpAOS1 and PpAOS2 single knock-out mutants showed that disruption of PpAOS1, in contrast to PpAOS2, results in a significantly decreased cis(+)-12-oxo phytodienoic acid formation. However, the knock-out mutants of neither PpAOS1 nor PpAOS2 showed reduced fertility, aberrant sporophyte morphology or interrupted sporogenesis. Conclusions Our study highlights five findings regarding the oxylipin metabolism in P. patens: (i) Both AOS isoforms are capable of metabolizing C18- and C20-derived substrates with different specificities suggesting that both enzymes might have different functions. (ii) Site directed mutagenesis demonstrated that the catalytic trajectories of 9-/13-PpAOS1 and PpHPL are closely inter-connected and PpAOS1 can be inter-converted by a single amino acid exchange into a HPL. (iii) In contrast to PpAOS1, PpAOS2 is localized in the plastid where oxylipin metabolism takes place. (iv) PpAOS1 is essential for wound-induced accumulation of cis(+)-12-oxo phytodienoic acid while PpAOS2 appears not to be involved in the process. (v) Knock-out mutants of neither AOS showed a deviating morphological phenotype suggesting that there are overlapping functions with other Cyp74 enzymes. PMID:23194461

[Preparation and activity validation of PP7 bacteriophage-like particles displaying PAP114-128 peptide].

PubMed

Sun, Yanli; Sun, Yanhua

2016-10-01

Objective To obtain the PP7 bacteriophage-like particles carrying the peptide of prostatic acid phosphatase PAP 114-128 , and prove that they retain the original biological activity. Methods First, the plasmid pETDuet-2PP7 was constructed as follows: the gene of PP7 coat protein dimer was amplified by gene mutation combined with overlapping PCR technology, and inserted into the vector pETDuet-1. Following that, the plasmid pETDuet-2PP7-PAP 114-128 was constructed as follows: the PP7 coat protein gene carrying the coding gene of PAP 114-128 peptide was amplified using PCR, and then inserted into the vector pETDuet-2PP7. Both pETDuet-2PP7 and pETDuet-2PP7-PAP 114-128 were transformed into E.coli and expressed. The expression product was verified by SDS-PAGE, double immunodiffusion assay and ELISA. Results The gene fragment of PP7 coat protein dimer was obtained by overlapping PCR using Ex Taq DNA polymerase, and the antigenicity of its expression product was the same as that of the coat protein of wild-type PP7 bacteriophage. Moreover, the PAP 114-128 peptide epitope that was displayed on the surface of PP7 bacteriophage was identical with the corresponding epitope of natural human PAP, and it was able to induce high levels of antibodies. Conclusion The gene of PP7 coat protein dimer with repeated sequences can be prepared by gene mutation combined with overlapping PCR. Based on this, PP7 bacteriophage-like particles carrying PAP peptide can be prepared, which not only solves the problem of the instability of the peptides, but also lays a foundation for the study on their delivery and function.

Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.

PubMed

Meyer-Roxlau, Stefanie; Lämmle, Simon; Opitz, Annett; Künzel, Stephan; Joos, Julius P; Neef, Stefan; Sekeres, Karolina; Sossalla, Samuel; Schöndube, Friedrich; Alexiou, Konstantin; Maier, Lars S; Dobrev, Dobromir; Guan, Kaomei; Weber, Silvio; El-Armouche, Ali

2017-07-01

Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

24-h pulse pressure cutoff point definition by office pulse pressure in a population of Spanish older hypertensive patients.

PubMed

Vinyoles, Ernest; de la Sierra, Alejandro; Roso-Llorach, Albert; Banegas, José R; de la Cruz, Juan José; Gorostidi, Manuel; Segura, Julián; Divisón, Juan Antonio; Ruíz-Hurtado, Gema; Ruilope, Luis Miguel

2017-05-01

The European Guidelines on Hypertension define an office pulse pressure (PP) at least 60 mmHg in the elderly patient as asymptomatic organ damage. Our objective was to estimate the cutoff point of 24-h PP that best predicts office PP associated with higher cardiovascular risk (≥60 mmHg) in hypertensive older patients. We studied all hypertensive patients at least 60 years with a first valid ambulatory blood pressure monitoring drawn from the Spanish ambulatory blood pressure monitoring registry. Receiver operating characteristic curves were used to estimate the best 24-h PP cutoff predictor of office PP at least 60 mmHg that maximized the sum of sensitivity and specificity. We included 52 246 hypertensive patients [52.4%, female; mean age (SD) 69.0 (7.0) years]. From these, 34 530 (66.1%) patients had an office PP at least 60 mmHg. The value of 24-h PP that best predicts higher risk clinic PP is 54.9 mmHg [sensitivity: 69.2%; specificity: 70.3%; area under the receiver operating characteristic curve of 0.761 (95% confidence interval 0.756-0.765)]. Mean clinic and 24-h PPs were progressively higher as the study participants were classified at higher cardiovascular risk group. Some 20.5% of patients presented isolated office high PP and 10% a masked high 24-h PP. In a large clinical sample of older hypertensive patients, the cutoff point of 24-h PP that best predicts office PP at least 60 mmHg is 55 mmHg. In 30.5% of cases, there is a discrepancy between office PP and ambulatory 24-h PP.

Mixing of Isotactic and Syndiotactic Polypropylenes in the Melt

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

CLANCY,THOMAS C.; PUTZ,MATHIAS; WEINHOLD,JEFFREY D.

2000-07-14

The miscibility of polypropylene (PP) melts in which the chains differ only in stereochemical composition has been investigated by two different procedures. One approach used detailed local information from a Monte Carlo simulation of a single chain, and the other approach takes this information from a rotational isomeric state model devised decades ago, for another purpose. The first approach uses PRISM theory to deduce the intermolecular packing in the polymer blend, while the second approach uses a Monte Carlo simulation of a coarse-grained representation of independent chains, expressed on a high-coordination lattice. Both approaches find a positive energy change uponmore » mixing isotactic PP (iPP) and syndiotactic polypropylene (sPP) chains in the melt. This conclusion is qualitatively consistent with observations published recently by Muelhaupt and coworkers. The size of the energy chain on mixing is smaller in the MC/PRISM approach than in the RIS/MC simulation, with the smaller energy change being in better agreement with the experiment. The RIS/MC simulation finds no demixing for iPP and atactic polypropylene (aPP) in the melt, consistent with several experimental observations in the literature. The demixing of the iPP/sPP blend may arise from attractive interactions in the sPP melt that are disrupted when the sPP chains are diluted with aPP or iPP chains.« less

Analyses of expression and localization of two mammalian-type transglutaminases in Physarum polycephalum, an acellular slime mold.

PubMed

Wada, Fumitaka; Ogawa, Atsuko; Hanai, Yuko; Nakamura, Akio; Maki, Masatoshi; Hitomi, Kiyotaka

2004-11-01

Transglutaminase (TGase) is an enzyme that modifies proteins by crosslinking or polyamination. Physarum polycephalum, an acellular slime mold, is the evolutionally lowest organism that has a mammalian-type transglutaminase. We have cloned a cDNA for Physarum polycephalum TGase (PpTGB), homologous to a previously identified TGase (PpTGA), whose sequence is similar to that of mammalian TGases. PpTGB encodes a primary sequence identical to that of PpTGA except for 11 amino acid residues at the N-terminus. Reverse transcription-PCR and Western blotting analyses showed that both PpTGA and PpTGB are expressed in microplasmodia and macroplasmodia during their life cycle, except for in sporangia. For biochemical characterization, we carried out the ectopical expressions of PpTGA and PpTGB in Dictyostelium discoideum. Subcellular fractionation of these Dictyostelium cells showed that the expressed PpTGA, but not PpTGB, localizes to the membrane fraction. Furthermore, in Physarum, subcellular fractionation and immunostaining indicated specific localization at the plasma membrane in macroplasmodia, while the localization was entirely cytoplasmic in microplasmodia.

Evaluation of foaming polypropylene modified with ramified polymer

NASA Astrophysics Data System (ADS)

Demori, Renan; de Azeredo, Ana Paula; Liberman, Susana A.; Mauler, Raquel S.

2015-05-01

Polypropylene foams have great industrial interest because of balanced physical and mechanical properties, recyclability as well as low material cost. During the foaming process, the elongational forces applied to produce the expanded polymer are strong enough to rupture cell walls. As a result, final foam has a high amount of coalesced as well as opened cells which decreases mechanical and also physical properties. To increase melt strength and also avoid the coalescence effect, one of the current solution is blend PP with ramified polymers as well as branched polypropylene (LCBPP) or ethylene-octene copolymer (POE). In this research to provide extensional properties and achieve uniform cellular structures of expanded PP, 20 phr of LCBPP or POE was added into PP matrix. The blend of PP with ramified polymers was prepared by twin-screw extrusion. Injection molding process was used to produce PP foams using azodicarbonamide (ACA) as chemical blowing agent. The morphological results of the expanded PP displayed a non-uniform geometrical cell, apparent density of 0.48 g/cm3 and cell density of 13.9.104 cell/cm3. Otherwise, the expanded PP blended with LCBPP or POE displayed a homogeneous cell structure and increased the amount of smaller cells (50-100 μm of size). The apparent density slightly increased with addition of LCBPP or POE, 0.64 and 0.57 g/cm3, respectively. Thus, the cell density reduced to 65% in PP/LCBPP 100/20 and 75% in the sample PP/POE 100/20 compared to expanded PP. The thermo-mechanical properties (DMTA) of PP showed specific stiffness of 159 MPa.cm-3.g-1, while the sample PP/LCBPP 100/20 increased the stiffness values of 10%. Otherwise, the expanded PP/POE 100/20 decreased the specific stiffness values at -30%, in relation to expanded PP. In summary, blending PP with ramified polymers showed increasing of the homogenous cellular structure as well as the amount of smaller cells in the expanded material.

Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

PubMed Central

Xu, Haiyan; Gopal, Srihari; Nuamah, Isaac; Ravenstijn, Paulien; Janik, Adam; Schotte, Alain; Hough, David; Fleischhacker, Wolfgang W.

2016-01-01

Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID:26902950

Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit

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

Boylan, Joan M.; Salomon, Arthur R.; Department of Chemistry, Brown University, Providence, RI

Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase inmore » apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders. - Highlights: • Lentiviral-transduced shRNA was used to generate a stable knockdown of PP6 in HepG2 cells. • Cells adapted to reduced PP6; cell proliferation was unaffected, and cell survival was normal. • However, PP6 knockdown was associated with a transition to a tetraploid state. • Genomic profiling showed downregulated anti-inflammatory signaling and DNA replication. • Phosphoproteomic profiling showed changes in proteins associated with DNA replication and repair.« less

TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFκB-mediated inflammation and accelerate Nrf2-induced antioxidative potential through the modulation of PI3K-Akt signaling pathway in RAW 264.7 cells.

PubMed

Park, Chung Mu; Cho, Chung Won; Song, Young Sun

2014-04-01

Anti-inflammatory and anti-oxidative activities of polysaccharides from Taraxacum officinale (TOP 1 and 2) were analyzed in RAW 264.7 cells. First, lipopolysaccharide (LPS) was applied to identify anti-inflammatory activity of TOPs, which reduced expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. TOPs treatment inhibited phosphorylation of inflammatory transcription factor, nuclear factor (NF)κB, and its upstream signaling molecule, PI3K/Akt. Second, cytoprotective potential of TOPs against oxidative stress was investigated via heme oxygenase (HO)-1 induction. HO-1, one of phase II enzymes shows antioxidative activity, was potently induced by TOPs treatment, which was in accordance with the nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). In addition, TOPs treatment phosphorylated PI3K/Akt with slight activation of c-Jun NH2-terminal kinase (JNK). TOPs-mediated HO-1 induction protected macrophage cells from oxidative stress-induced cell death, which was confirmed by SnPP and CoPP (HO-1 inhibitor and inducer, respectively). Consequently, TOPs potently inhibited NFκB-mediated inflammation and accelerated Nrf2-mediated antioxidative potential through the modulation of PI3K/Akt pathway, which would contribute to their promising strategy for novel anti-inflammatory and anti-oxidative agents. Copyright © 2014. Published by Elsevier Ltd.

Restricted Protein Phosphatase 2A Targeting by Merkel Cell Polyomavirus Small T Antigen

PubMed Central

Kwun, Hyun Jin; Shuda, Masahiro; Camacho, Carlos J.; Gamper, Armin M.; Thant, Mamie; Chang, Yuan

2015-01-01

ABSTRACT Merkel cell polyomavirus (MCV) is a newly discovered human cancer virus encoding a small T (sT) oncoprotein. We performed MCV sT FLAG-affinity purification followed by mass spectroscopy (MS) analysis, which identified several protein phosphatases (PP), including PP2A A and C subunits and PP4C, as potential cellular interacting proteins. PP2A targeting is critical for the transforming properties of nonhuman polyomaviruses, such as simian virus 40 (SV40), but is not required for MCV sT-induced rodent cell transformation. We compared similarities and differences in PP2A binding between MCV and SV40 sT. While SV40 sT coimmunopurified with subunits PP2A Aα and PP2A C, MCV sT coimmunopurified with PP2A Aα, PP2A Aβ, and PP2A C. Scanning alanine mutagenesis at 29 sites across the MCV sT protein revealed that PP2A-binding domains lie on the opposite molecular surface from a previously described large T stabilization domain (LSD) loop that binds E3 ligases, such as Fbw7. MCV sT-PP2A interactions can be functionally distinguished by mutagenesis from MCV sT LSD-dependent 4E-BP1 hyperphosphorylation and viral DNA replication enhancement. MCV sT has a restricted range for PP2A B subunit substitution, inhibiting only the assembly of B56α into the phosphatase holoenzyme. In contrast, SV40 sT inhibits the assembly of B55α, B56α and B56ε into PP2A. We conclude that MCV sT is required for Merkel cell carcinoma growth, but its in vitro transforming activity depends on LSD interactions rather than PP2A targeting. IMPORTANCE Merkel cell polyomavirus is a newly discovered human cancer virus that promotes cancer, in part, through expression of its small T (sT) oncoprotein. Animal polyomavirus sT oncoproteins have been found to cause experimental tumors by blocking the activities of a group of phosphatases called protein phosphatase 2A (PP2A). Our structural analysis reveals that MCV sT also displaces the B subunit of PP2A to inhibit PP2A activity. MCV sT, however, only displaces a restricted subset of PP2A B subunits, which is insufficient to cause tumor cell formation in vitro. MCV sT instead transforms tumor cells through another region called the large T stabilization domain. The PP2A targeting and transforming activities lie on opposite faces of the MCV sT molecule and can be genetically separated from each other. PMID:25631078

Effect of cyclical thermal to mechanical properties of Hybrid Laminate Composites (HLC) with skin recycle polypropylene/natural fiber/halloysite and core PP/KF composites

NASA Astrophysics Data System (ADS)

Sri Suharty, Neng; Ismail, Hanafi; Suci Handayani, Desi; Diharjo, Kuncoro; Rachman Wibowo, Fajar; Arnita Wuri, Margaretha

2016-02-01

This research has successfully synthesized six hybrid laminate composites (HLC). These HLC consist of two layers skin composites and one layer of core PP/KF composites. There are sticked with epoxy adhesive by using cold press method. In this research 6 types of skin are used, namely the rPP (recycled polypropylene, HC1); rPP/DVB/PP-g-AA/KF (HC2); rPP/DVB/PP-g-AA/Hall (HC3); rPP/DVB/PP-g-AA/Hall+ZB (HC4); rPP/DVB/PP-g-AA/KF/Hall (HC5) and rPP/DVB/PP-g-AA/KF/Hall+ZB (HC6) composites. The mechanical properties assessment tensile strength (TS) of various HLC before and after cyclical thermal (CT) was done by ASTM D638. While testing the flame retardant: such as time to ignition (TTI) and burning rate (BR) was done by ASTM D635. Heat stability of HLC can be recognized by conducting the CT treatment. It is to determine the effect of fluctuating heat loads on mechanical properties of HLC materials. The TS result of five HLCs (HC2, HC3, HC4, HC5 and HC6) before CT treatment were higher than HC1 (blank HLC). Those five HLC are also able to increase the TTI and reduce the BR compared to HC1. The CT treatment conditions performed at 45 oC as much as 125 times. After CT treatment, the TS values only slightly decline compared to before CT treatment.

Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia.

PubMed

De Villiers, Carin P; Hedley, Paula L; Placing, Sophie; Wøjdemann, Karen R; Shalmi, Anne-Cathrine; Carlsen, Anting L; Rode, Line; Sundberg, Karin; Tabor, Ann; Christiansen, Michael

2017-11-27

Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified. PP13 was measured in first trimester (week 10+3-13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation. In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8-85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1-50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4-142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI. PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

Molecular characterization of a phloem-specific gene encoding the filament protein, phloem protein 1 (PP1), from Cucurbita maxima.

PubMed

Clark, A M; Jacobsen, K R; Bostwick, D E; Dannenhoffer, J M; Skaggs, M I; Thompson, G A

1997-07-01

Sieve elements in the phloem of most angiosperms contain proteinaceous filaments and aggregates called P-protein. In the genus Cucurbita, these filaments are composed of two major proteins: PP1, the phloem filament protein, and PP2, the phloem lactin. The gene encoding the phloem filament protein in pumpkin (Cucurbita maxima Duch.) has been isolated and characterized. Nucleotide sequence analysis of the reconstructed gene gPP1 revealed a continuous 2430 bp protein coding sequence, with no introns, encoding an 809 amino acid polypeptide. The deduced polypeptide had characteristics of PP1 and contained a 15 amino acid sequence determined by N-terminal peptide sequence analysis of PP1. The sequence of PP1 was highly repetitive with four 200 amino acid sequence domains containing structural motifs in common with cysteine proteinase inhibitors. Expression of the PP1 gene was detected in roots, hypocotyls, cotyledons, stems, and leaves of pumpkin plants. PP1 and its mRNA accumulated in pumpkin hypocotyls during the period of rapid hypocotyl elongation after which mRNA levels declined, while protein levels remained elevated. PP1 was immunolocalized in slime plugs and P-protein bodies in sieve elements of the phloem. Occasionally, PP1 was detected in companion cells. PP1 mRNA was localized by in situ hybridization in companion cells at early stages of vascular differentiation. The developmental accumulation and localization of PP1 and its mRNA paralleled the phloem lactin, further suggesting an interaction between these phloem-specific proteins.

Campaigns and Operations: Selected Bibliographies

DTIC Science & Technology

1989-04-01

pp. D763 Majdalany, Fred . The Battle of Cassino. Boston: •182 Houghton Mifflin, 1957. 309 pp. maps. M646 D783 Mason, David. Salerno: Foothold in...Quarterly, July 1972, pp. 483-495. Thorp, Johan J. "Anzio--A Sedentary Affair.* Marine Corps Gazette. September 1984. pp. 60-08. Walker, Fred L. ’My Story of...1968. .A4M3 160 pp. U55 .---------- Rommel: Battles and Campaigns. New York: Mayflower .R6M3 Books, 1979. 224 pp. D766.9 Majdalany, Fred . The Battle of

Urinary tract infection after retrograde urethrogram in children: A multicenter study.

PubMed

Malhotra, Neha R; Green, Jared R; Rigsby, Cynthia K; Holl, Jane L; Cheng, Earl Y; Johnson, Emilie K

2017-12-01

The risk of post-procedural urinary tract infection (ppUTI) after retrograde urethrogram (RUG) has not been well quantified. Prophylactic antibiotics may reduce the risk, but must be weighed against the risks of antibiotic resistance. Prior research has shown that this risk is variable after voiding cystourethrogram (0-42% reported ppUTI rate) and appears to be low after urodynamics (0-4.8%) but this risk has not been well documented for patients undergoing RUG. We aimed to (1) describe the rate of ppUTI after RUG, and (2) examine factors associated with use of antibiotics at the time of RUG. We conducted a retrospective cohort study of children undergoing RUG at two hospitals January 1, 2004, to December 31, 2014. ppUTI within 7 days was measured. Antibiotic prophylaxis was determined. Relationships between clinical characteristics and receipt of pre-procedure antibiotics were evaluated using univariate statistics. Forty-two patients (100% male, median age 11.7 years) underwent 47 RUGs. Indications included trauma (27%), hypospadias (17%), and non-hypospadias (27%) stricture. Study indication and antibiotic administration practices are illustrated in the Figure. Three patients (6.4%) had a history of posterior urethral valves (PUV); one had neurogenic bladder (NGB) (2.4%). Two (4%) studies were performed within 30 days of a clinical UTI and 11% had a positive urinalysis or culture within 30 days pre-RUG. UTI in the 30 days before RUG was not associated with antibiotic prescription (p > 0.99). One child (2.1%; 95% CI 0-6.3%) had a ppUTI: a 7-year-old, uncircumcised male with a history of PUV and voiding dysfunction who was asymptomatic at the time of RUG. Although the risk of ppUTI after RUG appears to be low, the rare occurrence of an iatrogenic UTI can lead to high cost and patient morbidity, particularly in cases similar to our patients who required inpatient admission for intravenous antibiotics. To help balance the risk of UTI with the associated healthcare costs and morbidity with the concerns about antibiotic overuse and potential exposure to drug reaction, data from this study may inform future development of evidence-based guidelines targeting only patients at highest risk for ppUTI with antibiotic prophylaxis. The risk of ppUTI after RUG is low. Antibiotic prophylaxis was unrelated pre-RUG UTI in our population. These results indicate the need for pre-procedural antibiotic prescribing guidelines, and suggest that routine antibiotics prior to RUG are not indicated unless the patient has another indication for antibiotics. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

HUMAN PANCREATIC POLYPEPTIDE IN A PHOSPHOLIPID BASED MICELLAR FORMULATION

PubMed Central

Banerjee, Amrita; Onyuksel, Hayat

2012-01-01

Purpose Pancreatic polypeptide (PP) has important glucoregulatory functions and thereby holds significance in the treatment of diabetes and obesity. However, short plasma half-life and aggregation propensity of PP in aqueous solution, limits its therapeutic application. To address these issues, we prepared and characterized a formulation of PP in sterically stabilized micelles (SSM) that protects and stabilizes PP in its active conformation. Methods PP-SSM was prepared by incubating PP with SSM dispersion in buffer. Peptide-micelle association and freeze-drying efficacy of the formulation was characterized in phosphate buffers with or without sodium chloride using dynamic light scattering, fluorescence spectroscopy and circular dichroism. The degradation kinetics of PP-SSM in presence of proteolytic enzyme was determined using HPLC and bioactivity of the formulation was evaluated by in vitro cAMP inhibition. Results PP self-associated with SSM and this interaction was influenced by presence/absence of sodium chloride in the buffer. The formulation was effectively lyophilized, demonstrating feasibility for its long-term storage. The stability of peptide against proteolytic degradation was significantly improved and PP in SSM retained its bioactivity in vitro. Conclusions Self-association of PP with phospholipid micelles addressed the delivery issues of the peptide. This PP nanomedicine should be further developed for the treatment of diabetes. PMID:22399387

Improving amphiphilic polypropylenes by grafting poly(vinylpyrrolidone) and poly(ethylene glycol) methacrylate segments on a polypropylene microporous membrane

NASA Astrophysics Data System (ADS)

Chen, Huirong; Ma, Wenzhong; Xia, Yanping; Gu, Yi; Cao, Zheng; Liu, Chunlin; Yang, Haicun; Tao, Shengxi; Geng, Haoran; Tao, Guoliang; Matsuyama, Hideto

2017-10-01

An amphiphilic polypropylene-g-poly[vinylpyrrolidone-co-poly(ethylene glycol) methacrylate] (PP-g-(NVP-co-PEGMA)) modifier was prepared by melt grafting polymerization using N-vinyl pyrrolidone (NVP) as the grafting monomer and poly(ethylene glycol) (PEGMA) as the comonomer. Fourier transform infrared (FTIR) spectroscopy and elemental analysis showed that the hydrophilic branched chains (NVP-g-PEGMA) were successfully grafted to polypropylene (PP) macromolecular chains. The largest NVP grafting degree for PP-g-(NVP-co-PEGMA) (up to 20.4%) was obtained when the mass ratio of PP/NVP/PEGMA was 100/30/15. Hydrophilic PP microporous membranes were prepared by stretching cast films of PP/PP-g-(NVP-co-PEGMA) blends. The membrane thermostability (including the modifier) was better than that of the pure PP membrane with a similar surface pore structure. The porosity of the modified membranes was only slightly lower than that of the pure PP membranes. Contact angle measurements were used to examine the hydrophilicity of the membranes. The water contact angle of the membranes decreased when PP-g-(NVP-co-PEGMA) was added, and the minimum contact angle was 64.5°. Therefore, this work provides a good application for stretched hydrophilic PP membrane fabrication.

Neoplastic causes of abnormal puberty.

PubMed

Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

2014-04-01

Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

Study of the Outflow and Disk surrounding a Post-Outburst FU-Orionis Star

NASA Astrophysics Data System (ADS)

Mellon, Samuel N.; Perez, L. M.

2014-01-01

PP 13 is a fan-shaped cometary nebula located in the constellation of Perseus and embedded in the L1473 dark cloud. At optical wavelengths this region is obscured by the surrounding dark cloud, while at infrared and longer wavelengths two northern objects (PP13Na & PP13Nb) and one southern object (PP13S) are revealed. In the past, the young stellar object inside PP13S, called PP13S*, experienced an FU-Orionis type outburst due to a massive accretion episode and is currently returning to its quiescent state. Studying the FU-Orionis phase is crucial to our understanding of how low mass stars form; it is theorized that all low-mass stars go through this outburst phase while they are forming. I used CARMA 3mm interferometric observations of the PP13 region to study the continuum and molecular line emissions from PP13. With these observations, I determined the source of the previously detected outflow and learned new information about the double star system PP13Na and PP13Nb. Although I was not able to detect the accretion disk in the gas emissions, I plan to use computer modeling to help provide constraints on the properties of PP13S* and its outflow.

A wheat (Triticum aestivum) protein phosphatase 2A catalytic subunit gene provides enhanced drought tolerance in tobacco.

PubMed

Xu, Chongyi; Jing, Ruilian; Mao, Xinguo; Jia, Xiaoyun; Chang, Xiaoping

2007-03-01

Multiple copies of genes encoding the catalytic subunit (c) of protein phosphatase 2A (PP2A) are commonly found in plants. For some of these genes, expression is up-regulated under water stress. The aim of this study was to investigate expression and characterization of TaPP2Ac-1 from Triticum aestivum, and to evaluate the effects of TaPP2Ac-1 on Nicotiana benthamiana in response to water stress. TaPP2Ac-1 cDNA was isolated from wheat by in silico identification and RT-PCR amplification. Transcript levels of TaPP2Ac-1 were examined in wheat responding to water deficit. Copy numbers of TaPP2Ac-1 in wheat genomes and subcellular localization in onion epidermal cells were studied. Enzyme properties of the recombinant TaPP2Ac-1 protein were determined. In addition, studies were carried out in tobacco plants with pCAPE2-TaPP2Ac-1 under water-deficit conditions. TaPP2Ac-1 cDNA was cloned from wheat. Transcript levels of TaPP2Ac-1 in wheat seedlings were up-regulated under drought condition. One copy for this TaPP2Ac-1 was present in each of the three wheat genomes. TaPP2Ac-1 fused with GFP was located in the nucleus and cytoplasm of onion epidermis cells. The recombinant TaPP2Ac-1 gene was over-expressed in Escherichia coli and encoded a functional serine/threonine phosphatase. Transgenic tobacco plants over-expressing TaPP2Ac-1 exhibited stronger drought tolerance than non-transgenic tobacco plants. Tobacco plants with pCAPE2-TaPP2Ac-1 appeared to be resistant to water deficit, as shown by their higher capacity to maintain leaf relative water content, leaf cell-membrane stability index, water-retention ability and water use efficiency under water stress. The results suggest that the physiological role of TaPP2Ac-1 is related to drought stress response, possibly through its involvement in drought-responding signal transduction pathways.

Phrase Length and Prosody in On-Line Ambiguity Resolution

ERIC Educational Resources Information Center

Webman-Shafran, Ronit; Fodor, Janet Dean

2016-01-01

We investigated the processing of ambiguous double-PP constructions in Hebrew. Selection restrictions forced the first prepositional phrase (PP1) to attach low, but PP2 could attach maximally high to VP or maximally low to the NP inside PP1. A length contrast in PP2 was also examined. This construction affords more potential locations for prosodic…

Mechanisms of pulse pressure amplification dipping pattern during sleep time: the SAFAR study.

PubMed

Argyris, Antonios A; Nasothimiou, Efthimia; Aissopou, Evaggelia; Papaioannou, Theodoros G; Zhang, Yi; Blacher, Jacques; Safar, Michel E; Sfikakis, Petros P; Protogerou, Athanase D

2018-02-01

The difference in pulse pressure (PP) between peripheral arteries and the aorta, called pulse pressure amplification (PPamp), is a well-described physiological phenomenon independently associated with cardiovascular events. Recent studies suggest that it exhibits circadian variability. Our aim was to detect the factors associated with the circadian variability of PPamp. In 497 consecutive subjects (aged 54 years, 56.7% male, 79.7% hypertensives), we assessed the circadian pattern of peripheral and central arterial hemodynamics by 24-hour evaluation of brachial and aortic blood pressure (BP), augmentation index (AI), and pulse wave velocity (PWV) using a validated oscillometric device (Mobil-O-Graph). All parameters exhibited a circadian variation. Sleep dipping (decrease) pattern was observed for PPamp, brachial and aortic systolic BP, mean BP, and PWV, whereas a rising pattern (higher sleep than wake values) was observed for brachial PP, aortic PP, and AI. The factors independently associated with the less sleep dipping in PPamp were older age, lower height, the use of antihypertensive medication, and sleep decrease in arterial stiffness (PWV), whereas female gender, the presence of hypertension, sleep increase of pressure wave reflections (AI), sleep decrease in heart rate, and mean BP were associated with a greater sleep-dipping in PPamp. These data provide further pathophysiological understanding of the mechanisms leading to PPamp dipping. Several implications regarding the clinical use of the aortic and brachial BP, especially during sleep time, are raised that should be addressed in future research. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Competition between two virulent Marek's disease virus strains in vivo.

PubMed

Dunn, John R; Silva, Robert F; Lee, Lucy F; Witter, Richard L

2012-01-01

Previous studies have demonstrated the presence of multiple strains of Marek's disease virus simultaneously circulating within poultry flocks, leading to the assumption that individual birds are repeatedly exposed to a variety of virus strains in their lifetime. Virus competition within individual birds may be an important factor that influences the outcome of co-infection under field conditions, including the potential outcome of emergence or evolution of more virulent strains. A series of experiments was designed to evaluate virus competition within chickens following simultaneous challenge with two virulent serotype 1 Marek's disease virus strains, using either pathogenically similar (rMd5 and rMd5/pp38CVI) or dissimilar (JM/102W and rMd5/pp38CVI) virus pairs. Bursa of Fabricius, feather follicle epithelium, spleen, and tumour samples were collected at multiple time points to determine the frequency and distribution of each virus present using pyrosequencing, immunohistochemistry and virus isolation. In the similar pair, rMd5 appeared to have a competitive advantage over rMd5/pp38CVI, which in turn had a competitive advantage over the less virulent JM/102W in the dissimilar virus pair. Dominance of one strain over the other was not absolute for either virus pair, as the subordinate virus was rarely eliminated. Interestingly, competition between two viruses with either pair rarely ended in a draw. Further work is needed to identify factors that influence virus-specific dominance to better understand what characteristics favour emergence of one strain in chicken populations at the expense of other strains.

Search for ZH → l+ l- bb production in 4.2 fb(-1) of pp collisions at sqrt[s] =1 .96 TeV.

PubMed

Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Ancu, L S; Aoki, M; Arnoud, Y; Arov, M; Askew, A; Asman, B; Atramentov, O; Avila, C; BackusMayes, J; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brandt, O; Brock, R; Brooijmans, G; Bross, A; Brown, D; Brown, J; Bu, X B; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Calpas, B; Calvet, S; Camacho-Pérez, E; Carrasco-Lizarraga, M A; Carrera, E; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Chen, G; Chevalier-Théry, S; Cho, D K; Cho, S W; Choi, S; Choudhary, B; Christoudias, T; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Croc, A; Cutts, D; Cwiok, M; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; DeVaughan, K; Diehl, H T; Diesburg, M; Dominguez, A; Dorland, T; Dubey, A; Dudko, L V; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fuess, S; Gadfort, T; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Geng, W; Gerbaudo, D; Gerber, C E; Gershtein, Y; Ginther, G; Golovanov, G; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Hagopian, S; Haley, J; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Hebbeker, T; Hedin, D; Hegab, H; Heinson, A P; Heintz, U; Hensel, C; Heredia-De La Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hohlfeld, M; Hossain, S; Hubacek, Z; Huske, N; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jamin, D; Jesik, R; Johns, K; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Joshi, J; Juste, A; Kaadze, K; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Khatidze, D; Kirby, M H; Kohli, J M; Kozelov, A V; Kraus, J; Kumar, A; Kupco, A; Kurča, T; Kuzmin, V A; Kvita, J; Lammers, S; Landsberg, G; Lebrun, P; Lee, H S; Lee, S W; Lee, W M; Lellouch, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Mackin, D; Madar, R; Magaña-Villalba, R; Malik, S; Malyshev, V L; Maravin, Y; Martínez-Ortega, J; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Menezes, D; Mercadante, P G; Merkin, M; Meyer, A; Meyer, J; Mondal, N K; Muanza, G S; Mulhearn, M; Nagy, E; Naimuddin, M; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Novaes, S F; Nunnemann, T; Obrant, G; Onoprienko, D; Orduna, J; Osman, N; Osta, J; Otero y Garzón, G J; Owen, M; Padilla, M; Pangilinan, M; Parashar, N; Parihar, V; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Penning, B; Perfilov, M; Peters, K; Peters, Y; Petrillo, G; Pétroff, P; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pol, M-E; Polozov, P; Popov, A V; Prewitt, M; Price, D; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Ranjan, K; Ratoff, P N; Razumov, I; Renkel, P; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Rominsky, M; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Santos, A S; Savage, G; Sawyer, L; Scanlon, T; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shary, V; Shchukin, A A; Shivpuri, R K; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Smith, K J; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Stolin, V; Stoyanova, D A; Strauss, E; Strauss, M; Strom, D; Stutte, L; Svoisky, P; Takahashi, M; Tanasijczuk, A; Taylor, W; Titov, M; Tokmenin, V V; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Uvarov, L; Uvarov, S; Uzunyan, S; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vilanova, D; Vint, P; Vokac, P; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, M; Wetstein, M; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Xu, C; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, Z; Yin, H; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L

2010-12-17

We present a search for the standard model Higgs boson produced in association with a Z boson in 4.2 fb(-1) of pp collisions, collected with the D0 detector at the Fermilab Tevatron at sqrt[s] =1 .96 TeV. Selected events contain one reconstructed Z → e+ e- or Z → μ+ μ- candidate and at least two jets, including at least one b-tagged jet. In the absence of an excess over the background expected from other standard model processes, limits on the ZH cross section multiplied by the branching ratios are set. The limit at M(H) = 115  GeV is a factor of 5.9 larger than the standard model prediction.

Quantum dot-based western blot for sensitive detection of pig serum antibody to actinobacillus pleuropneumoniae

NASA Astrophysics Data System (ADS)

Cişmileanu, Ana; Sima, Cornelia; Grigoriu, Constantin

2007-08-01

A quantum dot - immunoglobulin conjugate specific for pig IgG, was obtained by carbodiimide chemistry. We used a Western blot technique for detecting specific antibodies against Actinobacillus pleuropneumoniae (A. pp), which cause porcine pleuropneumonia. The antigen used in this technique was Apx haemolysin which is an important virulence factor of A. pp and it induces protective immunity in vaccined pigs. The detection on Western blot membrane was possible at 1/50 dilution of quantum dot conjugate at a dilution of pig serum till 1/6400. The results for pig serum demonstrated a higher sensitivity of QD-based Western blot technique for the presence of antibodies specific for Apx haemolysin in comparison with similar classical techniques (with coloured substrate for enzyme present in secondary antibody conjugate).

Search for V+A current in top-quark decays in pp collisions at sqrts=1.96 TeV.

PubMed

Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Carron, S; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Almenar, C Cuenca; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; Daronco, S; Datta, M; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; Cecco, S De; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; Dituro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Grundler, U; da Costa, J Guimaraes; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Fernandez, P Movilla; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; Denis, R St; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-02-16

We report an upper limit on the fraction of V+A current, fV+A, in top-quark decays, using approximately 700 pb-1 of pp[over ] collisions at sqrts=1.96 TeV acquired by the upgraded Collider Detector at Fermilab. For the decay t-->Wb-->lnub (where l=e or micro), the invariant mass of the charged lepton and the bottom quark jet is sensitive to the polarization of the W boson. We determine fV+A=-0.06+/-0.25 given a top-quark mass of 175 GeV/c2. We set an upper limit on fV+A of 0.29 at the 95% confidence level, an improvement by a factor of 2 on the previous best direct limit.

Effect of Photon Radiations in Semi-Rigid Artificial Tissue Sensitized by Protoporphyrin IX Encapsulated with Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Makhadmeh, Ghaseb N.; Aziz, Azlan Abdul; Razak, Khairunisak Abdul; Al-Akhras, M.-Ali H.

2018-02-01

This study involves the synthesis of Protoporphyrin IX (PpIX) encapsulated with Silica Nanoparticles (SiNPs) as an application for Photodynamic therapy. Semi-rigid artificial tissues with optical features similar to human tissue were used as sample materials to ascertain the efficacy of PpIX encapsulated with SiNPs. The disparity in optical characteristics (transmittance, reflectance, scattering, and absorption) of tissues treated with encapsulated PpIX and naked PpIX under light exposure (Intensity at 408 nm ~1.19 mW/cm2) was explored. The optimal exposure times required for naked PpIX and SiNPs encapsulated PpIX to engulf Red Blood Cells (RBCs) in the artificial tissue were subsequently measured. Comparative analysis showed that the encapsulated PpIX has a 91.5 % higher efficacy than naked PpIX. The results prove the applicability of PpIX encapsulated with SiNP on artificial tissue and possible use on human tissue.

Correction to Sahakyan and Delaney (2005)

ERIC Educational Resources Information Center

Sahakyan, Lili; Delaney, Peter F.

2005-01-01

This article reports an error concerning the article "Directed Forgetting in Incidental Learning and Recognition Testing: Support for a Two-Factor Account" by Lili Sahakyan and Peter F. Delaney ("Journal of Experimental Psychology: Learning, Memory, and Cognition," Vol. 31, No. 4, pp. 789-801). The article was misidentified in the July issue as an…

Is Behavior Change a Legitimate Objective for the Health Educator?

ERIC Educational Resources Information Center

Russell, Robert D.

1983-01-01

Pros and cons of making behavior change a primary objective of health education are summarized. The individual's right to choose his/her lifestyle is emphasized; health educators are encouraged to use holistic approaches to health education, emphasizing not only physical consequences of behavior but emotional and social factors as well. (PP)

Stress-Intensity Factors for Three-Point Bend Specimens by Boundary Collocation

DTIC Science & Technology

1965-12-01

ref. 5) and by Kies, Smith, Romine, and Bernstein (ref. 6). Limited results of an analytical study by H. F. Bueckner have been published by Wundt (ref...Weldments. Fracture Toughness Testing and Its Applications, STP No. 381, ASTM, 1965, pp. 328-356. 7. Wundt , B. M.: A Unified Interpretation of Room

A Framework for Event Prioritization in Cyber Network Defense

DTIC Science & Technology

2014-07-15

U.S.," Reuters (US online Edition), pp. http://www.reuters.com/article/2013/11/06/net-us-usa-china- hacking - idUSBRE9A51AN20131106, 6 Nov 2013. [2...expressed individually, or as a single vector by using the magnitude of these three factors (cell J5 in Table 5

Microcystins from tap water could be a risk factor for liver and colorectal cancer: a risk intensified by global change.

PubMed

Martínez Hernández, Juan; López-Rodas, V; Costas, E

2009-05-01

An increasing number of people drink water from fresh water supply reservoirs. However, with the global change a lot of reservoirs become eutrophic, which facilitates the occurrence of toxin-producing cyanobacterial blooms. Microcystins (powerful hepatotoxic water-soluble heptapeptides) are the most important cyanobacterial toxins affecting humans. High doses of microcystins produce hepatic necrosis. Consequently, WHO Guidelines limit microcystins to 1 ppb in drinking waters. However, microcystins are present frequently in tap water at lower doses. Here, we hypothesized that chronic consume of tap water containing low doses of microcystins may be a risk factor for liver and colorectal cancer. Two kinds of evidences support this hypothesis. On one hand some epidemiological data (mainly in China). On the other hand, the molecular mechanism of microcystins toxicity (inhibition of protein phosphatases PP1 and PP2) is just like okadaic acid (a potent tumor promoter). Cancer risk from drinking water is certainly less than smoking, occupational exposures or some foods. But it is significant and with a rapid increase of toxic cyanobacterial blooms by eutrophycation, become more frequent.

Measurement of prompt $$\\psi$$(2S) production cross sections in proton-lead and proton-proton collisions at $$\\sqrt{s_{_\\mathrm{NN}}}=$$ 5.02 TeV

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

Sirunyan, Albert M; et al.

2018-05-06

Measurements of promptmore » $$\\psi$$(2S) meson production cross sections in proton-lead (pPb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of $$\\sqrt{s_{_\\mathrm{NN}}}=$$ 5.02 TeV are reported. The results are based on pPb and pp data collected by the CMS experiment at the LHC, corresponding to integrated luminosities of 34.6 nb$$^{-1}$$ and 28.0 pb$$^{-1}$$, respectively. The nuclear modification factor $$R_\\mathrm{pPb}$$ is measured for prompt $$\\psi$$(2S) in the transverse momentum range 4 $<$ p$$_\\mathrm{T}$$ $<$ 30 GeV$/c$ and the center-of-mass rapidity range $-$2.4 $$< y_\\mathrm{cm} <$$ 1.93. The results on $$\\psi$$(2S) $$R_\\mathrm{pPb}$$ are compared to the corresponding modification factor for prompt J$$/\\psi$$ mesons and are found to be more suppressed than the J$$/\\psi$$ states over the entire kinematic range studied.« less

Losing oneself upon placement in another's position: the influence of perspective on self-referential processing.

PubMed

Zhang, Tianyang; Zhu, Ying; Wu, Yanhong

2014-07-01

Self-referential processing is considered to be an essential index for exploring self-consciousness. However, whether perspective is the determining factor of the self-reference effect (SRE), which is accompanied by self-referential processing, has not been established. The present study aims to address this issue by using a self-reference paradigm, in which the participants perform a self-reference task while adopting different perspectives. Our results showed that trait words presented with the self in the first-person perspective (1PP) were better remembered compared to trait words presented with others. Interestingly, these SREs were decreased and even reversed in the third-person perspective. When the participants viewed themselves based on their friend's perspective, no significant difference was found between the recognition performances of self- and friend-trait words. Moreover, an improved "remember" recognition performance of friend-trait words was found. These findings support the assumption that the 1PP is a necessary factor for self-advantage in self-referential processing. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficient technical solution for recycling textile materials by manufacturing nonwoven geotextiles

NASA Astrophysics Data System (ADS)

Leon, A. L.; Potop, G. L.; Hristian, L.; Manea, L. R.

2016-08-01

This paper aims to support the concept "circular economy" that was developed recently. It presents an efficient method for creating a closed loop in the Romanian textile industry by recycling textile materials, such as polyacrylonitrile knitted old products (collected from population) and small polyester woven patches from pre-consumer waste (garments manufacturing companies). Because of their properties, nonwoven geotextiles have many advantages in railways reinforcement, slopes stabilization, erosion control, drainage, filtration, paving roads, crops coverings, etc. The nonwoven geotextiles were obtained from three fibrous blends based on recovered fibers (PES and PAN) and fibers at first usage (PP) in different ratios. All experimental variants were processed on the same manufacturing line with the same technological parameters. There were tested the main physical and mechanical parameters and it was applied single factor ANOVA method for thickness, bulk density, air permeability and static puncture strength. The conclusion is that adding PP fibers in the blends represents a very important factor for geotextiles characteristics but it possible to decrease the ratio from economical reasons and still maintain a high quality level of nonwovens.

Variations and controlling factors of the coccolith weight in the Western Pacific Warm Pool over the last 200 ka

NASA Astrophysics Data System (ADS)

Liang, Dan; Liu, Chuanlian

2016-06-01

Using a coccolith weight analytic software (Particle Analyser), we analyze most abundant coccolith species in a sediment core from the central Western Pacific Warm Pool (WPWP) and calculate coccolith size and weight variations over the last 200 ka. These variations are compared with the trends of sea surface temperature (SST), primary productivity (PP), sea surface salinity (SSS), and insolation. Our results demonstrate that the size and weight of the coccoliths varied in response to variations of these factors, and their average total weight is primarily related to the relative abundance of the dominant species GEO ( Gephyrocapsa oceanica). The variation in weight of EMI ( Emiliania huxleyi) and GEE ( Gephyrocapsa ericsonii) are mainly influenced by nutrients, and the variation of GEM ( G. muellerae conformis) and GEO ( G. oceanica) weight are mainly influenced by SST. For all of the taxa weight, PP and SST present apparent precession or semi-precession cycles, we consider that the mono-coccolith weight of the Equatorial Western Pacific is primarily affected by precession drived thermocline and nutricline variation.

[Adhesion loss of syrups in a metering glass which consists of a low surface free energy material].

PubMed

Yamamoto, Yoshihisa; Suzuki, Toyofumi; Hashizaki, Kaname; Ogura, Masao; Umeda, Yukiko; Hidaka, Shinji; Fukami, Toshiro; Tomono, Kazuo

2010-08-01

We previously reported a strong positive correlation between syrup viscosity and the rate of syrup loss due to adhesion to a glass metering device. In this study, we examined differences in the surface free energies of metering devices made of different polymeric materials, since reducing adhesion loss to metering devices could improve the efficiency of drug preparation involving highly viscous syrups. Among metering devices made of glass only, glass with a silicone coating (SLC), polypropylene (PP), and polymethylpentene (PMP) the surface free energy of the glass-only metering device was the highest (49.2 mN/m). The adhesion loss obtained for highly viscous syrups in the PP and PMP metering devices was significantly lower than that of the glass metering device. Measurements of syrup contact angles suggested that in metering devices made of PP and PMP, which have low surface free energies, a decrease in the spreading wetting of syrups was a factor in reducing the rate of adhesion loss. Thus irrespective of the syrup viscosity being measured, metering devices produced from materials with low surface free energies can reduce the time required to prepare prescriptions without compromising the accuracy of drug preparation.

Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice.

PubMed

Yulyaningsih, Ernie; Loh, Kim; Lin, Shu; Lau, Jackie; Zhang, Lei; Shi, Yanchuan; Berning, Britt A; Enriquez, Ronaldo; Driessler, Frank; Macia, Laurence; Khor, Ee Cheng; Qi, Yue; Baldock, Paul; Sainsbury, Amanda; Herzog, Herbert

2014-01-07

Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r(-/-)) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. Npy6r(-/-) mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r(-/-), mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r(-/-), mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition. Copyright © 2014 Elsevier Inc. All rights reserved.

Bio-composites fabricated by sandwiching sisal fibers with polypropylene (PP)

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

Sosiati, H., E-mail: hsosiati@gmail.com; Nahyudin, A., E-mail: ahmadnahyudin@yahoo.co.id; Fauzi, I., E-mail: ikhsannurfauzi@gmail.com

Sisal fibers reinforced polypropylene (PP) composites were successfully fabricated using sandwiching sisal fibers with PP sheets. The ratio of fiber and polymer matrix was 50:50 (wt. %). Untreated short and long sisal fibers, and alkali treated short sisal fibers in 6% NaOH at 100°C for 1 and 3 h were used as reinforcement or fillers. A small amount (3 wt. %) of maleic anhydride grafted polypropylene (MAPP) was added as a coupling agent. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were used to characterize the surface morphology and chemical composition of the fibers, respectively. Flexural test of sisal/PPmore » composites was done according to ASTM D 790-02. The results showed that flexural strength of untreated long fiber reinforced composite is much higher than that of the untreated and alkali treated short fibers reinforced composites with and without the addition of MAPP. Alkalization related to fiber surface modification, fiber length/fiber orientation and a composite fabrication technique are important factors in contributing to the fiber distribution within the matrix, the bonding between the fiber and the matrix and the enhancement of flexural strength of the bio-composite.« less

The geographical distribution and prevalence of Echinococcus multilocularis in animals in the European Union and adjacent countries: a systematic review and meta-analysis.

PubMed

Oksanen, Antti; Siles-Lucas, Mar; Karamon, Jacek; Possenti, Alessia; Conraths, Franz J; Romig, Thomas; Wysocki, Patrick; Mannocci, Alice; Mipatrini, Daniele; La Torre, Giuseppe; Boufana, Belgees; Casulli, Adriano

2016-09-28

This study aimed to provide a systematic review on the geographical distribution of Echinococcus multilocularis in definitive and intermediate hosts in the European Union (EU) and adjacent countries (AC). The relative importance of the different host species in the life-cycle of this parasite was highlighted and gaps in our knowledge regarding these hosts were identified. Six databases were searched for primary research studies published from 1900 to 2015. From a total of 2,805 identified scientific papers, 244 publications were used for meta-analyses. Studies in 21 countries reported the presence of E. multilocularis in red foxes, with the following pooled prevalence (PP): low (≤ 1 %; Denmark, Slovenia and Sweden); medium (> 1 % to < 10 %; Austria, Belgium, Croatia, Hungary, Italy, the Netherlands, Romania and the Ukraine); and high (> 10 %; Czech Republic, Estonia, France, Germany, Latvia, Lithuania, Poland, Slovakia, Liechtenstein and Switzerland). Studies from Finland, Ireland, the United Kingdom and Norway reported the absence of E. multilocularis in red foxes. However, E. multilocularis was detected in Arctic foxes from the Arctic Archipelago of Svalbard in Norway. Raccoon dogs (PP 2.2 %), golden jackals (PP 4.7 %) and wolves (PP 1.4 %) showed a higher E. multilocularis PP than dogs (PP 0.3 %) and cats (PP 0.5 %). High E. multilocularis PP in raccoon dogs and golden jackals correlated with high PP in foxes. For intermediate hosts (IHs), muskrats (PP 4.2 %) and arvicolids (PP 6.0 %) showed similar E. multilocularis PP as sylvatic definitive hosts (DHs), excluding foxes. Nutrias (PP 1.0 %) and murids (PP 1.1 %) could play a role in the life-cycle of E. multilocularis in areas with medium to high PP in red foxes. In areas with low PP in foxes, no other DH was found infected with E. multilocularis. When fox E. multilocularis PP was >3 %, raccoon dogs and golden jackals could play a similar role as foxes. In areas with high E. multilocularis fox PP, the wolf emerged as a potentially important DH. Dogs and cats could be irrelevant in the life-cycle of the parasite in Europe, although dogs could be important for parasite introduction into non-endemic areas. Muskrats and arvicolids are important IHs. Swine, insectivores, murids and nutrias seem to play a minor or no role in the life-cycle of the parasite within the EU and ACs.

The ability of pulse pressure variations obtained with CNAP™ device to predict fluid responsiveness in the operating room.

PubMed

Biais, Matthieu; Stecken, Laurent; Ottolenghi, Laetitia; Roullet, Stéphanie; Quinart, Alice; Masson, Françoise; Sztark, François

2011-09-01

Respiratory-induced pulse pressure variations obtained with an arterial line (ΔPP(ART)) indicate fluid responsiveness in mechanically ventilated patients. The Infinity® CNAP™ SmartPod® (Dräger Medical AG & Co. KG, Lübeck, Germany) provides noninvasive continuous beat-to-beat arterial blood pressure measurements and a near real-time pressure waveform. We hypothesized that respiratory-induced pulse pressure variations obtained with the CNAP system (ΔPP(CNAP)) predict fluid responsiveness as well as ΔPP(ART) predicts fluid responsiveness in mechanically ventilated patients during general anesthesia. Thirty-five patients undergoing vascular surgery were studied after induction of general anesthesia. Stroke volume (SV) measured with the Vigileo™/FloTrac™ (Edwards Lifesciences, Irvine, CA), ΔPP(ART), and ΔPP(CNAP) were recorded before and after intravascular volume expansion (VE) (500 mL of 6% hydroxyethyl starch 130/0.4). Subjects were defined as responders if SV increased by ≥15% after VE. Twenty patients responded to VE and 15 did not. The correlation coefficient between ΔPP(ART) and ΔPP(CNAP) before VE was r = 0.90 (95% confidence interval [CI] = 0.84-0.96; P < 0.0001). Before VE, ΔPP(ART) and ΔPP(CNAP) were significantly higher in responders than in nonresponders (P < 0.0001). The values of ΔPP(ART) and ΔPP(CNAP) before VE were significantly correlated with the percent increase in SV induced by VE (respectively, r(2) = 0.50; P < 0.0001 and r(2) = 0.57; P < 0.0001). Before VE, a ΔPP(ART) >10% discriminated between responders and nonresponders with a sensitivity of 90% (95% CI = 69%-99%) and a specificity of 87% (95% CI = 60%-98%). The area under the receiver operating characteristic (ROC) curve was 0.957 ± 0.035 for ΔPP(ART). Before VE, a ΔPP(CNAP) >11% discriminated between responders and nonresponders with a sensitivity of 85% (95% CI = 62%-97%) and a specificity of 100% (95% CI = 78%-100%). The area under the ROC curve was 0.942 ± 0.040 for ΔPP(CNAP). There was no significant difference between the area under the ROC curve for ΔPP(ART) and ΔPP(CNAP). A value of ΔPP(CNAP) >11% has a sensitivity of at least 62% in predicting preload-dependent responders to VE in mechanically ventilated patients during general anesthesia.

A Generalization of SAT and #SAT for Robust Policy Evaluation

DTIC Science & Technology

2014-06-30

PNP [1]. Corollary 1. PPNP [1] ⊆ NP PP Proof. Follows from Toda’s theorem [ Toda , 1991] (middle inclusion): PPNP [1] ⊆ PP PH ⊆ P PP ⊆ NP PP . 8 This...dynamic programming for first-order POMDPs. In AAAI, 2010. S. Toda . PP is as hard as the polynomial-time hierarchy. SIAM Journal on Computing, 20:865

Expression of peach sucrose transporters in heterologous systems points out their different physiological role.

PubMed

Zanon, Laura; Falchi, Rachele; Hackel, Aleksandra; Kühn, Christina; Vizzotto, Giannina

2015-09-01

Sucrose is the major phloem-translocated component in a number of economically important plant species. The comprehension of the mechanisms involved in sucrose transport in peach fruit appears particularly relevant, since the accumulation of this sugar, during ripening, is crucial for the growth and quality of the fruit. Here, we report the functional characterisation and subcellular localisation of three sucrose transporters (PpSUT1, PpSUT2, PpSUT4) in peach, and we formulate novel hypotheses about their role in accumulation of sugar. We provide evidence, about the capability of both PpSUT1 and PpSUT4, expressed in mutant yeast strains to transport sucrose. The functionality of PpSUT1 at the plasma membrane, and of PpSUT4 at the tonoplast, has been demonstrated. On the other hand, the functionality of PpSUT2 was not confirmed: this protein is unable to complement two sucrose uptake-deficient mutant yeast strains. Our results corroborate the hypotheses that PpSUT1 partakes in phloem loading in leaves, and PpSUT4 sustains cell metabolism by regulating sucrose efflux from the vacuole. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Preparation and Compatibility Evaluation of Polypropylene/High Density Polyethylene Polyblends

PubMed Central

Lin, Jia-Horng; Pan, Yi-Jun; Liu, Chi-Fan; Huang, Chien-Lin; Hsieh, Chien-Teng; Chen, Chih-Kuang; Lin, Zheng-Ian; Lou, Ching-Wen

2015-01-01

This study proposes melt-blending polypropylene (PP) and high density polyethylene (HDPE) that have a similar melt flow index (MFI) to form PP/HDPE polyblends. The influence of the content of HDPE on the properties and compatibility of polyblends is examined by using a tensile test, flexural test, Izod impact test, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and X-ray diffraction (XRD). The SEM results show that PP and HDPE are incompatible polymers with PP being a continuous phase and HDPE being a dispersed phase. The FTIR results show that the combination of HDPE does not influence the chemical structure of PP, indicating that the polyblends are made of a physical blending. The DSC and XRD results show that PP and HDPE are not compatible, and the combination of HDPE is not correlated with the crystalline structure and stability of PP. The PLM results show that the combination of HDPE causes stacking and incompatibility between HDPE and PP spherulites, and PP thus has incomplete spherulite morphology and a smaller spherulite size. However, according to mechanical property test results, the combination of HDPE improves the impact strength of PP. PMID:28793750

Preparation and Compatibility Evaluation of Polypropylene/High Density Polyethylene Polyblends.

PubMed

Lin, Jia-Horng; Pan, Yi-Jun; Liu, Chi-Fan; Huang, Chien-Lin; Hsieh, Chien-Teng; Chen, Chih-Kuang; Lin, Zheng-Ian; Lou, Ching-Wen

2015-12-17

This study proposes melt-blending polypropylene (PP) and high density polyethylene (HDPE) that have a similar melt flow index (MFI) to form PP/HDPE polyblends. The influence of the content of HDPE on the properties and compatibility of polyblends is examined by using a tensile test, flexural test, Izod impact test, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and X-ray diffraction (XRD). The SEM results show that PP and HDPE are incompatible polymers with PP being a continuous phase and HDPE being a dispersed phase. The FTIR results show that the combination of HDPE does not influence the chemical structure of PP, indicating that the polyblends are made of a physical blending. The DSC and XRD results show that PP and HDPE are not compatible, and the combination of HDPE is not correlated with the crystalline structure and stability of PP. The PLM results show that the combination of HDPE causes stacking and incompatibility between HDPE and PP spherulites, and PP thus has incomplete spherulite morphology and a smaller spherulite size. However, according to mechanical property test results, the combination of HDPE improves the impact strength of PP.

Effects of bioDensity Training and Power Plate Whole-Body Vibration on Strength, Balance, and Functional Independence in Older Adults.

PubMed

Smith, Derek T; Judge, Stacey; Malone, Ashley; Moynes, Rebecca C; Conviser, Jason; Skinner, James S

2016-01-01

Reduced strength, balance, and functional independence diminish quality of life and increase health care costs. Sixty adults (82.2 ± 4.9 years) were randomized to a control or three 12-week intervention groups: bioDensity (bD); Power Plate (PP) whole-body vibration (WBV); or bD+PP. bD involved one weekly 5-s maximal contraction of four muscle groups. PP involved two 5-min WBV sessions. Primary outcomes were strength, balance, and Functional Independence Measure (FIM). No groups differed initially. Strength significantly increased 22-51% for three muscle groups in bD and bD+PP (P < .001), with no changes in control and PP. Balance significantly improved in PP and bD+PP but not in control or bD. bD, PP, and bD+PP differentially improved FIM self-care and mobility. Strength improvements from weekly 5-min sessions of bD may impart health/clinical benefits. Balance and leg strength improvements suggest WBV beneficially impacts fall risk and incidence. Improved FIM scores are encouraging and justify larger controlled trials on bD and bD+PP efficacy.

Study of Protein Phosphatase 2A (PP2A) Activity in LPS-Induced Tolerance Using Fluorescence-Based and Immunoprecipitation-Aided Methodology.

PubMed

Sun, Lei; Ii, Adlai L Pappy; Pham, Tiffany T; Shanley, Thomas P

2015-06-29

Protein phosphatase 2A (PP2A) is one of the most abundant intracellular serine/threonine (Ser/Thr) phosphatases accounting for 1% of the total cellular protein content. PP2A is comprised of a heterodimeric core enzyme and a substrate-specific regulatory subunit. Potentially, at least seventy different compositions of PP2A exist because of variable regulatory subunit binding that accounts for various activity modulating numerous cell functions. Due to the constitutive phosphatase activity present inside cells, a sensitive assay is required to detect the changes of PP2A activity under various experimental conditions. We optimized a fluorescence assay (DIFMU assay) by combining it with prior anti-PP2A immunoprecipitation to quantify PP2A-specific phosphatase activity. It is also known that prior exposure to lipopolysaccharides (LPS) induces "immune tolerance" of the cells to subsequent stimulation. Herein we report that PP2A activity is upregulated in tolerized peritoneal macrophages, corresponding to decreased TNF-α secretion upon second LPS stimulation. We further examined the role of PP2A in the tolerance effect by using PP2ACαl°xl°x;lyM-Cre conditional knockout macrophages. We found that PP2A phosphatase activity cannot be further increased by tolerance. TNF-α secretion from tolerized PP2ACαl°xl°x;lyM-Cre macrophages is higher than tolerized control macrophages. Furthermore, we showed that the increased TNF-α secretion may be due to an epigenetic transcriptionally active signature on the promoter of TNF-α gene rather than regulation of the NFκB/IκB signaling pathway. These results suggest a role for increased PP2A activity in the regulation of immune tolerance.

Characterisation and expression of a PP1 serine/threonine protein phosphatase (PfPP1) from the malaria parasite, Plasmodium falciparum: demonstration of its essential role using RNA interference

PubMed Central

Kumar, Rajinder; Adams, Brian; Oldenburg, Anja; Musiyenko, Alla; Barik, Sailen

2002-01-01

Background Reversible protein phosphorylation is relatively unexplored in the intracellular protozoa of the Apicomplexa family that includes the genus Plasmodium, to which belong the causative agents of malaria. Members of the PP1 family represent the most highly conserved protein phosphatase sequences in phylogeny and play essential regulatory roles in various cellular pathways. Previous evidence suggested a PP1-like activity in Plasmodium falciparum, not yet identified at the molecular level. Results We have identified a PP1 catalytic subunit from P. falciparum and named it PfPP1. The predicted primary structure of the 304-amino acid long protein was highly similar to PP1 sequences of other species, and showed conservation of all the signature motifs. The purified recombinant protein exhibited potent phosphatase activity in vitro. Its sensitivity to specific phosphatase inhibitors was characteristic of the PP1 class. The authenticity of the PfPP1 cDNA was further confirmed by mutational analysis of strategic amino acid residues important in catalysis. The protein was expressed in all erythrocytic stages of the parasite. Abrogation of PP1 expression by synthetic short interfering RNA (siRNA) led to inhibition of parasite DNA synthesis. Conclusions The high sequence similarity of PfPP1 with other PP1 members suggests conservation of function. Phenotypic gene knockdown studies using siRNA confirmed its essential role in the parasite. Detailed studies of PfPP1 and its regulation may unravel the role of reversible protein phosphorylation in the signalling pathways of the parasite, including glucose metabolism and parasitic cell division. The use of siRNA could be an important tool in the functional analysis of Apicomplexan genes. PMID:12057017

SILAC-based phosphoproteomics reveals new PP2A-Cdc55-regulated processes in budding yeast.

PubMed

Baro, Barbara; Játiva, Soraya; Calabria, Inés; Vinaixa, Judith; Bech-Serra, Joan-Josep; de LaTorre, Carolina; Rodrigues, João; Hernáez, María Luisa; Gil, Concha; Barceló-Batllori, Silvia; Larsen, Martin R; Queralt, Ethel

2018-05-01

Protein phosphatase 2A (PP2A) is a family of conserved serine/threonine phosphatases involved in several essential aspects of cell growth and proliferation. PP2ACdc55 phosphatase has been extensively related to cell cycle events in budding yeast; however, few PP2ACdc55 substrates have been identified. Here, we performed a quantitative mass spectrometry approach to reveal new substrates of PP2ACdc55 phosphatase and new PP2A-related processes in mitotic arrested cells. We identified 62 statistically significant PP2ACdc55 substrates involved mainly in actin-cytoskeleton organization. In addition, we validated new PP2ACdc55 substrates such as Slk19 and Lte1, involved in early and late anaphase pathways, and Zeo1, a component of the cell wall integrity pathway. Finally, we constructed docking models of Cdc55 and its substrate Mob1. We found that the predominant interface on Cdc55 is mediated by a protruding loop consisting of residues 84-90, thus highlighting the relevance of these aminoacids for substrate interaction. We used phosphoproteomics of Cdc55-deficient cells to uncover new PP2ACdc55 substrates and functions in mitosis. As expected, several hyperphosphorylated proteins corresponded to Cdk1-dependent substrates, although other kinases' consensus motifs were also enriched in our dataset, suggesting that PP2ACdc55 counteracts and regulates other kinases distinct from Cdk1. Indeed, Pkc1 emerged as a novel node of PP2ACdc55 regulation, highlighting a major role of PP2ACdc55 in actin cytoskeleton and cytokinesis, gene ontology terms significantly enriched in the PP2ACdc55-dependent phosphoproteome.

Iron Bioavailability from Ferric Pyrophosphate in Extruded Rice Cofortified with Zinc Sulfate Is Greater than When Cofortified with Zinc Oxide in a Human Stable Isotope Study.

PubMed

Hackl, Laura; Zimmermann, Michael B; Zeder, Christophe; Parker, Megan; Johns, Paul W; Hurrell, Richard F; Moretti, Diego

2017-03-01

Background: Extruded rice grains are often cofortified with iron and zinc. However, it is uncertain if the addition of zinc to iron-fortified rice affects iron absorption and whether this is zinc-compound specific. Objective: We investigated whether zinc, added as zinc oxide (ZnO) or zinc sulfate (ZnSO 4 ), affects human iron absorption from extruded rice fortified with ferric pyrophosphate (FePP). Methods: In 19 iron-depleted Swiss women (plasma ferritin ≤16.5 μ/L) aged between 20 and 39 y with a normal body mass index (in kg/m 2 ; 18.7-24.8), we compared iron absorption from 4 meals containing fortified extruded rice with 4 mg Fe and 3 mg Zn. Three of the meals contained extruded rice labeled with FePP ( 57 FePP): 1 ) 1 meal without added zinc ( 57 FePP-Zn), 2 ) 1 cofortified with ZnO ( 57 FePP+ZnO), and 3 ) 1 cofortified with ZnSO 4 ( 57 FePP+ZnSO 4 ). The fourth meal contained extruded rice without iron or zinc, extrinsically labeled with ferrous sulfate ( 58 FeSO 4 ) added as a solution after cooking. All 4 meals contained citric acid. Iron bioavailability was measured by isotopic iron ratios in red blood cells. We also measured relative in vitro iron solubility from 57 FePP-Zn, 57 FePP+ZnO, and 57 FePP+ZnSO 4 expressed as a fraction of FeSO 4 solubility. Results: Geometric mean fractional iron absorption (95% CI) from 57 FePP+ZnSO 4 was 4.5% (3.4%, 5.8%) and differed from 57 FePP+ZnO (2.7%; 1.8%, 4.1%) ( P < 0.03); both did not differ from 57 FePP-Zn: 4.0% (2.8%, 5.6%). Relative iron bioavailabilities compared with 58 FeSO 4 were 62%, 57%, and 38% from 57 FePP+ZnSO 4 , 57 FePP-Zn, and 57 FePP+ZnO, respectively. In vitro solubility from 57 FePP+ZnSO 4 differed from that of 57 FePP-Zn (14.3%; P < 0.02) but not from that of 57 FePP+ZnO (10.2% compared with 13.1%; P = 0.08). Conclusions: In iron-depleted women, iron absorption from FePP-fortified extruded rice cofortified with ZnSO 4 was 1.6-fold (95% CI: 1.4-, 1.9-fold) that of rice cofortified with ZnO. These findings suggest that ZnSO 4 may be the preferable zinc cofortificant for optimal iron bioavailability of iron-fortified extruded rice. This trial was registered at clinicaltrials.gov as NCT02255942. © 2017 American Society for Nutrition.

Why the Short-War Scenario is Wrong for Naval Planning.

DTIC Science & Technology

1982-07-01

34On Singular Chaaecteristic Initial Value In Springer Verlag Lecture Notes In Physics. 106, (1979), Proble m with Unique Solution," 20 pp., Jun 1978...34 Huntzinger, R. L&ar, " Market Analysis wilth Rational Epc’ 50 pp., Jan 1978, AD A08 541 tations: Theory end Estimation," 60 Pp., Wg 78, AD A054 422 PP 230 PP...1979 (Presanted at the Nlow Conference on -Low AD A077 636 Inome Lor Markets ," Cuicago. Jun 1978), AD AD%6 629 pp 246 Thie, Jawse A., Jr., "The

Leaf patch clamp pressure probe measurements on olive leaves in a nearly turgorless state.

PubMed

Ehrenberger, W; Rüger, S; Rodríguez-Domínguez, C M; Díaz-Espejo, A; Fernández, J E; Moreno, J; Zimmermann, D; Sukhorukov, V L; Zimmermann, U

2012-07-01

The non-invasive leaf patch clamp pressure (LPCP) probe measures the attenuated pressure of a leaf patch, P(p) , in response to an externally applied magnetic force. P(p) is inversely coupled with leaf turgor pressure, P(c) , i.e. at high P(c) values the P(p) values are small and at low P(c) values the P(p) values are high. This relationship between P(c) and P(p) could also be verified for 2-m tall olive trees under laboratory conditions using the cell turgor pressure probe. When the laboratory plants were subjected to severe water stress (P(c) dropped below ca. 50 kPa), P(p) curves show reverse diurnal changes, i.e. during the light regime (high transpiration) a minimum P(p) value, and during darkness a peak P(p) value is recorded. This reversal of the P(p) curves was completely reversible. Upon watering, the original diurnal P(p) changes were re-established within 2-3 days. Olive trees in the field showed a similar turnover of the shape of the P(p) curves upon drought, despite pronounced fluctuations in microclimate. The reversal of the P(p) curves is most likely due to accumulation of air in the leaves. This assumption was supported with cross-sections through leaves subjected to prolonged drought. In contrast to well-watered leaves, microscopic inspection of leaves exhibiting inverse diurnal P(p) curves revealed large air-filled areas in parenchyma tissue. Significantly larger amounts of air could also be extracted from water-stressed leaves than from well-watered leaves using the cell turgor pressure probe. Furthermore, theoretical analysis of the experimental P(p) curves shows that the propagation of pressure through the nearly turgorless leaf must be exclusively dictated by air. Equations are derived that provide valuable information about the water status of olive leaves close to zero P(c) . © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.