High Production of LukMF' in Staphylococcus aureus Field Strains Is Associated with Clinical Bovine Mastitis.

PubMed

Hoekstra, Jurriaan; Rutten, Victor; Sommeling, Laura; van Werven, Tine; Spaninks, Mirlin; Duim, Birgitta; Benedictus, Lindert; Koop, Gerrit

2018-05-15

Staphylococcus aureus , a major cause of bovine mastitis, produces a wide range of immune-evasion molecules. The bi-component leukocidin LukMF' is a potent killer of bovine neutrophils in vitro. Since the role of LukMF' in development of bovine mastitis has not been studied in natural infections, we aimed to clarify whether presence of the lukM-lukF' genes and production levels of LukMF' are associated with clinical severity of the disease. Staphylococcus aureus was isolated from mastitis milk samples (38 clinical and 17 subclinical cases) from 33 different farms. The lukM - lukF' genes were present in 96% of the isolates. Remarkably, 22% of the lukM-lukF' -positive S. aureus isolates displayed a 10-fold higher in vitro LukMF' production than the average of the lower-producing ones. These high producing isolates were cultured significantly more frequently from clinical than subclinical mastitis cases. Also, the detection of LukM protein in milk samples was significantly associated with clinical mastitis and high production in vitro. The high producing LukMF' strains all belonged to the same genetic lineage, spa -type t543. Analysis of their global toxin gene regulators revealed a point mutation in the Repressor of toxins ( rot ) gene which results in a non-functional start codon, preventing translation of rot . This mutation was only identified in high LukMF' producing isolates and not in low LukMF' producing isolates. Since rot suppresses the expression of various toxins including leukocidins, this mutation is a possible explanation for increased LukMF' production. Identification of high LukMF' producing strains is of clinical relevance and can potentially be used as a prognostic marker for severity of mastitis.

Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT.

PubMed

Alchalby, H; Badbaran, A; Bock, O; Fehse, B; Bacher, U; Zander, A R; Kröger, N

2010-09-01

Monitoring of minimal residual disease (MRD) after allogeneic (allo)-SCT for myelofibrosis (MF) allows recognizing the depth of remission and thus guides application of appropriate therapeutic interventions. MPL W515L/K mutations, which are detected in 5-10% of JAK2V617F-negative patients, may be useful for this purpose. Using a highly sensitive quantitative PCR method, we tested 90 patients with MF who underwent allo-SCT for the presence of MPL W515L/K mutations. Two patients with primary MF were found to harbor MPLW515L while no patient was positive for MPLW515K mutation. Both patients were JAK2V617F negative and cleared the mutation rapidly after allo-SCT and remained negative for a median follow-up of 19 months. The results of molecular monitoring correlated well with other remission parameters such as normalization of peripheral blood counts and morphology and complete donor chimerism. We conclude that MPLW515L can be cleared after allo-SCT and hence may be used as an MRD marker in a proportion of JAK2V617F-negative MF patients.

UVB-induced mutagenesis in hairless {lambda}lacZ-transgenic mice

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

Frijhoff, A.F.W.; Rebel, H.; Mientjes, E.J.

UVB-induced mutagenesis was studied in hairless 40.6 transgenic mice (Muta{trademark}Mouse), which contain the {lambda}gt1OlacZ shuttle vector as a target for mutagenesis. Mice were exposed at the dorsal side to either single doses of 200, 500, 800, or 1000 J/m{sup 2} UVB or to two successive irradiations of either 200 and 800 J/m{sup 2} UVB, with intervals of 1,3, or 5 days, or to 800 and 200 J/m{sup 2} UVB with a 5-day interval. At 23 days after the last exposure, lacZ mutant frequencies (MF) were determined in the epidermis. The lacZ MF increased linearly with increasing dose of UVB. Themore » mutagenic effect of two successive irradiations appeared to be additive. The UV-induced mutation spectrum was dominated by G:C{r_arrow}A:T transitions at dipyrimidine sites. DNA-sequence analysis of spontaneously mutated phages showed a diverse spectrum consisting of insertions, deletions and G:C {r_arrow} A:T transitions at CpG sites. the results indicate that the hairless {lambda}lacZ-transgenic mouse is a suitable in vivo model for studying UVB-induced mutations. 29 refs., 5 tabs.« less

Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.

PubMed

Montgomery, Beverly A; Murphy, Jessica; Chen, James J; Desai, Varsha G; McGarrity, Lynda; Morris, Suzanne M; Casciano, Daniel A; Aidoo, Anane

2002-01-01

The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P < 0.0009) increase in MF was found in animals exposed to MeIQx at 25 mg/kg. PhIP was the most mutagenic of the HCAs, with increases (P < 0.0001) in MF detected at all dose levels compared with controls. Because PhIP was the most mutagenic, it was selected for studies using the dietary antioxidant vitamins. Addition of antioxidant vitamins, singly or in a mixture, caused a significant (P < 0.0001) decrease in PhIP-induced Hprt MF. Vitamin E was the most effective at decreasing Hprt MF. In addition, we determined whether carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P < 0.05) in GPx activity. Also a modest increase in GPx activity was seen in animals that received the antioxidant mixture alone. Although the mechanisms of action of the antioxidants remain to be determined, the results indicate that dietary-derived HCA treatment induced MF in rat lymphocytes and suggest that antioxidants in food or taken as supplements could, in part, counteract such mutagenic activities.

Tamoxifen mutagenesis and carcinogenesis in livers of lambda/lacI transgenic rats: selective influence of phenobarbital promotion.

PubMed

Styles, J A; Davies, R; Fenwick, S; Walker, J; White, I N; Smith, L L

2001-01-10

Administration of tamoxifen (TAM) (20 mg/kg per day p.o.) for 6 weeks to female lambda/lacI transgenic rats caused a 4-fold increase in mutation frequency (MF) at the lacI gene locus in the livers of dosed animals compared with controls. After cessation of dosing, the MF showed a further increase with time at 2, 12 and 24 weeks, respectively. Phenobarbital promotion of similarly treated animals resulted in no increase in mutation frequency compared with TAM alone. Treatment with phenobarbital or TAM+phenobarbital resulted in time-dependent increases in liver weight compared with the corresponding controls. There was an increase in cell proliferation in the phenobarbital and TAM+phenobarbital groups, and at 24 weeks in the TAM dosed animals compared with controls. There was also a progressive increase in the number of GST-P expressing foci in the livers of TAM and TAM + phenobarbital rats compared with controls. The induction of cell proliferation and GSTP foci in the rat liver by phenobarbital is consistent with its ability to promote tamoxifen-initiated liver tumours in the rat. If the lacI gene is regarded as being representative of the rat genome in general (albeit that the gene is bacterial) the above observations suggest that promotion by tamoxifen confers selective advantage on mutated genes at loci that contribute to the tumour phenotype and that promotion of rat liver tumours by tamoxifen is not dependent simply upon the enhancement of cellular proliferation.

Molecular analysis of hprt mutations induced by chromium picolinate in CHO AA8 cells.

PubMed

Coryell, Virginia H; Stearns, Diane M

2006-11-07

Chromium picolinate (CrPic) is a popular dietary supplement, marketed to the public for weight loss, bodybuilding, and control of blood sugar. Recommendations for long-term use at high dosages have led to questions regarding its safety. Previous studies have reported that CrPic can cause chromosomal aberrations and mutations. The purpose of the current work was to compare the mutagenicity of CrPic as a suspension in acetone versus a solution in DMSO, and to characterize the hprt mutations induced by CrPic in CHO AA8 cells. Treatments of 2% acetone or 2% DMSO alone produced no significant increase in 6-thioguanine (6-TG)-resistant mutants after 48 h exposures. Mutants resistant to 6-TG were generated by exposing cells for 48 h to 80 microg/cm(2) CrPic in acetone or to 1.0mM CrPic in DMSO. CrPic in acetone produced an average induced mutation frequency (MF) of 56 per 10(6) surviving cells relative to acetone solvent. CrPic in acetone was 3.5-fold more mutagenic than CrPic in DMSO, which produced an MF of 16.2. Characterization of 61 total mutations in 48 mutants generated from exposure to CrPic in acetone showed that base substitutions comprised 33% of the mutations, with transversions being predominant; deletions made up 62% of the mutations, with one-exon deletions predominating; and 1-4 bp insertions made up 5% of the characterized mutations. CrPic induced a statistically greater number of deletions and a statistically smaller number of base substitutions than have been measured in spontaneously generated mutants. These data confirm previous studies showing that CrPic is mutagenic, and support the contention that further study is needed to verify the safety of CrPic for human consumption.

Biased Gene Fractionation and Dominant Gene Expression among the Subgenomes of Brassica rapa

PubMed Central

Cheng, Feng; Wu, Jian; Fang, Lu; Sun, Silong; Liu, Bo; Lin, Ke; Bonnema, Guusje; Wang, Xiaowu

2012-01-01

Polyploidization, both ancient and recent, is frequent among plants. A “two-step theory" was proposed to explain the meso-triplication of the Brassica “A" genome: Brassica rapa. By accurately partitioning of this genome, we observed that genes in the less fractioned subgenome (LF) were dominantly expressed over the genes in more fractioned subgenomes (MFs: MF1 and MF2), while the genes in MF1 were slightly dominantly expressed over the genes in MF2. The results indicated that the dominantly expressed genes tended to be resistant against gene fractionation. By re-sequencing two B. rapa accessions: a vegetable turnip (VT117) and a Rapid Cycling line (L144), we found that genes in LF had less non-synonymous or frameshift mutations than genes in MFs; however mutation rates were not significantly different between MF1 and MF2. The differences in gene expression patterns and on-going gene death among the three subgenomes suggest that “two-step" genome triplication and differential subgenome methylation played important roles in the genome evolution of B. rapa. PMID:22567157

Biased gene fractionation and dominant gene expression among the subgenomes of Brassica rapa.

PubMed

Cheng, Feng; Wu, Jian; Fang, Lu; Sun, Silong; Liu, Bo; Lin, Ke; Bonnema, Guusje; Wang, Xiaowu

2012-01-01

Polyploidization, both ancient and recent, is frequent among plants. A "two-step theory" was proposed to explain the meso-triplication of the Brassica "A" genome: Brassica rapa. By accurately partitioning of this genome, we observed that genes in the less fractioned subgenome (LF) were dominantly expressed over the genes in more fractioned subgenomes (MFs: MF1 and MF2), while the genes in MF1 were slightly dominantly expressed over the genes in MF2. The results indicated that the dominantly expressed genes tended to be resistant against gene fractionation. By re-sequencing two B. rapa accessions: a vegetable turnip (VT117) and a Rapid Cycling line (L144), we found that genes in LF had less non-synonymous or frameshift mutations than genes in MFs; however mutation rates were not significantly different between MF1 and MF2. The differences in gene expression patterns and on-going gene death among the three subgenomes suggest that "two-step" genome triplication and differential subgenome methylation played important roles in the genome evolution of B. rapa.

A Lipid-Anchored NAC Transcription Factor Is Translocated into the Nucleus and Activates Glyoxalase I Expression during Drought Stress[OPEN

PubMed Central

Duan, Mei; Zhang, Rongxue; Zhu, Fugui; Gou, Lanming; Dong, Jiangli

2017-01-01

The plant-specific NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) play a vital role in the response to drought stress. Here, we report a lipid-anchored NACsa TF in Medicago falcata. MfNACsa is an essential regulator of plant tolerance to drought stress, resulting in the differential expression of genes involved in oxidation reduction and lipid transport and localization. MfNACsa is associated with membranes under unstressed conditions and, more specifically, is targeted to the plasma membrane through S-palmitoylation. However, a Cys26-to-Ser mutation or inhibition of S-palmitoylation results in MfNACsa retention in the endoplasmic reticulum/Golgi. Under drought stress, MfNACsa translocates to the nucleus through de-S-palmitoylation mediated by the thioesterase MtAPT1, as coexpression of APT1 results in the nuclear translocation of MfNACsa, whereas mutation of the catalytic site of APT1 results in colocalization with MfNACsa and membrane retention of MfNACsa. Specifically, the nuclear MfNACsa binds the glyoxalase I (MtGlyl) promoter under drought stress, resulting in drought tolerance by maintaining the glutathione pool in a reduced state, and the process is dependent on the APT1-NACsa regulatory module. Our findings reveal a novel mechanism for the nuclear translocation of an S-palmitoylated NAC in response to stress. PMID:28684428

Hmga2 promotes the development of myelofibrosis in Jak2V617F knockin mice by enhancing TGF-β1 and Cxcl12 pathways.

PubMed

Dutta, Avik; Hutchison, Robert E; Mohi, Golam

2017-08-17

Myelofibrosis (MF) is a devastating blood disorder. The JAK2V617F mutation has been detected in ∼50% cases of MF. Elevated expression of high-mobility group AT hook 2 (HMGA2) has also been frequently observed in patients with MF. Interestingly, upregulation of HMGA2 expression has been found in association with the JAK2V617F mutation in significant cases of MF. However, the contribution of HMGA2 in the pathogenesis of MF remains elusive. To determine the effects of concurrent expression of HMGA2 and JAK2V617F mutation in hematopoiesis, we transduced bone marrow cells from Jak2 V617F knockin mice with lentivirus expressing Hmga2 and performed bone marrow transplantation. Expression of Hmga2 enhanced megakaryopoiesis, increased extramedullary hematopoiesis, and accelerated the development of MF in mice expressing Jak2 V617F Mechanistically, the data show that expression of Hmga2 enhances the activation of transforming growth factor-β1 (TGF-β1) and Cxcl12 pathways in mice expressing Jak2 V617F In addition, expression of Hmga2 causes upregulation of Fzd2, Ifi27l2a, and TGF-β receptor 2. Forced expression of Cxcl12, Fzd2, or Ifi27l2a increases megakaryocytic differentiation and proliferation in the bone marrow of Jak2 V617F mice, whereas TGF-β1 or Cxcl12 stimulation induces collagen deposition in the bone marrow mesenchymal stromal cells. Together, these findings demonstrate that expression of Hmga2 cooperates with Jak2 V617F in the pathogenesis of MF. © 2017 by The American Society of Hematology.

The chromosomal mapping of four genes encoding winged helix proteins expressed early in mouse development

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

Labosky, P.A.; Sakaki, Hiroshi; Hogan, B.L.M.

1996-06-01

Members of the winged helix family of transcription factors are required for the normal embryonic development of the mouse. Using the interspecific backcross panel from The Jackson Laboratory, we have determined the chromosomal locations of four genes that encode winged helix containing proteins. Mf1 was assigned to mouse Chromosome 8, Mf2 to Chromosome 4, Mf3 to Chromosome 9, and Mf4 to Chromosome 13. Since Mf3 is located in a region of Chromosome 9 containing many well-characterized mouse mutations such as short ear (se), ashen (ash), and dilute (d), we have analyzed deletion mutants to determine the location of Mf3 moremore » precisely. 14 refs., 3 figs.« less

Molecular methods for the detection of mutations.

PubMed

Monteiro, C; Marcelino, L A; Conde, A R; Saraiva, C; Giphart-Gassler, M; De Nooij-van Dalen, A G; Van Buuren-van Seggelen, V; Van der Keur, M; May, C A; Cole, J; Lehmann, A R; Steinsgrimsdottir, H; Beare, D; Capulas, E; Armour, J A

2000-01-01

We report the results of a collaborative study aimed at developing reliable, direct assays for mutation in human cells. The project used common lymphoblastoid cell lines, both with and without mutagen treatment, as a shared resource to validate the development of new molecular methods for the detection of low-level mutations in the presence of a large excess of normal alleles. As the "gold standard, " hprt mutation frequencies were also measured on the same samples. The methods under development included i) the restriction site mutation (RSM) assay, in which mutations lead to the destruction of a restriction site; ii) minisatellite length-change mutation, in which mutations lead to alleles containing new numbers of tandem repeat units; iii) loss of heterozygosity for HLA epitopes, in which antibodies can be used to direct selection for mutant cells; iv) multiple fluorescence-based long linker arm nucleotides assay (mf-LLA) technology, for the detection of substitutional mutations; v) detection of alterations in the TP53 locus using a (CA) array as the target for the screening; and vi) PCR analysis of lymphocytes for the presence of the BCL2 t(14:18) translocation. The relative merits of these molecular methods are discussed, and a comparison made with more "traditional" methods.

Increased meal frequency attenuates fat-free mass losses and some markers of health status with a portion-controlled weight loss diet.

PubMed

Alencar, Michelle K; Beam, Jason R; McCormick, James J; White, Ailish C; Salgado, Roy M; Kravitz, Len R; Mermier, Christine M; Gibson, Ann L; Conn, Carole A; Kolkmeyer, Deborah; Ferraro, Robert T; Kerksick, Chad M

2015-05-01

Increased meal frequency (MF) may be associated with improvements in blood markers of health and body composition during weight loss; however, this claim has not been validated. The purpose of the study was to determine if either a 2-meal (2 MF) or 6-meal frequency (6 MF) regimen can improve body composition and blood-based markers of health while consuming a portion-controlled equihypocaloric diet. Eleven (N=11) obese women (52 ± 7 years, 101.7 ± 22.6 kg, 39.1 ± 7.6 kg/m(2)) were randomized into treatment condition (2 MF or 6 MF) for 2 weeks, completed a 2-week washout, and alternated treatment conditions. In pre/post fashion, changes in body composition, glucose, insulin, and lipid components were measured in response to a test meal. Body mass was successfully lost (P ≤ .05) under both feeding regimens (2 MF: -2.8 ± 1.5 vs 6 MF: -1.9 ± 1.5 kg). Altering MF did not impact glucose, insulin, total cholesterol, or low-density lipoprotein cholesterol (P>.05). On average, fat-free mass (FFM) decreased by -3.3% ± 2.6% following the 2 MF condition and, on average, increased by 1.2% ± 1.7% following the 6 MF condition (P ≤ .05). Fasting high-density lipoprotein cholesterol (HDL-C) percentage increased during the 2 MF condition; this was significantly greater than that in the 6 MF condition (1.3% ± 12.2% vs 0.12% ± 10.3%) (P ≤ .05). Overall, reductions in MF (2 MF) were associated with improved HDL-C levels; but the clinical significance is not clear. Alternatively, increased MF (6 MF) did appear to favorably preserve FFM during weight loss. In conclusion, caloric restriction was effective in reducing body mass and attenuating FFM changes in body composition; however, glucose, insulin, and lipid metabolism had no significant differences between MF. Copyright © 2015 Elsevier Inc. All rights reserved.

DEMETER observations of bursty MF emissions and their relation to ground-level auroral MF burst

NASA Astrophysics Data System (ADS)

Broughton, M. C.; LaBelle, J.; Parrot, M.

2014-12-01

A survey of medium frequency (MF) electric field data from selected orbits of the Detection of Electro-Magnetic Emissions Transmitted from Earthquakes (DEMETER) spacecraft reveals 68 examples of a new type of bursty MF emissions occurring at high latitudes associated with auroral phenomena. These resemble auroral MF burst, a natural radio emission observed at ground level near local substorm onsets. Similar to MF burst, the bursty MF waves observed by DEMETER have broadband, impulsive frequency structure covering 1.5-3.0 MHz, amplitudes of 50-100 μV/m, an overall occurrence rate of ˜0.76% with higher occurrence during active times, and strong correlation with auroral hiss. The magnetic local time distribution of the MF waves observed by DEMETER shows peak occurrence rate near 18 MLT, somewhat earlier than the equivalent peak in the occurrence rate of ground level MF burst, though propagation effects and differences in the latitudes sampled by the two techniques may explain this discrepancy. Analysis of solar wind and SuperMAG data suggests that while the bursty MF waves observed by DEMETER are associated with enhanced auroral activity, their coincidence with substorm onset may not be as exact as that of ground level MF burst. One conjunction occurs in which MF burst is observed at Churchill, Manitoba, within 8 min of MF emissions detected by DEMETER on field lines approximately 1000 km southeast of Churchill. These observations may plausibly be associated with the same auroral event detected by ground level magnetometers at several Canadian observatories. Although it is uncertain, the balance of the evidence suggests that the bursty MF waves observed with DEMETER are the same phenomenon as the ground level MF burst. Hence, theories of MF burst generation in the ionosphere, such as beam-generated Langmuir waves excited over a range of altitudes or strong Langmuir turbulence generating a range of frequencies within a narrow altitude range, need to be revisited to see whether they predict in situ detection of MF burst.

Matrix infrared spectroscopy and quantum-chemical calculations for the coinage-metal fluorides: comparisons of Ar-AuF, Ne-AuF, and Molecules MF2 and MF3.

PubMed

Wang, Xuefeng; Andrews, Lester; Brosi, Felix; Riedel, Sebastian

2013-01-21

The reactions of laser-ablated Au, Ag, and Cu atoms with F(2) in excess argon and neon gave new absorptions in the M-F stretching region of their IR spectra, which were assigned to metal-fluoride species. For gold, a Ng-AuF bond was identified in mixed neon/argon samples. However, this bonding was much weaker with AgF and CuF. Molecules MF(2) and MF(3) (M=Au, Ag, Cu) were identified from the isotopic distribution of the Cu and Ag atoms, comparison of the frequencies for three metal fluorides, and theoretical frequency calculations. The AuF(5) molecule was characterized by its strongest stretching mode and theoretical frequency calculations. Additional evidence was observed for the formation of the Au(2) F(6) molecule. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serum of myeloproliferative neoplasms stimulates hematopoietic stem and progenitor cells.

PubMed

Lubberich, Richard K; Walenda, Thomas; Goecke, Tamme W; Strathmann, Klaus; Isfort, Susanne; Brümmendorf, Tim H; Koschmieder, Steffen; Wagner, Wolfgang

2018-01-01

Myeloproliferative neoplasms (MPN)-such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF)-are typically diseases of the elderly caused by acquired somatic mutations. However, it is largely unknown how the malignant clone interferes with normal hematopoiesis. In this study, we analyzed if serum of MPN patients comprises soluble factors that impact on hematopoietic stem and progenitor cells (HPCs). CD34+ HPCs were cultured in medium supplemented with serum samples of PV, ET, or MF patients, or healthy controls. The impact on proliferation, maintenance of immature hematopoietic surface markers, and colony forming unit (CFU) potential was systematically analyzed. In addition, we compared serum of healthy young (<25 years) and elderly donors (>50 years) to determine how normal aging impacts on the hematopoiesis-supportive function of serum. Serum from MF, PV and ET patients significantly increased proliferation as compared to controls. In addition, serum from MF and ET patients attenuated the loss of a primitive immunophenotype during in vitro culture. The CFU counts were significantly higher if HPCs were cultured with serum of MPN patients as compared to controls. Furthermore, serum of healthy young versus old donors did not evoke significant differences in proliferation or immunophenotype of HPCs, whereas the CFU frequency was significantly increased by serum from elderly patients. Our results indicate that serum derived from patients with MPN comprises activating feedback signals that stimulate the HPCs-and this stimulatory signal may result in a viscous circle that further accelerates development of the disease.

Multiplex Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) for diagnosis of natural infection with canine distemper virus

PubMed Central

2010-01-01

Background Canine distemper virus (CDV) is present worldwide and produces a lethal systemic infection of wild and domestic Canidae. Pre-existing antibodies acquired from vaccination or previous CDV infection might interfere the interpretation of a serologic diagnosis method. In addition, due to the high similarity of nucleic acid sequences between wild-type CDV and the new vaccine strain, current PCR derived methods cannot be applied for the definite confirmation of CD infection. Hence, it is worthy of developing a simple and rapid nucleotide-based assay for differentiation of wild-type CDV which is a cause of disease from attenuated CDVs after vaccination. High frequency variations have been found in the region spanning from the 3'-untranslated region (UTR) of the matrix (M) gene to the fusion (F) gene (designated M-F UTR) in a few CDV strains. To establish a differential diagnosis assay, an amplification refractory mutation analysis was established based on the highly variable region on M-F UTR and F regions. Results Sequences of frequent polymorphisms were found scattered throughout the M-F UTR region; the identity of nucleic acid between local strains and vaccine strains ranged from 82.5% to 93.8%. A track of AAA residue located 35 nucleotides downstream from F gene start codon highly conserved in three vaccine strains were replaced with TGC in the local strains; that severed as target sequences for deign of discrimination primers. The method established in the present study successfully differentiated seven Taiwanese CDV field isolates, all belonging to the Asia-1 lineage, from vaccine strains. Conclusions The method described herein would be useful for several clinical applications, such as confirmation of nature CDV infection, evaluation of vaccination status and verification of the circulating viral genotypes. PMID:20534175

Multiplex Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) for diagnosis of natural infection with canine distemper virus.

PubMed

Chulakasian, Songkhla; Lee, Min-Shiuh; Wang, Chi-Young; Chiou, Shyan-Song; Lin, Kuan-Hsun; Lin, Fong-Yuan; Hsu, Tien-Huan; Wong, Min-Liang; Chang, Tien-Jye; Hsu, Wei-Li

2010-06-10

Canine distemper virus (CDV) is present worldwide and produces a lethal systemic infection of wild and domestic Canidae. Pre-existing antibodies acquired from vaccination or previous CDV infection might interfere the interpretation of a serologic diagnosis method. In addition, due to the high similarity of nucleic acid sequences between wild-type CDV and the new vaccine strain, current PCR derived methods cannot be applied for the definite confirmation of CD infection. Hence, it is worthy of developing a simple and rapid nucleotide-based assay for differentiation of wild-type CDV which is a cause of disease from attenuated CDVs after vaccination. High frequency variations have been found in the region spanning from the 3'-untranslated region (UTR) of the matrix (M) gene to the fusion (F) gene (designated M-F UTR) in a few CDV strains. To establish a differential diagnosis assay, an amplification refractory mutation analysis was established based on the highly variable region on M-F UTR and F regions. Sequences of frequent polymorphisms were found scattered throughout the M-F UTR region; the identity of nucleic acid between local strains and vaccine strains ranged from 82.5% to 93.8%. A track of AAA residue located 35 nucleotides downstream from F gene start codon highly conserved in three vaccine strains were replaced with TGC in the local strains; that severed as target sequences for deign of discrimination primers. The method established in the present study successfully differentiated seven Taiwanese CDV field isolates, all belonging to the Asia-1 lineage, from vaccine strains. The method described herein would be useful for several clinical applications, such as confirmation of nature CDV infection, evaluation of vaccination status and verification of the circulating viral genotypes.

Patient characteristics and outcomes in adolescents and young adults with classical Philadelphia chromosome-negative myeloproliferative neoplasms.

PubMed

Boddu, Prajwal; Masarova, Lucia; Verstovsek, Srdan; Strati, Paolo; Kantarjian, Hagop; Cortes, Jorge; Estrov, Zeev; Pierce, Sherry; Pemmaraju, Naveen

2018-01-01

Little is known about the outcomes of Philadelphia-negative myeloproliferative neoplasms (MPNs) in adolescents and young adults (AYA). We reviewed all patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) treated at our institution from 1988 to 2016 who were aged 16 to 39 years (AYA) and described their outcomes in comparison to older MPN population. Of 2206 patients, 185 (8.3%) were identified as AYA: 105 (57%) ET, 43 (23%) PV, and 37 (20%) MF. The median age was 33 years [range, 16-39], and median follow-up time 3 years [range, 0.04-25]. JAK2 allele burdens were significantly lower among AYA JAK2V617F-mutated patients in both PV (p = 0.001) and MF (p = 0.005). Seven percent of MPN AYA patients were diagnosed with a thrombotic event at, or prior to, diagnosis. Over the short median follow-up, 4 thrombotic (PV = 1, MF = 3) and 3 leukemia (ET = 2, MF = 1) events occurred. In multivariate analysis, AYA did not predict for thrombotic or transformational events across three cohorts. In the MF cohort, there was a reduced frequency of negative prognostic variables of anemia (p = 0.011) and leukocytosis (p = 0.048) in AYA when compared with non-AYA. Overall survival was significantly superior in the AYA cohorts in all three MPN groups, namely MF (p < 0.001), PV (p < 0.001), and ET (p = 0.002). Our findings suggest that MPN AYA patients exhibit an indolent clinical phenotype characterized by favorable survival outcomes.

Extremely Low Frequency-Magnetic Field (ELF-MF) Exposure Characteristics among Semiconductor Workers

PubMed Central

Choi, Sangjun; Cha, Wonseok; Kim, Won; Yoon, Chungsik; Park, Ju-Hyun; Ha, Kwonchul; Park, Donguk

2018-01-01

We assessed the exposure of semiconductor workers to extremely low frequency-magnetic fields (ELF-MF) and identified job characteristics affecting ELF-MF exposure. These were demonstrated by assessing the exposure of 117 workers involved in wafer fabrication (fab) and chip packaging wearing personal dosimeters for a full shift. A portable device was used to monitor ELF-MF in high temporal resolution. All measurements were categorized by operation, job and working activity during working time. ELF-MF exposure of workers were classified based on the quartiles of ELF-MF distribution. The average levels of ELF-MF exposure were 0.56 µT for fab workers, 0.59 µT for chip packaging workers and 0.89 µT for electrical engineers, respectively. Exposure to ELF-MF differed among types of factory, operation, job and activity. Workers engaged in the diffusion and chip testing activities showed the highest ELF-MF exposure. The ELF-MF exposures of process operators were found to be higher than those of maintenance engineers, although peak exposure and/or patterns varied. The groups with the highest quartile ELF-MF exposure level are operators in diffusion, ion implantation, module and testing operations, and maintenance engineers in diffusion, module and testing operations. In conclusion, ELF-MF exposure among workers can be substantially affected by the type of operation and job, and the activity or location. PMID:29614730

A Frequency-Domain Adaptive Matched Filter for Active Sonar Detection.

PubMed

Zhao, Zhishan; Zhao, Anbang; Hui, Juan; Hou, Baochun; Sotudeh, Reza; Niu, Fang

2017-07-04

The most classical detector of active sonar and radar is the matched filter (MF), which is the optimal processor under ideal conditions. Aiming at the problem of active sonar detection, we propose a frequency-domain adaptive matched filter (FDAMF) with the use of a frequency-domain adaptive line enhancer (ALE). The FDAMF is an improved MF. In the simulations in this paper, the signal to noise ratio (SNR) gain of the FDAMF is about 18.6 dB higher than that of the classical MF when the input SNR is -10 dB. In order to improve the performance of the FDAMF with a low input SNR, we propose a pre-processing method, which is called frequency-domain time reversal convolution and interference suppression (TRC-IS). Compared with the classical MF, the FDAMF combined with the TRC-IS method obtains higher SNR gain, a lower detection threshold, and a better receiver operating characteristic (ROC) in the simulations in this paper. The simulation results show that the FDAMF has higher processing gain and better detection performance than the classical MF under ideal conditions. The experimental results indicate that the FDAMF does improve the performance of the MF, and can adapt to actual interference in a way. In addition, the TRC-IS preprocessing method works well in an actual noisy ocean environment.

Multi-frequency bioimpedance in equine muscle assessment.

PubMed

Harrison, Adrian Paul; Elbrønd, Vibeke Sødring; Riis-Olesen, Kiwa; Bartels, Else Marie

2015-03-01

Multi-frequency BIA (mfBIA) equipment has been shown to be a non-invasive and reliable method to assess a muscle as a whole or at fibre level. In the equine world this may be the future method of assessment of training condition or of muscle injury. The aim of this study was to test if mfBIA reliably can be used to assess the condition of a horse's muscles in connection with health assessment, injury and both training and re-training. mfBIA measurements was carried out on 10 'hobby' horses and 5 selected cases with known anamnesis. Impedance, resistance, reactance, phase angle, centre frequency, membrane capacitance and both extracellular and intracellular resistance were measured. Platinum electrodes in connection with a conductance paste were used to accommodate the typical BIA frequencies and to facilitate accurate measurements. Use of mfBIA data to look into the effects of myofascial release treatment was also demonstrated. Our findings indicate that mfBIA provides a non-invasive, easily measurable and very precise assessment of the state of muscles in horses. This study also shows the potential of mfBIA as a diagnostic tool as well as a tool to monitor effects of treatment e.g. myofascial release therapy and metabolic diseases, respectively.

Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology

PubMed Central

Sciacchitano, Salvatore; Lavra, Luca; Ulivieri, Alessandra; Magi, Fiorenza; De Francesco, Gian Paolo; Bellotti, Carlo; Salehi, Leila B.; Trovato, Maria; Drago, Carlo; Bartolazzi, Armando

2017-01-01

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is <30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay. We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings. In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions. PMID:28472764

Potential role of meal frequency as a strategy for weight loss and health in overweight or obese adults.

PubMed

Kulovitz, Michelle G; Kravitz, Len R; Mermier, Christine; Gibson, Ann L; Conn, Carole A; Kolkmeyer, Deborah; Kerksick, Chad M

2014-04-01

Improved dietary strategies for weight loss are necessary to decrease metabolic disease risk in overweight or obese adults. Varying meal frequency (MF; i.e., increasing or decreasing eating occasions beyond the traditional pattern of three meals daily) has been thought to have an influence on body weight regulation, hunger control, and blood markers of health. It is common practice for weight management clinicians to recommend increasing MF as a strategy for weight management and to improve metabolic parameters. However, limited research exists investigating the effect of MF during controlled hypocaloric dietary interventions. Furthermore, MF literature often speculates with regard to efficacy of MF treatments based on research using normal weight, overweight/obese, or some combination, where much diversity exists within these various populations. In this review, we suggest that normal-weight and overweight/obese populations, as well as free-living versus investigator-controlled research trials, should be studied independently. Therefore, the objective of the present review is to survey the literature to assess whether the alteration of MF influences body weight regulation, hunger control, and/or blood markers of health in overweight/obese participants undergoing a controlled hypocaloric diet to induce weight loss. Findings of this review indicate that there is uncertainty in the literature when interpreting the optimal MF for obesity treatment, where reduced MF may even show more favorable lipid profiles in obese individuals compared with increased MF. Furthermore, the simple relationship of comparing MF with body fatness or body mass index should also consider whether eating frequency is associated with other healthy factors (e.g., increased physical activity). Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of macular structure and function in two Swedish families with genetically identified autosomal dominant retinitis pigmentosa

PubMed Central

Abdulridha-Aboud, Wissam; Kjellström, Ulrika; Andréasson, Sten

2016-01-01

Purpose To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype. PMID:27212874

Multi-frequency bioimpedance in human muscle assessment

PubMed Central

Bartels, Else Marie; Sørensen, Emma Rudbæk; Harrison, Adrian Paul

2015-01-01

Bioimpedance analysis (BIA) is a well-known and tested method for body mass and muscular health assessment. Multi-frequency BIA (mfBIA) equipment now makes it possible to assess a particular muscle as a whole, as well as looking at a muscle at the fiber level. The aim of this study was to test the hypothesis that mfBIA can be used to assess the anatomical, physiological, and metabolic state of skeletal muscles. mfBIA measurements focusing on impedance, resistance, reactance, phase angle, center frequency, membrane capacitance, and both extracellular and intracellular resistance were carried out. Eight healthy human control subjects and three selected cases were examined to demonstrate the extent to which this method may be used clinically, and in relation to training in sport. The electrode setup is shown to affect the mfBIA parameters recorded. Our recommendation is the use of noble metal electrodes in connection with a conductance paste to accommodate the typical BIA frequencies, and to facilitate accurate impedance and resistance measurements. The use of mfBIA parameters, often in conjunction with each other, can be used to reveal indications of contralateral muscle loss, extracellular fluid differences, contracted state, and cell transport/metabolic activity, which relate to muscle performance. Our findings indicate that mfBIA provides a noninvasive, easily measurable and very precise momentary assessment of skeletal muscles. PMID:25896978

Lumbar multifidus and erector spinae electromyograms during back bridge exercise in time and frequency domains.

PubMed

Mello, Roger Gomes Tavares; Carriço, Igor Rodrigues; da Matta, Thiago Torres; Nadal, Jurandir; Oliveira, Liliam Fernandes

2016-01-01

Muscle activity is studied during trunk stabilization exercises using electromyograms (EMG) in time domain. However, the frequency domain analysis provides information that would be important to understand fatigue process. To assess EMG of lumbar multifidus (LM) and erector spinae (ES) muscles, in time and frequency domains, during back bridge exercise. Nineteen healthy young men performed the exercise for one minute and EMG was monitored by surface electromyography. Normalized root mean square (RMS) value and spectral median frequency (MF) were compared between beginning and final epochs of test. The dynamics of the MF during whole test was also obtained by short-time Fourier transform. RMS values were about 30% of maximum voluntary contraction, and LM muscle showed greater MF than ES, which did not decrease at the final of exercise. However, the slope of MF was significant mainly for LM. Muscle activation of 30% is sufficient to keep lumbar stability and is suitable to improve muscular endurance. The significance of MF slope without decreasing at the final of exercise indicates challenging muscular endurance without imply on high fatigability. Due to lower muscular demand, this exercise might be recommended for trunk stabilizing for low back pain patients.

Cytogenetic correlates of TET2 mutations in 199 patients with myeloproliferative neoplasms

PubMed Central

Hussein, Kebede; Abdel-Wahab, Omar; Lasho, Terra L.; Van Dyke, Daniel L.; Levine, Ross L.; Hanson, Curtis A.; Pardanani, Animesh; Tefferi, Ayalew

2015-01-01

TET2 is a putative tumor suppressor gene located at chromosome 4q24. TET2 mutations were recently described in several myeloid neoplasms but correlations with cytogenetic findings have not been studied. Among a recently described cohort of patients with myeloproliferative neoplasms (MPN) who underwent TET2 mutation analysis, 199 had information on karyotype at diagnosis or time of TET2 testing: 71 polycythemia vera (PV), 55 primary myelofibrosis (PMF), 43 essential thrombocythemia (ET), 13 post-PV MF, 7 post-ET MF, and 10 blast phase MPN. Forty eight patients (24%) exhibited abnormal karyotype: 15 favorable (sole 20q-, 13q-, or +9), 8 unfavorable (complex karyotype or sole +8), and 25 “other” cytogenetic abnormalities. We found no significant difference either in the incidence or type of cytogenetic abnormalities between TET2 mutated (n = 25) and unmutated (n = 174) cases. Seventy nine patients, including 14 with TET2 mutations, underwent follow-up cytogenetic testing and the findings were again not affected by TET2 mutational status. We conclude that TET2 mutated MPN patients are not cytogenetically different than their TET2 unmutated counterparts. PMID:19957346

Molecular genetic tests for JAK2V617F, Exon12_JAK2 and MPLW515K/L are highly informative in the evaluation of patients suspected to have BCR-ABL1-negative myeloproliferative neoplasms.

PubMed

dos Santos, Marcos Tadeu; Mitne-Neto, Miguel; Miyashiro, Kozue; Chauffaille, Maria de Lourdes L Ferrari; Rizzatti, Edgar Gil

2014-02-01

Polycythaemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (MF), are the most common myeloproliferative neoplasms (MPN) in patients without the BCR-ABL1 gene rearrangement. They are caused by clonal expansion of haematopoietic stem cells and share, as a diagnostic criterion, the identification of JAK2V617F mutation. Classically, when other clinical criteria are present, a JAK2V617F negative case requires the analysis of Exon12_JAK2 for the diagnosis of PV, and of MPL515K/L mutations for the diagnosis of ET and MF. Here, we evaluated 78 samples from Brazilian patients suspected to have MPN, without stratification for PV, ET or MF. We found that 28 (35.9%) are JAK2V617F carriers; from the 50 remaining samples, one (2%) showed an Exon12_JAK2 mutation, and another (2%) was positive for MPLW515L mutation. In summary, the investigation of JAK2V617F, Exon12_JAK2 and MPLW515K/L was relevant for the diagnosis of 38.4% of patients suspected to have BCR-ABL1-negative MPN, suggesting that molecular genetic tests are useful for a quick and unequivocal diagnosis of MPN.

Molecular genetic tests for JAK2V617F, Exon12_JAK2 and MPLW515K/L are highly informative in the evaluation of patients suspected to have BCR-ABL1-negative myeloproliferative neoplasms

PubMed Central

dos Santos, Marcos Tadeu; Mitne-Neto, Miguel; Miyashiro, Kozue; Chauffaille, Maria de Lourdes L Ferrari; Rizzatti, Edgar Gil

2014-01-01

Polycythaemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (MF), are the most common myeloproliferative neoplasms (MPN) in patients without the BCR-ABL1 gene rearrangement. They are caused by clonal expansion of haematopoietic stem cells and share, as a diagnostic criterion, the identification of JAK2V617F mutation. Classically, when other clinical criteria are present, a JAK2V617F negative case requires the analysis of Exon12_JAK2 for the diagnosis of PV, and of MPL515K/L mutations for the diagnosis of ET and MF. Here, we evaluated 78 samples from Brazilian patients suspected to have MPN, without stratification for PV, ET or MF. We found that 28 (35.9%) are JAK2V617F carriers; from the 50 remaining samples, one (2%) showed an Exon12_JAK2 mutation, and another (2%) was positive for MPLW515L mutation. In summary, the investigation of JAK2V617F, Exon12_JAK2 and MPLW515K/L was relevant for the diagnosis of 38.4% of patients suspected to have BCR-ABL1-negative MPN, suggesting that molecular genetic tests are useful for a quick and unequivocal diagnosis of MPN. PMID:23986553

A single mutation that causes phosphatidylglycerol deficiency impairs synthesis of photosystem II cores in Chlamydomonas reinhardtii.

PubMed

Pineau, Bernard; Girard-Bascou, Jacqueline; Eberhard, Stephan; Choquet, Yves; Trémolières, Antoine; Gérard-Hirne, Catherine; Bennardo-Connan, Annick; Decottignies, Paulette; Gillet, Sylvie; Wollman, Francis-André

2004-01-01

Two mutants of Chlamydomonas reinhardtii, mf1 and mf2, characterized by a marked reduction in their phosphatidylglycerol content together with a complete loss in its Delta3-trans hexadecenoic acid-containing form, also lost photosystem II (PSII) activity. Genetic analysis of crosses between mf2 and wild-type strains shows a strict cosegregation of the PSII and lipid deficiencies, while phenotypic analysis of phototrophic revertant strains suggests that one single nuclear mutation is responsible for the pleiotropic phenotype of the mutants. The nearly complete absence of PSII core is due to a severely decreased synthesis of two subunits, D1 and apoCP47, which is not due to a decrease in translation initiation. Trace amounts of PSII cores that were detected in the mutants did not associate with the light-harvesting chlorophyll a/b-binding protein antenna (LHCII). We discuss the possible role of phosphatidylglycerol in the coupled process of cotranslational insertion and assembly of PSII core subunits.

Frequency-doubling technology perimetry and multifocal visual evoked potential in glaucoma, suspected glaucoma, and control patients

PubMed Central

Kanadani, Fabio N; Mello, Paulo AA; Dorairaj, Syril K; Kanadani, Tereza CM

2014-01-01

Introduction The gold standard in functional glaucoma evaluation is standard automated perimetry (SAP). However, SAP depends on the reliability of the patients’ responses and other external factors; therefore, other technologies have been developed for earlier detection of visual field changes in glaucoma patients. The frequency-doubling perimetry (FDT) is believed to detect glaucoma earlier than SAP. The multifocal visual evoked potential (mfVEP) is an objective test for functional evaluation. Objective To evaluate the sensitivity and specificity of FDT and mfVEP tests in normal, suspect, and glaucomatous eyes and compare the monocular and interocular mfVEP. Methods Ninety-five eyes from 95 individuals (23 controls, 33 glaucoma suspects, 39 glaucomatous) were enrolled. All participants underwent a full ophthalmic examination, followed by SAP, FDT, and mfVEP tests. Results The area under the curve for mean deviation and pattern standard deviation were 0.756 and 0.761, respectively, for FDT, 0.564 and 0.512 for signal and alpha for interocular mfVEP, and 0.568 and 0.538 for signal and alpha for monocular mfVEP. This difference between monocular and interocular mfVEP was not significant. Conclusion The FDT Matrix was superior to mfVEP in glaucoma detection. The difference between monocular and interocular mfVEP in the diagnosis of glaucoma was not significant. PMID:25075173

Assessment of the mutagenic potential of hexavalent chromium in the duodenum of big blue® rats.

PubMed

Thompson, Chad M; Young, Robert R; Dinesdurage, Harshini; Suh, Mina; Harris, Mark A; Rohr, Annette C; Proctor, Deborah M

2017-09-01

A cancer bioassay on hexavalent chromium Cr(VI) in drinking water reported increased incidences of duodenal tumors in B6C3F1 mice at exposures of 30-180ppm, and oral cavity tumors in F344 rats at 180ppm. A subsequent transgenic rodent (TGR) in vivo mutation assay in Big Blue® TgF344 rats found that exposure to 180ppm Cr(VI) in drinking water for 28days did not increase cII transgene mutant frequency (MF) in the oral cavity (Thompson et al., 2015). Herein, we extend our analysis to the duodenum of these same TgF344 rats. At study termination, duodenum chromium levels were below either the limit of detection or quantification in control rats, but were 24.6±3.8μg/g in Cr(VI)-treated rats. The MF in control (23.2×10 -6 ) and Cr(VI)-treated rats (22.7×10 -6 ) were nearly identical. In contrast, the MF in the duodenum of rats exposed to 1-ethyl-1-nitrosourea for six days (study days 1, 2, 3, 12, 19, 26) increased 24-fold to 557×10 -6 . These findings indicate that mutagenicity is unlikely an early initiating event in Cr(VI)-induced intestinal carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Medium frequency propagation characteristics of different transmission lines in an underground coal mine

PubMed Central

Li, Jingcheng; Waynert, Joseph A.; Whisner, Bruce G.

2015-01-01

A medium frequency (MF) communication system operating in an underground coal mine couples its signals to a long conductor, which acts as an MF transmission line (TL) in a tunnel to permit communications among transceivers along the line. The TL is generally the longest signal path for the system, and its propagation characteristics will have a major impact on the performance of the MF communication system. In this study, the propagation characteristics of three types of MF TLs in two layouts—on the roof and on the floor of a coal mine tunnel—were obtained in an effort to understand the propagation characteristics of different TLs in different locations. The study confirmed a low MF signal loss on all of these TLs. The study also found that the TLs in different layouts had substantially different propagation characteristics. The propagation characteristics of these different TLs in different layouts are presented in the paper. PMID:26203349

Dose and temporal evaluation of ethylene oxide-induced mutagenicity in the lungs of male big blue mice following inhalation exposure to carcinogenic concentrations.

PubMed

Manjanatha, Mugimane G; Shelton, Sharon D; Chen, Ying; Parsons, Barbara L; Myers, Meagan B; McKim, Karen L; Gollapudi, B Bhaskar; Moore, Nigel P; Haber, Lynne T; Allen, Bruce; Moore, Martha M

2017-04-01

Ethylene oxide (EO) is a direct acting alkylating agent; in vitro and in vivo studies indicate that it is both a mutagen and a carcinogen. However, it remains unclear whether the mode of action (MOA) for cancer for EO is a mutagenic MOA, specifically via point mutation. To investigate the MOA for EO-induced mouse lung tumors, male Big Blue (BB) B6C3F1 mice (10/group) were exposed to EO by inhalation, 6 hr/day, 5 days/week for 4 (0, 10, 50, 100, or 200 ppm EO), 8, or 12 weeks (0, 100, or 200 ppm EO). Lung DNA samples were analyzed for cII mutant frequency (MF) at 4, 8 and 12 weeks of exposure; the mutation spectrum was analyzed for mutants from control and 200 ppm EO treatments. Although EO-induced cII MFs were 1.5- to 2.7-fold higher than the concurrent controls at 4 weeks, statistically significant increases in the cII MF were found only after 8 and 12 weeks of exposure and only at 200 ppm EO (P ≤ 0.05), which is twice the highest concentration used in the cancer bioassay. Consistent with the positive response, DNA sequencing of cII mutants showed a significant shift in the mutational spectra between control and 200 ppm EO following 8 and 12 week exposures (P ≤ 0.035), but not at 4 weeks. Thus, EO mutagenic activity in vivo was relatively weak and required higher than tumorigenic concentrations and longer than 4 weeks exposure durations. These data do not follow the classical patterns for a MOA mediated by point mutations. Environ. Mol. Mutagen. 58:122-134, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

p53 deficiency alters the yield and spectrum of radiation-induced lacZ mutants in the brain of transgenic mice

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Kanazawa, N.; Lutze-Mann, L.; Winegar, R. A.

2001-01-01

Exposure to heavy particle radiation in the galacto-cosmic environment poses a significant risk in space exploration and the evaluation of radiation-induced genetic damage in tissues, especially in the central nervous system, is an important consideration in long-term manned space missions. We used a plasmid-based transgenic mouse model system, with the pUR288 lacZ transgene integrated in the genome of every cell of C57Bl/6(lacZ) mice, to evaluate the genetic damage induced by iron particle radiation. In order to examine the importance of genetic background on the radiation sensitivity of individuals, we cross-bred p53 wild-type lacZ transgenic mice with p53 nullizygous mice, producing lacZ transgenic mice that were either hemizygous or nullizygous for the p53 tumor suppressor gene. Animals were exposed to an acute dose of 1 Gy of iron particles and the lacZ mutation frequency (MF) in the brain was measured at time intervals from 1 to 16 weeks post-irradiation. Our results suggest that iron particles induced an increase in lacZ MF (2.4-fold increase in p53+/+ mice, 1.3-fold increase in p53+/- mice and 2.1-fold increase in p53-/- mice) and that this induction is both temporally regulated and p53 genotype dependent. Characterization of mutants based on their restriction patterns showed that the majority of the mutants arising spontaneously are derived from point mutations or small deletions in all three genotypes. Radiation induced alterations in the spectrum of deletion mutants and reorganization of the genome, as evidenced by the selection of mutants containing mouse genomic DNA. These observations are unique in that mutations in brain tissue after particle radiation exposure have never before been reported owing to technical limitations in most other mutation assays.

Decreased IL-10-producing regulatory B cells in patients with advanced mycosis fungoides.

PubMed

Akatsuka, Taro; Miyagaki, Tomomitsu; Nakajima, Rina; Kamijo, Hiroaki; Oka, Tomonori; Takahashi, Naomi; Suga, Hiraku; Yoshizaki, Ayumi; Asano, Yoshihide; Sugaya, Makoto; Sato, Shinichi

2018-06-28

Historically, B cells have been considered as positive regulators of humoral immune responses. Specific B-cell subsets, however, negatively regulate immune responses and are termed "regulatory B cells" (Bregs). Recently, Bregs have been linked to not only inflammatory and autoimmune diseases, but also malignancies via suppressing anti-tumour immunity. To investigate the involvement of Bregs in advanced mycosis fungoides (MF). The frequency of CD19 + CD24 hi CD27 + memory B cells and CD19 + CD24 hi CD38 hi transitional B cells (which enrich IL-10-producing Bregs) was examined in peripheral blood from patients with advanced MF (n = 11) and healthy controls (n = 9) by flow cytometry. The frequency of IL-10-producing Bregs was also measured by flow cytometry. The correlation between frequency or number of B-cell subsets and disease severity markers was also analysed. The frequency of CD19 + CD24 hi CD27 + B cells, CD19 + CD24 hi CD38 hi B cells, and IL-10-producing B cells was decreased in peripheral blood of advanced MF patients. The frequency and number of these B-cell subsets inversely correlated with serum soluble IL-2 receptor and serum lactate dehydrogenase levels. The development of IL-10-producing Bregs is impaired in patients with advanced MF and a decrease in IL-10-producing Bregs may play an important role in the progression of advanced MF.

Effects of aluminum and extremely low frequency electromagnetic radiation on oxidative stress and memory in brain of mice.

PubMed

Deng, Yuanxin; Zhang, Yanwen; Jia, Shujie; Liu, Junkang; Liu, Yanxia; Xu, Weiwei; Liu, Lei

2013-12-01

This study was aimed to investigate the effect of aluminum and extremely low-frequency magnetic fields (ELF-MF) on oxidative stress and memory of SPF Kunming mice. Sixty male SPF Kunming mice were divided randomly into four groups: control group, ELF-MF group (2 mT, 4 h/day), load aluminum group (200 mg aluminum/kg, 0.1 ml/10 g), and ELF-MF + aluminum group (2 mT, 4 h/day, 200 mg aluminum/kg). After 8 weeks of treatment, the mice of three experiment groups (ELF-MF group, load aluminum group, and ELF-MF + aluminum group) exhibited firstly the learning memory impairment, appearing that the escaping latency to the platform was prolonged and percentage in the platform quadrant was reduced in the Morris water maze (MWM) task. Secondly are the pathologic abnormalities including neuronal cell loss and overexpression of phosphorylated tau protein in the hippocampus and cerebral cortex. On the other hand, the markers of oxidative stress were determined in mice brain and serum. The results showed a statistically significant decrease in superoxide dismutase activity and increase in the levels of malondialdehyde in the ELF-MF group (P < 0.05 or P < 0.01), load aluminum group (P < 0.01), and ELF-MF + aluminum group (P < 0.01). However, the treatment with ELF-MF + aluminum induced no more damage than ELF-MF and aluminum did, respectively. In conclusion, both aluminum and ELF-MF could impact on learning memory and pro-oxidative function in Kunming mice. However, there was no evidence of any association between ELF-MF exposure with aluminum loading.

Guidelines on the diagnosis of noise-induced hearing loss for medicolegal purposes.

PubMed

Coles, R R; Lutman, M E; Buffin, J T

2000-08-01

These guidelines aim to assist in the diagnosis of noise-induced hearing loss (NIHL) in medicolegal settings. The task is to distinguish between possibility and probability, the legal criterion being 'more probable than not'. It is argued that the amount of NIHL needed to qualify for that diagnosis is that which is reliably measurable and identifiable on the audiogram. The three main requirements for the diagnosis of NIHL are defined: R1, high-frequency hearing impairment; R2, potentially hazardous amount of noise exposure; R3, identifiable high-frequency audiometric notch or bulge. Four modifying factors also need consideration: MF1, the clinical picture; MF2, compatibility with age and noise exposure; MF3, Robinson's criteria for other causation; MF4, complications such as asymmetry, mixed disorder and conductive hearing impairment.

Response of Cultured Neuronal Network Activity After High-Intensity Power Frequency Magnetic Field Exposure

PubMed Central

Saito, Atsushi; Takahashi, Masayuki; Makino, Kei; Suzuki, Yukihisa; Jimbo, Yasuhiko; Nakasono, Satoshi

2018-01-01

High-intensity and low frequency (1–100 kHz) time-varying electromagnetic fields stimulate the human body through excitation of the nervous system. In power frequency range (50/60 Hz), a frequency-dependent threshold of the external electric field-induced neuronal modulation in cultured neuronal networks was used as one of the biological indicator in international guidelines; however, the threshold of the magnetic field-induced neuronal modulation has not been elucidated. In this study, we exposed rat brain-derived neuronal networks to a high-intensity power frequency magnetic field (hPF-MF), and evaluated the modulation of synchronized bursting activity using a multi-electrode array (MEA)-based extracellular recording technique. As a result of short-term hPF-MF exposure (50–400 mT root-mean-square (rms), 50 Hz, sinusoidal wave, 6 s), the synchronized bursting activity was increased in the 400 mT-exposed group. On the other hand, no change was observed in the 50–200 mT-exposed groups. In order to clarify the mechanisms of the 400 mT hPF-MF exposure-induced neuronal response, we evaluated it after blocking inhibitory synapses using bicuculline methiodide (BMI); subsequently, increase in bursting activity was observed with BMI application, and the response of 400 mT hPF-MF exposure disappeared. Therefore, it was suggested that the response of hPF-MF exposure was involved in the inhibitory input. Next, we screened the inhibitory pacemaker-like neuronal activity which showed autonomous 4–10 Hz firing with CNQX and D-AP5 application, and it was confirmed that the activity was reduced after 400 mT hPF-MF exposure. Comparison of these experimental results with estimated values of the induced electric field (E-field) in the culture medium revealed that the change in synchronized bursting activity occurred over 0.3 V/m, which was equivalent to the findings of a previous study that used the external electric fields. In addition, the results suggested that the potentiation of neuronal activity after 400 mT hPF-MF exposure was related to the depression of autonomous activity of pacemaker-like neurons. Our results indicated that the synchronized bursting activity was increased by hPF-MF exposure (E-field: >0.3 V/m), and the response was due to reduced inhibitory pacemaker-like neuronal activity. PMID:29662453

Power adaptive multi-filter carrierless amplitude and phase access scheme for visible light communication network

NASA Astrophysics Data System (ADS)

Li, Wei; Huang, Zhitong; Li, Haoyue; Ji, Yuefeng

2018-04-01

Visible light communication (VLC) is a promising candidate for short-range broadband access due to its integration of advantages for both optical communication and wireless communication, whereas multi-user access is a key problem because of the intra-cell and inter-cell interferences. In addition, the non-flat channel effect results in higher losses for users in high frequency bands, which leads to unfair qualities. To solve those issues, we propose a power adaptive multi-filter carrierless amplitude and phase access (PA-MF-CAPA) scheme, and in the first step of this scheme, the MF-CAPA scheme utilizing multiple filters as different CAP dimensions is used to realize multi-user access. The character of orthogonality among the filters in different dimensions can mitigate the effect of intra-cell and inter-cell interferences. Moreover, the MF-CAPA scheme provides different channels modulated on the same frequency bands, which further increases the transmission rate. Then, the power adaptive procedure based on MF-CAPA scheme is presented to realize quality fairness. As demonstrated in our experiments, the MF-CAPA scheme yields an improved throughput compared with multi-band CAP access scheme, and the PA-MF-CAPA scheme enhances the quality fairness and further improves the throughput compared with the MF-CAPA scheme.

Role of JAK-STAT signaling in the pathogenesis of myeloproliferative disorders.

PubMed

Levine, Ross L; Wernig, Gerlinde

2006-01-01

The identification of JAK2V617F mutations in polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis (MF) represents an important advance in our understanding of these myeloproliferative disorders (MPD). Most, if not all, patients with PV and a significant number of patients with ET and MF are JAK2V617F positive, and the mutation likely arises in the hematopoietic stem cell compartment. JAK2V617F is a constitutively active tyrosine kinase that is able to activate JAK-STAT signaling most efficiently when co-expressed with the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte colony-stimulating factor receptor (GCSFR). Data from murine models supports the central role of JAK2V617F in the pathogenesis of MPD, as expression of JAK2V617F in a bone marrow transplantation assay results in polycythemia and myelofibrosis in recipient mice. Activation of JAK-STAT signaling by JAK2V617F in some, but not all MPD patients with ET and MF led to the identification of the constitutively active MPLW515L allele in ET and MF. Small molecule inhibitors of JAK-STAT signaling are currently being developed, which offer potential for molecularly targeted therapy for patients with PV, ET, and MF. Despite these advances, many questions remain regarding the role of a single disease allele in three phenotypically distinct MPD, the potential clinical efficacy of JAK2 inhibitors, and the identity of oncogenic alleles in JAK2V617F/MPLW515-negative MPD.

The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma.

PubMed

Yuan, Lin-Qing; Wang, Can; Zhu, Kun; Li, Hua-Mei; Gu, Wei-Zhong; Zhou, Dong-Ming; Lai, Jia-Qi; Zhou, Duo; Lv, Yao; Tofani, Santi; Chen, Xi

2018-05-02

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 2018;9999:1-11. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Synapsin- and Actin-Dependent Frequency Enhancement in Mouse Hippocampal Mossy Fiber Synapses

PubMed Central

Owe, Simen G.; Jensen, Vidar; Evergren, Emma; Ruiz, Arnaud; Shupliakov, Oleg; Kullmann, Dimitri M.; Storm-Mathisen, Jon; Walaas, S. Ivar; Hvalby, Øivind

2009-01-01

The synapsin proteins have different roles in excitatory and inhibitory synaptic terminals. We demonstrate a differential role between types of excitatory terminals. Structural and functional aspects of the hippocampal mossy fiber (MF) synapses were studied in wild-type (WT) mice and in synapsin double-knockout mice (DKO). A severe reduction in the number of synaptic vesicles situated more than 100 nm away from the presynaptic membrane active zone was found in the synapsin DKO animals. The ultrastructural level gave concomitant reduction in F-actin immunoreactivity observed at the periactive endocytic zone of the MF terminals. Frequency facilitation was normal in synapsin DKO mice at low firing rates (∼0.1 Hz) but was impaired at firing rates within the physiological range (∼2 Hz). Synapses made by associational/commissural fibers showed comparatively small frequency facilitation at the same frequencies. Synapsin-dependent facilitation in MF synapses of WT mice was attenuated by blocking F-actin polymerization with cytochalasin B in hippocampal slices. Synapsin III, selectively seen in MF synapses, is enriched specifically in the area adjacent to the synaptic cleft. This may underlie the ability of synapsin III to promote synaptic depression, contributing to the reduced frequency facilitation observed in the absence of synapsins I and II. PMID:18550596

Associations between meal and snack frequency and overweight and abdominal obesity in US children and adolescents from National Health and Nutrition Examination Survey (NHANES) 2003-2012.

PubMed

Murakami, Kentaro; Livingstone, M Barbara E

2016-05-28

The association between eating frequency (EF) and adiposity in young populations is inconsistent. This cross-sectional study examined associations of EF, meal frequency (MF) and snack frequency (SF) with adiposity measures in US children aged 6-11 years (n 4346) and adolescents aged 12-19 years (n 6338) participating in the National Health and Nutrition Examination Survey 2003-2012. Using data from two 24-h dietary recalls, all eating occasions providing ≥210 kJ of energy were divided into meals or snacks based on contribution to energy intake (≥15 or <15 %), self-report and time (06.00-09.00, 12.00-14.00 and 17.00-20.00 hours or others). When analysed without adjustment for the ratio of reported energy intake:estimated energy requirement (EI:EER), all measures of EF, MF and SF showed inverse or null associations with overweight (BMI≥85th percentile of BMI-for-age) and abdominal obesity (waist circumference≥90th percentile) in both children and adolescents. After adjustment for EI:EER, however, EF and SF, but not MF, showed positive associations in children, irrespective of the definition of meals and snacks. In adolescents, after adjustment for EI:EER, positive associations were observed for EF (abdominal obesity only), SF based on energy contribution and MF based on self-report, whereas there was an inverse association between MF based on energy contribution and overweight. In conclusion, higher SF and EF, but not MF, were associated with higher risks of overweight and abdominal obesity in children, whereas associations varied in adolescents, depending on the definition of meals and snacks. Prospective studies are needed to establish the associations observed here.

Extremely Low Frequency Magnetic Field (50 Hz, 0.5 mT) Reduces Oxidative Stress in the Brain of Gerbils Submitted to Global Cerebral Ischemia

PubMed Central

Rauš Balind, Snežana; Selaković, Vesna; Radenović, Lidija; Prolić, Zlatko; Janać, Branka

2014-01-01

Magnetic field as ecological factor has influence on all living beings. The aim of this study was to determine if extremely low frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) affects oxidative stress in the brain of gerbils submitted to 10-min global cerebral ischemia. After occlusion of both carotid arteries, 3-month-old gerbils were continuously exposed to ELF-MF for 7 days. Nitric oxide and superoxide anion production, superoxide dismutase activity and index of lipid peroxidation were examined in the forebrain cortex, striatum and hippocampus on the 7th (immediate effect of ELF-MF) and 14th day after reperfusion (delayed effect of ELF-MF). Ischemia per se increased oxidative stress in the brain on the 7th and 14th day after reperfusion. ELF-MF also increased oxidative stress, but to a greater extent than ischemia, only immediately after cessation of exposure. Ischemic gerbils exposed to ELF-MF had increased oxidative stress parameters on the 7th day after reperfusion, but to a lesser extent than ischemic or ELF-MF-exposed animals. On the 14th day after reperfusion, oxidative stress parameters in the brain of these gerbils were mostly at the control levels. Applied ELF-MF decreases oxidative stress induced by global cerebral ischemia and thereby reduces possible negative consequences which free radical species could have in the brain. The results presented here indicate a beneficial effect of ELF-MF (50 Hz, 0.5 mT) in the model of global cerebral ischemia. PMID:24586442

Comparison of two bioelectrical impedance devices and dual-energy X-ray absorptiometry to evaluate body composition in heart failure.

PubMed

Alves, F D; Souza, G C; Biolo, A; Clausell, N

2014-12-01

The utilisation of bioelectrical impedance analysis (BIA) in heart failure can be affected by many factors and its applicability remains controversial. The present study aimed to verify the adequacy of single-frequency BIA (SF-BIA) and multifrequency BIA (MF-BIA) compared to dual-energy x-ray absorptiometry (DEXA) for evaluating body composition in outpatients with heart failure. In this cross-sectional study, 55 patients with stable heart failure and left ventricle ejection fraction ≤45% were evaluated for fat mass percentage, fat mass and fat-free mass by DEXA and compared with the results obtained by SF-BIA (single frequency of 50 kHz) and MF-BIA (frequencies of 20 and 100 kHz). MF-BIA and DEXA gave similar mean values for fat mass percentage, fat mass and fat-free mass, whereas values from SF-BIA were significantly different from DEXA. Both SF-BIA and MF-BIA measures of body composition correlated strongly with DEXA (r > 0.8; P < 0.001), except for fat mass assessed by SF-BIA, which showed a moderate correlation (r = 0.760; P < 0.001). MF-BIA also showed a better agreement with DEXA by Bland-Altman analysis in all measurements. However, both types of equipment showed wide limits of agreement and a significant relationship between variance and bias (Pitmans's test P > 0.05), except MF-BIA for fat-free mass. Compared with DEXA, MF-BIA showed better accuracy than SF-BIA, although both types of equipment showed wide limits of agreement. The BIA technique should be used with caution, and regression equations might be useful for correcting the observed variations, mainly in extreme values of body composition. © 2014 The British Dietetic Association Ltd.

Development of a μO-Conotoxin Analogue with Improved Lipid Membrane Interactions and Potency for the Analgesic Sodium Channel NaV1.8*

PubMed Central

Deuis, Jennifer R.; Dekan, Zoltan; Inserra, Marco C.; Lee, Tzong-Hsien; Aguilar, Marie-Isabel; Craik, David J.; Lewis, Richard J.; Alewood, Paul F.; Mobli, Mehdi; Schroeder, Christina I.; Henriques, Sónia Troeira; Vetter, Irina

2016-01-01

The μO-conotoxins MrVIA, MrVIB, and MfVIA inhibit the voltage-gated sodium channel NaV1.8, a well described target for the treatment of pain; however, little is known about the residues or structural elements that define this activity. In this study, we determined the three-dimensional structure of MfVIA, examined its membrane binding properties, performed alanine-scanning mutagenesis, and identified residues important for its activity at human NaV1.8. A second round of mutations resulted in (E5K,E8K)MfVIA, a double mutant with greater positive surface charge and greater affinity for lipid membranes compared with MfVIA. This analogue had increased potency at NaV1.8 and was analgesic in the mouse formalin assay. PMID:27026701

Assessment of occupational exposure to extremely low frequency magnetic fields in hospital personnel.

PubMed

Úbeda, Alejandro; Martínez, María Antonia; Cid, María Antonia; Chacón, Lucía; Trillo, María A; Leal, Jocelyne

2011-07-01

It has been proposed that chronic exposure to extremely low frequency (ELF) magnetic fields (MF) in occupational environments could represent a risk factor for a number of disorders. Medical and technical workers in hospitals have been reported to be exposed to relatively strong ELF fields. The present work aims to characterize exposure to MF in the 5 Hz to 2 kHz frequency range in a large hospital through both instantaneous environmental measurements and personal monitoring of workers. The study was conducted in different working environments of a hospital with about 4400 employees, many of them working at two or more different work stations and consequently, exposed to MF levels that were expected to be unevenly distributed in space and time. The results indicate that: (1) The dominant frequency at the studied environments was 50 Hz (average 90.8 ± 6% of the total B value); (2) The best descriptive information on a worker's exposure is obtained from personal monitoring of volunteer workers; (3) The arithmetic averages of exposure levels obtained from the monitoring ranged from 0.03 ± 0.01 µT in nurses to 0.39 ± 0.13 µT in physiotherapists; and (4) The description of the MF environment through spot measurements in the workplace, although coherent with the data from personal monitoring, might not adequately estimate MF exposure in some professional categories. Copyright © 2011 Wiley-Liss, Inc.

The first full-resolution measurements of Auroral Medium Frequency Burst Emissions

NASA Astrophysics Data System (ADS)

Bunch, N. L.; Labelle, J.; Weatherwax, A.; Hughes, J.

2008-12-01

Auroral MF burst is a naturally occurring auroral radio emission which appears unstructured on resolution of previous measurements, is observed in the frequency range of 0.8-4.5 MHz, and has typical amplitudes of around 10-14 V2/m2Hz, and durations of a few minutes. The emission occurs at substorm onset. Since Sept 2006, Dartmouth has operated a broadband (0-5 MHz) interferometer at Toolik Lake, Alaska (68° 38' N, 149° 36' W, 68.51 deg. magnetic latitude), designed for the study of auroral MF burst emissions. Normal operation involves taking snapshots of waveforms from four spaced antennas from which wave spectral and directional information is obtained. However, the experiment can also be run in "continuous mode" whereby the signal from a selected antenna is sampled continuously at 10 M samples/second. A "continuous mode" campaign was run 0800-1200 UT (~2200-0200 MLT) daily from March 21 to April 19, 2008. During this campaign more than twenty auroral MF burst emissions were observed, including three extraordinarily intense examples lasting approximately two minutes each. These observations represent the highest time and frequency resolution data ever collected of MF burst emissions. These data allow us to better characterize the null near twice the electron gyrofrequency identified in previous experiments, since examples of this feature observed during this campaign display a strong null ~50 kHz in bandwidth, with sharp boundaries and occasionally coincident with 2 fce auroral roar. These data also allow us to search for frequency-time structures embedded in MF-burst. One prominent feature appears to be a strong single frequency emission which broadens down to lower frequencies over time, spreading to approximately 500 kHz in bandwidth over ~10 ms. Among other features observed are a diffuse and unstructured emission, as well as what could potentially be several separate emission sources, with multiple emissions occurring simultaneously, appearing as weaker "ghosts" behind the main MF burst emission. These data in will additionally allow us to search for the presence of sub-millisecond wave packets, sometimes quasi-periodic, reported by LaBelle et al. [1997, J. Geophys. Res. 102, 22221]. Finally, a search for frequency dispersion or absence thereof will provide a test of theories which speculate that different frequencies originate at different altitudes in the ionosphere.

Relation Between Macular Retinal Ganglion Cell/Inner Plexiform Layer Thickness and Multifocal Electroretinogram Measures in Experimental Glaucoma

PubMed Central

Luo, Xunda; Patel, Nimesh B.; Rajagopalan, Lakshmi P.; Harwerth, Ronald S.; Frishman, Laura J.

2014-01-01

Purpose. We investigated relations between macular retinal ganglion cell plus inner plexiform layer (RGC+IPL) thickness and macular retinal function revealed by multifocal electroretinonography (mfERG) in a nonhuman primate model of experimental glaucoma. Methods. Retinal ganglion cell (RGC) structure and function were followed with spectral-domain optical coherence tomography (SD-OCT) and ERGs in five macaques with unilateral experimental glaucoma. Linear regression was used to study correlations in control (Con) and experimental (Exp) eyes between peripapillary retinal nerve fiber layer (RNFL) thickness, macular RGC+IPL thickness, multifocal photopic negative response (mfPhNR) and high-frequency multifocal oscillatory potentials (mfOP) in slow-sequence mfERG, and low-frequency component (mfLFC) in global-flash mfERG. We used ANOVA and paired t-tests to compare glaucoma-related mfERG changes between superior and inferior hemifields, foveal hexagon, inner three rings, and four quadrants of macula. Results. Average macular RGC+IPL and temporal RNFL thickness were strongly correlated (r2 = 0.90, P < 0.001). In hexagon-by-hexagon analysis, all three mfERG measures were correlated (P < 0.001) with RGC+IPL thickness for Con (r2, 0.33–0.51) and Exp eyes (r2, 0.17–0.35). The RGC structural and functional metrics decreased as eccentricity increased. The reduction in amplitude of mfERG measures in Exp eyes relative to Con eyes was proportionally greater, in general, than the relative thinning of RGC+IPL at the same location for eyes in which structural loss was not evident, or mild to moderate. Although not statistically significant, percent amplitude reduction of mfERG measures was greatest in the inferior temporal quadrant. Conclusions. Macular RGC+IPL thickness and mfERG measures of RGC function can be complementary tools in assessing glaucomatous neuropathy. PMID:24970256

MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia

PubMed Central

Pikman, Yana; Lee, Benjamin H; Mercher, Thomas; McDowell, Elizabeth; Ebert, Benjamin L; Gozo, Maricel; Cuker, Adam; Wernig, Gerlinde; Moore, Sandra; Galinsky, Ilene; DeAngelo, Daniel J; Clark, Jennifer J; Lee, Stephanie J; Golub, Todd R; Wadleigh, Martha; Gilliland, D. Gary; Levine, Ross L

2006-01-01

Background The JAK2V617F allele has recently been identified in patients with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis with myeloid metaplasia (MF). Subsequent analysis has shown that constitutive activation of the JAK-STAT signal transduction pathway is an important pathogenetic event in these patients, and that enzymatic inhibition of JAK2V617F may be of therapeutic benefit in this context. However, a significant proportion of patients with ET or MF are JAK2V617F-negative. We hypothesized that activation of the JAK-STAT pathway might also occur as a consequence of activating mutations in certain hematopoietic-specific cytokine receptors, including the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte-colony stimulating factor receptor (GCSFR). Methods and Findings DNA sequence analysis of the exons encoding the transmembrane and juxtamembrane domains of EPOR, MPL, and GCSFR, and comparison with germline DNA derived from buccal swabs, identified a somatic activating mutation in the transmembrane domain of MPL (W515L) in 9% (4/45) of JAKV617F-negative MF. Expression of MPLW515L in 32D, UT7, or Ba/F3 cells conferred cytokine-independent growth and thrombopoietin hypersensitivity, and resulted in constitutive phosphorylation of JAK2, STAT3, STAT5, AKT, and ERK. Furthermore, a small molecule JAK kinase inhibitor inhibited MPLW515L-mediated proliferation and JAK-STAT signaling in vitro. In a murine bone marrow transplant assay, expression of MPLW515L, but not wild-type MPL, resulted in a fully penetrant myeloproliferative disorder characterized by marked thrombocytosis (Plt count 1.9–4.0 × 10 12/L), marked splenomegaly due to extramedullary hematopoiesis, and increased reticulin fibrosis. Conclusions Activation of JAK-STAT signaling via MPLW515L is an important pathogenetic event in patients with JAK2V617F-negative MF. The bone marrow transplant model of MPLW515L-mediated myeloproliferative disorders (MPD) exhibits certain features of human MF, including extramedullary hematopoiesis, splenomegaly, and megakaryocytic proliferation. Further analysis of positive and negative regulators of the JAK-STAT pathway is warranted in JAK2V617F-negative MPD. PMID:16834459

MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.

PubMed

Pikman, Yana; Lee, Benjamin H; Mercher, Thomas; McDowell, Elizabeth; Ebert, Benjamin L; Gozo, Maricel; Cuker, Adam; Wernig, Gerlinde; Moore, Sandra; Galinsky, Ilene; DeAngelo, Daniel J; Clark, Jennifer J; Lee, Stephanie J; Golub, Todd R; Wadleigh, Martha; Gilliland, D Gary; Levine, Ross L

2006-07-01

The JAK2V617F allele has recently been identified in patients with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis with myeloid metaplasia (MF). Subsequent analysis has shown that constitutive activation of the JAK-STAT signal transduction pathway is an important pathogenetic event in these patients, and that enzymatic inhibition of JAK2V617F may be of therapeutic benefit in this context. However, a significant proportion of patients with ET or MF are JAK2V617F-negative. We hypothesized that activation of the JAK-STAT pathway might also occur as a consequence of activating mutations in certain hematopoietic-specific cytokine receptors, including the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte-colony stimulating factor receptor (GCSFR). DNA sequence analysis of the exons encoding the transmembrane and juxtamembrane domains of EPOR, MPL, and GCSFR, and comparison with germline DNA derived from buccal swabs, identified a somatic activating mutation in the transmembrane domain of MPL (W515L) in 9% (4/45) of JAKV617F-negative MF. Expression of MPLW515L in 32D, UT7, or Ba/F3 cells conferred cytokine-independent growth and thrombopoietin hypersensitivity, and resulted in constitutive phosphorylation of JAK2, STAT3, STAT5, AKT, and ERK. Furthermore, a small molecule JAK kinase inhibitor inhibited MPLW515L-mediated proliferation and JAK-STAT signaling in vitro. In a murine bone marrow transplant assay, expression of MPLW515L, but not wild-type MPL, resulted in a fully penetrant myeloproliferative disorder characterized by marked thrombocytosis (Plt count 1.9-4.0 x 10(12)/L), marked splenomegaly due to extramedullary hematopoiesis, and increased reticulin fibrosis. Activation of JAK-STAT signaling via MPLW515L is an important pathogenetic event in patients with JAK2V617F-negative MF. The bone marrow transplant model of MPLW515L-mediated myeloproliferative disorders (MPD) exhibits certain features of human MF, including extramedullary hematopoiesis, splenomegaly, and megakaryocytic proliferation. Further analysis of positive and negative regulators of the JAK-STAT pathway is warranted in JAK2V617F-negative MPD.

47 CFR 97.301 - Authorized frequency bands.

Code of Federal Regulations, 2013 CFR

2013-10-01

...: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements see § 97.303... Advanced Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements... General Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements...

47 CFR 97.301 - Authorized frequency bands.

Code of Federal Regulations, 2012 CFR

2012-10-01

...: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements see § 97.303... Advanced Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements... General Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements...

47 CFR 97.301 - Authorized frequency bands.

Code of Federal Regulations, 2011 CFR

2011-10-01

...: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements see § 97.303... Advanced Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements... General Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements...

47 CFR 97.301 - Authorized frequency bands.

Code of Federal Regulations, 2014 CFR

2014-10-01

...: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements see § 97.303... Advanced Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements... General Class: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements...

5-Methoxyflavanone induces cell cycle arrest at the G2/M phase, apoptosis and autophagy in HCT116 human colon cancer cells

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

Shin, Soon Young; Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul 143-701; Hyun, Jiye

2011-08-01

Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the molecular mechanism underlying the action of 5-methoxyflavanone (5-MF) which has a strong bioavailability and metabolic stability. Our results show that 5-MF inhibited the growth and clonogenicity of HCT116 human colon cancer cells, and that it activated DNA damage responses, as revealed by the accumulation of p53 and the phosphorylation of DNA damage-sensitive proteins, including ataxia-telangiectasia mutated (ATM) at Ser1981, checkpoint kinase 2 (Chk2) at Thr68, and histone H2AX at Ser139. 5-MF-induced DNA damage was confirmed in a comet tail assay. We alsomore » found that 5-MF increased the cleavage of caspase-2 and -7, leading to the induction of apoptosis. Pretreatment with the ATM inhibitor KU55933 enhanced 5-MF-induced {gamma}-H2AX formation and caspase-7 cleavage. HCT116 cells lacking p53 (p53{sup -/-}) or p21 (p21{sup -/-}) exhibited increased sensitivity to 5-MF compared to wild-type cells. 5-MF further induced autophagy via an ERK signaling pathway. Blockage of autophagy with the MEK inhibitor U0126 potentiated 5-MF-induced {gamma}-H2AX formation and caspase-2 activation. These results suggest that a caspase-2 cascade mediates 5-MF-induced anti-tumor activity, while an ATM/Chk2/p53/p21 checkpoint pathway and ERK-mediated autophagy act as a survival program to block caspase-2-mediated apoptosis induced by 5-MF. - Graphical abstract: Display Omitted Highlights: > 5-MF inhibits the proliferation of HCT116 colon cancer cells. > 5-MF inhibits cell cycle progression and induces apoptosis. > Inhibition of autophagy triggers 5-MF-induced apoptosis. > Inhibition of ERK signaling blocks 5-MF-induced autophagy but activates apoptosis. > Treatment with 5-MF in combination with an ERK inhibitor may be a potential therapeutic strategy in human colon cancer.« less

Low-frequency magnetic fields do not aggravate disease in mouse models of Alzheimer's disease and amyotrophic lateral sclerosis

PubMed Central

Liebl, Martina P.; Windschmitt, Johannes; Besemer, Anna S.; Schäfer, Anne-Kathrin; Reber, Helmut; Behl, Christian; Clement, Albrecht M.

2015-01-01

Low-frequency magnetic fields (LF-MF) generated by power lines represent a potential environmental health risk and are classified as possibly carcinogenic by the World Health Organization. Epidemiological studies indicate that LF-MF might propagate neurodegenerative diseases like Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). We conducted a comprehensive analysis to determine whether long-term exposure to LF-MF (50 Hz, 1 mT) interferes with disease development in established mouse models for AD and ALS, namely APP23 mice and mice expressing mutant Cu/Zn-superoxide dismutase (SOD1), respectively. Exposure for 16 months did not aggravate learning deficit of APP23 mice. Likewise, disease onset and survival of SOD1G85R or SOD1G93A mice were not altered upon LF-MF exposure for ten or eight months, respectively. These results and an extended biochemical analysis of protein aggregation, glial activation and levels of toxic protein species suggests that LF-MF do not affect cellular processes involved in the pathogenesis of AD or ALS. PMID:25717019

Associations between meal and snack frequency and diet quality and adiposity measures in British adults: findings from the National Diet and Nutrition Survey.

PubMed

Murakami, Kentaro; Livingstone, M Barbara E

2016-06-01

To examine how different definitions of meals and snacks can affect the associations of meal frequency (MF) and snack frequency (SF) with dietary intake and adiposity measures. Based on 7 d weighed dietary record data, all eating occasions providing ≥210 kJ of energy were divided into meals or snacks based on contribution to energy intake (≥15 % or <15 %) or time (06.00-10.00, 12.00-15.00 and 18.00-21.00 hours; other). Diet quality was assessed using the Healthy Diet Indicator (HDI) and Mediterranean Diet Score (MDS). Great Britain. British adults aged 19-64 years (n 1487). MF based on energy contribution was associated with higher intake of dietary fibre, lower intakes of non-milk extrinsic sugars and alcohol, and higher HDI (only men) and MDS. MF based on time was associated with higher HDI and MDS in women only. Conversely, irrespective of the definition of snacks, SF was associated with higher intakes of confectionery and alcohol, lower intakes of cereals, protein, fat and dietary fibre, and lower HDI (except for SF based on energy contribution in women) and MDS. After adjustment for potential confounders, MF based on time, but not MF based on energy contribution, was positively associated with BMI and waist circumference in men only. SF was positively associated with BMI and waist circumference, irrespective of the definition of snacks. Higher SF was consistently associated with lower diet quality and higher adiposity measures, while associations with MF varied depending on the definition of meals and sex.

Commentary on "Inherited DNA-repair gene mutations in men with metastatic prostate cancer". Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, Beightol M, Morrissey C, Nghiem B, Cheng HH, Montgomery B, Walsh T, Casadei S, Berger M, Zhang L, Zehir A, Vijai J, Scher HI, Sawyers C, Schultz N, Kantoff PW, Solit D, Robson M, Van Allen EM, Offit K, de Bono J, Nelson PS. N Engl J Med. 2016;375(5):443-53.

PubMed

Freedland, Stephen J; Aronson, William J

2017-08-01

Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes. A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001). In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Commentary on: "Inherited DNA-repair gene mutations in men with metastatic prostate cancer." Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, Beightol M, Morrissey C, Nghiem B, Cheng HH, Montgomery B, Walsh T, Casadei S, Berger M, Zhang L, Zehir A, Vijai J, Scher HI, Sawyers C, Schultz N, Kantoff PW, Solit D, Robson M, Van Allen EM, Offit K, de Bono J, Nelson PS. N Engl J Med. 2016 Aug 4;375(5):443-53.

PubMed

Lee, Byron H

2017-09-01

Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes. A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001). In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer. (Funded by Stand Up To Cancer and others.). Copyright © 2017 Elsevier Inc. All rights reserved.

EMG median frequency changes in the neck-shoulder stabilizers of symptomatic office workers when challenged by different physical stressors.

PubMed

Szeto, Grace Pui Yuk; Straker, Leon Melville; O'Sullivan, Peter Bruce

2005-12-01

The problem of work-related neck and upper limb disorders among computer users has been reported extensively in the literature, and commonly cited risk factors include static posture, speed and force of keyboard operation. The present study examined changes in median frequency (MF) of the neck-shoulder muscles in symptomatic and asymptomatic office workers when they were exposed to these three physical stressors. A quasi-experimental Case-Control design was used to examine MF changes in two groups of female office workers when they were subjected to controlled doses of computer work involving prolonged static posture, increased typing speed and increased typing force. The MF of four major neck-shoulder muscles were examined bilaterally and compared between groups. The MF changes over time-at-task did not clearly illustrate any muscle fatigue mechanism. However, Case Group consistently showed trends for higher MF than the Control Group, and this pattern was observed in response to all three physical stressors. The consistent group differences in MF suggest different muscle recruitment strategies between symptomatic and asymptomatic office workers. These results implied that symptomatic individuals had altered motor control, which may have important implications in understanding the etiology of work-related musculoskeletal disorders.

FreeContact: fast and free software for protein contact prediction from residue co-evolution.

PubMed

Kaján, László; Hopf, Thomas A; Kalaš, Matúš; Marks, Debora S; Rost, Burkhard

2014-03-26

20 years of improved technology and growing sequences now renders residue-residue contact constraints in large protein families through correlated mutations accurate enough to drive de novo predictions of protein three-dimensional structure. The method EVfold broke new ground using mean-field Direct Coupling Analysis (EVfold-mfDCA); the method PSICOV applied a related concept by estimating a sparse inverse covariance matrix. Both methods (EVfold-mfDCA and PSICOV) are publicly available, but both require too much CPU time for interactive applications. On top, EVfold-mfDCA depends on proprietary software. Here, we present FreeContact, a fast, open source implementation of EVfold-mfDCA and PSICOV. On a test set of 140 proteins, FreeContact was almost eight times faster than PSICOV without decreasing prediction performance. The EVfold-mfDCA implementation of FreeContact was over 220 times faster than PSICOV with negligible performance decrease. EVfold-mfDCA was unavailable for testing due to its dependency on proprietary software. FreeContact is implemented as the free C++ library "libfreecontact", complete with command line tool "freecontact", as well as Perl and Python modules. All components are available as Debian packages. FreeContact supports the BioXSD format for interoperability. FreeContact provides the opportunity to compute reliable contact predictions in any environment (desktop or cloud).

Efficacy of ALK5 inhibition in myelofibrosis

PubMed Central

Zhao, Wanke; Ho, Wanting Tina; Han, Ying; Murdun, Cem; Mailloux, Adam W.; Zhang, Ling; Wang, Xuefeng; Budhathoki, Anjali; Pradhan, Kith; Rapaport, Franck; Wang, Huaquan; Shao, Zonghong; Ren, Xiubao; Steidl, Ulrich; Levine, Ross L.; Zhao, Zhizhuang Joe; Verma, Amit; Epling-Burnette, Pearlie K.

2017-01-01

Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples. Significant overexpression of TGF-β1 was also observed in murine clonal MPLW515L megakaryocytic cells. TGF-β1 stimulated the deposition of excessive collagen by mesenchymal stromal cells (MSCs) by activating the TGF-β receptor I kinase (ALK5)/Smad3 pathway. MSCs derived from MPLW515L mice demonstrated sustained overproduction of both collagen I and collagen III, effects that were abrogated by ALK5 inhibition in vitro and in vivo. Importantly, use of galunisertib, a clinically active ALK5 inhibitor, significantly improved MF in both MPLW515L and JAK2V617F mouse models. These data demonstrate the role of malignant hematopoietic stem cell (HSC)/TGF-β/MSC axis in the pathogenesis of MF, and provide a preclinical rationale for ALK5 blockade as a therapeutic strategy in MF. PMID:28405618

Early Exposure to Intermediate-Frequency Magnetic Fields Alters Brain Biomarkers without Histopathological Changes in Adult Mice

PubMed Central

Win-Shwe, Tin-Tin; Ohtani, Shin; Ushiyama, Akira; Kunugita, Naoki

2015-01-01

Recently we have reported that intermediate-frequency magnetic field (IF-MF) exposure transiently altered the mRNA expression levels of memory function-related genes in the hippocampi of adult male mice. However, the effects of IF-MF exposure during brain development on neurological biomarkers have not yet been clarified. In the present study, we investigated the effect of IF-MF exposure during development on neurological and immunological markers in the mouse hippocampus in 3- and 7-week-old male mice. Pregnant C57BL/6J mice were exposed to IF-MF (21 kHz, 3.8 mT) for one hour per day from organogenesis period day 7 to 17. At adolescence, some IF-MF-exposed mice were further divided into exposure, recovery, and sham-exposure groups. The adolescent-exposure groups were exposed again to IF-MF from postnatal day 27 to 48. The expression of mRNA in the hippocampi was examined using a real-time RT-PCR method, and microglia activation was examined by immunohistochemical analysis. The expression levels of NR1 and NR2B as well as transcription factors (CaMKIV, CREB1), inflammatory mediators (COX2, IL-1 β,TNF-α), and the oxidative stress marker heme-oxygenase (HO)-1 were significantly increased in the IF-MF-exposed mice, compared with the control group, in the 7-week-old mice, but not in the 3-week-old mice. Microglia activation was not different between the control and other groups. This study provides the first evidence that early exposure to IF-MF reversibly affects the NMDA receptor, its related signaling pathways, and inflammatory mediators in the hippocampus of young adult mice; these changes are transient and recover after termination of exposure without histopathological changes. PMID:25913185

Effects of extremely low frequency magnetic field on oxidative balance in brain of rats.

PubMed

Ciejka, Elzbieta; Kleniewska, P; Skibska, B; Goraca, A

2011-12-01

Extremely low frequency magnetic field (ELF-MF) may result in oxidative DNA damage and lipid peroxidation with an ultimate effect on a number of systemic disturbances and cell death. The aim of the study is to assess the effect of ELF-MF parameters most frequently used in magnetotherapy on reactive oxygen species generation (ROS) in brain tissue of experimental animals depending on the time of exposure to this field. The research material included adult male Sprague-Dawley rats, aged 3-4 months. The animals were divided into 3 groups: I - control (shame) group; II - exposed to the following parameters of the magnetic field: 7 mT, 40 Hz, 30 min/day, 10 days; III - exposed to the ELF-MF parameters of 7 mT, 40 Hz, 60 min/day, 10 days. The selected parameters of oxidative stress: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and protein in brain homogenates were measured after the exposure of rats to the magnetic field. ELF-MF parameters of 7 mT, 40 Hz, 30 min/day for 10 days caused a significant increase in lipid peroxidation and insignificant increase in H(2)O(2) and free -SH groups. The same ELF-MF parameters but applied for 60 min/day caused a significant increase in free -SH groups and protein concentration in the brain homogenates indicating the adaptive mechanism. The study has shown that ELF-MF applied for 30 min/day for 10 days can affect free radical generation in the brain. Prolongation of the exposure to ELF-MF (60/min/day) caused adaptation to this field. The effect of ELF-MF irradiation on oxidative stress parameters depends on the time of animal exposure to magnetic field.

Multifocal and pattern-reversal visual evoked potentials vs. automated perimetry frequency-doubling technology matrix in optic neuritis

PubMed Central

Nebbioso, Marcella; Steigerwalt, Robert D; Pecori-Giraldi, Josè; Vingolo, Enzo M

2013-01-01

Background: To compare the usefulness of the traditional pattern-reversal Visual Evoked Potentials (VEP) with multifocal VEP (mfVEP) and Frequency-Doubling Technology (FDT) perimetry in the evaluation of the ocular abnormalities induced by acute or subacute optic neuritis (ON). Materials and Methods: The test results of 24 ON patients were compared with those obtained in 40 normal control subjects. MfVEP recordings were obtained by using an Optoelectronic Stimulator that extracts topographic VEP using a pseudorandom m-sequence stimulus. Receiver operator characteristic (ROC) curves were calculated to determine the sensitivity and specificity of abnormal values. Results: The frequency of the abnormal ocular findings differed in the ON patients according to the used technique. Reduced visual sensitivity was demonstrated in 12 eyes (54.5%) using FDT perimetry; 17 eyes (77.2%) showed decreased amplitude and/or an increase in the implicit time of the P1 wave in mfVEP and 20 eyes (90.9%) showed an abnormal decrease in the amplitude and/or an increase in the latency of the P100 peak at VEP examination. The areas under the ROC curves ranged from 0.743 to 0.935, with VEP having the largest areas. The VEP and mfVEP amplitudes and latencies yielded the greatest sensitivity and specificity. Conclusions: The mfVEP and the FDT perimetry can be used for the evaluation and monitoring of visual impairment in patients with ON. The most sensitive and practical diagnostic tool in patients with ON is, however, the traditional VEP. The mfVEP can be utilized in those cases with doubtful or negative VEP results. PMID:23412522

Rapid-onset/offset, variably scheduled 60 Hz electric and magnetic field exposure reduces nocturnal serum melatonin concentration in nonhuman primates

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

Rogers, W.R.; Smith, H.D.; Reiter, R.J.

Experiments with rodents indicate that power-frequency electric field (EF) or magnetic field (MF) exposure can suppress the normal nocturnal increase in melatonin concentration in pineal gland and blood. In a separate set of three experiments conducted with nonhuman primates, the authors did not observe melatonin suppression as a result of 6 weeks of day-time exposure to combined 60 Hz electric and magnetic fields (E/MF) with regularly schedule ``slow`` E/MF onsets/offsets. The study described here used a different exposure paradigm in which two baboons were exposed to E/MF with ``rapid`` E/MF onsets/offsets accompanied by EF transients not found with slowly rampedmore » E/MF onset/offset; profound reductions in nocturnal serum melatonin concentration were observed in this experiment. If replicated in a more extensive experiment, the observation of melatonin suppression only in the presence of E/MF transients would suggest that very specific exposure parameters determine the effects of 60 Hz E/MF on melatonin.« less

ACB-PCR MEASUREMENT OF K-RAS CODON 12 MUTATION IN A/J MOUSE LUNG EXPOSED TO BENZO[A]PYRENE: A DOSE-RESPONSE ASSESSMENT

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is a known human carcinogen and environmental contaminant. The direct measurement of K-Ras mutant fraction (MF) was developed as a metric with which to examine the default assumption of low dose linearity in the mutational response to B...

Quantum-chemical calculations and IR spectra of the (F2)MF2 molecules (M = B, Al, Ga, In, Tl) in solid matrices: a new class of very high electron affinity neutral molecules.

PubMed

Wang, Xuefeng; Andrews, Lester

2011-03-23

Electron-deficient group 13 metals react with F(2) to give the compounds MF(2) (M = B, Al, Ga, In, Tl), which combine with F(2) to form a new class of very high electron affinity neutral molecules, (F(2))MF(2), in solid argon and neon. These (F(2))MF(2) fluorine metal difluoride molecules were identified through matrix IR spectra containing new antisymmetric and symmetric M-F stretching modes. The assignments were confirmed through close comparisons with frequency calculations using DFT methods, which were calibrated against the MF(3) molecules observed in all of the spectra. Electron affinities calculated at the CCSD(T) level fall between 7.0 and 7.8 eV, which are in the range of the highest known electron affinities.

Effects of extremely low frequency magnetic field on production of mannatide by α-hemolytic Streptococcus.

PubMed

Zhang, Jialan; Xu, Cui; Wan, Yunlei; Gao, Mengxiang

2016-07-01

The effect of the extremely low frequency magnetic field (ELF-MF) on biomass and mannatide production by α-hemolytic Streptococcus in liquid-state fermentation culture medium was studied during shake flask culture. Magnetic field (MF) inductions, exposure times, and exposure periods varied in a range of 0-1.5 mT, 0-16 h, and six periods of incubation time, respectively. Results showed both biomass and mannatide production increased significantly at MF induction 0.4, 0.6, and 0.9 mT and decreased at both 1.2 and 1.5 mT. Biomass increased by exposure for initial and middle stages of fermentation. Mannatide production increased significantly at 4-8, 8-12, and 17-21 h. Peak yield of biomass and mannatide production increased by 10.7% and 14.0% at 25 and 27 h of incubation at 0.6 mT MF induction and exposure to 8-12 h of incubation time, compared with the control experiment, respectively. ELF-MF could also enhance the growth rate and mannatide production rate of α-hemolytic Streptococcus. However, ELF-MF did not alter α-hemolytic Streptococcus cell growth and mannatide metabolizing regulation or fermentation pattern. Mannatide production was not associated with cellular growth but rather only partially associated. Bioelectromagnetics. 37:331-337, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Comparison BMC assessed by dual-energy X-ray absorptiometry and multi-frequency bioelectrical impedance in Chinese overweight and obesity adults].

PubMed

Wang, Zhenghe; Fu, Lianguo; Yang, Yide; Wang, Shuo; Ma, Jun

2016-05-01

To compare consistency of Body Mineral Content (BMC, kg) assessed by Multi-frequency Bioelectrical Impedance Analysis ( MF-BIA) and Dual Energy X-ray Absorptiometry (DXA) measurement, providing evidence for MF-BIA accurate application in Chinese overweight/obese adults. A total of 1323 overweight/obesity adults aged 22-55 years were recruited voluntarily. All the subjects received the measurement of BMC both using MF-BIA and DXA. To evaluate the agreement of BMC measured by MF-BIA and DXA using interclass correlation coefficients (ICC), then establish correction prediction models. The mean difference of BMC between two methods was significant different with 0, overweight male subgroup was 0.28 kg, and 0.38 kg for obesity male, 0.24 kg for overweight female and 0.36 kg for obesity female, respectively (P < 0.05). The ICC of BMC between MF-BIA and DXA measurement were statistically significant in all subgroups (P < 0.01). The ICC for overweight male subgroup was 0.787, 0.796 for obesity male, 0.741 for overweight female and 0.788 for obesity female, respectively. Correction prediction model: overweight male population: BMC (DXA method) = -0.297 + 1.005 x BMC (MF-BIA method). Obese male population: BMC (DXA method) =0.302 + 0.799 x BMC (MF-BIA method). Overweight female groups: BMC (DXA method) = 0.780 + 0.598 x BMC (MF-BIA method). Obese female group: BMC (DXA method) = 0.755 + 0.597 x BMC (MF-BIA method). Upon examination, correction prediction models were better. Co The correlation and agreement of BMC measured by BIA and DXA are weak in Chinese overweight/obese adults. Therefore, consideration should be given to BMC measured by BIA method in Chinese overweight/obese adults. It should be corrected or adjusted to reduce errors compared with DXA method.

Genetics Home Reference: hepatic veno-occlusive disease with immunodeficiency

MedlinePlus

... Donald JA, Kirk EP, Ziegler JB, Salzer U, McDonald GB, Wong M, Lindeman R, Buckley MF. Mutations ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

Pre-exposure to 50 Hz magnetic fields modifies menadione-induced genotoxic effects in human SH-SY5Y neuroblastoma cells.

PubMed

Luukkonen, Jukka; Liimatainen, Anu; Höytö, Anne; Juutilainen, Jukka; Naarala, Jonne

2011-03-23

Extremely low frequency (ELF) magnetic fields (MF) are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis) to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells. Exposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS). Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone. The results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome.

A population-based job exposure matrix for power-frequency magnetic fields.

PubMed

Bowman, Joseph D; Touchstone, Jennifer A; Yost, Michael G

2007-09-01

A population-based job exposure matrix (JEM) was developed to assess personal exposures to power-frequency magnetic fields (MF) for epidemiologic studies. The JEM compiled 2,317 MF measurements taken on or near workers by 10 studies in the United States, Sweden, New Zealand, Finland, and Italy. A database was assembled from the original data for six studies plus summary statistics grouped by occupation from four other published studies. The job descriptions were coded into the 1980 Standard Occupational Classification system (SOC) and then translated to the 1980 job categories of the U.S. Bureau of the Census (BOC). For each job category, the JEM database calculated the arithmetic mean, standard deviation, geometric mean, and geometric standard deviation of the workday-average MF magnitude from the combined data. Analysis of variance demonstrated that the combining of MF data from the different sources was justified, and that the homogeneity of MF exposures in the SOC occupations was comparable to JEMs for solvents and particulates. BOC occupation accounted for 30% of the MF variance (p < 10(-6)), and the contrast (ratio of the between-job variance to the total of within- and between-job variances) was 88%. Jobs lacking data had their exposures inferred from measurements on similar occupations. The JEM provided MF exposures for 97% of the person-months in a population-based case-control study and 95% of the jobs on death certificates in a registry study covering 22 states. Therefore, we expect this JEM to be useful in other population-based epidemiologic studies.

Ground and space observations of medium frequency auroral radio emissions

NASA Astrophysics Data System (ADS)

Broughton, Matthew C.

The auroral zone is a rich source of natural radio emissions that can be observed in space and at ground-level. By studying these waves, scientists can gain insight into the plasma processes that generate them and use the near-Earth space environment as a large-scale plasma physics laboratory. This thesis uses both ground-level and in situ observations to study two kinds of natural radio emissions. First, we report observations of a new kind of auroral radio emission. The waves have frequencies ranging from 1.3-2.2 MHz, bandwidths ranging from 90-272 kHz, and durations ranging from 16-355 s. Spectral analysis of the waveform data has revealed that the emission has a complex combination of at least three kinds of fine structures. For model auroral electron distributions, calculations indicate that Langmuir waves could be excited at frequencies consistent with observations. The remainder of the thesis discusses auroral medium frequency (MF) burst, an impulsive, broadband natural radio emission observed at ground-level within a few minutes of local substorm onset. LaBelle [2011] proposed that MF burst originates as Langmuir/Z-mode waves on the topside of the ionosphere that subsequently mode convert to L-mode waves and propagate to ground-level. Using continuous waveform measurements and combined observations with the Sondrestrom Incoherent Scatter Radar, we have performed two tests of this mechanism. The results of these tests are consistent with the mechanism described in LaBelle [2011]. A survey of 8,624 half-orbits of the DEMETER spacecraft has revealed 68 observations of bursty MF waves. We have compared the wave properties of these waves to those of MF burst and have found that although it is uncertain, the balance of the evidence suggests that the bursty MF waves observed with DEMETER are the same phenomenon as the ground-level MF burst. Finally, we have used numerical simulations to model both the fine structure of MF burst and to estimate the attenuation the waves would experience due to Landau damping on the topside ionosphere and mode conversion on the bottomside ionosphere. The amount of Landau damping is sensitive to the ratio of secondary to background electrons nse/ne0. Ignoring collisional damping in the lower ionosphere, these calculations suggest that for nse/n e0<0.4%, 0.01-45% of the initial Langmuir wave power would reach ground-level. The above experimental and numerical studies constrain the conditions under which MF burst could plausibly originate as Langmuir/Z-mode waves on the topside of the ionosphere.

Ionosphere research with a HF/MF cubesat radio instrument

NASA Astrophysics Data System (ADS)

Kallio, Esa; Aikio, Anita; Alho, Markku; Fontell, Mathias; Harri, Ari-Matti; Kauristie, Kirsti; Kestilä, Antti; Koskimaa, Petri; Mäkelä, Jakke; Mäkelä, Miika; Turunen, Esa; Vanhamäki, Heikki; Verronen, Pekka

2017-04-01

New technology provides new possibilities to study geospace and 3D ionosphere by using spacecraft and computer simulations. A type of nanosatellites, CubeSats, provide a cost effective possibility to provide in-situ measurements in the ionosphere. Moreover, combined CubeSat observations with ground-based observations gives a new view on auroras and associated electromagnetic phenomena. Especially joint and active CubeSat - ground based observation campaigns enable the possibility of studying the 3D structure of the ionosphere. Furthermore using several CubeSats to form satellite constellations enables much higher temporal resolution. At the same time, increasing computation capacity has made it possible to perform simulations where properties of the ionosphere, such as propagation of the electromagnetic waves in the medium frequency, MF (0.3-3 MHz) and high frequency, HF (3-30 MHz), ranges is based on a 3D ionospheric model and on first-principles modelling. Electromagnetic waves at those frequencies are strongly affected by ionospheric electrons and, consequently, those frequencies can be used for studying the plasma. On the other hand, even if the ionosphere originally enables long-range telecommunication at MF and HF frequencies, the frequent occurrence of spatiotemporal variations in the ionosphere disturbs communication channels, especially at high latitudes. Therefore, study of the MF and HF waves in the ionosphere has both a strong science and technology interests. We introduce recently developed simulation models as well as measuring principles and techniques to investigate the arctic ionosphere by a polar orbiting CubeSat whose novel AM radio instrument measures HF and MF waves. The cubesat, which contains also a white light aurora camera, is planned to be launched in late 2017 (http://www.suomi100satelliitti.fi/eng). The new models are (1) a 3D ray tracing model and (2) a 3D full kinetic electromagnetic simulation. We also introduce how combining of the cubesat measurements to ground based measurements provides new research possibilities to study 3D ionosphere.

Steady-state multifocal visual evoked potential (ssmfVEP) using dartboard stimulation as a possible tool for objective visual field assessment.

PubMed

Horn, Folkert K; Selle, Franziska; Hohberger, Bettina; Kremers, Jan

2016-02-01

To investigate whether a conventional, monitor-based multifocal visual evoked potential (mfVEP) system can be used to record steady-state mfVEP (ssmfVEP) in healthy subjects and to study the effects of temporal frequency, electrode configuration and alpha waves. Multifocal pattern reversal VEP measurements were performed at 58 dartboard fields using VEP recording equipment. The responses were measured using m-sequences with four pattern reversals per m-step. Temporal frequencies were varied between 6 and 15 Hz. Recordings were obtained from nine normal subjects with a cross-shaped, four-electrode device (two additional channels were derived). Spectral analyses were performed on the responses at all locations. The signal to noise ratio (SNR) was computed for each response using the signal amplitude at the reversal frequency and the noise at the neighbouring frequencies. Most responses in the ssmfVEP were significantly above noise. The SNR was largest for an 8.6-Hz reversal frequency. The individual alpha electroencephalogram (EEG) did not strongly influence the results. The percentage of the records in which each of the 6 channels had the largest SNR was between 10.0 and 25.2 %. Our results in normal subjects indicate that reliable mfVEP responses can be achieved by steady-state stimulation using a conventional dartboard stimulator and multi-channel electrode device. The ssmfVEP may be useful for objective visual field assessment as spectrum analysis can be used for automated evaluation of responses. The optimal reversal frequency is 8.6 Hz. Alpha waves have only a minor influence on the analysis. Future studies must include comparisons with conventional mfVEP and psychophysical visual field tests.

Translesion Synthesis of the N(2)-2'-Deoxyguanosine Adduct of the Dietary Mutagen IQ in Human Cells: Error-Free Replication by DNA Polymerase κ and Mutagenic Bypass by DNA Polymerases η, ζ, and Rev1.

PubMed

Bose, Arindam; Millsap, Amy D; DeLeon, Arnie; Rizzo, Carmelo J; Basu, Ashis K

2016-09-19

Translesion synthesis (TLS) of the N(2)-2'-deoxyguanosine (dG-N(2)-IQ) adduct of the carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was investigated in human embryonic kidney 293T cells by replicating plasmid constructs in which the adduct was individually placed at each guanine (G1, G2, or G3) of the NarI sequence (5'-CG1G2CG3CC-3'). TLS efficiency was 38%, 29%, and 25% for the dG-N(2)-IQ located at G1, G2, and G3, respectively, which suggests that dG-N(2)-IQ is bypassed more efficiently by one or more DNA polymerases at G1 than at either G2 or G3. TLS efficiency was decreased 8-35% in cells with knockdown of pol η, pol κ, pol ι, pol ζ, or Rev1. Up to 75% reduction in TLS occurred when pol η, pol ζ, and Rev1 were simultaneously knocked down, suggesting that these three polymerases play important roles in dG-N(2)-IQ bypass. Mutation frequencies (MFs) of dG-N(2)-IQ at G1, G2, and G3 were 23%, 17%, and 11%, respectively, exhibiting a completely reverse trend of the previously reported MF of the C8-dG adduct of IQ (dG-C8-IQ), which is most mutagenic at G3 ( ( 2015 ) Nucleic Acids Res. 43 , 8340 - 8351 ). The major type of mutation induced by dG-N(2)-IQ was targeted G → T, as was reported for dG-C8-IQ. In each site, knockdown of pol κ resulted in an increase in MF, whereas MF was reduced when pol η, pol ι, pol ζ, or Rev1 was knocked down. The reduction in MF was most pronounced when pol η, pol ζ, and Rev1 were simultaneously knocked down and especially when the adduct was located at G3, where MF was reduced by 90%. We conclude that pol κ predominantly performs error-free TLS of the dG-N(2)-IQ adduct, whereas pols η, pol ζ, and Rev1 cooperatively carry out the error-prone TLS. However, in vitro experiments using yeast pol ζ and κ showed that the former was inefficient in full-length primer extension on dG-N(2)-IQ templates, whereas the latter was efficient in both error-free and error-prone extensions. We believe that the observed differences between the in vitro experiments using purified DNA polymerases, and the cellular results may arise from several factors including the crucial roles played by the accessory proteins in TLS.

Translesion Synthesis of the N2-2′-Deoxyguanosine Adduct of the Dietary Mutagen IQ in Human Cells: Error-Free Replication by DNA Polymerase κ and Mutagenic Bypass by DNA Polymerases η, ζ, and Rev1

PubMed Central

2016-01-01

Translesion synthesis (TLS) of the N2-2′-deoxyguanosine (dG-N2-IQ) adduct of the carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was investigated in human embryonic kidney 293T cells by replicating plasmid constructs in which the adduct was individually placed at each guanine (G1, G2, or G3) of the NarI sequence (5′-CG1G2CG3CC-3′). TLS efficiency was 38%, 29%, and 25% for the dG-N2-IQ located at G1, G2, and G3, respectively, which suggests that dG-N2-IQ is bypassed more efficiently by one or more DNA polymerases at G1 than at either G2 or G3. TLS efficiency was decreased 8–35% in cells with knockdown of pol η, pol κ, pol ι, pol ζ, or Rev1. Up to 75% reduction in TLS occurred when pol η, pol ζ, and Rev1 were simultaneously knocked down, suggesting that these three polymerases play important roles in dG-N2-IQ bypass. Mutation frequencies (MFs) of dG-N2-IQ at G1, G2, and G3 were 23%, 17%, and 11%, respectively, exhibiting a completely reverse trend of the previously reported MF of the C8-dG adduct of IQ (dG-C8-IQ), which is most mutagenic at G3 ((2015) Nucleic Acids Res.43, 8340−835126220181). The major type of mutation induced by dG-N2-IQ was targeted G → T, as was reported for dG-C8-IQ. In each site, knockdown of pol κ resulted in an increase in MF, whereas MF was reduced when pol η, pol ι, pol ζ, or Rev1 was knocked down. The reduction in MF was most pronounced when pol η, pol ζ, and Rev1 were simultaneously knocked down and especially when the adduct was located at G3, where MF was reduced by 90%. We conclude that pol κ predominantly performs error-free TLS of the dG-N2-IQ adduct, whereas pols η, pol ζ, and Rev1 cooperatively carry out the error-prone TLS. However, in vitro experiments using yeast pol ζ and κ showed that the former was inefficient in full-length primer extension on dG-N2-IQ templates, whereas the latter was efficient in both error-free and error-prone extensions. We believe that the observed differences between the in vitro experiments using purified DNA polymerases, and the cellular results may arise from several factors including the crucial roles played by the accessory proteins in TLS. PMID:27490094

Unique fluorophores in the dimeric archaeal histones hMfB and hPyA1 reveal the impact of nonnative structure in a monomeric kinetic intermediate

PubMed Central

Stump, Matthew R.; Gloss, Lisa M.

2008-01-01

Homodimeric archaeal histones and heterodimeric eukaryotic histones share a conserved structure but fold through different kinetic mechanisms, with a correlation between faster folding/association rates and the population of kinetic intermediates. Wild-type hMfB (from Methanothermus fervidus) has no intrinsic fluorophores; Met35, which is Tyr in hyperthermophilic archaeal histones such as hPyA1 (from Pyrococcus strain GB-3A), was mutated to Tyr and Trp. Two Tyr-to-Trp mutants of hPyA1 were also characterized. All fluorophores were introduced into the long, central α-helix of the histone fold. Far-UV circular dichroism (CD) indicated that the fluorophores did not significantly alter the helical content of the histones. The equilibrium unfolding transitions of the histone variants were two-state, reversible processes, with ΔG°(H2O) values within 1 kcal/mol of the wild-type dimers. The hPyA1 Trp variants fold by two-state kinetic mechanisms like wild-type hPyA1, but with increased folding and unfolding rates, suggesting that the mutated residues (Tyr-32 and Tyr-36) contribute to transition state structure. Like wild-type hMfB, M35Y and M35W hMfB fold by a three-state mechanism, with a stopped-flow CD burst-phase monomeric intermediate. The M35 mutants populate monomeric intermediates with increased secondary structure and stability but exhibit decreased folding rates; this suggests that nonnative interactions occur from burial of the hydrophobic Tyr and Trp residues in this kinetic intermediate. These results implicate the long central helix as a key component of the structure in the kinetic monomeric intermediates of hMfB as well as the dimerization transition state in the folding of hPyA1. PMID:18096639

Cellular detection of 50 Hz magnetic fields and weak blue light: effects on superoxide levels and genotoxicity.

PubMed

Höytö, Anne; Herrala, Mikko; Luukkonen, Jukka; Juutilainen, Jukka; Naarala, Jonne

2017-06-01

We tested the hypothesis that the effects of 50 Hz magnetic fields (MFs) on superoxide levels and genotoxicity depend on the presence of blue light. Human SH-SY5Y neuroblastoma cells were exposed to a 50 Hz, 100 μT MF with or without non-phototoxic level of blue light for 24 h. We also studied whether these treatments alter responses to menadione, an agent that induces mitochondrial superoxide (O 2 • - ) production and DNA damage. Micronuclei, proliferation, viability, cytosolic and mitochondrial O 2 • - levels were assessed. MF (without blue light) increased cytosolic O 2 • - production and blue light suppressed this effect. Mitochondrial O 2 • - production was reduced by both MF and blue light, but these effects were not additive. Micronucleus frequency was not affected by blue light or MF alone, but blue light (significantly when combined with MF) enhanced menadione-induced micronuclei. The original simple hypothesis (blue light is needed for MF effects) was not supported, but interaction of MF and blue light was nevertheless observed. The results are consistent with MF effects on light-independent radical reactions.

ELF-MF Occupational Exposure in Die-casting and Electroplating Workers in Korea.

PubMed

Rajitha Kawshalya, Mailan Arachchige Don; Jung, Joon-Sig; Lee, Yun-Jin; Hong, Seung-Cheol

2018-04-26

A 24-h exposure assessment was performed in two groups of blue-collar workers from a die-casting and an electroplating plant to investigate levels of exposure to extremely low-frequency magnetic fields (ELF-MF), using EMDEX Lite. ELF-MF exposure of workers from the die-casting plant AM±SD (AM=arithmetic mean, SD=standard deviation) (0.649±1.343µT)] is higher than in electroplating workers (0.138±0.045µT). Higher ELF-MF exposure was found among workers living in same building as their workplace compared to that among other workers. This study suggests that ELF-MF exposure levels should be taken into consideration when providing dormitories for workers to minimize the levels of residential ELF-MF exposure due to emission from plants. The study recommends that blue-collar workers should be made aware of measures to minimize their exposure to environmental agents such as ELF-MF and electromagnetic field (EMF) during work, such as maintaining a safe distance between machines and avoiding undesirable behavior with equipment.

Determination of the Landau Lifshitz damping parameter of composite magnetic fluids

NASA Astrophysics Data System (ADS)

Fannin, P. C.; Malaescu, I.; Marin, C. N.

2007-01-01

Measurements of the frequency dependent, complex magnetic susceptibility, χ(ω)= χ‧( ω)- iχ″( ω), in the GHz range, are used to investigate the effect which the mixing of two different magnetic fluids has on the value of the damping parameter, α, of the Landau-Lifshitz equation. The magnetic fluid samples investigated in this study were three kerosene-based magnetic fluids, stabilised with oleic acid, denoted as MF1, MF2 and MF3. Sample MF1 was a magnetic fluid with Mn 0.6Fe 0.4Fe 2O 4 particles, sample MF2 was a magnetic fluid with Ni 0.4Zn 0.6Fe 2O 4 particles and sample MF3 was a composite magnetic fluid obtained by mixing a part of sample MF1 with a part of sample MF2, in proportion of 1:1. The experimental results revealed that the value of the damping parameter of the composite sample (sample MF3) is between the α values obtained for its constituents (samples MF1 and MF2). Based on the superposition principle, which states that the susceptibility of a magnetic fluid sample is a superposition of individual contributions of the magnetic particles, a theoretical model is proposed. The experimental results are shown to be in close agreement with the theoretical results. This result is potentially useful in the design of microwave-operating materials, in that it enables one to determine a particular value of damping parameter.

Evaluation of biological effects of intermediate frequency magnetic field on differentiation of embryonic stem cell.

PubMed

Yoshie, Sachiko; Ogasawara, Yuki; Ikehata, Masateru; Ishii, Kazuyuki; Suzuki, Yukihisa; Wada, Keiji; Wake, Kanako; Nakasono, Satoshi; Taki, Masao; Ohkubo, Chiyoji

2016-01-01

The embryotoxic effect of intermediate frequency (IF) magnetic field (MF) was evaluated using murine embryonic stem (ES) cells and fibroblast cells based on the embryonic stem cell test (EST). The cells were exposed to 21 kHz IF-MF up to magnetic flux density of 3.9 mT during the cell proliferation process (7 days) or the cell differentiation process (10 days) during which an embryonic body differentiated into myocardial cells. As a result, there was no significant difference in the cell proliferation between sham- and IF-MF-exposed cells for both ES and fibroblast cells. Similarly, the ratio of the number of ES-derived cell aggregates differentiated to myocardial cells to total number of cell aggregates was not changed by IF-MF exposure. In addition, the expressions of a cardiomyocytes-specific gene, Myl2 , and an early developmental gene, Hba-x , in the exposed cell aggregate were not altered. Since the magnetic flux density adopted in this study is much higher than that generated by an inverter of the electrical railway, an induction heating (IH) cooktop, etc . in our daily lives, these results suggested that IF-MF in which the public is exposed to in general living environment would not have embryotoxic effect.

Pre-Exposure to 50 Hz Magnetic Fields Modifies Menadione-Induced Genotoxic Effects in Human SH-SY5Y Neuroblastoma Cells

PubMed Central

Luukkonen, Jukka; Liimatainen, Anu; Höytö, Anne; Juutilainen, Jukka; Naarala, Jonne

2011-01-01

Background Extremely low frequency (ELF) magnetic fields (MF) are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis) to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells. Methodology/Principal Findings Exposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS). Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone. Conclusions The results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome. PMID:21448285

Human exposure to power frequency magnetic fields up to 7.6 mT: An integrated EEG/fMRI study.

PubMed

Modolo, Julien; Thomas, Alex W; Legros, Alexandre

2017-09-01

We assessed the effects of power-line frequency (60 Hz in North America) magnetic fields (MF) in humans using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twenty-five participants were enrolled in a pseudo-double-blind experiment involving "real" or "sham" exposure to sinusoidal 60 Hz MF exposures delivered using the gradient coil of an MRI scanner following two conditions: (i) 10 s exposures at 3 mT (10 repetitions); (ii) 2 s exposures at 7.6 mT (100 repetitions). Occipital EEG spectral power was computed in the alpha range (8-12 Hz, reportedly the most sensitive to MF exposure in the literature) with/without exposure. Brain functional activation was studied using fMRI blood oxygen level-dependent (BOLD, inversely correlated with EEG alpha power) maps. No significant effects were detected on occipital EEG alpha power during or post-exposure for any exposure condition. Consistent with EEG results, no effects were observed on fMRI BOLD maps in any brain region. Our results suggest that acute exposure (2-10 s) to 60 Hz MF from 3 to 7.6 mT (30,000 to 76,000 times higher than average public exposure levels for 60 Hz MF) does not induce detectable changes in EEG or BOLD signals. Combined with previous findings in which effects were observed on the BOLD signal after 1 h exposure to 3 mT, 60 Hz MF, this suggests that MF exposure in the low mT range (<10 mT) might require prolonged durations of exposure to induce detectable effects. Bioelectromagnetics. 38:425-435, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects on micronuclei formation of 60-Hz electromagnetic field exposure with ionizing radiation, hydrogen peroxide, or c-Myc overexpression.

PubMed

Jin, Yeung Bae; Kang, Ga-Young; Lee, Jae Seon; Choi, Jong-Il; Lee, Ju-Woon; Hong, Seung-Cheol; Myung, Sung Ho; Lee, Yun-Sil

2012-04-01

Epidemiological studies have demonstrated a possible correlation between exposure to extremely low-frequency magnetic fields (ELF-MF) and cancer. However, this correlation has yet to be definitively confirmed by epidemiological studies. The principal objective of this study was to assess the effects of 60 Hz magnetic fields in a normal cell line system, and particularly in combination with various external factors, via micronucleus (MN) assays. Mouse embryonic fibroblast NIH3T3 cells and human lung fibroblast WI-38 cells were exposed for 4 h to a 60 Hz, 1 mT uniform magnetic field with or without ionizing radiation (IR, 2 Gy), H(2)O(2) (100 μM) and cellular myelocytomatosis oncogene (c-Myc) activation. The results obtained showed no significant differences between the cells exposed to ELF-MF alone and the unexposed cells. Moreover, no synergistic effects were observed when ELF-MF was combined with IR, H(2)O(2), and c-Myc activation. Our results demonstrate that ELF-MF did not enhance MN frequency by IR, H(2)O(2) and c-Myc activation.

Evidence for Excitation of Polar Motion by Fortnightly Ocean Tides

NASA Technical Reports Server (NTRS)

Gross, Richard S.; Hamdan, Kamal H.; Boggs, Dale H.

1996-01-01

The second-degree zonal tide raising potential, which is responsible for tidal changes in the Earth's rotation rate and length-of-day, is symmetric about the polar axis and hence can excite the Earth's polar motion only through its action upon nonaxisymmetric features of the Earth such as the oceans. Ocean tidal excitation of polar motion in the diurnal and semidiurnal tidal bands has been previously detected and examined. Here, the detection of ocean tidal excitation of polar motion in the long-period tidal band, specifically at the Mf' (13.63-day) and Mf (13.66-day) tidal frequencies, is reported. Spectra of the SPACE94 polar motion excitation series exhibit peaks at the prograde and retrograde fortnightly tidal periods. After removing effects of atmospheric wind and pressure changes, an empirical model for the effect of the fortnightly ocean tides upon polar motion excitation is obtained by least-squares fitting periodic terms at the Mf and Mf' tidal frequencies to the residual polar motion excitation series. The resulting empirical model is then compared with the predictions of two hydrodynamic ocean tide models.

Effects of A 60 Hz Magnetic Field of Up to 50 milliTesla on Human Tremor and EEG: A Pilot Study.

PubMed

Davarpanah Jazi, Shirin; Modolo, Julien; Baker, Cadence; Villard, Sebastien; Legros, Alexandre

2017-11-24

Humans are surrounded by sources of daily exposure to power-frequency (60 Hz in North America) magnetic fields (MFs). Such time-varying MFs induce electric fields and currents in living structures which possibly lead to biological effects. The present pilot study examined possible extremely low frequency (ELF) MF effects on human neuromotor control in general, and physiological postural tremor and electroencephalography (EEG) in particular. Since the EEG cortical mu-rhythm (8-12 Hz) from the primary motor cortex and physiological tremor are related, it was hypothesized that a 60 Hz MF exposure focused on this cortical region could acutely modulate human physiological tremor. Ten healthy volunteers (age: 23.8 ± 4 SD) were fitted with a MRI-compatible EEG cap while exposed to 11 MF conditions (60 Hz, 0 to 50 mT rms , 5 mT rms increments). Simultaneously, physiological tremor (recorded from the contralateral index finger) and EEG (from associated motor and somatosensory brain regions) were measured. Results showed no significant main effect of MF exposure conditions on any of the analyzed physiological tremor characteristics. In terms of EEG, no significant effects of the MF were observed for C1, C3, C5 and CP1 electrodes. However, a significant main effect was found for CP3 and CP5 electrodes, both suggesting a decreased mu-rhythm spectral power with increasing MF flux density. This is however not confirmed by Bonferroni corrected pairwise comparisons. Considering both EEG and tremor findings, no effect of the MF exposure on human motor control was observed. However, MF exposure had a subtle effect on the mu-rhythm amplitude in the brain region involved in tactile perception. Current findings are to be considered with caution due to the small size of this pilot work, but they provide preliminary insights to international agencies establishing guidelines regarding electromagnetic field exposure with new experimental data acquired in humans exposed to high mT-range MFs.

A dinoflagellate mutant with higher frequency of multiple fission.

PubMed

Lam, C M; Chong, C; Wong, J T

2001-01-01

The dinoflagellate Crypthecodinium cohnii Biecheler propagates by both binary and multiple fission. By a newly developed mutagenesis protocol based on using ethyl methanesulfonate and a cell size screening method, a cell cycle mutant, mf2, was isolated with giant cells which predominantly divide by multiple fission. The average cell size of the mutant mf2 is larger than the control C. cohnii. Cell cycle synchronization experiments suggest that mutant mf2, when compared with the control strain, has a prolonged G1 phase with a corresponding delay of the G2 + M phase.

Effect of 24 sessions of high-intensity aerobic interval training carried out at either high or moderate frequency, a randomized trial.

PubMed

Hatle, Håvard; Støbakk, Per Kristian; Mølmen, Harald Edvard; Brønstad, Eivind; Tjønna, Arnt Erik; Steinshamn, Sigurd; Skogvoll, Eirik; Wisløff, Ulrik; Ingul, Charlotte Björk; Rognmo, Øivind

2014-01-01

The training response of an intensified period of high-intensity exercise is not clear. Therefore, we compared the cardiovascular adaptations of completing 24 high-intensity aerobic interval training sessions carried out for either three or eight weeks, respectively. Twenty-one healthy subjects (23.0±2.1 years, 10 females) completed 24 high-intensity training sessions throughout a time-period of either eight weeks (moderate frequency, MF) or three weeks (high frequency, HF) followed by a detraining period of nine weeks without any training. In both groups, maximal oxygen uptake (VO2max) was evaluated before training, at the 9(th) and 17(th) session and four days after the final 24(th) training session. In the detraining phase VO2max was evaluated after 12 days and thereafter every second week for eight weeks. Left ventricular echocardiography, carbon monoxide lung diffusion transfer factor, brachial artery flow mediated dilatation and vastus lateralis citrate maximal synthase activity was tested before and after training. The cardiovascular adaptation after HF training was delayed compared to training with MF. Four days after ending training the HF group showed no improvement (+3.0%, p = 0.126), whereas the MF group reached their highest VO2max with a 10.7% improvement (p<0.001: group difference p = 0.035). The HF group reached their highest VO2max (6.1% increase, p = 0.026) twelve days into the detraining period, compared to a concomitant reduction to 7.9% of VO2max (p<0.001) above baseline in the MF group (group difference p = 0.609). Both HF and MF training of high-intensity aerobic exercise improves VO2max. The cardiovascular adaptation following a HF programme of high-intensity exercise is however delayed compared to MF training. ClinicalTrials.gov NCT00733941.

Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia.

PubMed

Bouhouche, A; Benomar, A; Bouslam, N; Chkili, T; Yahyaoui, M

2006-05-01

Mutilating sensory neuropathy with spastic paraplegia is a very rare disease with both autosomal dominant and recessive modes of inheritance. We previously mapped the locus of the autosomal recessive form to a 25 cM interval between markers D5S2048 and D5S648 on chromosome 5p. In this candidate interval, the Cct5 gene encoding the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (CCT) was the most obvious candidate gene since mutation in the Cct4 gene encoding the CCT delta subunit has been reported to be associated with autosomal recessive mutilating sensory neuropathy in mutilated foot (mf) rat mutant. A consanguineous Moroccan family with four patients displaying mutilating sensory neuropathy associated with spastic paraplegia was investigated. To identify the disease causing gene, the 11 coding exons of the Cct5 gene were screened for mutations by direct sequencing in all family members including the four patients, parents, and six at risk relatives. Sequence analysis of the Cct5 gene revealed a missense A492G mutation in exon 4 that results in the substitution of a highly conserved histidine for arginine amino acid 147. Interestingly, R147 was absent in 384 control matched chromosomes tested. This is the first disease causing mutation that has been identified in the human CCT subunit genes; the mf rat mutant could serve as an animal model for studying these chaperonopathies.

Magnetically coupled flextensional transducer for wideband vibration energy harvesting: Design, modeling and experiments

NASA Astrophysics Data System (ADS)

Zou, Hong-Xiang; Zhang, Wen-Ming; Li, Wen-Bo; Wei, Ke-Xiang; Hu, Kai-Ming; Peng, Zhi-Ke; Meng, Guang

2018-03-01

The combination of nonlinear bistable and flextensional mechanisms has the advantages of wide operating frequency and high equivalent piezoelectric constant. In this paper, three magnetically coupled flextensional vibration energy harvesters (MF-VEHs) are designed from three magnetically coupled vibration systems which utilize a magnetic repulsion, two symmetrical magnetic attractions and multi-magnetic repulsions, respectively. The coupled dynamic models are developed to describe the electromechanical transitions. Simulations under harmonic excitation and random excitation are carried out to investigate the performance of the MF-VEHs with different parameters. Experimental validations of the MF-VEHs are performed under different excitation levels. The experimental results verify that the developed mathematical models can be used to accurately characterize the MF-VEHs for various magnetic coupling modes. A comparison of three MF-VEHs is provided and the results illustrate that a reasonable arrangement of multiple magnets can reduce the threshold excitation intensity and increase the harvested energy.

Multifocal visual evoked potentials for early glaucoma detection.

PubMed

Weizer, Jennifer S; Musch, David C; Niziol, Leslie M; Khan, Naheed W

2012-07-01

To compare multifocal visual evoked potentials (mfVEP) with other detection methods in early open-angle glaucoma. Ten patients with suspected glaucoma and 5 with early open-angle glaucoma underwent mfVEP, standard automated perimetry (SAP), short-wave automated perimetry, frequency-doubling technology perimetry, and nerve fiber layer optical coherence tomography. Nineteen healthy control subjects underwent mfVEP and SAP for comparison. Comparisons between groups involving continuous variables were made using independent t tests; for categorical variables, Fisher's exact test was used. Monocular mfVEP cluster defects were associated with an increased SAP pattern standard deviation (P = .0195). Visual fields that showed interocular mfVEP cluster defects were more likely to also show superior quadrant nerve fiber layer thinning by OCT (P = .0152). Multifocal visual evoked potential cluster defects are associated with a functional and an anatomic measure that both relate to glaucomatous optic neuropathy. Copyright 2012, SLACK Incorporated.

Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet.

PubMed

Barbui, Tiziano; Tefferi, Ayalew; Vannucchi, Alessandro M; Passamonti, Francesco; Silver, Richard T; Hoffman, Ronald; Verstovsek, Srdan; Mesa, Ruben; Kiladjian, Jean-Jacques; Hehlmann, Rȕdiger; Reiter, Andreas; Cervantes, Francisco; Harrison, Claire; Mc Mullin, Mary Frances; Hasselbalch, Hans Carl; Koschmieder, Steffen; Marchetti, Monia; Bacigalupo, Andrea; Finazzi, Guido; Kroeger, Nicolaus; Griesshammer, Martin; Birgegard, Gunnar; Barosi, Giovanni

2018-05-01

This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.

[Effect of low frequency magnetic fields used in magnetotherapy and magnetostimulation on the rehabilitation results of patients after ischemic stroke].

PubMed

Woldańska-Okońska, Marta; Czernicki, Jan

2007-01-01

New methods of rehabilitation should be introduced in order to reduce disability resulting from stroke. During the twelve months of follow-up, effect of low frequency magnetic field (If mf) on the course of patient rehabilitation following ischemic stroke was evaluated on in-patient (acute and subacute period of the stroke) and outpatient (chronic period) basis with the use of Mathew et al's and Barthel's scales. Lf mf (20 procedures of 20-min. duration) of magnetotherapy (I group--placebo, II--group 5.6 mT induction, 10 Hz frequency and sinusoidal shape, III group--2.8 mT induction, 10 Hz frequency and sinusoidal shape) and magnetostimulation (IV group--M1P1 program of Viofor JPS system, 16 min a day) was applied as early as in the subacute period of the stroke (1-8 weeks). The data obtained were presented in the form of percentage changes in the pain levels as well as in the form of the arithmetical mean and standard deviation (X +/- SD). The ANOVA test was used for a statistical evaluation of the data obtained in the tests. The results obtained indicate beneficial effects of If mf in the III and IV group of patients in the Barthel's scale and Mathew scale, which were observed during the examination 12 months after the stroke. The recommended doses of If mf seem to be adequate to obtain therapeutic effects and may be used in the early period of rehabilitation. The neurological and functional improvement persisted for a long-period of the out-patient treatment, which was confirmed during the control examination 12 months after the ischemic stroke. As no adverse effects (which could be attributed to If mf), were observed, this method of physical therapy can be recognized as a safe one and worth making popular in clinical practice.

Geospace ionosphere research with a MF/HF radio instrument on a cubesat

NASA Astrophysics Data System (ADS)

Kallio, E. J.; Aikio, A. T.; Alho, M.; Fontell, M.; van Gijlswijk, R.; Kauristie, K.; Kestilä, A.; Koskimaa, P.; Makela, J. S.; Mäkelä, M.; Turunen, E.; Vanhamäki, H.

2016-12-01

Modern technology provides new possibilities to study geospace and its ionosphere, using spacecraft and and computer simulations. A type of nanosatellites, CubeSats, provide a cost effective possibility to provide in-situ measurements in the ionosphere. Moreover, combined CubeSat observations with ground-based observations gives a new view on auroras and associated electromagnetic phenomena. Especially joint and active CubeSat - ground based observation campaigns enable the possibility of studying the 3D structure of the ionosphere. Furthermore using several CubeSats to form satellite constellations enables much higher temporal resolution. At the same time, increasing computation capacity has made it possible to perform simulations where properties of the ionosphere, such as propagation of the electromagnetic waves in the medium frequency, MF (0.3-3 MHz) and high frequency, HF (3-30 MHz), ranges is based on a 3D ionospheric model and on first-principles modelling. Electromagnetic waves at those frequencies are strongly affected by ionospheric electrons and, consequently, those frequencies can be used for studying the plasma. On the other hand, even if the ionosphere originally enables long-range telecommunication at MF and HF frequencies, the frequent occurrence of spatiotemporal variations in the ionosphere disturbs communication channels, especially at high latitudes. Therefore, study of the MF and HF waves in the ionosphere has both a strong science and technology interests. We present computational simulation results and measuring principles and techniques to investigate the arctic ionosphere by a polar orbiting CubeSat whose novel AM radio instrument measures HF and MF waves. The cubesat, which contains also a white light aurora camera, is planned to be launched in 2017 (http://www.suomi100satelliitti.fi/eng). We have modelled the propagation of the radio waves, both ground generated man-made waves and space formed space weather related waves, through the 3D arctic ionosphere with (1) a new 3D ray tracing model and (2) a new 3D full kinetic electromagnetic simulation. These simulations are used to analyse the origin of the radio waves observed by the MH/HF radio instrument and, consequently, to derive information about the 3D ionosphere and its spatial and temporal variations.

Ethnic analogies and differences in fetal heart rate variability signal: A retrospective study.

PubMed

Tagliaferri, Salvatore; Esposito, Francesca Giovanna; Fagioli, Rosa; Di Cresce, Marco; Sacchi, Lucia; Signorini, Maria Gabriella; Campanile, Marta; Martinelli, Pasquale; Magenes, Giovanni

2017-02-01

We aimed to analyze computerized cardiotocographic (cCTG) parameters (including fetal heart rate baseline, short-term variability, Delta, long-term irregularity [LTI], interval index [II], low frequency [LF], movement frequency [MF], high frequency [HF], and approximate entropy [ApEn]) in physiological term pregnancies in order to correlate them with ethnic differences. The clinical meaning of numerical parameters may explain physiological or paraphysiological phenomena that occur in fetuses of different ethnic origins. A total of 696 pregnant women, including 384 from Europe, 246 from sub-Saharan Africa, 45 from South-East Asia, and 21 from South America, were monitored from the 37th to the 41st week of gestation. Statistical analysis was performed with the analysis of variance test, Pearson correlation test and receiver-operator curves (P < 0.05). Our results showed statistically significant differences (P < 0.05) between white and black women for Delta, LTI, LF, MF, HF, and ApEn; between white and Asian women for Delta, LTI, MF, and the LF/(HF + MF) ratio; and between white and Latina women for Delta, LTI, and ApEn. In particular, Delta and LTI performed better in the white group than in the black, Asian, and Latina groups. Instead, LF, MF, HF, and ApEn performed better in the black than in the white group. Our results confirmed the integrity and normal functionality of both central and autonomic nervous system components for all fetuses investigated. Therefore, CTG monitoring should include both linear and nonlinear components of fetal heart rate variability in order to avoid misinterpretations of the CTG trace among ethnic groups. © 2016 Japan Society of Obstetrics and Gynecology.

Extremely low frequency magnetic field measurements in buildings with transformer stations in Switzerland.

PubMed

Röösli, Martin; Jenni, Daniela; Kheifets, Leeka; Mezei, Gabor

2011-08-15

The aim of this study was to evaluate an exposure assessment method that classifies apartments in three exposure categories of extremely low frequency magnetic fields (ELF-MF) based on the location of the apartment relative to the transformer room. We completed measurements in 39 apartments in 18 buildings. In each room of the apartments ELF-MF was concurrently measured with 5 to 6 EMDEX II meters for 10 min. Measured arithmetic mean ELF-MF was 0.59 μT in 8 apartments that were fully adjacent to a transformer room, either directly above the transformer or touching the transformer room wall-to-wall. In apartments that only partly touched the transformer room at corners or edges, average ELF-MF level was 0.14 μT. Average exposure in the remaining apartments was 0.10 μT. Kappa coefficient for exposure classification was 0.64 (95%-CI: 0.45-0.82) if only fully adjacent apartments were considered as highly exposed (>0.4 μT). We found a distinct ELF-MF exposure gradient in buildings with transformer. Exposure classification based on the location of the apartment relative to the transformer room appears feasible. Such an approach considerably reduces effort for exposure assessment and may be used to eliminate selection bias in future epidemiologic studies. Copyright © 2011 Elsevier B.V. All rights reserved.

EMG changes in thigh and calf muscles in fin swimming exercise.

PubMed

Jammes, Y; Delliaux, S; Coulange, M; Jammes, C; Kipson, N; Brerro-Saby, C; Bregeon, F

2010-08-01

Because previous researchers have reported a reduced lactic acid production that accompanies a delayed or an absent ventilatory threshold (VTh) in water-based exercise, we hypothesized that the metaboreflex, activated by muscle acidosis, might be absent in fin swimming. This motor response, delaying the occurrence of fatigue, is characterized by a decreased median frequency (MF) of electromyographic (EMG) power spectrum. Seven healthy subjects performed a maximal fin swimming exercise protocol with simultaneous recordings of surface EMGs in VASTUS MEDIALIS (VM), TIBIALIS ANTERIOR (TA) and GASTROCNEMIUS MEDIALIS (GM). We computed the root mean square (RMS) and MF and recorded the compound evoked muscle potential (M-wave) in VM. We also measured the propulsive force and oxygen uptake (VO (2)), and determined VTh. VTh was absent in 4/7 subjects and measured at 70-90% of VO (2max) in the other three. In the three studied muscles, the global EMG activity (RMS) increased while the MF decreased in proportion of VO (2), the MF changes being significantly higher in VM (-29%) and GM (-39%) than in TA (-19%). Because no M-wave changes were noted, the MF decline was attributed to the recruitment of low-frequency, fatigue-resistant motor units. Our most important finding is the persistence of the metaboreflex even in a situation of reduced muscle acidosis. (c) Georg Thieme Verlag KG Stuttgart . New York.

EXEL-8232, a small-molecule JAK2 inhibitor, effectively treats thrombocytosis and extramedullary hematopoiesis in a murine model of myeloproliferative neoplasm induced by MPLW515L.

PubMed

Wernig, G; Kharas, M G; Mullally, A; Leeman, D S; Okabe, R; George, T; Clary, D O; Gilliland, D G

2012-04-01

About 10% of patients with essential thrombocythemia (ET) or myelofibrosis (MF) that lack mutations in JAK2 harbor an activating mutation in the thrombopoietin receptor, MPLW515L. Distinct from the JAK2V617F retroviral transplant model, the MPLW515L model recapitulates many features of ET and MF, including severe fibrosis and thrombocytosis. We have tested EXEL-8232, an experimental potent JAK2 inhibitor, for efficacy in suppression of thrombocytosis in vivo and for its ability to attenuate MPLW515L myeloproliferative disease. EXEL-8232 was administered for 28 days q12 h by oral gavage at doses of 30 or 100 mg/kg, prospectively. Animals treated with EXEL-8232 at 100 mg/kg had normalized high platelet counts, eliminated extramedullary hematopoiesis in the spleen and eliminated bone marrow fibrosis, whereas the wild-type controls did not develop thrombocytopenia. Consistent with a clinical response in this model, we validated surrogate end points for response to treatment, including a reduction of endogenous colony growth and signaling inhibition in immature erythroid and myeloid primary cells both in vitro and upon treatment in vivo. We conclude that EXEL-8232 has efficacy in treatment of thrombocytosis in vivo in a murine model of ET and MF, and may be of therapeutic benefit for patients with MPL-mutant MPN.

Analysis of the mdr-1 Gene in Patients Co-Infected with Onchocerca volvulus and Loa loa Who Experienced a Post-Ivermectin Serious Adverse Event

PubMed Central

Bourguinat, Catherine; Kamgno, Joseph; Boussinesq, Michel; Mackenzie, Charles D.; Prichard, Roger K.; Geary, Timothy G.

2010-01-01

Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Loa loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Loa mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs. PMID:20595473

Mutations of Electrons as Constituents of Hadrons

NASA Astrophysics Data System (ADS)

Driscoll, R. B.

1997-04-01

Conjecture (C) 1: Coulomb-charged constituents of electron (e) are attracted to its barycentre by lepto-strong force F=K/r^2+f; f is stably perturbative for r < the "radius" of e. An exterior magnetic field (MF) with gradient (G) secularly perturbs the eccentricities but not the energies of the constituents' orbits, changing the spin (s) and magnetic moment (μ) of e. (C) 2: F coheres two or more e's dynamically with r approximately equal to the "radius" of e. The resulting MF and G at each e oscillate. Stable values of s and μ result for each e which differs from the atomic values. Binding energies change the masses of the e's. A hadron results. (C) 3: An e similarly may bind to a proton to form a Rutherford- Santilli neutron. The proton is negligibly mutated.(References: H. Dehmelt, Science 247, 539 (1990); T.E. Phipps, Jr., Heretical Verities (Classic Non-fiction Library, Urbana, 1986); R.M. Santilli, Hadronic Mechanics (Ukrainian Academy of Sciences, Kiev, 1995 and 1996), 3 volumes.)

Historical views, conventional approaches, and evolving management strategies for myeloproliferative neoplasms.

PubMed

Stein, Brady L; Gotlib, Jason; Arcasoy, Murat; Nguyen, Marie Huong; Shah, Neil; Moliterno, Alison; Jamieson, Catriona; Pollyea, Daniel A; Scott, Bart; Wadleigh, Martha; Levine, Ross; Komrokji, Rami; Klisovic, Rebecca; Gundabolu, Krishna; Kropf, Patricia; Wetzler, Meir; Oh, Stephen T; Ribeiro, Raul; Paschal, Rita; Mohan, Sanjay; Podoltsev, Nikolai; Prchal, Josef; Talpaz, Moshe; Snyder, David; Verstovsek, Srdan; Mesa, Ruben A

2015-04-01

The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2(V617F) and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for hematologists/oncologists, and are discussed in this article. Copyright © 2015 by the National Comprehensive Cancer Network.

Analysis of linear electrode array EMG for assessment of hemiparetic biceps brachii muscles.

PubMed

Yao, Bo; Zhang, Xu; Li, Sheng; Li, Xiaoyan; Chen, Xiang; Klein, Cliff S; Zhou, Ping

2015-01-01

This study presents a frequency analysis of surface electromyogram (EMG) signals acquired by a linear electrode array from the biceps brachii muscles bilaterally in 14 hemiparetic stroke subjects. For different levels of isometric contraction ranging from 10 to 80% of the maximum voluntary contraction (MVC), the power spectra of 19 bipolar surface EMG channels arranged proximally to distally along the muscle fibers were examined in both paretic and contralateral muscles. It was found that across all stroke subjects, the median frequency (MF) and the mean power frequency (MPF), averaged from different surface EMG channels, were significantly smaller in the paretic muscle compared to the contralateral muscle at each of the matched percent MVC contractions. The muscle fiber conduction velocity (MFCV) was significantly slower in the paretic muscle than in the contralateral muscle. No significant correlation between the averaged MF, MPF, or MFCV vs. torque was found in both paretic and contralateral muscles. However, there was a significant positive correlation between the global MFCV and MF. Examination of individual EMG channels showed that electrodes closest to the estimated muscle innervation zones produced surface EMG signals with significantly higher MF and MPF than more proximal or distal locations in both paretic and contralateral sides. These findings suggest complex central and peripheral neuromuscular alterations (such as selective loss of large motor units, disordered control of motor units, increased motor unit synchronization, and atrophy of muscle fibers, etc.) which can collectively influence the surface EMG signals. The frequency difference with regard to the innervation zone also confirms the relevance of electrode position in surface EMG analysis.

The influence of confounding factors on the relationship between muscle contraction level and MF and MPF values of EMG signal: a review.

PubMed

Roman-Liu, Danuta

2016-01-01

The purpose of this article is to gather results of studies on the relationship between median frequency (MF) and mean power frequency (MPF) and the level of muscle contraction, and to use those results to discuss the differences in the trends according to factors related to measurement technique and subject. Twenty-one studies with 63 cases for upper limb muscles and nine studies with 31 cases for lower limb muscles were analysed. Most results showed an increase in parameters with an increased level of muscle contraction, only some studies showed a decrease. The influence on parameters of the level of muscle contraction and factors such as subjects, type of contraction, muscle length and electrodes was analysed for each muscle. It was concluded that when analysing the influence of different factors on MF and MPF, because those factors interact they should be considered together, not separately.

Modification of mutagenesis initiated by ultraviolet light through posttreatment of bacteria with basic dyes

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

Witkin, E M

1961-12-01

Post treatment with basic dyes, in concentrations that retard cell division, was found to influence the tnduction of mutations to prototrophy by UV light in a tyrosine-requirtng strain of E.Coli. Pyronin, which is unique among the dyes in tts selective affinity for RNA, was found to duplicate the effects of chloramphenicol or amino acfd deprtvatfon in causfng the rapid and irreversible loss of potential prototrophs (mutation frequency decline, or MFD). Acriflavtne, methyl green. crystal violet, methylene blue, and toluidine blue, all of which are known to combine with DNA, delay or retard the occurrence of MFD under conditions of aminomore » acid deprivation. When acriflavine is removed from its combination with cellular components by the addition of an excess of sodium deoxyrtbonucleate, MFD begins promptly. The same basic dyes that delay MFD were also found to interfere with the fixation of mutations (MF) in an amino acid- enriched medium, and to cause marked enhancement of the mutagenic potency of low doses of UV light. While showing no independent mutagenic activity for unirradiated bacteria, all the dyes except pyronin increased the yield of induced mutations signtficantly when added to the enriched medium upon which trradiated bacteria were incubated.These results were interpreted as evidence that UV light initiates mutagenesis by producing unstable changas directly in genic DNA. MFD is interpreted as a repair process, blocked by the machinery of RNA and protein synthesis and by the presence of certain basic dyes.« less

47 CFR 97.301 - Authorized frequency bands.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., or who holds a Class 1 IARP license: Wavelength band MF ITU region 1 kHz ITU region 2 kHz ITU region 3 kHz Sharing requirements see § 97.303(paragraph) 160 m 1810-1850 1800-2000 1800-2000 (a), (c), (g... who has been granted an operator license of Advanced Class: Wavelength band MF ITU region 1 kHz ITU...

Efficacy of extremely low-frequency magnetic field in fibromyalgia pain: A pilot study.

PubMed

Paolucci, Teresa; Piccinini, Giulia; Iosa, Marco; Piermattei, Cristina; de Angelis, Simona; Grasso, Maria Rosaria; Zangrando, Federico; Saraceni, Vincenzo Maria

2016-01-01

The purpose of this pilot study was to determine the efficacy of an extremely low-frequency magnetic field (ELF-MF) in decreasing chronic pain in fibromyalgia (FM) patients. Thirty-seven females were recruited and randomized into two groups: one group was first exposed to systemic ELF-MF therapy (100 microtesla, 1 to 80 Hz) and then to sham therapy, and the other group received the opposite sequence of intervention. Pain, FM-related symptoms, and the ability to perform daily tasks were measured using the Visual Analog Scale, Fibromyalgia Impact Questionnaire (FIQ), Fibromyalgia Assessment Scale (FAS), and Health Assessment Questionnaire (HAQ) at baseline, end of first treatment cycle, beginning of second treatment cycle (after 1 mo washout), end of second treatment cycle, and end of 1 mo follow-up. ELF-MF treatment significantly reduced pain, which increased on cessation of therapy but remained significantly lower than baseline levels. Short-term benefits were also observed in FIQ, FAS, and HAQ scores, with less significant effects seen in the medium term. ELF-MF therapy can be recommended as part of a multimodal approach for mitigating pain in FM subjects and improving the efficacy of drug therapy or physiotherapy.

ACB-PCR measurement of H-ras codon 61 CAA→CTA mutation provides an early indication of aristolochic acid I carcinogenic effect in tumor target tissues.

PubMed

Wang, Yiying; Arlt, Volker M; Roufosse, Candice A; McKim, Karen L; Myers, Meagan B; Phillips, David H; Parsons, Barbara L

2012-08-01

Aristolochic acid (AA) is a strong cytotoxic nephrotoxin and carcinogen, which induces forestomach and kidney tumors in mice and is associated with development of urothelial cancer in humans. This study sought to gain mechanistic insight into AAI-induced carcinogenesis through analysis of a tumor-relevant endpoint. Female Hupki mice were treated daily with 5 mg AAI/kg body weight by gavage for 3, 12, or 21 days. Histopathology and DNA adduct analysis confirmed kidney and forestomach as target tissues for AAI-induced toxicity. H-ras codon 61 CAA→CTA mutations were measured in mouse kidney and forestomach, as well as liver and glandular stomach (nontarget organs) by allele-specific competitive blocker-PCR (ACB-PCR), because A→T transversion is the predominant mutation induced by AA and this particular mutation was found previously in AA-induced rodent forestomach tumors. Treatment-related differences were observed, with the H-ras mutant fraction (MF) of mouse kidney and forestomach exposed to 5 mg AAI/kg body weight for 21 days significantly higher than that of vehicle-treated controls (Fisher's exact test, P < 0.05). Statistically significant correlations between dA-AAI adduct levels (measured previously in the same animals) and induced H-ras MFs were evident in forestomach of mice treated for 21 days (linear regression, P < 0.05). The significant increase in H-ras MF in kidney and forestomach, along with the correlation between DNA adducts, histopathology, and oncogene mutation, provide definitive evidence that AA induces tumors through a directly mutagenic mode of action. Thus, measurement of tumor-associated mutations is a useful tool for elucidating the mechanisms underlying the tissue specificity of carcinogenesis. Copyright © 2012 Wiley Periodicals, Inc.

ACB-PCR measurement of spontaneous and furan-induced H-ras codon 61 CAA to CTA and CAA to AAA mutation in B6C3F1 mouse liver.

PubMed

Banda, Malathi; Recio, Leslie; Parsons, Barbara L

2013-10-01

Furan is a rodent liver carcinogen, but the mode of action for furan hepatocarcinogenicity is unclear. H-ras codon 61 mutations have been detected in spontaneous liver tumors of B6C3F1 mice, and the fraction of liver tumors carrying H-ras codon 61 CAA to AAA mutation increased in furan-treated mice. Allele-specific competitive blocker PCR (ACB-PCR) has been used previously to quantify early, carcinogen-induced increases in tumor-associated mutations. The present pilot study investigated whether furan drives clonal expansion of pre-existing H-ras mutant cells in B6C3F1 mouse liver. H-ras codon 61 CAA to CTA and CAA to AAA mutations were measured in DNA isolated from liver tissue of female mice treated with 0, 1, 2, 4, or 8 mg furan/kg body weight, five days per week for three weeks, using five mice per treatment group. Spontaneous levels of mutation were low, with two of five control mice having an H-ras codon 61 CTA or AAA mutant fraction (MF) greater than 10(-5) . Several furan-treated mice had H-ras codon 61 AAA or CTA MFs greater than those measured in control mice and lower bound estimates of induced MF were calculated. However, no statistically-significant differences were observed between treatment groups. Therefore, while sustained exposure to furan is carcinogenic, at the early stage of carcinogenesis examined in this study (three weeks), there was not a significant expansion of H-ras mutant cells. Copyright © 2013 Wiley Periodicals, Inc.

76 FR 67604 - Maritime Communications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-02

... aviation and marine radio services use a marine very high frequency (VHF), medium frequency (MF), or high... aviation and marine radio services use a very high frequency (VHF) marine or aircraft radio and, as..., the Federal Communications Commission amends 47 CFR parts 2 and 80 as follows: PART 2--FREQUENCY...

Exposure of Surgeons to Extremely Low-Frequency Magnetic Fields During Laparoscopic and Robotic Surgeries

PubMed Central

Park, Jee Soo; Chung, Jai Won; Kim, Nam Kyu; Cho, Min Soo; Kang, Chang Moo; Choi, Soo Beom; Kim, Deok Won

2015-01-01

Abstract The development of new medical electronic devices and equipment has increased the use of electrical apparatuses in surgery. Many studies have reported the association of long-term exposure to extremely low-frequency magnetic fields (ELF-MFs) with diseases or cancer. Robotic surgery has emerged as an alternative tool to overcome the disadvantages of conventional laparoscopic surgery. However, there has been no report regarding how much ELF-MF surgeons are exposed to during laparoscopic and robotic surgeries. In this observational study, we aimed to measure and compare the ELF-MFs that surgeons are exposed to during laparoscopic and robotic surgery. The intensities of the ELF-MFs surgeons are exposed to were measured every 4 seconds for 20 cases of laparoscopic surgery and 20 cases of robotic surgery using portable ELF-MF measuring devices with logging capability. The mean ELF-MF exposures were 0.6 ± 0.1 mG for laparoscopic surgeries and 0.3 ± 0.0 mG for robotic surgeries (significantly lower with P < 0.001 by Mann–Whitney U test). Our results show that the ELF-MF exposure levels of surgeons in both robotic and conventional laparoscopic surgery were lower than 2 mG, which is the most stringent level considered safe in many studies. However, we should not overlook the effects of long-term ELF-MF exposure during many surgeries in the course of a surgeon's career. PMID:25674758

Complex-Spectrum Magnetic Environment enhances and/or modifies Bioeffects of Hypokinetic Stress Condition: an Animal Study

NASA Astrophysics Data System (ADS)

Temuriantz, N. A.; Martinyuk, V. S.; Ptitsyna, N. G.; Villoresi, G.; Iucci, N.; Tyasto, M. I.; Dorman, L. I.

During last decades it was shown by many authors that ultra-low and extremely low frequency electric and magnetic fields ULF 0-10 Hz ELF 10-1000 Hz may produce biological effects and consequently may be a possible source for health problems Spaceflight electric and magnetic environments are characterized by complex combination of static and time-varying components in ULF-ELF range and by high variability The objective of this study was to investigate the possible influence of such magnetic fields on rats to understand the pathway regarding functional state of cardiovascular system Magnetic field MF pattern with variable complex spectra in 0-150 Hz frequency range was simulated using 3-axial Helmholtz coils and special computer-based equipment The effect of the real world MF exposure on rats was also tested in combination with hypokinetic stress condition which is typical for spaceflights It was revealed that variable complex-spectrum MF acts as a weak or moderate stress-like factor which amplifies and or modifies the functional shifts caused by other stress-factors The value and direction of the functional shifts caused by MF exposure significantly depend on gender individual-typological constitutional features and also on the physiological state norm stress of organism Our results support the idea that variable complex-spectrum MF action involves sympathetic activation overload in cholesterol transport in blood and also secretor activation of tissue basophyls mast cells that can influence the regional haemodynamics These

Direction of Arrival Studies of Medium Frequency Burst Radio Emissions at Toolik Lake, AK

NASA Astrophysics Data System (ADS)

Bunch, N.; Labelle, J.; Weatherwax, A.; Lummerzheim, D.; Stenbaek-Nielsen, H.

2008-05-01

MF burst is an impulsive radio emission of auroral origin, which can be detected by ground-based instruments at frequencies between 1,300 and 4,500kHz. MF burst has been shown to be associated with substorm onset, but its exact generation mechanism remains unknown, although it is thought to arise from mode conversion radiation [see review by LaBelle and Treumann, 2002] . In search of the generation mechanism of this emission, Dartmouth College has deployed radio interferometers in Alaska, Northern Canada, Greenland, and Antarctica, including a three-element interferometer deployed to Toolik Field Station in Alaska during the summer of 2006. This instrument measured spectra, amplitudes and directions of arrival (DOA's) of over 47 MF burst events between November 30, 2006 and May 26, 2007. These data represent the first DOA measurements of impulsive MF burst, of which selected case studies were presented at the Fall 2007 AGU conference. Here we present a statistical survey of all 47 events as well as detailed analysis of three events occurring on: Mar 5, Mar 23, and Nov 20, 2007. For the statistical survey, we present distributions of DOA as a function of local time and frequency. In each case study we analyze the direction of arrival of the emissions as a function of both time and frequency within each event. The time variations will be compared with the time variations of optical auroral forms simultaneously measured with all-sky cameras. The dependence of the arrival direction on frequency enables a significant test of the generation mechanism whereby the waves are emitted at the local plasma or upper hybrid frequency in the topside ionosphere, predicting that higher frequencies should originate at lower altitudes. These three events have been selected because All-Sky camera data are available at these times from Toolik Lake and Fort Yukon, Alaska. These are critical both for identifying which optical features are associated with the radio emissions as well as for constraining the electron density profiles used for ray tracing. Ray tracing is a critical tool for this study, and several alternative models will be used in order to understand the uncertainty in these events.

Clinicopathological features of mycosis fungoides in patients exposed to Agent Orange during the Vietnam War.

PubMed

Jang, Min Soo; Jang, Jun Gyu; Han, Sang Hwa; Park, Jong Bin; Kang, Dong Young; Kim, Sang Tae; Suh, Kee Suck

2013-08-01

There are no reports on the clinicopathological features of mycosis fungoides (MF) among veterans exposed to Agent Orange, one of the herbicides used during the Vietnam War. To evaluate the clinical, histopathological and genotypic findings of Vietnam War veterans with MF and a positive history of exposure to Agent Orange, we performed a comparative clinicopathological study between MF patients with a history of Agent Orange exposure and those without a history of Agent Orange exposure. Twelve Vietnam War veterans with MF were identified. The mean interval from Agent Orange exposure to diagnosis was 24.5 years (range, 9-35). Skin lesions were significantly present on exposed and unexposed areas. Most patients (75%) experienced pruritus (mean visual analog scale score of 6.7). MF was manifested by plaques in 10 patients and by lichenification in five. Histopathological features of most cases were consistent with MF. Biopsy specimens also demonstrated irregular acanthosis (66.7%). In the comparative study, MF patients with a history of Agent Orange exposure differed significantly from those without exposure to Agent Orange in demographic and clinical characteristics. In addition, patients with exposure had an increased tendency for lesions in the exposed area. Notably, our patients showed a higher frequency (33.3%) of mycosis fungoides palmaris et plantaris than in previous studies. Histologically, irregular acanthosis was more frequently observed than ordinary MF. Our results indicate that dermatologists should pay close attention to these clinicopathological differences. Careful assessment of history of exposure to defoliants is warranted in some cases suspicious for MF. © 2013 Japanese Dermatological Association.

Age, FSH dose and follicular aspiration frequency affect oocyte yield from juvenile donor lambs.

PubMed

Valasi, I; Leontides, L; Papanikolaou, Th; Amiridis, G S

2007-06-01

Experiments were conducted to determine the effects of lamb age, frequency of follicular aspirations, and hormone stimulation by fixed or variable FSH dose, on the number of collected oocytes and their maturational competence. In trial 1, the characteristics of follicular population (number and diameter of follicles) were studied in 40 lambs which were slaughtered at the age of 30 days (S1), 42 days (S2), 60 days (S3) and 5-6 months (S4), each n = 10. In trial 2, 27 lambs were divided into four groups. group MF lambs (n = 6) had follicular aspiration (OPU) in four monthly intervals commencing from the age of 8-9 weeks (sessions MF1, MF2, MF3 and MF4). In groups SF2, SF3 and SF4 (each n = 6), OPU was conducted once during the 12-13, 16-17 and 20-21 week of age, respectively. Ovarian stimulation was conducted with fixed FSH dose (3.52 mg/animal). In trial 3, 10 lambs (group MV) were treated as those of group MF apart from the FSH dose, which was administered according to the body weight in a dose of 0.27 mg/kg. The number and the size of follicles, the number and the quality of collected oocytes and the maturational competence of the oocytes were compared between and within groups. In trial 1, the total number and the number of small follicles were greater in groups S1 and S2 compared with those of S3 and S4 (p < 0.01). Similarly, the follicular population was greater in group MF1 than in group SF3 (p < 0.01). In sessions MF2, MF3, MV2, MV3 and MV4, more oocytes were collected in comparison with those from the respective once-aspirated age mates (groups SF2, SF3 and SF4). In total, more (p = 0.02) oocytes per donor were collected from group MV (15.2 +/- 5.5) than from group MF (9.0 +/- 3.2). An absolute maturational failure was observed in oocytes collected from groups SF2 and SF3. Maturational competence varied between 16.7% and 58.3% (p = 0.017) among sessions of group MF, but it was more uniform among sessions of group MV (range 12.5-42.9%, p > 0.05). Our results indicate that firstly, the number and the quality of harvested oocytes from juvenile lambs can be much improved if follicular stimulation regime is adjusted to the body weight. Secondly, in terms of follicular population and oocyte quality, 3 and 4-month-old lambs are naturally bad oocyte donors, but this characteristic can be reversed by a previous follicular ablation.

Magnetic Stimulation Therapy in Patients with COPD: A Systematic Review.

PubMed

Polastri, Massimiliano; Comellini, Vittoria; Pacilli, Angela Maria Grazia; Nava, Stefano

2018-03-20

Magnetotherapy (MT) is a therapeutic treatment based on the use of magnetic fields (MF) that can have an anti-inflammatory and analgesic effect. MT represents a possible treatment or an ancillary therapeutic intervention for a wide range of diseases and it is often used in the field of physiotherapeutic practices. A crucial point in the treatment of chronic obstructive pulmonary disease (COPD) patients, to counteract muscular depletion and respiratory symptoms, is represented by physiotherapy. Nevertheless, the knowledge about the application of MF as a therapeutic option in COPD patients is very limited. The purpose of the present study was to define what is currently known about the use of MF in patients with COPD. A systematic review of the literature was conducted during the month of October 2017, searching three main databases. Only those citations providing detailed informations about the use of MF to treat COPD symptoms either during an acute or a chronic phase of the disease, were selected. Following the selection process three articles were included in the final analysis. The present review focused on a total of thirty-six patients with COPD, and on the effects of the application of MF. In the majority of cases, the treatment sessions with MF were carried-out in an outpatient setting, and they differed with regard to the duration; frequency of application; dosage; intensity of the applied MF. Basing on the available informations, it seems that MF is a feasible, well tolerated, safe therapeutic option, for the treatment of motor-related COPD symptoms.

The influence of confounding factors on the relationship between muscle contraction level and MF and MPF values of EMG signal: a review

PubMed Central

Roman-Liu, Danuta

2016-01-01

The purpose of this article is to gather results of studies on the relationship between median frequency (MF) and mean power frequency (MPF) and the level of muscle contraction, and to use those results to discuss the differences in the trends according to factors related to measurement technique and subject. Twenty-one studies with 63 cases for upper limb muscles and nine studies with 31 cases for lower limb muscles were analysed. Most results showed an increase in parameters with an increased level of muscle contraction, only some studies showed a decrease. The influence on parameters of the level of muscle contraction and factors such as subjects, type of contraction, muscle length and electrodes was analysed for each muscle. It was concluded that when analysing the influence of different factors on MF and MPF, because those factors interact they should be considered together, not separately. PMID:26654476

Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats.

PubMed

Chen, Tao; Hutts, Robert C; Mei, Nan; Liu, Xiaoli; Bishop, Michelle E; Shelton, Sharon; Manjanatha, Mugimane G; Aidoo, Anane

2005-06-01

A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.

Intermittency of gravity wave momentum flux in the mesopause region observed with an all-sky airglow imager

NASA Astrophysics Data System (ADS)

Cao, Bing; Liu, Alan Z.

2016-01-01

The intermittency of gravity wave momentum flux (MF) near the OH airglow layer (˜87 km) in the mesopause region is investigated for the first time using observation of all-sky airglow imager over Maui, Hawaii (20.7°N, 156.3°W), and Cerro Pachón, Chile (30.3°S, 70.7°W). At both sites, the probability density function (pdf) of gravity wave MF shows two distinct distributions depending on the magnitude of the MF. For MF smaller (larger) than ˜16 m2 s-2 (0.091 mPa), the pdf follows a lognormal (power law) distribution. The intermittency represented by the Bernoulli proxy and the percentile ratio shows that gravity waves have higher intermittency at Maui than at Cerro Pachón, suggesting more intermittent background variation above Maui. It is found that most of the MF is contributed by waves that occur very infrequently. But waves that individually contribute little MF are also important because of their higher occurrence frequencies. The peak contribution is from waves with MF around ˜2.2 m2 s-2 at Cerro Pachón and ˜5.5 m2 s-2 at Maui. Seasonal variations of the pdf and intermittency imply that the background atmosphere has larger influence on the observed intermittency in the mesopause region.

Influence of the Addition of Minced Fish on the Preparation of Fish Sausage: Effects on Sensory Properties.

PubMed

Lago, Amanda M T; Vidal, Ana C C; Schiassi, Maria C E V; Reis, Tatiana; Pimenta, Carlos; Pimenta, Maria E S G

2017-02-01

In this study, we evaluated the effect of minced fish (MF) inclusion on the acceptance of tilapia sausages. One hundred consumers participated in the sensory acceptance test in relation to the attributes appearance, color, aroma, flavor, texture, overall impression, and purchase intent. The tests were conducted using the same composition of ingredients, varying only the raw material (MF and fillet), resulting in 5 different formulations. To represent the results of the sensory attributes, we generated internal preference maps through principal component analysis and parallel factor analysis, as well as frequency histograms. The data showed greater acceptability for the sample produced with 50% MF, although all had shown satisfactory results. We conclude that inclusion of MF can be suitable in the preparation of fish sausage due to high consumer acceptance. © 2017 Institute of Food Technologists®.

Effect of extremely low frequency magnetic field on antioxidant activity in plasma and red blood cells in spot welders.

PubMed

Sharifian, Akbar; Gharavi, Marjan; Pasalar, Parvin; Aminian, Omid

2009-01-01

The purpose of this study was to determine a possible relation between exposure to extremely low frequency magnetic field (ELF-MF) and the human antioxidant activity. The total serum antioxidant status (TAS), red blood cells (RBCs) glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in 46 spot welders who were occupationally exposed to ELF-MF (magnetic field strength = 8.8-84 microTesla (microT), frequency = 50 Hertz (Hz) and electric field strength = 20-133 V/m). The results were compared with a nonexposed ELF-MF control group. The correlation between magnetic field strength and antioxidant activity in RBCs and plasma was then assessed. No significant differences in TAS levels were observed (P value = 0.065). However, in RBCs of exposed group, a significant decrease in SOD and GPX activities was observed (P value = 0.001 and 0.003, respectively). This decrease was measured as 22 and 12.3%, respectively. Furthermore, a significant negative correlation between SOD/GPX activities and magnetic field intensity was observed (coefficients of SOD: -0.625, significance: 0.0001 and coefficients of GPX: -0.348, significance: 0.018). The results of this study indicate that ELF-MF could influence the RBC antioxidant activity and might act as an oxidative stressor. Intracellular antioxidant enzymes such as SOD and GPX were found to be the most important markers involving in this process. The influence of magnetic field on the antioxidant activity of RBCs might occur even at the recommended levels of exposure.

The diagnostic accuracy of multi-frequency bioelectrical impedance analysis in diagnosing dehydration after stroke.

PubMed

Kafri, Mohannad W; Myint, Phyo Kway; Doherty, Danielle; Wilson, Alexander Hugh; Potter, John F; Hooper, Lee

2013-07-10

Non-invasive methods for detecting water-loss dehydration following acute stroke would be clinically useful. We evaluated the diagnostic accuracy of multi-frequency bioelectrical impedance analysis (MF-BIA) against reference standards serum osmolality and osmolarity. Patients admitted to an acute stroke unit were recruited. Blood samples for electrolytes and osmolality were taken within 20 minutes of MF-BIA. Total body water (TBW%), intracellular (ICW%) and extracellular water (ECW%), as percentages of total body weight, were calculated by MF-BIA equipment and from impedance measures using published equations for older people. These were compared to hydration status (based on serum osmolality and calculated osmolarity). The most promising Receiver Operating Characteristics curves were plotted. 27 stroke patients were recruited (mean age 71.3, SD10.7). Only a TBW% cut-off at 46% was consistent with current dehydration (serum osmolality >300 mOsm/kg) and TBW% at 47% impending dehydration (calculated osmolarity ≥295-300 mOsm/L) with sensitivity and specificity both >60%. Even here diagnostic accuracy of MF-BIA was poor, a third of those with dehydration were wrongly classified as hydrated and a third classified as dehydrated were well hydrated. Secondary analyses assessing diagnostic accuracy of TBW% for men and women separately, and using TBW as a percentage of lean body mass showed some promise, but did not provide diagnostically accurate measures across the population. MF-BIA appears ineffective at diagnosing water-loss dehydration after stroke and cannot be recommended as a test for dehydration, but separating assessment by sex, and using TBW as a percentage of lean body weight may warrant further investigation.

Characteristics of Paraspinal Muscle Spindle Response to Mechanically Assisted Spinal Manipulation: A Preliminary Report.

PubMed

Reed, William R; Pickar, Joel G; Sozio, Randall S; Liebschner, Michael A K; Little, Joshua W; Gudavalli, Maruti R

The purpose of this preliminary study is to determine muscle spindle response characteristics related to the use of 2 solenoid powered clinical mechanically assisted manipulation (MAM) devices. L6 muscle spindle afferents with receptive fields in paraspinal muscles were isolated in 6 cats. Neural recordings were made during L7 MAM thrusts using the Activator V (Activator Methods Int. Ltd., Phoenix, AZ) and/or Pulstar (Sense Technology Inc., Pittsburgh, PA) devices at their 3 lowest force settings. Mechanically assisted manipulation response measures included (a) the time required post-thrust until the first action potential, (b) differences in mean frequency (MF) and mean instantaneous frequency (MIF) 2 seconds before and after MAM, and (c) the time required for muscle spindle discharge (MF and MIF) to return to 95% of baseline after MAM. Depending on device setting, between 44% to 80% (Pulstar) and 11% to 63% (Activator V) of spindle afferents required >6 seconds to return to within 95% of baseline MF values; whereas 66% to 89% (Pulstar) and 75% to 100% (Activator V) of spindle responses returned to within 95% of baseline MIF in <6 seconds after MAM. Nonparametric comparisons between the 22 N and 44 N settings of the Pulstar yielded significant differences for the time required to return to baseline MF and MIF. Short duration (<10 ms) MAM thrusts decrease muscle spindle discharge with a majority of afferents requiring prolonged periods (>6 seconds) to return to baseline MF activity. Physiological consequences and clinical relevance of described MAM mechanoreceptor responses will require additional investigation. Copyright © 2017. Published by Elsevier Inc.

Gender Inequalities in Remote Settings: Analysis of 105,025 Medical Records of a Rural Hospital in Ethiopia (2005-2015).

PubMed

Accorsi, Sandro; Somigliana, Edgardo; Farese, Pasquale; Ademe, Tsegaye; Desta, Yonas; Putoto, Giovanni; Manenti, Fabio

2017-08-01

Gender inequalities in Sub-Saharan Africa are deemed relevant but data to support this view are scanty. Retrospective analysis of a large dataset of 105,025 patients admitted to an Ethiopian rural private, non-for-profit hospital over a 11 years period (2005-2015). Since 2001, the hospital and the local community are involved in a long-term, comprehensive and externally-supported health care intervention. The total number of admissions was higher for females (61.9% of the total) mainly because of the high frequency of admissions for obstetrics conditions. The total male-to-female ratio (M:F) was 0.6. Except for malaria, men had more admissions for the other leading causes, with the highest M:F being found for injuries (2.7) and musculoskeletal diseases (1.7). Overall, excluding admissions for pregnancy-related issues, the M:F was 1.4. The frequency of admissions changed with age and gender. Female admissions prevailed in the reproductive age period (from 15 to 44 years of age) while males admissions prevailed in the younger and older age groups. The case fatality rate was higher for men (M:F = 2.0). The total M:F and the M:F excluding pregnancy-related admissions did not change during the study period. Gender inequalities do exist in rural remote setting but tend to affect women differently during their lifespan. Even if gender inequalities generally favor males, the substantial proportion of admissions for pregnancy-related situations is encouraging.

Estimation of Electron Density profile Using the Propagation Characteristics of Radio Waves by S-520-29 Sounding Rocket

NASA Astrophysics Data System (ADS)

Itaya, K.; Ishisaka, K.; Ashihara, Y.; Abe, T.; Kumamoto, A.; Kurihara, J.

2015-12-01

S-520-29 sounding rocket experiment was carried out at Uchinoura Space Center (USC) at 19:10 JST on 17 August, 2014. The purpose of this sounding rocket experiments is observation of sporadic E layer that appears in the lower ionosphere at near 100km. Three methods were used in order to observe the sporadic E layer. The first method is an optical method that observe the light of metal ion emitted by the resonance scattering in sporadic E layer using the imager. The second method is observation of characteristic of radio wave propagation that the LF/MF band radio waves transmitted from the ground. The third method is measuring the electron density in the vicinity of sounding rocket using the fast Langmuir probe and the impedance probe. We analyze the propagation characteristics of radio wave in sporadic E layer appeared from the results of the second method observation. This rocket was equipped with LF/MF band radio receiver for observe the LF/MF band radio waves in rocket flight. Antenna of LF/MF band radio receiver is composed of three axis loop antenna. LF/MF band radio receiver receives three radio waves of 873kHz (JOGB), 666kHz (JOBK), 60kHz (JJY) from the ground. 873kHz and 60kHz radio waves are transmitting from north side, and 666kHz radio waves are transmitting from the east side to the trajectory of the rocket. In the sounding rocket experiment, LF/MF band radio receiver was working properly. We have completed the observation of radio wave intensity. We analyze the observation results using a Doppler shift calculations by frequency analysis. Radio waves received by the sounding rocket include the influences of Doppler shift by polarization and the direction of rocket spin and the magnetic field of the Earth. So received radio waves that are separate into characteristics waves using frequency analysis. Then we calculate the Doppler shift from the separated data. As a result, 873kHz, 666kHz radio waves are reflected by the ionosphere. 60kHz wave was able to propagate in ionosphere because wavelength of 60kHz was longer than the thickness of the sporadic E layer. In this study, we explain the result of LF/MF band radio receiver observations and the electron density of the ionosphere using frequency analysis by S-520-29 sounding rocket experiment.

Meal frequency of pre-exercise carbohydrate feedings.

PubMed

Chryssanthopoulos, C; Petridou, A; Maridaki, M; Mougios, V

2008-04-01

This study compared the effect of single and multiple carbohydrate feedings before exercise on biochemical and physiological responses during exercise. Eight males performed 3 runs for 1 h at 70 % VO(2max) after consuming a meal containing 2.5 g carbohydrate per kg body mass in a single dose 3 h before exercise (SF), the same meal in 5 equal doses at 3, 2.5, 2, 1.5, and 1 h before exercise (MF), or a liquid placebo 3 h before exercise (P). RER and carbohydrate oxidation rates were higher in SF and MF compared to P trials, but there was no difference between SF and MF trials. Pre-exercise insulin was 2.0- and 3.4- fold higher in SF and MF, respectively, compared to P, and 1.7-fold higher in MF compared to SF. Glycerol and NEFA were higher in P compared to SF and MF trials before and at the end of exercise. In conclusion, a carbohydrate meal containing 2.5 g . kg(-1) ingested in doses over 3 h before running produced higher hyperinsulinemia pre-exercise than that produced when the meal was consumed in a single dose. Nevertheless, estimated carbohydrate utilization and adipose tissue lipolysis during exercise after multiple feedings seemed to be as high as after a single feeding.

[The specific features of the development of metabolic and regenerative processes under the action of low-intensity electromagnetic radiation in radiation exposure conditions (an experimental study)].

PubMed

Korolev, Yu N; Mihajlik, L V; Nikulina, L A; Geniatulina, M S

The experiments on male white rats with the use of biochemical, photo-optical, and electron-microscopic techniques have demonstrated that the use of low-intensity electromagnetic radiation of ultrahigh frequency (EMR UHF) and low-intensity low-frequency magnetic field (MF) during the post-irradiation period (within 21 days after exposure to radiation) enhanced the metabolic and regenerative processes in the testes and liver. It was shown that the application of MF largely intensified the antioxidant activity whereas EMR UHF preferentially stimulated the biosynthetic processes as well as the processes of cellular and intracellular regeneration.

Juvenile X-linked retinoschisis with normal scotopic b-wave in the electroretinogram at an early stage of the disease.

PubMed

Eksandh, Louise; Andréasson, Sten; Abrahamson, Magnus

2005-09-01

To report four cases of genetically verified juvenile X-linked retinoschisis (XLRS) with normal scotopic b-waves in full-field ERG, including one patient with a novel mutation (W50X) in the RS1 gene. Four XLRS patients from different families were examined with regard to visual acuity, kinetic perimetry, fundus photography, full-field ERG, and OCT. Two of these patients were also examined with multifocal-ERG (mfERG). Mutations in the RS1 gene were identified by sequence analysis. The full-field ERG presented normal b-wave amplitudes on scotopic white-light stimulation. OCT and mfERG presented macular schisis and macular dysfunction. Genetic analysis revealed a deletion of exon 1 and the promotor region in one patient and mutations giving rise to the amino acid substitutions R209C and W96R in two others. The fourth patient carried a novel mutation in exon 3 of the RS1 gene (nt 149 G-->A), causing the introduction of a stop codon after amino acid 49 in the RS protein. Four young males with XLRS did not present with reduction in the scotopic b-wave amplitude on full-field ERG, which is otherwise often considered to be characteristic of the disease. Full-field ERG and molecular genetic analysis of the RS1 gene still remain the most important diagnostic tools for this retinal disorder, although the OCT can be a valuable complement in order to make the diagnosis at an early stage.

Can safe and long-term exposure to extremely low frequency (50 Hz) magnetic fields affect apoptosis, reproduction, and oxidative stress?

PubMed

Akdag, Mehmet Zulkuf; Dasdag, Suleyman; Uzunlar, Ali Kemal; Ulukaya, Engin; Oral, Arzu Yilmaztepe; Çelik, Necla; Akşen, Feyzan

2013-12-01

To determine whether 50 Hz extremely low frequency-magnetic fields (ELF-MF) affects apoptotic processes, oxidative damage, and reproductive characteristics such as sperm count and morphology in rat testes. Thirty male Sprague-Dawley rats were used in the present study, which were divided into three groups (sham group, n = 10, and two experimental groups, n = 10 for each group). Rats in the experimental group were exposed to 100 and 500 μT ELF-MF (2 h/day, 7 days/week, for 10 months) corresponding to exposure levels that are considered safe for humans. The same experimental procedures were applied to the sham group, but the ELF generator was turned off. Tissues from the testes were immunohistochemically stained for active (cleaved) caspase-3 in order to measure the apoptotic index by a semi-quantitative scoring system. The levels of catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidative capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were also measured. Additionally, epididymal sperm count and sperm morphology was evaluated. There were no significant differences in the reproductive and oxidative stress parameters between the sham group and the exposed groups (p > 0.05). While no difference was observed between the final apoptosis score of the sham and the 100 μT ELF-MF group (p > 0.05), the final apoptosis score was higher in the 500 μT ELF-MF exposure group than in the sham group (p < 0.05). Long-term exposure to 100 μT and 500 μT ELF-MF did not affect oxidative or antioxidative processes, lipid peroxidation, or reproductive components such as sperm count and morphology in testes tissue of rats. However, long-term exposure to 500 μT ELF-MF did affect active-caspase-3 activity, which is a well-known apoptotic indicator.

Role of the ATM Gene in Bilateral Breast Cancer Following Radiotherapy.

DTIC Science & Technology

1999-08-01

Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal 0, Lavin MF, Jaspers NGJ, Taylor AMR, Arlett CF, Miki T, Weissman SM , Lovett M, Collins FS, Shiloh Y: A...1995 35. Maslen C, Babcock D, Raghunath M, Steinmann B: A rare branch-point mutation is associated with missplicing of fibrillin-Z in a large family

Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins

PubMed Central

Li, Jianchao; He, Yunyun; Weck, Meredith L.; Lu, Qing; Tyska, Matthew J.; Zhang, Mingjie

2017-01-01

Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in their cargo binding tails and are essential for the growth and function of microvilli and stereocilia. Numerous mutations have been identified in the MyTH4-FERM tandems of these myosins in patients suffering visual and hearing impairment. Although a number of MF domain binding partners have been identified, the molecular basis of interactions with the C-terminal MF domain (CMF) of these myosins remains poorly understood. Here we report the high-resolution crystal structure of Myo7b CMF in complex with the extended PDZ3 domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted, based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a. PMID:28439001

Simulation and Measurement of Medium-Frequency Signals Coupling From a Line to a Loop Antenna

PubMed Central

Damiano, Nicholas W.; Li, Jingcheng; Zhou, Chenming; Brocker, Donovan E.; Qin, Yifeng; Werner, Douglas H.; Werner, Pingjuan L.

2016-01-01

The underground-mining environment can affect radio-signal propagation in various ways. Understanding these effects is especially critical in evaluating communications systems used during normal mining operations and during mine emergencies. One of these types of communications systems relies on medium-frequency (MF) radio frequencies. This paper presents the simulation and measurement results of recent National Institute for Occupational Safety and Health (NIOSH) research aimed at investigating MF coupling between a transmission line (TL) and a loop antenna in an underground coal mine. Two different types of measurements were completed: 1) line-current distribution and 2) line-to-antenna coupling. Measurements were taken underground in an experimental coal mine and on a specially designed surface test area. The results of these tests are characterized by current along a TL and voltage induced in the loop from a line. This paper concludes with a discussion of issues for MF TLs. These include electromagnetic fields at the ends of the TL, connection of the ends of the TL, the effect of other conductors underground, and the proximity of coal or earth. These results could help operators by providing examples of these challenges that may be experienced underground and a method by which to measure voltage induced by a line. PMID:27784954

Ultrahigh-rate supercapacitors with large capacitance based on edge oriented graphene coated carbonized cellulous paper as flexible freestanding electrodes

NASA Astrophysics Data System (ADS)

Ren, Guofeng; Li, Shiqi; Fan, Zhao-Xia; Hoque, Md Nadim Ferdous; Fan, Zhaoyang

2016-09-01

Large-capacitance and ultrahigh-rate electrochemical supercapacitors (UECs) with frequency response up to kilohertz (kHz) range are reported using light, thin, and flexible freestanding electrodes. The electrode is formed by perpendicularly edge oriented multilayer graphene/thin-graphite (EOG) sheets grown radially around individual fibers in carbonized cellulous paper (CCP), with cellulous carbonization and EOG deposition implemented in one step. The resulted ∼10 μm thick EOG/CCP electrode is light and flexible. The oriented porous structure of EOG with large surface area, in conjunction with high conductivity of the electrode, ensures ultrahigh-rate performance of the fabricated cells, with large areal capacitance of 0.59 mF cm-2 and 0.53 mF cm-2 and large phase angle of -83° and -80° at 120 Hz and 1 kHz, respectively. Particularly, the hierarchical EOG/CCP sheet structure allows multiple sheets stacked together for thick electrodes with almost linearly increased areal capacitance while maintaining the volumetric capacitance nearly no degradation, a critical merit for developing practical faraday-scale UECs. 3-layers of EOG/CCP electrode achieved an areal capacitance of 1.5 mF cm-2 and 1.4 mF cm-2 at 120 Hz and 1 kHz, respectively. This demonstration moves a step closer to the goal of bridging the frequency/capacitance gap between supercapacitors and electrolytic capacitors.

Children’s Personal Exposure Measurements to Extremely Low Frequency Magnetic Fields in Italy

PubMed Central

Liorni, Ilaria; Parazzini, Marta; Struchen, Benjamin; Fiocchi, Serena; Röösli, Martin; Ravazzani, Paolo

2016-01-01

Extremely low frequency magnetic fields (ELF-MFs) exposure is still a topic of concern due to their possible impact on children’s health. Although epidemiological studies claimed an evidence of a possible association between ELF-MF above 0.4 μT and childhood leukemia, biological mechanisms able to support a causal relationship between ELF-MF and this disease were not found yet. To provide further knowledge about children’s ELF-MF exposure correlated to children’s daily activities, a measurement study was conducted in Milan (Italy). Eighty-six children were recruited, 52 of whom were specifically chosen with respect to the distance to power lines and built-in transformers to oversample potentially highly exposed children. Personal and bedroom measurements were performed for each child in two different seasons. The major outcomes of this study are: (1) median values over 24-h personal and bedroom measurements were <3 μT established by the Italian law as the quality target; (2) geometric mean values over 24-h bedroom measurements were mostly <0.4 μT; (3) seasonal variations did not significantly influence personal and bedroom measurements; (4) the highest average MF levels were mostly found at home during the day and outdoors; (5) no significant differences were found in the median and geometric mean values between personal and bedroom measurements, but were found in the arithmetic mean. PMID:27258295

Association between childhood leukaemia and exposure to power-frequency magnetic fields in Middle Europe.

PubMed

Jirik, Vitezslav; Pekarek, Ludek; Janout, Vladimir; Tomaskova, Hana

2012-10-01

Higher levels of exposure to extremely low-frequency magnetic fields (ELF-MF) are associated with a slightly increased risk of childhood leukaemia. Compared with more-developed Western countries, higher exposure levels are evident in the Czech Republic, probably because of the different types of housing. In light of this, we aimed to examine the association between ELF-MF exposure and childhood leukaemia in the Czech Republic. We conducted a paired case-control study. The cases (children with leukaemia) were age- sex- and permanent residence-matched to controls (children without leukaemia). Although this limited potential bias and confounding, it also limited our number of participants. The matched analyses included 79 case-control pairs. No significant association between ELF-MF exposure and childhood leukaemia was observed for exposures over 0.2 μT (odds ratio [OR]=0.93, confidence interval [CI]=0.45-1.93), 0.3 μT (OR=0.77, CI=0.34-1.75), or 0.4 μT (OR=0.9, CI=0.37-2.22). Despite higher levels of exposure in Middle and Eastern Europe, no indication of an association between ELF-MF exposure and childhood leukaemia was determined. This in contrast to the findings of previous studies conducted in different countries. Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Intracellular Activation of Interferon Regulatory Factor-1 by Nanobodies to the Multifunctional (Mf1) Domain*

PubMed Central

Möller, Angeli; Pion, Emmanuelle; Narayan, Vikram; Ball, Kathryn L.

2010-01-01

IRF-1 is a tumor suppressor protein that activates gene expression from a range of promoters in response to stimuli spanning viral infection to DNA damage. Studies on the post-translational regulation of IRF-1 have been hampered by a lack of suitable biochemical tools capable of targeting the endogenous protein. In this study, phage display technology was used to develop a monoclonal nanobody targeting the C-terminal Mf1 domain (residues 301–325) of IRF-1. Intracellular expression of the nanobody demonstrated that the transcriptional activity of IRF-1 is constrained by the Mf1 domain as nanobody binding gave an increase in expression from IRF-1-responsive promoters of up to 8-fold. Furthermore, Mf1-directed nanobodies have revealed an unexpected function for this domain in limiting the rate at which the IRF-1 protein is degraded. Thus, the increase in IRF-1 transcriptional activity observed on nanobody binding is accompanied by a significant reduction in the half-life of the protein. In support of the data obtained using nanobodies, a single point mutation (P325A) involving the C-terminal residue of IRF-1 has been identified, which results in greater transcriptional activity and a significant increase in the rate of degradation. The results presented here support a role for the Mf1 domain in limiting both IRF-1-dependent transcription and the rate of IRF-1 turnover. In addition, the data highlight a route for activation of downstream genes in the IRF-1 tumor suppressor pathway using biologics. PMID:20817723

Interplay between low threshold voltage-gated K+ channels and synaptic inhibition in neurons of the chicken nucleus laminaris along its frequency axis

PubMed Central

Hamlet, William R.; Liu, Yu-Wei; Tang, Zheng-Quan; Lu, Yong

2014-01-01

Central auditory neurons that localize sound in horizontal space have specialized intrinsic and synaptic cellular mechanisms to tightly control the threshold and timing for action potential generation. However, the critical interplay between intrinsic voltage-gated conductances and extrinsic synaptic conductances in determining neuronal output are not well understood. In chicken, neurons in the nucleus laminaris (NL) encode sound location using interaural time difference (ITD) as a cue. Along the tonotopic axis of NL, there exist robust differences among low, middle, and high frequency (LF, MF, and HF, respectively) neurons in a variety of neuronal properties such as low threshold voltage-gated K+ (LTK) channels and depolarizing inhibition. This establishes NL as an ideal model to examine the interactions between LTK currents and synaptic inhibition across the tonotopic axis. Using whole-cell patch clamp recordings prepared from chicken embryos (E17–E18), we found that LTK currents were larger in MF and HF neurons than in LF neurons. Kinetic analysis revealed that LTK currents in MF neurons activated at lower voltages than in LF and HF neurons, whereas the inactivation of the currents was similar across the tonotopic axis. Surprisingly, blockade of LTK currents using dendrotoxin-I (DTX) tended to broaden the duration and increase the amplitude of the depolarizing inhibitory postsynaptic potentials (IPSPs) in NL neurons without dependence on coding frequency regions. Analyses of the effects of DTX on inhibitory postsynaptic currents led us to interpret this unexpected observation as a result of primarily postsynaptic effects of LTK currents on MF and HF neurons, and combined presynaptic and postsynaptic effects in LF neurons. Furthermore, DTX transferred subthreshold IPSPs to spikes. Taken together, the results suggest a critical role for LTK currents in regulating inhibitory synaptic strength in ITD-coding neurons at various frequencies. PMID:24904297

Interplay between low threshold voltage-gated K(+) channels and synaptic inhibition in neurons of the chicken nucleus laminaris along its frequency axis.

PubMed

Hamlet, William R; Liu, Yu-Wei; Tang, Zheng-Quan; Lu, Yong

2014-01-01

Central auditory neurons that localize sound in horizontal space have specialized intrinsic and synaptic cellular mechanisms to tightly control the threshold and timing for action potential generation. However, the critical interplay between intrinsic voltage-gated conductances and extrinsic synaptic conductances in determining neuronal output are not well understood. In chicken, neurons in the nucleus laminaris (NL) encode sound location using interaural time difference (ITD) as a cue. Along the tonotopic axis of NL, there exist robust differences among low, middle, and high frequency (LF, MF, and HF, respectively) neurons in a variety of neuronal properties such as low threshold voltage-gated K(+) (LTK) channels and depolarizing inhibition. This establishes NL as an ideal model to examine the interactions between LTK currents and synaptic inhibition across the tonotopic axis. Using whole-cell patch clamp recordings prepared from chicken embryos (E17-E18), we found that LTK currents were larger in MF and HF neurons than in LF neurons. Kinetic analysis revealed that LTK currents in MF neurons activated at lower voltages than in LF and HF neurons, whereas the inactivation of the currents was similar across the tonotopic axis. Surprisingly, blockade of LTK currents using dendrotoxin-I (DTX) tended to broaden the duration and increase the amplitude of the depolarizing inhibitory postsynaptic potentials (IPSPs) in NL neurons without dependence on coding frequency regions. Analyses of the effects of DTX on inhibitory postsynaptic currents led us to interpret this unexpected observation as a result of primarily postsynaptic effects of LTK currents on MF and HF neurons, and combined presynaptic and postsynaptic effects in LF neurons. Furthermore, DTX transferred subthreshold IPSPs to spikes. Taken together, the results suggest a critical role for LTK currents in regulating inhibitory synaptic strength in ITD-coding neurons at various frequencies.

Chromosomal aberrations in peripheral lymphocytes of train engine drivers.

PubMed

Nordenson, I; Mild, K H; Järventaus, H; Hirvonen, A; Sandström, M; Wilén, J; Blix, N; Norppa, H

2001-07-01

Studies of Swedish railway employees have indicated that railroad engine drivers have an increased cancer morbidity and incidence of chronic lymphatic leukemia. The drivers are exposed to relatively high magnetic fields (MF), ranging from a few to over a hundred microT. Although the possible genotoxic potential of MF is unclear, some earlier studies have indicated that occupational exposure to MF may increase chromosome aberrations in blood lymphocytes. Since an increased level of chromosomal aberrations has been suggested to predict elevated cancer risk, we performed a cytogenetic analysis on cultured (48 h) peripheral lymphocytes of Swedish train engine drivers. A pilot study of 18 engine drivers indicated a significant difference in the frequency of cells with chromosomal aberrations (gaps included or excluded) in comparison with seven concurrent referents (train dispatchers) and a control group of 16 office workers. The engine drivers had about four times higher frequency of cells with chromosome-type aberrations (excluding gaps) than the office workers (P < 0.01) and the dispatchers (P < 0.05). Seventy-eight percent of the engine drivers showed at least one cell per 100 with chromosome-type aberrations compared with 29% among the dispatchers and 31% among the office workers. In a follow-up study, another 30 engine drivers showed an increase (P < 0.05) in the frequency of cells with chromosome-type aberrations (gaps excluded) as compared with 30 referent policemen. Sixty percent of the engine drivers had one or more cells (per 100 cells) with chromosome-type aberrations compared with 30% among the policemen. In conclusion, the results of the two studies support the hypothesis that exposure to MF at mean intensities of 2-15 microT can induce chromosomal damage. Copyright 2001 Wiley-Liss, Inc.

Kick frequency affects the energy cost of aquatic locomotion in elite monofin swimmers.

PubMed

Boitel, Guillaume; Vercruyssen, Fabrice; Alberty, Morgan; Nesi, Xavier; Bourdon, Lionel; Brisswalter, Jeanick

2010-08-01

The aim of this study was to evaluate the influence of kick frequency (K(F)) on the energy cost of aquatic locomotion in elite monofin (Mf) swimmers at the surface. Eight subjects of international calibre (4 females, 4 males) were requested to perform in a 50-m outdoor swimming pool: (1) a continuous multi-stage incremental test to determine maximal physiological responses and (2) a submaximal exercise composed of five constant Mf-swimming tests (600-m exercise, 5-min rest) at an intensity corresponding to 90% of the velocity at the maximal oxygen uptake (VO2max). The first submaximal Mf-swimming test was systematically conducted at a freely chosen K(F) (FCK(F)) and the other tests were performed at FCK(F) - 15%, FCK(F) - 10%, FCK(F) + 10% and FCK(F) + 20% in a random order. No significant effect of K(F) on ventilation, heart rate and blood lactate concentration was observed throughout the submaximal Mf-swimming tests. However, mean values in Ec or fraction of VO2max were significantly lower during the FCK(F) + 10% condition as compared to those observed during the FCK(F) - 15% (-11.5 and -9.6%, respectively, P < 0.05) and FCK(F) - 10% (-10.4 and -9.3%, respectively, P < 0.05) conditions. In conclusion, the lack of significant differences between FCK(F) + 10% and FCK(F) or FCK(F) + 20% does not allow to identify a specific trend, but suggests the occurrence of an energetically optimal K(F) close to that freely chosen by the Mf swimmers. Variations in muscle activity level and active drag have been hypothesized to explain the observed differences in Ec consecutive to the selection of various K(F).

The diagnostic accuracy of multi-frequency bioelectrical impedance analysis in diagnosing dehydration after stroke

PubMed Central

Kafri, Mohannad W.; Myint, Phyo Kyaw; Doherty, Danielle; Wilson, Alexander Hugh; Potter, John F.; Hooper, Lee

2013-01-01

Background Non-invasive methods for detecting water-loss dehydration following acute stroke would be clinically useful. We evaluated the diagnostic accuracy of multi-frequency bioelectrical impedance analysis (MF-BIA) against reference standards serum osmolality and osmolarity. Material/Methods Patients admitted to an acute stroke unit were recruited. Blood samples for electrolytes and osmolality were taken within 20 minutes of MF-BIA. Total body water (TBW%), intracellular (ICW%) and extracellular water (ECW%), as percentages of total body weight, were calculated by MF-BIA equipment and from impedance measures using published equations for older people. These were compared to hydration status (based on serum osmolality and calculated osmolarity). The most promising Receiver Operating Characteristics curves were plotted. Results 27 stroke patients were recruited (mean age 71.3, SD10.7). Only a TBW% cut-off at 46% was consistent with current dehydration (serum osmolality >300 mOsm/kg) and TBW% at 47% impending dehydration (calculated osmolarity ≥295–300 mOsm/L) with sensitivity and specificity both >60%. Even here diagnostic accuracy of MF-BIA was poor, a third of those with dehydration were wrongly classified as hydrated and a third classified as dehydrated were well hydrated. Secondary analyses assessing diagnostic accuracy of TBW% for men and women separately, and using TBW as a percentage of lean body mass showed some promise, but did not provide diagnostically accurate measures across the population. Conclusions MF-BIA appears ineffective at diagnosing water-loss dehydration after stroke and cannot be recommended as a test for dehydration, but separating assessment by sex, and using TBW as a percentage of lean body weight may warrant further investigation. PMID:23839255

MF-101, an estrogen receptor beta agonist for the treatment of vasomotor symptoms in peri- and postmenopausal women.

PubMed

Stovall, Dale W; Pinkerton, Joann V

2009-04-01

During peri- and postmenopausal stages, the majority of women experience moderate-to-severe vasomotor symptoms, such as hot flashes and night sweats, that interfere with sleep and reduce quality of life. Estrogen alone or in combination with a progestagen has been the standard therapy for such vasomotor symptoms; however, this therapeutic regimen is associated with severe side effects, such as breast cancer or cardiovascular events. To provide a better treatment option for menopausal women, Bionovo Inc is developing the estrogen receptor (ER)beta-selective agonist MF-101. Selective ER agonists can stimulate either ERalpha or ERbeta and induce tissue-specific estrogen-like effects, thus providing a safer alternative to conventional hormone therapy. MF-101 is derived from 22 herbs that are traditionally used in Chinese medicine for the treatment of menopausal symptoms. MF-101 did not promote the growth of breast cancer cells or stimulate uterine growth in preclinical studies and, in a phase II trial, was demonstrated to be safe and more effective in reducing the frequency and severity of hot flashes in postmenopausal women compared with placebo. To confirm the safety and efficacy of MF-101, larger phase III trials were planned for 2009. Although MF-101 appears to be a promising therapeutic, the herbal composition of the drug may be a disadvantage, because of the increased risk of causing allergic reactions in the general population. Studies with the MF-101-isolated active compounds liquiritigen and chalcone demonstrated selectivity for ERbeta, with no induction of proliferative events. If these isolates were demonstrated to be as effective and safe in clinical trials as preliminary data suggest regarding MF-101, these compounds could change the way clinicians treat menopause-associated symptoms.

Effects of multifocal soft contact lenses used to slow myopia progression on quality of vision in young adults.

PubMed

Kang, Pauline; McAlinden, Colm; Wildsoet, Christine F

2017-02-01

To assess the effects of multifocal soft contact lenses (MF SCLs) used for myopia control on visual acuity (VA) and subjective quality of vision. Twenty-four young adult myopes had baseline high and low-contrast VAs and refractions measured and quality of vision assessed by the Quality of Vision (QoV) questionnaire with single vision SCLs. Additional VA and QoV questionnaire data were collected immediately after subjects were fitted with Proclear MF SCLs and again after a 2-week adaptation period of daily lens wear. Data were collected for two MF SCL designs, incorporating +1.50 and +3.00 D peripheral near additions, with a week washout period allowed between the two lens trials. High- and low-contrast VAs were initially reduced with both MF SCL designs, but subsequently improved to be not significantly reduced in the case of high-contrast VA by the end of the 2-week adaptation period. The quality of vision was also reduced, more so with the +3.00 D MF SCL. Quality of Vision (QoV) scores describing frequency, severity and bothersome nature of visual symptoms indicated symptoms worsening rather than resolving over the 2-week period, particularly so with the +3.00 D MF SCL. Low and high add MF SCLs adversely affected vision on initial insertion, with sustained effects on low-contrast VA and QoV scores but not high-contrast VA. Thus, high-contrast VA is not a suitable surrogate for quality of vision. In prescribing MF SCLs for myopia control, clinicians should educate patients about these effects on vision. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Mechanisms of mutations in myeloproliferative neoplasms.

PubMed

Levine, Ross L

2009-12-01

In recent years, a series of studies have provided genetic insight into the pathogenesis of myeloproliferative neoplasms (MPNs). It is now known that JAK2V617F mutations are present in 90% of patients with polycythaemia vera (PV), 60% of patients with essential thrombocytosis (ET) and 50% of patients with myelofibrosis (MF). Despite the high prevalence of JAK2V617F mutations in these three myeloid malignancies, several questions remain. For example, how does one mutation contribute to the pathogenesis of three clinically distinct diseases, and how do some patients develop these diseases in the absence of a JAK2V617F mutation? Single nucleotide polymorphisms at various loci and somatic mutations, such as those in MPLW515L/K, TET2 and in exon 12 of JAK2, may also contribute to the pathogenesis of these MPNs. There are likely additional germline and somatic genetic factors important to the MPN phenotype. Additional studies of large MPN and control cohorts with new techniques will help identify these factors.

Phase History Decomposition for efficient Scatterer Classification in SAR Imagery

DTIC Science & Technology

2011-09-15

frequency. Professor Rick Martin provided key advice on frequency parameter estimation and the relationship between likelihood ratio testing and the least...132 6.1.1 Imaging Error Due to Interpolation . . . . . . . . . . . . . . . . . . . . . . . . 135 6.2 Subwindow Design and Weighting... test . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 MF matched filter

Characterization of extremely low frequency magnetic fields from diesel, gasoline and hybrid cars under controlled conditions.

PubMed

Hareuveny, Ronen; Sudan, Madhuri; Halgamuge, Malka N; Yaffe, Yoav; Tzabari, Yuval; Namir, Daniel; Kheifets, Leeka

2015-01-30

This study characterizes extremely low frequency (ELF) magnetic field (MF) levels in 10 car models. Extensive measurements were conducted in three diesel, four gasoline, and three hybrid cars, under similar controlled conditions and negligible background fields. Averaged over all four seats under various driving scenarios the fields were lowest in diesel cars (0.02 μT), higher for gasoline (0.04-0.05 μT) and highest in hybrids (0.06-0.09 μT), but all were in-line with daily exposures from other sources. Hybrid cars had the highest mean and 95th percentile MF levels, and an especially large percentage of measurements above 0.2 μT. These parameters were also higher for moving conditions compared to standing while idling or revving at 2500 RPM and higher still at 80 km/h compared to 40 km/h. Fields in non-hybrid cars were higher at the front seats, while in hybrid cars they were higher at the back seats, particularly the back right seat where 16%-69% of measurements were greater than 0.2 μT. As our results do not include low frequency fields (below 30 Hz) that might be generated by tire rotation, we suggest that net currents flowing through the cars' metallic chassis may be a possible source of MF. Larger surveys in standardized and well-described settings should be conducted with different types of vehicles and with spectral analysis of fields including lower frequencies due to magnetization of tires.

Wavelet decomposition analysis in the two-flash multifocal ERG in early glaucoma: a comparison to ganglion cell analysis and visual field.

PubMed

Brandao, Livia M; Monhart, Matthias; Schötzau, Andreas; Ledolter, Anna A; Palmowski-Wolfe, Anja M

2017-08-01

To further improve analysis of the two-flash multifocal electroretinogram (2F-mfERG) in glaucoma in regard to structure-function analysis, using discrete wavelet transform (DWT) analysis. Sixty subjects [35 controls and 25 primary open-angle glaucoma (POAG)] underwent 2F-mfERG. Responses were analyzed with the DWT. The DWT level that could best separate POAG from controls was compared to the root-mean-square (RMS) calculations previously used in the analysis of the 2F-mfERG. In a subgroup analysis, structure-function correlation was assessed between DWT, optical coherence tomography and automated perimetry (mf103 customized pattern) for the central 15°. Frequency level 4 of the wavelet variance analysis (144 Hz, WVA-144) was most sensitive (p < 0.003). It correlated positively with RMS but had a better AUC. Positive relations were found between visual field, WVA-144 and GCIPL thickness. The highest predictive factor for glaucoma diagnostic was seen in the GCIPL, but this improved further by adding the mean sensitivity and WVA-144. mfERG using WVA analysis improves glaucoma diagnosis, especially when combined with GCIPL and MS.

A model explaining synchronization of neuron bioelectric frequency under weak alternating low frequency magnetic field

NASA Astrophysics Data System (ADS)

del Moral, A.; Azanza, María J.

2015-03-01

A biomagnetic-electrical model is presented that explains rather well the experimentally observed synchronization of the bioelectric potential firing rate ("frequency"), f, of single unit neurons of Helix aspersa mollusc under the application of extremely low frequency (ELF) weak alternating (AC) magnetic fields (MF). The proposed model incorporates to our widely experimentally tested model of superdiamagnetism (SD) and Ca2+ Coulomb explosion (CE) from lipid (LP) bilayer membrane (SD-CE model), the electrical quadrupolar long range interaction between the bilayer LP membranes of synchronized neuron pairs, not considered before. The quadrupolar interaction is capable of explaining well the observed synchronization. Actual extension of our SD-CE-model shows that the neuron firing frequency field, B, dependence becomes not modified, but the bioelectric frequency is decreased and its spontaneous temperature, T, dependence is modified. A comparison of the model with synchronization experimental results of pair of neurons under weak (B0 ≅0.2-15 mT) AC-MF of frequency fM=50 Hz is reported. From the deduced size of synchronized LP clusters under B, is suggested the formation of small neuron networks via the membrane lipid correlation.

Electrocardiogram frequency change by extracorporeal blood perfusion in a swine ventricular fibrillation model

PubMed Central

2013-01-01

Background Extracorporeal cardiopulmonary resuscitation (ECPR) refers to the application of extracorporeal blood circulation with oxygenation as a resuscitation tool. The objective of this study is to observe the frequency component changes in the electrocardiogram (ECG) by ECPR during prolonged ventricular fibrillation (VF). Methods Six swine were prepared as a VF model. Extracorporeal blood circulation with a pulsatile blood pump and oxygenator was set up for the model. ECG signals were measured for 13 min during VF and analyzed using frequency analysis methods. The median frequency (MF), dominant frequency (DF), and amplitude spectrum area (AMSA) were calculated from a spectrogram obtained using short-time Fourier transform (STFT). Results MF decreased from 11 Hz at the start to 9 Hz at 2 min after VF and then increased to 11 Hz at 4.5 min after VF. DF started at 7 Hz and increased to 11 Hz within the first min and decreased to 9 Hz at 2 min, then increased to 12 Hz at 4.5 min after VF. Both frequency components decreased gradually from 4.5 min until 10 min after VF. After the oxygenated blood perfusion was initiated, both MF and DF increased remarkably and exceeded 12 and 14 Hz, respectively. Similarly, AMSA decreased gradually for the first 10 min, but increased remarkably and varied beyond 13 mV∙Hz after the oxygenated blood supply started. Remarkable frequency increases in ECG due to the oxygenated blood perfusion during ECPR were observed in the swine VF model. Conclusions The ECG frequency analysis during ECPR can give the resuscitation provider important information about the cardiac perfusion status and the appropriateness of the ECPR setup as well as the prediction of defibrillation success. PMID:24274395

Frequency dispersion analysis of thin dielectric MOS capacitor in a five-element model

NASA Astrophysics Data System (ADS)

Zhang, Xizhen; Zhang, Sujuan; Zhu, Huichao; Pan, Xiuyu; Cheng, Chuanhui; Yu, Tao; Li, Xiangping; Cheng, Yi; Xing, Guichao; Zhang, Daming; Luo, Xixian; Chen, Baojiu

2018-02-01

An Al/ZrO2/IL/n-Si (IL: interface layer) MOS capacitor has been fabricated by metal organic decomposition of ZrO2 and thermal deposition Al. We have measured parallel capacitance (C m) and parallel resistance (R m) versus bias voltage curves (C m, R m-V) at different AC signal frequency (f), and C m, R m-f curves at different bias voltage. The curves of C m, R m-f measurements show obvious frequency dispersion in the range of 100 kHz-2 MHz. The energy band profile shows that a large voltage is applied on the ZrO2 layer and IL at accumulation, which suggests possible dielectric polarization processes by some traps in ZrO2 and IL. C m, R m-f data are used for frequency dispersion analysis. To exclude external frequency dispersion, we have extracted the parameters of C (real MOS capacitance), R p (parallel resistance), C IL (IL capacitance), R IL (IL resistance) and R s (Si resistance) in a five-element model by using a three-frequency method. We have analyzed intrinsic frequency dispersion of C, R p, C IL, R IL and R s by studying the dielectric characteristics and Si surface layer characteristics. At accumulation, the dispersion of C and R p is attributed to dielectric polarization such as dipolar orientation and oxide traps. The serious dispersion of C IL and R IL are relative to other dielectric polarization, such as border traps and fixed oxide traps. The dispersion of R s is mainly attributed to contact capacitance (C c) and contact resistance (R c). At depletion and inversion, the frequency dispersion of C, R p, C IL, R IL, and R s are mainly attributed to the depletion layer capacitance (C D). The interface trap capacitance (C it) and interface trap resistance (R it) are not dominant for the dispersion of C, R p, C IL, R IL, and R s.

Matrix isolation infrared and Raman spectra of binary and mixed group II B fluorides

NASA Astrophysics Data System (ADS)

Givan, A.; Loewenschuss, A.

1980-03-01

Infrared and Raman spectra of all MF2 and MFX molecules (M=Zn, Cd, Hg; X=Cl, Br) and the infrared spectrum of the fluoroidide HgFI isolated in solid krypton at 20 °K are reported. The MFX species were formed in a vapor mixture of the appropriate MF2 and MX2 dihalides, vaporized, at different temperatures, from separate compartments of a double-oven crucible. The spectra are the first experimental evidence for the existence of the molecular fluorohalides. All three fundamentals of the MF2 molecules and the two stretching mode frequencies of the MFX molecules are assigned. Harmonic force constants are evaluated and isotope effects are used to discuss their geometry. Thermodynamic functions are tabulated for the binary difluorides.

Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma.

PubMed

Tofani, S; Barone, D; Berardelli, M; Berno, E; Cintorino, M; Foglia, L; Ossola, P; Ronchetto, F; Toso, E; Eandi, M

2003-07-01

Previous works showed that exposure to static and extremely low frequency (ELF) magnetic fields (MF) over 3 mT slows down the growth kinetics of human tumors engrafted s.c. in immunodeficient mice, reducing their metastatizing power and prolonging mouse survival. In the experiments reported here, immunocompetent mice bearing murine Lewis Lung carcinomas (LLCs) or B16 melanotic melanomas were exposed to MF and treated respectively with two commonly used anti-cancer drugs: cis-diamminedichloroplatinum (cis-platin) and N,N-bis (2-chloroethyl)tetra-hydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (cyclophosphamide). The experiment endpoint was survival time. The survival time of mice treated with cis-platin (3mg/kg i.p.) and exposed to MF was significantly (P<0.01) longer than that of mice treated only with cis-platin or only exposed to MF, superimposing that of mice treated with 10mg/kg i.p. of the drug, showing that MF act synergically with the pharmacological treatment. On the contrary, when mice treated with cyclophosphamide (50mg/kg i.p.) were exposed to MF no synergic effects were observed, the survival curve being exactly the same as that of mice treated with the drug alone. No clinical signs or toxicity were seen in any of the mice exposed to MF alone or along with cis-platin or cyclophosphamide treatment, compared to mice given only the two known drugs.A possible explanation for the synergic effect of MF being found in mice treated with cis-platin could be that the platinum ion stimulates radical production and that MF enhance active oxygen production bringing about changes in tumor cell membrane permeability, influencing positively the drug uptake. Alternatively, or in addition to this, it has been demonstrated that the rate of conversion of cis-platin to reactive species able to bind to DNA, is increased by localized production of free radicals by MF.

Predicting hearing thresholds and occupational hearing loss with multiple-frequency auditory steady-state responses.

PubMed

Hsu, Ruey-Fen; Ho, Chi-Kung; Lu, Sheng-Nan; Chen, Shun-Sheng

2010-10-01

An objective investigation is needed to verify the existence and severity of hearing impairments resulting from work-related, noise-induced hearing loss in arbitration of medicolegal aspects. We investigated the accuracy of multiple-frequency auditory steady-state responses (Mf-ASSRs) between subjects with sensorineural hearing loss (SNHL) with and without occupational noise exposure. Cross-sectional study. Tertiary referral medical centre. Pure-tone audiometry and Mf-ASSRs were recorded in 88 subjects (34 patients had occupational noise-induced hearing loss [NIHL], 36 patients had SNHL without noise exposure, and 18 volunteers were normal controls). Inter- and intragroup comparisons were made. A predicting equation was derived using multiple linear regression analysis. ASSRs and pure-tone thresholds (PTTs) showed a strong correlation for all subjects (r = .77 ≈ .94). The relationship is demonstrated by the equationThe differences between the ASSR and PTT were significantly higher for the NIHL group than for the subjects with non-noise-induced SNHL (p < .001). Mf-ASSR is a promising tool for objectively evaluating hearing thresholds. Predictive value may be lower in subjects with occupational hearing loss. Regardless of carrier frequencies, the severity of hearing loss affects the steady-state response. Moreover, the ASSR may assist in detecting noise-induced injury of the auditory pathway. A multiple linear regression equation to accurately predict thresholds was shown that takes into consideration all effect factors.

Glucose-independent segmental phase angles from multi-frequency bioimpedance analysis to discriminate diabetes mellitus.

PubMed

Jun, Min-Ho; Kim, Soochan; Ku, Boncho; Cho, JungHee; Kim, Kahye; Yoo, Ho-Ryong; Kim, Jaeuk U

2018-01-12

We investigated segmental phase angles (PAs) in the four limbs using a multi-frequency bioimpedance analysis (MF-BIA) technique for noninvasively diagnosing diabetes mellitus. We conducted a meal tolerance test (MTT) for 45 diabetic and 45 control subjects stratified by age, sex and body mass index (BMI). HbA1c and the waist-to-hip-circumference ratio (WHR) were measured before meal intake, and we measured the glucose levels and MF-BIA PAs 5 times for 2 hours after meal intake. We employed a t-test to examine the statistical significance and the area under the curve (AUC) of the receiver operating characteristics (ROC) to test the classification accuracy using segmental PAs at 5, 50, and 250 kHz. Segmental PAs were independent of the HbA1c or glucose levels, or their changes caused by the MTT. However, the segmental PAs were good indicators for noninvasively screening diabetes In particular, leg PAs in females and arm PAs in males showed best classification accuracy (AUC = 0.827 for males, AUC = 0.845 for females). Lastly, we introduced the PA at maximum reactance (PAmax), which is independent of measurement frequencies and can be obtained from any MF-BIA device using a Cole-Cole model, thus showing potential as a useful biomarker for diabetes.

Computerized analysis of fetal heart rate variability signal during the stages of labor.

PubMed

Annunziata, Maria Laura; Tagliaferri, Salvatore; Esposito, Francesca Giovanna; Giuliano, Natascia; Mereghini, Flavia; Di Lieto, Andrea; Campanile, Marta

2016-03-01

To analyze computerized cardiotocographic (cCTG) parameters (baseline fetal heart rate, baseline FHR; short term variability, STV; approximate entropy, ApEn; low frequency, LF; movement frequency, MF; high frequency, HF) in physiological pregnancy in order to correlate them with the stages of labor. This could provide more information for understanding the mechanisms of nervous system control of FHR during labor progression. A total of 534 pregnant women were monitored on cCTG from the 37th week before the onset of spontaneous labor and during the first and the second stage of labor. Statistical analysis was performed using Kruskal-Wallis test and Wilcoxon rank-sum test with the Bonferroni adjusted α (< 0.05). Statistically significant differences were seen between baseline FHR, MF and HF (P < 0.001), in which the first two were reduced and the third was increased when compared between pre-labor, and the first and second stages of labor. Differences between some of the stages were found for ApEn, LF and for LF/(HF + MF), where the first and the third were reduced and the second was increased. cCTG modifications during labor may reflect the physiologic increased activation of the autonomous nervous system. Using computerized fetal heart rate analysis during labor it may be possible to obtain more information from the fetal cardiac signal, in comparison with the traditional tracing. © 2016 Japan Society of Obstetrics and Gynecology.

The effects of milking frequency on insulin-like growth factor I signaling within the mammary gland of dairy cows.

PubMed

Murney, R; Stelwagen, K; Wheeler, T T; Margerison, J K; Singh, K

2015-08-01

In dairy cows, short-term changes in milking frequency (MF) in early lactation have been shown to produce both an immediate and a long-term effect on milk yield. The effect of MF on milk yield is controlled locally within mammary glands and could be a function of changes in either number or activity of secretory mammary epithelial cells (MEC). Insulin-like growth factor I (IGF-I) signaling is one candidate factor that could mediate these effects, as it can be controlled locally within mammary glands. Both MEC number and activity can be affected by IGF-I signaling by activating the phosphoinositide 3-kinase (PI3K)/Akt and extracellular-signal-regulated kinase (ERK)1/2 pathways. To investigate the relationship between MF and IGF-I signaling, udder halves of 17 dairy cows were milked either 4 times a day (4×) or once a day (1×) for 14 d in early lactation. On d 14, between 3 and 5 h following milking, mammary biopsies were obtained from 10 cows from both udder halves, and changes in the expression of genes associated with IGF-I signaling and the activation of the PI3K/Akt and ERK1/2 pathways were measured. The mRNA abundance of IGF type I receptor, IGF binding protein (IGFBP)-3, and IGFBP-5 were lower following 4× milking relative to 1× milking. However, the mRNA abundance of IGF-I was not affected by MF. Both IGFBP3 and IGFBP5 are thought to inhibit IGF-I; therefore, decreases in their mRNA abundance may serve to stimulate the IGF-I signal in the 4×-milked mammary gland. The activation of PI3K/Akt pathway was lower in response to 4× milking relative to 1×, and the activation of the ERK1/2 was unaffected by MF, suggesting that they do not mediate the effects of MF. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Characterization of Extremely Low Frequency Magnetic Fields from Diesel, Gasoline and Hybrid Cars under Controlled Conditions

PubMed Central

Hareuveny, Ronen; Sudan, Madhuri; Halgamuge, Malka N.; Yaffe, Yoav; Tzabari, Yuval; Namir, Daniel; Kheifets, Leeka

2015-01-01

This study characterizes extremely low frequency (ELF) magnetic field (MF) levels in 10 car models. Extensive measurements were conducted in three diesel, four gasoline, and three hybrid cars, under similar controlled conditions and negligible background fields. Averaged over all four seats under various driving scenarios the fields were lowest in diesel cars (0.02 μT), higher for gasoline (0.04–0.05 μT) and highest in hybrids (0.06–0.09 μT), but all were in-line with daily exposures from other sources. Hybrid cars had the highest mean and 95th percentile MF levels, and an especially large percentage of measurements above 0.2 μT. These parameters were also higher for moving conditions compared to standing while idling or revving at 2500 RPM and higher still at 80 km/h compared to 40 km/h. Fields in non-hybrid cars were higher at the front seats, while in hybrid cars they were higher at the back seats, particularly the back right seat where 16%–69% of measurements were greater than 0.2 μT. As our results do not include low frequency fields (below 30 Hz) that might be generated by tire rotation, we suggest that net currents flowing through the cars’ metallic chassis may be a possible source of MF. Larger surveys in standardized and well-described settings should be conducted with different types of vehicles and with spectral analysis of fields including lower frequencies due to magnetization of tires. PMID:25647323

Behavioral testing of mice exposed to intermediate frequency magnetic fields indicates mild memory impairment.

PubMed

Kumari, Kajal; Koivisto, Hennariikka; Viluksela, Matti; Paldanius, Kaisa M A; Marttinen, Mikael; Hiltunen, Mikko; Naarala, Jonne; Tanila, Heikki; Juutilainen, Jukka

2017-01-01

Human exposure to intermediate frequency magnetic fields (MF) is increasing due to applications like electronic article surveillance systems and induction heating cooking hobs. However, limited data is available on their possible health effects. The present study assessed behavioral and histopathological consequences of exposing mice to 7.5 kHz MF at 12 or 120 μT for 5 weeks. No effects were observed on body weight, spontaneous activity, motor coordination, level of anxiety or aggression. In the Morris swim task, mice in the 120 μT group showed less steep learning curve than the other groups, but did not differ from controls in their search bias in the probe test. The passive avoidance task indicated a clear impairment of memory over 48 h in the 120 μT group. No effects on astroglial activation or neurogenesis were observed in the hippocampus. The mRNA expression of brain-derived neurotrophic factor did not change but expression of the proinflammatory cytokine tumor necrosis factor alpha mRNA was significantly increased in the 120 μT group. These findings suggest that 7.5 kHz MF exposure may lead to mild learning and memory impairment, possibly through an inflammatory reaction in the hippocampus.

Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy.

PubMed

Su, Yu-Lin; Fang, Jen-Hung; Liao, Chia-Ying; Lin, Chein-Ting; Li, Yun-Ting; Hu, Shang-Hsiu

2015-01-01

A magneto-responsive energy/drug carrier that enhances deep tumor penetration with a porous nano-composite is constructed by using a tumor-targeted lactoferrin (Lf) bio-gate as a cap on mesoporous iron oxide nanoparticles (MIONs). With a large payload of a gas-generated molecule, perfluorohexane (PFH), and a hydrophobic anti-cancer drug, paclitaxel (PTX), Lf-MIONs can simultaneously perform bursting gas generation and on-demand drug release upon high-frequency magnetic field (MF) exposure. Biocompatible PFH was chosen and encapsulated in MIONs due to its favorable phase transition temperature (56 °C) and its hydrophobicity. After a short-duration MF treatment induces heat generation, the local pressure increase via the gasifying of the PFH embedded in MION can substantially rupture the three-dimensional tumor spheroids in vitro as well as enhance drug and carrier penetration. As the MF treatment duration increases, Lf-MIONs entering the tumor spheroids provide an intense heat and burst-like drug release, leading to superior drug delivery and deep tumor thermo-chemo-therapy. With their high efficiency for targeting tumors, Lf-MIONs/PTX-PFH suppressed subcutaneous tumors in 16 days after a single MF exposure. This work presents the first study of using MF-induced PFH gasification as a deep tumor-penetrating agent for drug delivery.

Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy

PubMed Central

Su, Yu-Lin; Fang, Jen-Hung; Liao, Chia-Ying; Lin, Chein-Ting; Li, Yun-Ting; Hu, Shang-Hsiu

2015-01-01

A magneto-responsive energy/drug carrier that enhances deep tumor penetration with a porous nano-composite is constructed by using a tumor-targeted lactoferrin (Lf) bio-gate as a cap on mesoporous iron oxide nanoparticles (MIONs). With a large payload of a gas-generated molecule, perfluorohexane (PFH), and a hydrophobic anti-cancer drug, paclitaxel (PTX), Lf-MIONs can simultaneously perform bursting gas generation and on-demand drug release upon high-frequency magnetic field (MF) exposure. Biocompatible PFH was chosen and encapsulated in MIONs due to its favorable phase transition temperature (56 °C) and its hydrophobicity. After a short-duration MF treatment induces heat generation, the local pressure increase via the gasifying of the PFH embedded in MION can substantially rupture the three-dimensional tumor spheroids in vitro as well as enhance drug and carrier penetration. As the MF treatment duration increases, Lf-MIONs entering the tumor spheroids provide an intense heat and burst-like drug release, leading to superior drug delivery and deep tumor thermo-chemo-therapy. With their high efficiency for targeting tumors, Lf-MIONs/PTX-PFH suppressed subcutaneous tumors in 16 days after a single MF exposure. This work presents the first study of using MF-induced PFH gasification as a deep tumor-penetrating agent for drug delivery. PMID:26379789

Enhanced bioremediation of oil contaminated soil by graded modified Fenton oxidation.

PubMed

Xu, Jinlan; Xin, Lei; Huang, Tinglin; Chang, Kun

2011-01-01

Graded modified Fenton's (MF) oxidation is a strategy in which H2O2 is added intermittently to prevent a sharp temperature increase and undesired soil sterilization at soil circumneutral pH versus adding the same amount of H2O2 continuously. The primary objective of the present study was to investigate whether a mild MF pre-oxidation such as a stepwise addition of H2O2 can prevent sterilization and achieve a maximum degradation of tank oil in soil. Optimization experiments of graded MF oxidation were conducted using citric acid, oxalic acid and SOLV-X as iron chelators under different frequencies of H2O2 addition. The results indicated that the activity order of iron chelates decreased as: citric acid (51%) > SOLV-X (44%) > oxalic acid (9%), and citric acid was found to be an optimized iron chelating agent of graded MF oxidation. Three-time addition of H2O2 was found to be favorable and economical due to decreasing total petroleum hydrocarbon removal from three time addition (51%) to five time addition (59%). Biological experiments were conducted after graded MF oxidation of tank oil completed under optimum conditions mentioned above. After graded oxidation, substantially higher increase (31%) in microbial activity was observed with excessive H2O2 (1470 mmol/L, the mol ratio of H2O2:Fe2+ was 210:1) than that of non-oxidized soil. Removal efficiency of tank oil was up to 93% after four weeks. Especially, the oil fraction (C10-C40) became more biodagradable after graded MF oxidation than its absence. Therefore, graded MF oxidation is a mild pretreatment to achieve an effective bioremediation of oil contaminated soil.

A directed matched filtering algorithm (DMF) for discriminating hydrothermal alteration zones using the ASTER remote sensing data

NASA Astrophysics Data System (ADS)

Fereydooni, H.; Mojeddifar, S.

2017-09-01

This study introduced a different procedure to implement matched filtering algorithm (MF) on the ASTER images to obtain the distribution map of alteration minerals in the northwestern part of the Kerman Cenozoic Magmatic Arc (KCMA). This region contains many areas with porphyry copper mineralization such as Meiduk, Abdar, Kader, Godekolvari, Iju, Serenu, Chahfiroozeh and Parkam. Also argillization, sericitization and propylitization are the most common types of hydrothermal alteration in the area. Matched filtering results were provided for alteration minerals with a matched filtering score, called MF image. To identify the pixels which contain only one material (endmember), an appropriate threshold value should be used to the MF image. The chosen threshold classifies a MF image into background and target pixels. This article argues that the current thresholding process (the choice of a threshold) shows misclassification for MF image. To address the issue, this paper introduced the directed matched filtering (DMF) algorithm in which a spectral signature-based filter (SSF) was used instead of the thresholding process. SSF is a user-defined rule package which contains numeral descriptions about the spectral reflectance of alteration minerals. On the other hand, the spectral bands are defined by an upper and lower limit in SSF filter for each alteration minerals. SSF was developed for chlorite, kaolinite, alunite, and muscovite minerals to map alteration zones. The validation proved that, at first: selecting a contiguous range of MF values could not identify desirable results, second: unexpectedly, considerable frequency of pure pixels was observed in the MF scores less than threshold value. Also, the comparison between DMF results and field studies showed an accuracy of 88.51%.

Application of FTIR-ATR spectroscopy coupled with multivariate analysis for rapid estimation of butter adulteration.

PubMed

Fadzlillah, Nurrulhidayah Ahmad; Rohman, Abdul; Ismail, Amin; Mustafa, Shuhaimi; Khatib, Alfi

2013-01-01

In dairy product sector, butter is one of the potential sources of fat soluble vitamins, namely vitamin A, D, E, K; consequently, butter is taken into account as high valuable price from other dairy products. This fact has attracted unscrupulous market players to blind butter with other animal fats to gain economic profit. Animal fats like mutton fat (MF) are potential to be mixed with butter due to the similarity in terms of fatty acid composition. This study focused on the application of FTIR-ATR spectroscopy in conjunction with chemometrics for classification and quantification of MF as adulterant in butter. The FTIR spectral region of 3910-710 cm⁻¹ was used for classification between butter and butter blended with MF at various concentrations with the aid of discriminant analysis (DA). DA is able to classify butter and adulterated butter without any mistakenly grouped. For quantitative analysis, partial least square (PLS) regression was used to develop a calibration model at the frequency regions of 3910-710 cm⁻¹. The equation obtained for the relationship between actual value of MF and FTIR predicted values of MF in PLS calibration model was y = 0.998x + 1.033, with the values of coefficient of determination (R²) and root mean square error of calibration are 0.998 and 0.046% (v/v), respectively. The PLS calibration model was subsequently used for the prediction of independent samples containing butter in the binary mixtures with MF. Using 9 principal components, root mean square error of prediction (RMSEP) is 1.68% (v/v). The results showed that FTIR spectroscopy can be used for the classification and quantification of MF in butter formulation for verification purposes.

Apoptosis in the preimplantation mouse embryo: effect of strain difference and in vitro culture.

PubMed

Kamjoo, Marziel; Brison, Daniel R; Kimber, Susan J

2002-01-01

Cell death by apoptosis occurs predominantly in the inner cell mass (ICM) of the blastocyst, the cell population which carries the germ line and gives rise to the foetus. The frequency of apoptosis in blastocysts varies widely within outbred species such as human and cow. We have addressed the basis of this variation by examining the relative influence of strain difference and in vitro culture conditions on apoptosis, using embryos from two different strains of mice (MF1 and C57BL6/CBA) in two different culture media (M16 and kSOM). In both strains and all crosses apoptosis was first detected by nuclear fragmentation or TUNEL [Terminal deoxynucleotidyl transferase mediated d-UTP nick end-labelling] labelling at the early blastocyst stage. This was true for embryos which had developed in vivo, and in vitro in both M16 and kSOM. The apoptotic index in blastocysts was found to be significantly different between both media and strain (P < 0.0001). Blastocysts from MF1 x MF1 at equivalent stages had an apoptotic index of 32.4% in M16 and 20.3% in kSOM. Blastocysts from C57BL6/CBA x C57BL6/CBA had an apoptotic index of 19.3% in M16 and 14.4% in kSOM. When embryos of similar cell number were compared, a significantly greater apoptotic index was found for cultured MF1 x MF1 embryos with a cell number between 40 and 59 compared to similar directly flushed C57BL6/CBA embryos (P = 0.001), and MF1 embryos (P < 0.0005). MF1 x MF1 embryos and C57BL6/CBA x MF1 embryos of 60-79 cells had a greater apoptotic index in M16 than kSOM (P < 0.0005) but the difference between media was not significant for C57BL6/CBA x C57BL6/CBA. When strain was compared MF1 x MF1 embryos of 60-79 cells had a significantly greater apoptotic index than C57BL6/CBA x MF1 in both media (P < 0.0005 M16; P = 0.002 kSOM) and than C57BL6/CBA x C57BL6/CBA in M16 (P = 0.019). Our data suggest that genetic make-up and the chemical composition of simple medium are equally important in determining the level of apoptosis. Copyright 2002 Wiley-Liss, Inc.

Absence of DNA damage after 60-Hz electromagnetic field exposure combined with ionizing radiation, hydrogen peroxide, or c-Myc overexpression.

PubMed

Jin, Yeung Bae; Choi, Seo-Hyun; Lee, Jae Seon; Kim, Jae-Kyung; Lee, Ju-Woon; Hong, Seung-Cheol; Myung, Sung Ho; Lee, Yun-Sil

2014-03-01

The principal objective of this study was to assess the DNA damage in a normal cell line system after exposure to 60 Hz of extremely low frequency magnetic field (ELF-MF) and particularly in combination with various external factors, via comet assays. NIH3T3 mouse fibroblast cells, WI-38 human lung fibroblast cells, L132 human lung epithelial cells, and MCF10A human mammary gland epithelial cells were exposed for 4 or 16 h to a 60-Hz, 1 mT uniform magnetic field in the presence or absence of ionizing radiation (IR, 1 Gy), H(2)O(2) (50 μM), or c-Myc oncogenic activation. The results obtained showed no significant differences between the cells exposed to ELF-MF alone and the unexposed cells. Moreover, no synergistic or additive effects were observed after 4 or 16 h of pre-exposure to 1 mT ELF-MF or simultaneous exposure to ELF-MF combined with IR, H(2)O(2), or c-Myc activation.

Modifications in cell cycle kinetics and in expression of G1 phase-regulating proteins in human amniotic cells after exposure to electromagnetic fields and ionizing radiation.

PubMed

Lange, S; Viergutz, T; Simkó, M

2004-10-01

Low-frequency electromagnetic fields are suspected of being involved in carcinogenesis, particularly in processes that could be related to cancer promotion. Because development of cancer is associated with deregulated cell growth and we previously observed a magnetic field-induced decrease in DNA synthesis [Lange et al. (2002) Alterations in the cell cycle and in the protein level of cyclin D1p, 21CIP1, and p16INK4a after exposure to 50 HZ. MF in human cells. Radiat. Environ. Biophys.41, 131], this study aims to document the influence of 50 Hz, 1 mT magnetic fields (MF), with or without initial gamma-ionizing radiation (IR), on the following cell proliferation-relevant parameters in human amniotic fluid cells (AFC): cell cycle distribution, expression of the G1 phase-regulating proteins Cdk4, cyclin D1, p21CIP1 and p16INK4a, and Cdk4 activity. While IR induced a G1 delay and a dose-dependent G2 arrest, no discernible changes in cell cycle kinetics were observed due to MF exposure. However, a significant decrease in the protein expression of cyclin D1 and an increase in p21CIP1- and p16INK4a-expression could be detected after exposure to MF alone. IR-exposure caused an augmentation of p21CIP1- and p16INK4a- levels as well, but did not alter cyclin D1 expression. A slight diminution of Cdk4 activity was noticed after MF exposure only, indicating that Cdk4 appears not to act as a mediator of MF- or IR-induced changes in the cell cycle of AFC cells. Co-exposure to MF/IR affected neither cell cycle distribution nor protein expression or kinase activity additionally or synergistically, and therefore MF seems not to modify the mutagenic potency of IR.

Three-Dimensional Terahertz Coded-Aperture Imaging Based on Matched Filtering and Convolutional Neural Network.

PubMed

Chen, Shuo; Luo, Chenggao; Wang, Hongqiang; Deng, Bin; Cheng, Yongqiang; Zhuang, Zhaowen

2018-04-26

As a promising radar imaging technique, terahertz coded-aperture imaging (TCAI) can achieve high-resolution, forward-looking, and staring imaging by producing spatiotemporal independent signals with coded apertures. However, there are still two problems in three-dimensional (3D) TCAI. Firstly, the large-scale reference-signal matrix based on meshing the 3D imaging area creates a heavy computational burden, thus leading to unsatisfactory efficiency. Secondly, it is difficult to resolve the target under low signal-to-noise ratio (SNR). In this paper, we propose a 3D imaging method based on matched filtering (MF) and convolutional neural network (CNN), which can reduce the computational burden and achieve high-resolution imaging for low SNR targets. In terms of the frequency-hopping (FH) signal, the original echo is processed with MF. By extracting the processed echo in different spike pulses separately, targets in different imaging planes are reconstructed simultaneously to decompose the global computational complexity, and then are synthesized together to reconstruct the 3D target. Based on the conventional TCAI model, we deduce and build a new TCAI model based on MF. Furthermore, the convolutional neural network (CNN) is designed to teach the MF-TCAI how to reconstruct the low SNR target better. The experimental results demonstrate that the MF-TCAI achieves impressive performance on imaging ability and efficiency under low SNR. Moreover, the MF-TCAI has learned to better resolve the low-SNR 3D target with the help of CNN. In summary, the proposed 3D TCAI can achieve: (1) low-SNR high-resolution imaging by using MF; (2) efficient 3D imaging by downsizing the large-scale reference-signal matrix; and (3) intelligent imaging with CNN. Therefore, the TCAI based on MF and CNN has great potential in applications such as security screening, nondestructive detection, medical diagnosis, etc.

Is Matang Mangrove Forest in Malaysia Sustainably Rejuvenating after More than a Century of Conservation and Harvesting Management?

PubMed Central

Van der Stocken, Tom; Quispe Zuniga, Melissa; Mohd-Lokman, Husain; Sulong, Ibrahim

2014-01-01

Matang Mangrove Forest Reserve (MMFR) in Peninsular Malaysia is under systematic management since 1902 and still considered as the best managed mangrove forest in the world. The present study on silvimetrics assessed the ongoing MMFR forest management, which includes a first thinning after 15 years, a second thinning after 20 years and clear-felling of 30-year old forest blocks, for its efficiency and productivity in comparison to natural mangroves. The estimated tree structural parameters (e.g. density, frequency) from three different-aged mangrove blocks of fifteen (MF15), twenty (MF20), and thirty (MF30) years old indicated that Bruguiera and Excoecaria spp. did not constitute a significant proportion of the vegetation (<5%), and hence the results focused majorly on Rhizophora apiculata. The density of R. apiculata at MF15, MF20 and MF30 was 4,331, 2,753 and 1,767 stems ha−1, respectively. In relation to ongoing practices of the artificial thinnings at MMFR, the present study suggests that the first thinning could be made earlier to limit the loss of exploitable wood due to natural thinning. In fact, the initial density at MF15 was expected to drop down from 6,726 to 1,858 trees ha−1 before the first thinning. Therefore the trees likely to qualify for natural thinning, though having a smaller stem diameter, should be exploited for domestic/commercial purposes at an earlier stage. The clear-felling block (MF30) with a maximum stem diameter of 30 cm was estimated to yield 372 t ha−1 of the above-ground biomass and suggests that the mangrove management based on a 30-year rotation is appropriate for the MMFR. Since Matang is the only iconic site that practicing sustainable wood production, it could be an exemplary to other mangrove locations for their improved management. PMID:25144689

Exploiting LF/MF signals of opportunity for lower ionospheric remote sensing

NASA Astrophysics Data System (ADS)

Higginson-Rollins, Marc A.; Cohen, Morris B.

2017-08-01

We introduce a method to diagnose and track the D region ionosphere (60-100 km). This region is important for long-distance terrestrial communication and is impacted by a variety of geophysical phenomena, but it is traditionally very difficult to detect. Modern remote sensing methods used to study the D region are predominately near the very low frequency (VLF, 3-30 kHz) band, with some work also done in the high-frequency and very high frequency bands (HF/VHF, 3-300 MHz). However, the frequency band between VLF and HF has been largely ignored as a diagnostic tool for the ionosphere. In this paper, we evaluate the use of 300 kHz radio reflections as a diagnostic tool for characterizing the D region of the ionosphere. We present radio receiver data, analyze diurnal trends in the signal from these transmitters, and identify ionospheric disturbances impacting LF/MF propagation. We find that 300 kHz remote sensing may allow a unique method for D region diagnostics compared to both the VLF and HF/VHF frequency bands, due to a more direct ionospheric reflection coefficient calculation method with high temporal resolution without the use of forward modeling.

Risk factors for chronic subdural haematoma formation do not account for the established male bias.

PubMed

Marshman, Laurence A G; Manickam, Appukutty; Carter, Danielle

2015-04-01

The 'subdural space' is an artefact of inner dural border layer disruption: it is not anatomical but always pathological. A male bias has long been accepted for chronic subdural haematomas (CSDH), and increased male frequencies of trauma and/or alcohol abuse are often cited as likely explanations: however, no study has validated this. We investigated to see which risk factors accounted for the male bias with CSDH. Retrospective review of prospectively collected data. A male bias (M:F 97:58) for CSDH was confirmed in n=155 patients. The largest risk factor for CSDH was cerebral atrophy (M:F 94% vs. 91%): whilst a male bias prevailed in mild-moderate cases (M:F 58% vs. 41%), a female bias prevailed for severe atrophy (F:M 50% vs. 36%) (χ(2)=3.88, P=0.14). Risk factors for atrophy also demonstrated a female bias, some approached statistical significance: atrial fibrillation (P=0.05), stroke/TIA (P=0.06) and diabetes mellitus (P=0.07). There was also a trend for older age in females (F:M 72±13 years vs. 68±15 years, P=0.09). The third largest risk factor, after atrophy and trauma (i.e. anti-coagulant and anti-platelet use) was statistically significantly biased towards females (F:M 50% vs. 33%, P=0.04). No risk factor accounted for the established male bias with CSDH. In particular, a history of trauma (head injury or fall [M:F 50% vs. 57%, P=0.37]), and alcohol abuse (M:F 17% vs. 16%, P=0.89) was remarkably similar between genders. No recognised risk factor for CSDH formation accounted for the established male bias: risk factor trends generally favoured females. In particular, and in contrast to popular belief, a male CSDH bias did not relate to increased male frequencies of trauma and/or alcohol abuse. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

[Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6) contents in rat heart and brain].

PubMed

Ciejka, Elżbieta; Skibska, Beata; Gorąca, Anna

2017-06-27

The human population is exposed ever more frequently to magnetic fields (MF). This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF) used in magnetotherapy on the concentration of interleukin 6 (IL-6) in rat heart and brain. The male rats were randomly divided into 3 experimental groups: group I - control, without contact with magnetic field; group II - exposed to bipolar, rectangular magnetic field 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks; and group III - exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Exposure to ELFMF: 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05) and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05). The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4):517-523. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Pubertal Escape From Estradiol Negative Feedback in Ewe Lambs Is Not Accounted for by Decreased ESR1 mRNA or Protein in Kisspeptin Neurons.

PubMed

Bedenbaugh, Michelle N; D'Oliveira, Marcella; Cardoso, Rodolfo C; Hileman, Stanley M; Williams, Gary L; Amstalden, Marcel

2018-01-01

In this study, we investigated whether decreased sensitivity to estradiol negative feedback is associated with reduced estrogen receptor α (ESR1) expression in kisspeptin neurons as ewe lambs approach puberty. Lambs were ovariectomized and received no implant (OVX) or an implant containing estradiol (OVX+E). In the middle arcuate nucleus (mARC), ESR1 messenger RNA (mRNA) was greater in OVX than OVX+E lambs but did not differ elsewhere. Post hoc analysis of luteinizing hormone (LH) secretion from OVX+E lambs revealed three patterns of LH pulsatility: low [1 to 2 pulses per 12 hours; low frequency (LF), n = 3], moderate [6 to 7 pulses per 12 hours; moderate frequency (MF), n = 6], and high [>10 pulses per 12 hours; high frequency (HF), n = 5]. The percentage of kisspeptin neurons containing ESR1 mRNA in the preoptic area did not differ among HF, MF, or LF groups. However, the percentage of kisspeptin neurons containing ESR1 mRNA in the mARC was greater in HF (57%) than in MF (36%) or LF (27%) lambs and did not differ from OVX (50%) lambs. A higher percentage of kisspeptin neurons contained ESR1 protein in all regions of the arcuate nucleus (ARC) in OVX compared with OVX+E lambs. There were no differences in ESR1 protein among the HF, MF, or LF groups in the preoptic area or ARC. Contrary to our hypothesis, increases in LH pulsatility were associated with enhanced ESR1 mRNA abundance in kisspeptin neurons in the ARC, and absence of estradiol increased the percentage of kisspeptin neurons containing ESR1 protein in the ARC. Therefore, changes in the expression of ESR1, particularly in kisspeptin neurons in the ARC, do not explain the pubertal escape from estradiol negative feedback in ewe lambs. Copyright © 2018 Endocrine Society.

K-Ras mutant fraction in A/J mouse lung increases as a function of benzo[a]pyrene dose

EPA Science Inventory

K-Ras mutant fraction (MF) was measured to examine the default assumption of low dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of ten male A/J mice (7-9 weeks-old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P, and were sacrifi...

Mycosis fungoides: epidemiologic observations

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

Greene, M.H.; Dalager, N.A.; Lamberg, S.I.

1979-04-01

An analysis of cases from a multi-hospital, pathologically verified clinical series and of deaths from US mortality statistics available at the county level for 1950 to 1975 (excluding 1972) was made in order to obtain information on the etiology of mycosis fungoides (MF). Despite the absence of an appropriate comparison group, the cases seemed to have a high frequency of antecedent allergies, fungal and viral skin infections, sun sensitivity, familial aggregation of lymphoma and leukemia, and employment in a manufacturing occupation (especially petrochemical, textile, metal, and machinery industries). The mortality survey revealed a predominance among males, nonwhites, and residents ofmore » the northeastern US, the latter due partly to an association between MF mortality and population size. The influence of occupational exposures was suggested by the excessive MF mortality rates in counties where petroleum, rubber, primary and fabricated metal, machinery, and printing industries were located.« less

National culture moderates the influence of mental effort on subjective and cardiovascular measures.

PubMed

Widyanti, Ari; de Waard, Dick; Johnson, Addie; Mulder, Ben

2013-01-01

Subjective measures of mental effort have been shown to be relatively insensitive in Indonesian participants. An open question is whether this insensitivity reflects how mental effort is experienced or how it is reported. We compared the performance, subjective workload ratings, heart rate and heart-rate variability (HRV) of 31 Dutch and 30 Indonesian participants under single- and dual-task conditions. Indonesians performed faster but less accurately and used a narrower range of subjective workload ratings than did the Dutch. Dutch participants showed a decrease in HRV both in the mid-frequency (MF) and high-frequency bands and an increase in heart rate during task performance compared with the resting period. Indonesians showed this pattern in the MF band only. The decrease of HRV in the MF band in both groups suggests that the relative insensitivity of subjective mental effort scales among Indonesians has to do with how workload is reported rather than with how it is experienced. The sensitivity of the subjective measures of mental workload has been shown to depend on culture. Here, we show that heart-rate variability reacts similarly to workload in Eastern as in Western participants. This suggests that culture influences more how invested mental effort is reported than how it is experienced psychophysiologically.

Effects of intermediate frequency magnetic fields on male fertility indicators in mice.

PubMed

Kumari, K; Capstick, M; Cassara, A M; Herrala, M; Koivisto, H; Naarala, J; Tanila, H; Viluksela, M; Juutilainen, J

2017-08-01

Human exposure to intermediate frequency (IF) fields is increasing due to new applications such as electronic article surveillance systems, wireless power transfer and induction heating cookers. However, limited data is available on effects of IF magnetic fields (MF) on male fertility function. This study was conducted to assess possible effects on fertility indicators from exposure to IF MF. Male C57BL/6J mice were exposed continuously for 5 weeks to 7.5kHz MF at 12 and 120μT. Sperm cells from cauda epididymis were analysed for motility, total sperm counts, and head abnormalities. Motile sperm cells were classified as progressive or non-progressive. Testicular spermatid heads were counted as well. The body weight development and reproductive tissue weights were not affected. No exposure-related differences were observed in sperm counts or sperm head abnormalities. Proportion of non-motile cells was significantly decreased in the 120µT group, and a corresponding increase was seen in the percentage of motile cells (significant in non-progressive motile cells). In conclusion, no adverse effects on fertility indicators were observed. Increased sperm motility is an interesting finding that needs to be confirmed in further studies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Frequency measurement of the 2S(1/2)-2D(3/2) electric quadrupole transition in a single 171Yb+ ion.

PubMed

Webster, Stephen; Godun, Rachel; King, Steven; Huang, Guilong; Walton, Barney; Tsatourian, Veronika; Margolis, Helen; Lea, Stephen; Gill, Patrick

2010-03-01

We report on precision laser spectroscopy of the 2S(1/2)(F = 0)-2D(3/2) (F = 2, m(F) = 0) clock transition in a single ion of 171Yb+. The absolute value of the transition frequency, determined using an optical frequency comb referenced to a hydrogen maser, is 688358979309310 +/- 9 Hz. This corresponds to a fractional frequency uncertainty of 1.3 x 10(-14).

Adjusting for background mutation frequency biases improves the identification of cancer driver genes.

PubMed

Evans, Perry; Avey, Stefan; Kong, Yong; Krauthammer, Michael

2013-09-01

A common goal of tumor sequencing projects is finding genes whose mutations are selected for during tumor development. This is accomplished by choosing genes that have more non-synonymous mutations than expected from an estimated background mutation frequency. While this background frequency is unknown, it can be estimated using both the observed synonymous mutation frequency and the non-synonymous to synonymous mutation ratio. The synonymous mutation frequency can be determined across all genes or in a gene-specific manner. This choice introduces an interesting trade-off. A gene-specific frequency adjusts for an underlying mutation bias, but is difficult to estimate given missing synonymous mutation counts. Using a genome-wide synonymous frequency is more robust, but is less suited for adjusting biases. Studying four evaluation criteria for identifying genes with high non-synonymous mutation burden (reflecting preferential selection of expressed genes, genes with mutations in conserved bases, genes with many protein interactions, and genes that show loss of heterozygosity), we find that the gene-specific synonymous frequency is superior in the gene expression and protein interaction tests. In conclusion, the use of the gene-specific synonymous mutation frequency is well suited for assessing a gene's non-synonymous mutation burden.

Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood

PubMed Central

Nakaya, Helder I.; Clutterbuck, Elizabeth; Kazmin, Dmitri; Wang, Lili; Cortese, Mario; Bosinger, Steven E.; Patel, Nirav B.; Zak, Daniel E.; Aderem, Alan; Dong, Tao; Del Giudice, Giuseppe; Rappuoli, Rino; Cerundolo, Vincenzo; Pollard, Andrew J.; Pulendran, Bali; Siegrist, Claire-Anne

2016-01-01

The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4+ T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses. PMID:26755593

DNA polymerases κ and ζ cooperatively perform mutagenic translesion synthesis of the C8–2′-deoxyguanosine adduct of the dietary mutagen IQ in human cells

PubMed Central

Bose, Arindam; Pande, Paritosh; Jasti, Vijay P.; Millsap, Amy D.; Hawkins, Edward K.; Rizzo, Carmelo J.; Basu, Ashis K.

2015-01-01

The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8–2′-deoxyguanosine adduct (dG-C8-IQ) formed by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a highly mutagenic and carcinogenic heterocyclic amine found in cooked meats, were investigated. Three plasmid vectors containing the dG-C8-IQ adduct at the G1-, G2- or G3-positions of the NarI site (5′-G1G2CG3CC-3′) were replicated in HEK293T cells. Fifty percent of the progeny from the G3 construct were mutants, largely G→T, compared to 18% and 24% from the G1 and G2 constructs, respectively. Mutation frequency (MF) of dG-C8-IQ was reduced by 38–67% upon siRNA knockdown of pol κ, whereas it was increased by 10–24% in pol η knockdown cells. When pol κ and pol ζ were simultaneously knocked down, MF of the G1 and G3 constructs was reduced from 18% and 50%, respectively, to <3%, whereas it was reduced from 24% to <1% in the G2 construct. In vitro TLS using yeast pol ζ showed that it can extend G3*:A pair more efficiently than G3*:C pair, but it is inefficient at nucleotide incorporation opposite dG-C8-IQ. We conclude that pol κ and pol ζ cooperatively carry out the majority of the error-prone TLS of dG-C8-IQ, whereas pol η is involved primarily in its error-free bypass. PMID:26220181

Cooperative Regulation of the Interferon Regulatory Factor-1 Tumor Suppressor Protein by Core Components of the Molecular Chaperone Machinery*

PubMed Central

Narayan, Vikram; Eckert, Mirjam; Zylicz, Alicja; Zylicz, Maciej; Ball, Kathryn L.

2009-01-01

Our understanding of the post-translational processes involved in regulating the interferon regulatory factor-1 (IRF-1) tumor suppressor protein is limited. The introduction of mutations within the C-terminal Mf1 domain (amino acids 301–325) impacts on IRF-1-mediated gene repression and growth suppression as well as the rate of IRF-1 degradation. However, nothing is known about the proteins that interact with this region to modulate IRF-1 function. A biochemical screen for Mf1-interacting proteins has identified an LXXLL motif that is required for binding of Hsp70 family members and cooperation with Hsp90 to regulate IRF-1 turnover and activity. These conclusions are supported by the finding that Hsp90 inhibitors suppress IRF-1-dependent transcription shortly after treatment, although at later time points inhibition of Hsp90 leads to an Hsp70-dependent depletion of nuclear IRF-1. Conversely, the half-life of IRF-1 is increased by Hsp90 in an ATPase-dependent manner leading to the accumulation of nuclear but not cytoplasmic IRF-1. This study begins to elucidate the role of the Mf1 domain of IRF-1 in orchestrating the recruitment of regulatory factors that can impact on both its turnover and transcriptional activity. PMID:19502235

Genetic Control and Evolution of Anthocyanin Methylation1[W

PubMed Central

Provenzano, Sofia; Spelt, Cornelis; Hosokawa, Satoko; Nakamura, Noriko; Brugliera, Filippa; Demelis, Linda; Geerke, Daan P.; Schubert, Andrea; Tanaka, Yoshikazu; Quattrocchio, Francesca; Koes, Ronald

2014-01-01

Anthocyanins are a chemically diverse class of secondary metabolites that color most flowers and fruits. They consist of three aromatic rings that can be substituted with hydroxyl, sugar, acyl, and methyl groups in a variety of patterns depending on the plant species. To understand how such chemical diversity evolved, we isolated and characterized METHYLATION AT THREE2 (MT2) and the two METHYLATION AT FIVE (MF) loci from Petunia spp., which direct anthocyanin methylation in petals. The proteins encoded by MT2 and the duplicated MF1 and MF2 genes and a putative grape (Vitis vinifera) homolog Anthocyanin O-Methyltransferase1 (VvAOMT1) are highly similar to and apparently evolved from caffeoyl-Coenzyme A O-methyltransferases by relatively small alterations in the active site. Transgenic experiments showed that the Petunia spp. and grape enzymes have remarkably different substrate specificities, which explains part of the structural anthocyanin diversity in both species. Most strikingly, VvAOMT1 expression resulted in the accumulation of novel anthocyanins that are normally not found in Petunia spp., revealing how alterations in the last reaction can reshuffle the pathway and affect (normally) preceding decoration steps in an unanticipated way. Our data show how variations in gene expression patterns, loss-of-function mutations, and alterations in substrate specificities all contributed to the anthocyanins’ structural diversity. PMID:24830298

Effects of short term and long term Extremely Low Frequency Magnetic Field on depressive disorder in mice: Involvement of nitric oxide pathway.

PubMed

Madjid Ansari, Alireza; Farzampour, Shahrokh; Sadr, Ali; Shekarchi, Babak; Majidzadeh-A, Keivan

2016-02-01

Previous reports on the possible effects of Extremely Low Frequency Magnetic Fields (ELF MF) on mood have been paradoxical in different settings while no study has yet been conducted on animal behavior. In addition, it was shown that ELF MF exposure makes an increase in brain nitric oxide level. Therefore, in the current study, we aimed to assess the possible effect(s) of ELF MF exposure on mice Forced Swimming Test (FST) and evaluate the probable role of the increased level of nitric oxide in the observed behavior. Male adult mice NMRI were recruited to investigate the short term and long term ELF MF exposure (0.5 mT and 50 Hz, single 2h and 2 weeks 2h a day). Locomotor behavior was assessed by using open-field test (OFT) followed by FST to evaluate the immobility time. Accordingly, NΩ-nitro-l-arginine methyl ester 30 mg/kg was used to exert anti-depressant like effect. According to the results, short term exposure did not alter the immobility time, whereas long term exposure significantly reduces immobility time (p<0.01). However, it was revealed that the locomotion did not differ among all experimental groups. Short term exposure reversed the anti-depressant like effect resulting from 30 mg/kg of NΩ-nitro-l-arginine methyl ester (p<0.01). It has been concluded that long term exposure could alter the depressive disorder in mice, whereas short term exposure has no significant effect. Also, reversing the anti-depressant activity of L-NAME indicates a probable increase in the brain nitric oxide. Copyright © 2016 Elsevier Inc. All rights reserved.

Residential Exposure to 50 Hz Magnetic Fields and the Association with Miscarriage Risk: A 2-Year Prospective Cohort Study

PubMed Central

Wang, Qiang; Cao, Zhaojin; Qu, Yingli; Peng, Xiaowu; Guo, Shu; Chen, Li

2013-01-01

Objective The hypothesis of whether exposure to extremely low-frequency magnetic fields (ELF-MF) may increase miscarriage risk is controversial. A 2-year prospective cohort study was designed to study the association between exposure to 50 Hz magnetic fields (MF) and the miscarriage risk for women residing in the area of the Pearl-River Delta of China. Method Two towns with densely distributed power supply constructions were selected as the study sites. From 2010 to 2012, 552 women in the region who were at approximately 8 weeks of gestation or who planned to have a baby within 1 year were selected as candidate subjects. Exposure to MF was estimated by measurements at their front doors and in the alley in front of the subjects’ houses. The average exposure level was used as a cutoff point to define the exposed group. Clinical miscarriage was diagnosed by local obstetricians. Staffs from the local population and family planning service stations were responsible for the follow-up interviews every 2 months. Results Four hundred and thirteen pregnant women were selected for the cohort study. The average residential exposure to MF was 0.099 µT. No significantly increased risk of miscarriage was found to be associated with the average front-door exposure (p>0.05). However, miscarriage risk was found to be significantly associated with maximum alley exposure (p=0.001). The relative risk (RR) of miscarriage from maximum alley exposure was 2.35 (95% C.I.: 1.18-4.71). In addition, Cox regression analysis showed that the adjusted hazard ratio of maximum alley exposure for miscarriage was 1.72 (95% C.I.:1.10-2.69). Conclusion Although the miscarriage incidence was shown to be positively associated with the maximum alley MF exposure, the association between miscarriage risk and the exposure to MF was not confirmed in the study. The results of this study are of interest concerning MF exposure assessment and pregnancy outcomes. PMID:24312633

Long-term 12 year follow-up of X-linked congenital retinoschisis

PubMed Central

Kjellström, Sten; Vijayasarathy, Camasamudram; Ponjavic, Vesna; Sieving, Paul A.; Andréasson, Sten

2010-01-01

Purpose To investigate the retinal structure and function during the progression of X-linked retinoschisis (XLRS) from childhood to adulthood. Methods Ten patients clinically diagnosed with XLRS were investigated at 6–15 years of age (mean age 9 years) with a follow-up 8 to 14 years later (mean 12 years). The patients underwent regular ophthalmic examination as well as testing of best corrected visual acuity (BCVA), visual field (VF) and assessment of full-field electroretinography (ERG) during their first visit. During the follow-up, the same clinical protocols were repeated. In addition, macular structure and function was examined with multifocal electroretinography (mfERG) and optical coherence tomography (OCT). The patients were 18–25 years of age (mean age 21 years) at the follow-up examination. All exons and exon-intron boundaries of RS1-gene were sequenced for gene mutations in 9 out of the 10 patients. Results Best corrected VA and VF were stable during this follow-up period. No significant progression in cone or rod function could be measured by full-field ERG. Multifocal electroretinography and OCT demonstrated a wide heterogeneity of macular changes in retinal structure and function at the time of follow-up visit. Three different mutations were detected in these nine patients, including a known nonsense mutation in exon 3, a novel insertion in exon 5 and an intronic mutation at 5' splice site of intron 3. Conclusions Clinical follow-up (mean 12 years) of ten young XLRS patients (mean age of 9 years) with a typical congenital retinoschisis phenotype revealed no significant decline in retinal function during this time period. MfERG and OCT demonstrated a wide variety of macular changes including structure and dysfunction. The XLRS disease was relatively stable during this period of observation and would afford opportunity for therapy studies to judge benefit against baseline and against the fellow eye. PMID:20569020

What monitor can replace the cathode-ray tube for visual stimulation to elicit multifocal electroretinograms?

PubMed

Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Seki, Keisuke; Nagasaka, Eiichiro; Iwata, Takeshi; Mizota, Atsushi

2014-08-05

To compare a conventional cathode-ray tube (CRT) screen to organic light-emitting diode (OLED) and liquid crystal display (LCD) screens as visual stimulators to elicit multifocal electroretinograms (mfERGs), mfERGs were recorded from seven eyes of seven healthy volunteers (21 ± 2 years). The mfERGs elicited by a conventional CRT screen (S710, Compaq Computer Co.) were compared to those elicited by a studio-grade master OLED monitor (PVM-1741, Sony, Japan) and a conventional LCD (S1721, Flexscan, Eizo Nanao Corp., Japan). The luminance changes of each monitor were measured with a photodiode. CRT, OLED, and LCD screens with a frame frequency of 60 Hz were studied. A hexagonal stimulus array with 61 stimulus elements was created on each monitor. The serial white stimuli of the OLED screen at 60 Hz did not fuse, and that of the LCD screens fused. The amplitudes of P1 and P2 of the first-order kernels of the mfERGs were not significantly different from those elicited by the CRT and OLED screens, and the P1 amplitude of the first-order kernel elicited by the LCD stimuli was significantly smaller than that elicited by the CRT in all the groups of the averaged hexagonal elements. The implicit times were approximately 10 ms longer in almost all components elicited by the LCD screen compared to those elicited by the CRT screen. The mfERGs elicited by monitors other than the CRT should be carefully interpreted, especially those elicited by LCD screens. The OLED had good performance, and we conclude that it can replace the CRT as a stimulator for mfERGs; however, a collection of normative data is recommended. © 2014 ARVO.

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

PubMed

de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

2018-05-09

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses.

PubMed

Kakegawa, Wataru; Tsuzuki, Keisuke; Yoshida, Yukari; Kameyama, Kimihiko; Ozawa, Seiji

2004-07-01

Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. This implies that molecular and functional properties differ between MF and AF synapses at both presynaptic and postsynaptic sites. In this study, we focused on the difference in the postsynaptic trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) between these synapses. To trace the subunit-specific trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were inserted into both MF and AF postsynaptic sites in a neuronal activity-independent manner. Endogenous Ca(2+)-impermeable AMPARs at these synapses were replaced with exogenous Ca(2+)-permeable receptors, and Ca(2+) influx via the newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses. In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca(2+)/calmodulin-dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.

Roles of charged residues in pH-dependent redox properties of cytochrome c3 from Desulfovibrio vulgaris Miyazaki F

PubMed Central

Yahata, Naoki; Ozawa, Kiyoshi; Tomimoto, Yusuke; Morita, Kumiko; Komori, Hirofumi; Ogata, Hideaki; Higuchi, Yoshiki; Akutsu, Hideo

2006-01-01

Complicated pH-properties of the tetraheme cytochrome c3 (cyt c3) from Desulfovibrio vulgaris Miyazaki F (DvMF) were examined by the pH titrations of 1H-15N HSQC spectra in the ferric and ferrous states. The redox-linked pKa shift for the propionate group at C13 of heme 1 was observed as the changes of the NH signals around it. This pKa shift is consistent with the redox-linked conformational alteration responsible for the cooperative reduction between hemes 1 and 2. On the other hand, large chemical shift changes caused by the protonation/deprotonation of Glu41 and/or Asp42, and His67 were redox-independent. Nevertheless, these charged residues affect the redox properties of the four hemes. Furthermore, one of interesting charged residues, Glu41, was studied by site-directed mutagenesis. E41K mutation increased the microscopic redox potentials of heme 1 by 46 and 34 mV, and heme 2 by 35 and 30 mV at the first and last reduction steps, respectively. Although global folding in the crystal structure of E41K cyt c3 is similar to that of wild type, local change was observed in 1H NMR spectrum. Glu41 is important to keep the stable conformation in the region between hemes 1 and 2, controlling the redox properties of DvMF cyt c3. In contrast, the kinetic parameters for electron transfer from DvMF [NiFe] hydrogenase were not influenced by E41K mutation. This suggests that the region between hemes 1 and 2 is not involved in the interaction with [NiFe] hydrogenase, and it supports the idea that heme 4 is the exclusive entrance gate to accept the electron in the initial reduction stage. PMID:27857559

Roles of charged residues in pH-dependent redox properties of cytochrome c3 from Desulfovibrio vulgaris Miyazaki F.

PubMed

Yahata, Naoki; Ozawa, Kiyoshi; Tomimoto, Yusuke; Morita, Kumiko; Komori, Hirofumi; Ogata, Hideaki; Higuchi, Yoshiki; Akutsu, Hideo

2006-01-01

Complicated pH-properties of the tetraheme cytochrome c 3 (cyt c 3 ) from Desulfovibrio vulgaris Miyazaki F ( Dv MF) were examined by the pH titrations of 1 H- 15 N HSQC spectra in the ferric and ferrous states. The redox-linked p K a shift for the propionate group at C13 of heme 1 was observed as the changes of the NH signals around it. This p K a shift is consistent with the redox-linked conformational alteration responsible for the cooperative reduction between hemes 1 and 2. On the other hand, large chemical shift changes caused by the protonation/deprotonation of Glu41 and/or Asp42, and His67 were redox-independent. Nevertheless, these charged residues affect the redox properties of the four hemes. Furthermore, one of interesting charged residues, Glu41, was studied by site-directed mutagenesis. E41K mutation increased the microscopic redox potentials of heme 1 by 46 and 34 mV, and heme 2 by 35 and 30 mV at the first and last reduction steps, respectively. Although global folding in the crystal structure of E41K cyt c 3 is similar to that of wild type, local change was observed in 1 H NMR spectrum. Glu41 is important to keep the stable conformation in the region between hemes 1 and 2, controlling the redox properties of Dv MF cyt c 3 . In contrast, the kinetic parameters for electron transfer from Dv MF [NiFe] hydrogenase were not influenced by E41K mutation. This suggests that the region between hemes 1 and 2 is not involved in the interaction with [NiFe] hydrogenase, and it supports the idea that heme 4 is the exclusive entrance gate to accept the electron in the initial reduction stage.

Contact allergy to corticosteroids and Malassezia furfur in seborrhoeic dermatitis patients.

PubMed

Ljubojevic, S; Lipozencic, J; Basta-Juzbasic, A

2011-06-01

Seborrhoeic dermatitis (SD) is a chronic skin disease, requiring long-term treatment, which might promote sensitization. Malassezia furfur (Mf) plays an important role in seborrhoeic dermatitis. Objectives  The aim of this study was to determine the frequency of contact sensitivity in SD patients. A total of 100 patients and 20 healthy controls (HC) were investigated: 50 suffering from SD with no previous local corticosteroid treatment (SDN), 50 SD patients treated with local corticosteroids (SDC). Mycological examination for Mf was performed. All patients were patch tested with the baseline standard, corticosteroid series, with 12 commercial corticosteroid preparations frequently used in Croatia; and also with Mf. Malassezia furfur was found in 44 (88%) SDN, 37 (74%) SDC, and in 4 (20%) HC; patch test reaction to Mf was positive in one SDN and in three SDC. Positive patch tests to standard allergens were observed in 17 (34%) SDN, 33 (66%) SDC and 2 (10%) HC. Patch tests to the corticosteroid series revealed positive reactions in 4 SDC and to commercial corticosteroids in seven patients, i.e. 2 SD and 5 SDC. Patch tests to the baseline series and to both individual corticosteroid and commercial corticosteroid preparations should be performed in SD patients with persistent dermatitis, as contact-allergic reactions may complicate their dermatitis. Sensitization to Mf was found to be infrequent. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Power Frequency Magnetic Fields Affect the p38 MAPK-Mediated Regulation of NB69 Cell Proliferation Implication of Free Radicals.

PubMed

Martínez, María Antonia; Úbeda, Alejandro; Moreno, Jorge; Trillo, María Ángeles

2016-04-06

The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38.

Power Frequency Magnetic Fields Affect the p38 MAPK-Mediated Regulation of NB69 Cell Proliferation Implication of Free Radicals

PubMed Central

Martínez, María Antonia; Úbeda, Alejandro; Moreno, Jorge; Trillo, María Ángeles

2016-01-01

The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38. PMID:27058530

(abstract) Effect of Long Period Ocean Tides on the Earth's Rotation

NASA Technical Reports Server (NTRS)

Gross, R. S.; Chao, B. F.; Desai, S.

1996-01-01

The second-degree zonal tide raising potential, which is responsible for tidal changes in the Earth's rotation rate and length-of-day, is symmetric about the polar axis and hence can excite the Earth's polar motion only through its action upon nonaxisymmetric features of the Earth such as the oceans. Ocean tidal excitation of polar motion in the diurnal and semidiurnal tidal bands has been previously detected and extensively examined. Here, the detection of ocean tidal excitation of polar motion in the long-period tidal band, specifically at the Mf' (13.63-day) and Mf (13.66-day) tidal frequencies, is reported.

Magnetic field measurements near stand-alone transformer stations.

PubMed

Kandel, Shaiela; Hareuveny, Ronen; Yitzhak, Nir-Mordechay; Ruppin, Raphael

2013-12-01

Extremely low-frequency (ELF) magnetic field (MF) measurements around and above three stand-alone 22/0.4-kV transformer stations have been performed. The low-voltage (LV) cables between the transformer and the LV switchgear were found to be the major source of strong ELF MFs of limited spatial extent. The strong fields measured above the transformer stations support the assessment method, to be used in future epidemiological studies, of classifying apartments located right above the transformer stations as highly exposed to MFs. The results of the MF measurements above the ground around the transformer stations provide a basis for the assessment of the option of implementing precautionary procedures.

Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort.

PubMed

Soylemezoglu, Oguz; Kandur, Yasar; Duzova, Ali; Ozkaya, Ozan; Kasapcopur, Ozgür; Baskin, Esra; Fidan, Kibriya; Yalcinkaya, Fatos

2015-01-01

Presence of common MEFV gene mutations strengthened the diagnosis of FMF in addition to the typical clinical characteristics of FMF. However, there are also rare mutations. P369S, A744S, R761H, K695R, F479L are the main rare mutations in Turkish population. We aimed to evaluate FMF patients with a single allele MEFV mutation and to compare patients with common and rare mutations. We retrospectively reviewed the medical records of FMF patients with a single allele mutation who were followed up between 2008 and 2013 in six centres. We compared the patients with rare and common mutations for disease severity score, frequent exacerbations ( >1 attack per month), long attack period (>3 day), symptoms, age at the onset of symptoms, gender, consanguinity, and family history. Two hundred and seventeen patients (M/F=101/116) with the diagnosis of FMF and single mutation were included. Heterozygote mutations were defined as common (M694V, V726A, M68OI) and rare mutations (A744S, P369S, K695R, R761H, F479L). Sixty-seven patients (27 males, 40 females) had one single rare mutation and 150 (74 males, 76 females) had one single common mutation. No difference was found between the rare and common mutations with respect to the disease severity score. There was no significant difference between common and rare heterozygote form of mutations in terms of disease severity. Patients with typical characteristics of FMF, with some rare mutations (A744S, P369S) should be treated in the same manner as patients with a common mutation.

Effects of Single and Repeated Exposure to a 50-Hz 2-mT Electromagnetic Field on Primary Cultured Hippocampal Neurons.

PubMed

Zeng, Ying; Shen, Yunyun; Hong, Ling; Chen, Yanfeng; Shi, Xiaofang; Zeng, Qunli; Yu, Peilin

2017-06-01

The prevalence of domestic and industrial electrical appliances has raised concerns about the health risk of extremely low-frequency magnetic fields (ELF-MFs). At present, the effects of ELF-MFs on the central nervous system are still highly controversial, and few studies have investigated its effects on cultured neurons. Here, we evaluated the biological effects of different patterns of ELF-MF exposure on primary cultured hippocampal neurons in terms of viability, apoptosis, genomic instability, and oxidative stress. The results showed that repeated exposure to 50-Hz 2-mT ELF-MF for 8 h per day after different times in culture decreased the viability and increased the production of intracellular reactive oxidative species in hippocampal neurons. The mechanism was potentially related to the up-regulation of Nox2 expression. Moreover, none of the repeated exposure patterns had significant effects on DNA damage, apoptosis, or autophagy, which suggested that ELF-MF exposure has no severe biological consequences in cultured hippocampal neurons.

Sequence and expression variation in SUPPRESSOR of OVEREXPRESSION of CONSTANS 1 (SOC1): homeolog evolution in Indian Brassicas.

PubMed

Sri, Tanu; Mayee, Pratiksha; Singh, Anandita

2015-09-01

Whole genome sequence analyses allow unravelling such evolutionary consequences of meso-triplication event in Brassicaceae (∼14-20 million years ago (MYA)) as differential gene fractionation and diversification in homeologous sub-genomes. This study presents a simple gene-centric approach involving microsynteny and natural genetic variation analysis for understanding SUPPRESSOR of OVEREXPRESSION of CONSTANS 1 (SOC1) homeolog evolution in Brassica. Analysis of microsynteny in Brassica rapa homeologous regions containing SOC1 revealed differential gene fractionation correlating to reported fractionation status of sub-genomes of origin, viz. least fractionated (LF), moderately fractionated 1 (MF1) and most fractionated (MF2), respectively. Screening 18 cultivars of 6 Brassica species led to the identification of 8 genomic and 27 transcript variants of SOC1, including splice-forms. Co-occurrence of both interrupted and intronless SOC1 genes was detected in few Brassica species. In silico analysis characterised Brassica SOC1 as MADS intervening, K-box, C-terminal (MIKC(C)) transcription factor, with highly conserved MADS and I domains relative to K-box and C-terminal domain. Phylogenetic analyses and multiple sequence alignments depicting shared pattern of silent/non-silent mutations assigned Brassica SOC1 homologs into groups based on shared diploid base genome. In addition, a sub-genome structure in uncharacterised Brassica genomes was inferred. Expression analysis of putative MF2 and LF (Brassica diploid base genome A (AA)) sub-genome-specific SOC1 homeologs of Brassica juncea revealed near identical expression pattern. However, MF2-specific homeolog exhibited significantly higher expression implying regulatory diversification. In conclusion, evidence for polyploidy-induced sequence and regulatory evolution in Brassica SOC1 is being presented wherein differential homeolog expression is implied in functional diversification.

Fortnightly Earth Rotation, Ocean Tides, and Mantle Anelasticity

NASA Technical Reports Server (NTRS)

Ray, Richard D.; Egbert, Gary D.

2011-01-01

Sustained accurate measurements of earth rotation are one of the prime goals of Global Geodetic Observing System (GGOS). We here concentrate on the fortnightly (Mf) tidal component of earth-rotation data to obtain new results concerning anelasticity of the mantle at this period. The study comprises three parts: (1) a new determination of the Mf component of polar motion and length-of-day from a multi-decade time series of space-geodetic data; (2) the use of the polar-motion determination as one constraint in the development of a hydrodynamic ocean model of the Mf tide; and (3) the use of these results to place new constraints on mantle anelasticity. Our model of the Mf ocean tide assimilates more than fourteen years of altimeter data from the Topex/Poseidon and Jason-1 satellites. The polar motion data, plus tide-gauge data and independent altimeter data, give useful additional information, with only the polar motion putting constraints on tidal current velocities. The resulting ocean-tide model, plus the dominant elastic body tide, leaves a small residual in observed length-of-day caused by mantle anelasticity. The inferred effective tidal 0 of the anelastic body tide is 90 and is in line with a omega-alpha frequency dependence with alpha in the range 0.2--0.3.

Magnetic field-induced modification of selection rules for Rb D 2 line monitored by selective reflection from a vapor nanocell

NASA Astrophysics Data System (ADS)

Klinger, Emmanuel; Sargsyan, Armen; Tonoyan, Ara; Hakhumyan, Grant; Papoyan, Aram; Leroy, Claude; Sarkisyan, David

2017-08-01

Magnetic field-induced giant modification of the probabilities of five transitions of 5S1 / 2,Fg = 2 → 5P3 / 2,Fe = 4 of 85Rb and three transitions of 5S1 / 2,Fg = 1 → 5P3 / 2,Fe = 3 of 87Rb forbidden by selection rules for zero magnetic field has been observed experimentally and described theoretically for the first time. For the case of excitation with circularly-polarized (σ+) laser radiation, the probability of Fg = 2,mF = - 2 → Fe = 4,mF = - 1 transition becomes the largest among the seventeen transitions of 85Rb Fg = 2 → Fe = 1,2,3,4 group, and the probability of Fg = 1, mF = - 1 → Fe = 3,mF = 0 transition becomes the largest among the nine transitions of 87Rb Fg = 1 → Fe = 0,1,2,3 group, in a wide range of magnetic field 200-1000 G. Complete frequency separation of individual Zeeman components was obtained by implementation of derivative selective reflection technique with a 300 nm-thick nanocell filled with Rb, allowing formation of narrow optical resonances. Possible applications are addressed. The theoretical model is well consistent with the experimental results.

Meal and snack frequency in relation to diet quality in US children and adolescents: the National Health and Nutrition Examination Survey 2003-2012.

PubMed

Murakami, Kentaro; Livingstone, M Barbara E

2016-06-01

To examine the associations of meal frequency (MF) and snack frequency (SF) with diet quality. Dietary intake was assessed using two 24 h dietary recalls. All eating occasions providing ≥210 kJ of energy were divided into meals or snacks on the basis of contribution to energy intake (≥15 % or <15 %), self-report and time (06.00-09.00, 12.00-14.00 and 17.00-20.00 hours, or others). Diet quality was assessed using the Healthy Eating Index (HEI)-2010. Nationally representative sample of the US population. Children aged 6-11 years (n 4269) and adolescents aged 12-19 years (n 6193) in the National Health and Nutrition Examination Survey 2003-2012. Irrespective of the definition of meals, higher MF was associated with higher HEI-2010 in both children and adolescents. One additional meal per day increased HEI-2010 by 1·45-3·59 points (all P<0·005). Conversely, the associations for SF were inconsistent. While SF based on energy contribution was positively associated with HEI-2010 in both children and adolescents (0·70 (P=0·001) and 1·00 (P<0·0001) point increase by one additional snack, respectively), there were no associations for SF based on self-report or time. In analyses in which only plausible energy reporters (3425 children and 3753 adolescents) were included, similar results were obtained. In a representative sample of US children and adolescents, MF was associated with better diet quality, while the associations for SF varied depending on the definition of snacks. The findings highlight the importance of applying different definitions of meals and snacks when assessing the impact of dietary patterns on health.

Acute and subchronic toxicity of 20  kHz and 60  kHz magnetic fields in rats

PubMed Central

Oshima, Atsushi; Shibuya, Kazumoto; Mitani, Takashi; Negishi, Tadashi

2015-01-01

Abstract Despite increasing use of intermediate frequency (IF) magnetic fields (MFs) in occupational and domestic settings, scientific evidence necessary for health risk assessments of IF MF is insufficient. Male and female Crl:CD(SD) rats (12 per sex per group) were exposed to 20 kHz, 0.20 mT(root mean square, rms) or 60 kHz, 0.10 mT(rms) sinusoidal MFs for 22 h day−1 for 14 days (acute) or 13 weeks (subchronic). Experiments were duplicated for each frequency to ensure outcome reproducibility, and examinations were blinded for quality assurance. All rats survived without significant clinical signs until the end of experiments. Some changes in body weight between the MF‐exposed and control groups were observed over the course of exposure, although the directions of the changes were inconsistent and not statistically significant after subchronic exposure. There were significant differences between MF‐exposed and control groups in some organ weights and parameters in hematology and clinical chemistry, but these were minor in magnitude and not repeated in duplicate experiments. Histopathological findings reflecting toxicity were sporadic. Frequencies of other findings were similar to historic data in this rat strain, and findings had no specific relationship to changes in organ weight or parameters of hematology and clinical chemistry in each animal. The changes observed throughout this study were considered biologically isolated and were attributable to chance associations rather than to MF exposure. The results, in particular the histopathological evidence, indicate an absence of toxicity in IF MF‐exposed rats and do not support the hypothesis that IF MF exposure produces significant toxicity. Copyright © 2015. The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd. PMID:25982482

[Influence of extremely low frequency magnetic field on total protein and -sh groups concentrations in liver homogenates].

PubMed

Ciejka, Elżbieta; Kowalczyk, Agata; Gorąca, Anna

2014-01-01

Free radicals are atoms, molecules or their fragments, whose excess leads to the development of oxidative stress, the cause of many neoplastic, neurodegenerative and inflammatory diseases, as well as aging of organisms. Industrial pollution, tobacco smoke, ionizing radiation, ultrasound and magnetic fields are the major exogenous sources of free radicals. The low frequency mag- netic field is commonly applied in physiotherapy. The aim of the present study was to evaluate the effect of extremely low frequency magnetic field (1L.F-MF) on the concentration ofsullhydryl groups (-SH) and proteins in liver tissues of experimental animals de- pending on the time of exposure to the field. Twenty one Sprague-D)awley male rats, aged 3-4 months were randomly divided into 3 experimental groups (each containing 7 animals): controls (group I), the rats exposed to IEI.F-MF of 40 Hz, 7 mT (this kind of the ELF-MF is mostly used in magnetotherapy), 30 min/day for 2 weeks (group II) and the rats exposed to 40 Hz, 7 mT for 60 min/day for 2 weeks (group III). The concentrations of proteins and sulfhydryl groups in the liver tissues were determined after exposure to magnetic fields. Exposure to low magnetic field: 40 Hz, 7 mT for 30 min/day and 60 min/day for 2 weeks caused a significant increase in the concentration of-SH groups and total protein levels in the liver tissues. The study results suggest that exposure to magnetic fields leads to the development of adaptive mechanisms to maintain the balance in the body oxidation-reduction and in the case of the studied parameters does not depend on the time of exposure.

JAK-STAT Pathway Activation in Malignant and Non-Malignant Cells Contributes to MPN Pathogenesis and Therapeutic Response

PubMed Central

Kleppe, Maria; Kwak, Minsuk; Koppikar, Priya; Riester, Markus; Keller, Matthew; Bastian, Lennart; Hricik, Todd; Bhagwat, Neha; McKenney, Anna Sophia; Papalexi, Efthymia; Abdel-Wahab, Omar; Rampal, Raajit; Marubayashi, Sachie; Chen, Jonathan J.; Romanet, Vincent; Fridman, Jordan S.; Bromberg, Jacqueline; Teruya-Feldstein, Julie; Murakami, Masato; Radimerski, Thomas; Michor, Franziska; Fan, Rong; Levine, Ross L.

2015-01-01

The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis (MF) and improves overall survival; however the mechanism by which JAK inhibitors achieve efficacy has not been delineated. MPN patients present with increased levels of circulating pro-inflammatory cytokines, which are mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which JAK inhibitors attenuate cytokine-mediated pathophysiology. Single cell profiling demonstrated that hematopoietic cells from MF models and patient samples aberrantly secrete inflammatory cytokines. Pan-hematopoietic Stat3 deletion reduced disease severity and attenuated cytokine secretion, with similar efficacy as observed with ruxolitinib therapy. By contrast, Stat3 deletion restricted to MPN cells did not reduce disease severity or cytokine production. Consistent with these observations, we found that malignant and non-malignant cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production from both populations. PMID:25572172

Genetic Control and Evolution of Anthocyanin Methylation.

PubMed

Provenzano, Sofia; Spelt, Cornelis; Hosokawa, Satoko; Nakamura, Noriko; Brugliera, Filippa; Demelis, Linda; Geerke, Daan P; Schubert, Andrea; Tanaka, Yoshikazu; Quattrocchio, Francesca; Koes, Ronald

2014-07-01

Anthocyanins are a chemically diverse class of secondary metabolites that color most flowers and fruits. They consist of three aromatic rings that can be substituted with hydroxyl, sugar, acyl, and methyl groups in a variety of patterns depending on the plant species. To understand how such chemical diversity evolved, we isolated and characterized METHYLATION AT THREE2 (MT2) and the two METHYLATION AT FIVE (MF) loci from Petunia spp., which direct anthocyanin methylation in petals. The proteins encoded by MT2 and the duplicated MF1 and MF2 genes and a putative grape (Vitis vinifera) homolog Anthocyanin O-Methyltransferase1 (VvAOMT1) are highly similar to and apparently evolved from caffeoyl-Coenzyme A O-methyltransferases by relatively small alterations in the active site. Transgenic experiments showed that the Petunia spp. and grape enzymes have remarkably different substrate specificities, which explains part of the structural anthocyanin diversity in both species. Most strikingly, VvAOMT1 expression resulted in the accumulation of novel anthocyanins that are normally not found in Petunia spp., revealing how alterations in the last reaction can reshuffle the pathway and affect (normally) preceding decoration steps in an unanticipated way. Our data show how variations in gene expression patterns, loss-of-function mutations, and alterations in substrate specificities all contributed to the anthocyanins' structural diversity. © 2014 American Society of Plant Biologists. All Rights Reserved.

Examining Hippocampal Mossy Fiber Synapses by 3D Electron Microscopy in Wildtype and Kirrel3 Knockout Mice

PubMed Central

Rawson, Randi L.

2017-01-01

Neural circuits balance excitatory and inhibitory activity and disruptions in this balance are commonly found in neurodevelopmental disorders. Mice lacking the intellectual disability and autism-associated gene Kirrel3 have an excitation-inhibition imbalance in the hippocampus but the precise synaptic changes underlying this functional defect are unknown. Kirrel3 is a homophilic adhesion molecule expressed in dentate gyrus (DG) and GABA neurons. It was suggested that the excitation-inhibition imbalance of hippocampal neurons in Kirrel3 knockout mice is due to loss of mossy fiber (MF) filopodia, which are DG axon protrusions thought to excite GABA neurons and thereby provide feed-forward inhibition to CA3 pyramidal neurons. Fewer filopodial structures were observed in Kirrel3 knockout mice but neither filopodial synapses nor DG en passant synapses, which also excite GABA neurons, were examined. Here, we used serial block-face scanning electron microscopy (SBEM) with 3D reconstruction to define the precise connectivity of MF filopodia and elucidate synaptic changes induced by Kirrel3 loss. Surprisingly, we discovered wildtype MF filopodia do not synapse exclusively onto GABA neurons as previously thought, but instead synapse with similar frequency onto GABA neurons and CA3 neurons. Moreover, Kirrel3 loss selectively reduces MF filopodial synapses onto GABA neurons but not those made onto CA3 neurons or en passant synapses. In sum, the selective loss of MF filopodial synapses with GABA neurons likely underlies the hippocampal activity imbalance observed in Kirrel3 knockout mice and may impact neural function in patients with Kirrel3-dependent neurodevelopmental disorders. PMID:28670619

Nocturnal 6-hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields

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

Juutilainen, J; Stevens, Richard G.; Anderson, Larry E.

The objective of this study was to determine whether daytime occupational exposure to extremely low frequency magnetic fields (MFs) suppresses nocturnal melatonin production. Sixty female volunteers were recruited. Thirty-nine worked in a garment factory, and 21 office workers served as a reference group. Exposure assessment was based on the type of sewing machine used and MF measurements around each type of machine. Eye-level MF flux density was used to classify the operators to higher (> 1 microT) and lower (0.3-1 microT) exposure categories. A third group of factory workers had diverse MF exposures from other sources. The reference group hadmore » average exposure of about 0.15 microT. Urine samples were collected on Friday and Monday for three consecutive weeks. Melatonin production was assessed as urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion. The ratio of Friday morning/Monday morning 6-OHMS was used to test the hypothesis that melatonin production is suppressed after 4 days of occupational MF exposure with significant recovery during the weekend. Possible chronic suppression of melatonin production was evaluated by studying exposure-related differences in the Friday values by multivariate regression analysis. The Monday/Friday ratios were close to 1.0, suggesting that there is no increase in melatonin production over the weekend. The average 6-OHMS excretion on Friday was lower among the factory workers than in the reference group, but no monotonous dose-response was observed. Multivariate regression analysis identified MF exposure, smoking, and age as significant explanatory variables associated with decreased 6-OHMS excretion.« less

Direction of Arrival Measurements of Auroral Medium Frequency Burst Radio Emissions at Toolik Lake, AK

NASA Astrophysics Data System (ADS)

Bunch, N. L.; Labelle, J. W.; Hughes, J. M.; Weatherwax, A. T.; Ye, S.; Lummerzheim, D.

2007-12-01

MF burst is an impulsive radio emission of auroral origin detected by ground-based instruments approximately between 1,300 and 3,700 kHz, and associated with substorm onsets. Its exact generation mechanism is unknown, though it has been speculated that it arises from mode conversion radiation. To discover the generation mechanism and the relation of MF burst to auroral processes, Dartmouth has deployed radio interferometers in Alaska, Northern Canada, Greenland, and Antarctica, including a three-element interferometer deployed at Toolik Lake Field Station in Alaska in 2006. This instrument measured spectra, amplitudes, and directions of arrival (DOA's) of over 47 MF burst events occurring between November 30, 2006 and May 26, 2007. These represent the first DOA measurements ever reported for the impulsive MF burst phenomenon. Preliminary analysis shows that the events originated from a wide range of directions in the sky, with all azimuths represented in the distribution of DOA's. The DOA of each individual event is well-defined, however. Many events show apparent motion, with southward motions more common than northward among the subset of events analyzed so far. Some of the events were detected simultaneously on an interferometer deployed at Kaktovik, Alaska, 400 km away. The all-sky imager at Toolik Lake was also operational for some events. Further analysis of these data promises to reveal first information about the locations and motions of MF burst sources, a first step towards discovering the generation mechanism of this mysterious radio emission and its relation to auroral processes.

Studies of Tidal and Planetary Wave Variability in the Middle Atmosphere using UARS and Correlative MF Radar Data

NASA Technical Reports Server (NTRS)

Fritts, David C.

1996-01-01

The goals of this research effort have been to use MF radar and UARS/HRDI wind measurements for correlative studies of large-scale atmospheric dynamics, focusing specifically on the tidal and various planetary wave structures occurring in the middle atmosphere. We believed that the two data sets together would provide the potential for much more comprehensive studies than either by itself, since they jointly would allow the removal of ambiguities in wave structure that are difficult to resolve with either data set alone. The joint data were to be used for studies of wave structure, variability, and the coupling of these motions to mean and higher-frequency motions.

Distribution Analysis of Sulphide Mineral (Pyrite) Using Induced Polarization Method in Libureng, Bone, South Sulawesi

NASA Astrophysics Data System (ADS)

Altin Massinai, Muhammad; Lantu; Latuconsina, Hidayat; Fawzy Ismullah M, Muhammad

2018-03-01

Sulphide minerals are any member of a group of compounds of sulphur with one or more metals. Some of these sulphide minerals are economically important. This study used induced polarization method to identify distribution and mineralized zone of sulphide mineral (Pyrite), in Libureng, Bone Regency, South Sulawesi. The data processing yielded resistivity value, percent frequency effect (PPE) value, and metal factor (MF) value which were then used to produce 2-D and 3-D section model. Based on the data interpretation, an anomaly linked to pyrite deposits was seen in four trajectories with resistivity value < = 50, PFE = > 3%, and MF > = 150, deposited in hydrothermal alteration zone, sericite zone.

Laser-induced rocket force on a microparticle in a complex (dusty) plasma

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

Nosenko, V.; Ivlev, A. V.; Morfill, G. E.

2010-12-15

The interaction of a focused powerful laser beam with micron-sized melamine formaldehyde (MF) particles was studied experimentally. The microspheres had a thin palladium coating on their surface and were suspended in a radio frequency argon plasma as a single layer (plasma crystal). A particle hit by the laser beam usually accelerated in the direction of the laser beam, consistent with the radiation pressure force mechanism. However, random-direction acceleration up to the speeds on the order 1 m/s was sometimes observed. Rocket-force mechanism is proposed to account for the random-direction acceleration. Similar, but much less pronounced, effect was also observed formore » MF particles without palladium coating.« less

Affective response to 5 microT ELF magnetic field-induced physiological changes.

PubMed

Stevens, Paul

2007-02-01

Research into effects of weak magnetic fields (MFs) at biologically relevant frequencies has produced ambiguous results. Although they do affect human physiology and behaviour, the direction of effects is inconsistent, with a range of complex and unrelated behaviours being susceptible. A possible explanation is that these effects, rather than being directly caused, are instead related to changes in affective state. A previous study showed that MFs altered the affective content of concurrent perceptions, but it was unclear whether the emotional response was direct or indirect. Here it is shown that exposure to a 0-5 microT MF (DC-offset sinudsoidal wave form) within EEG alpha-band frequencies (8-12 Hz), results in a reported change in emotional state. This relates to a decrease global field power but lacks the frontal alpha-asymmetry that would physiologically indicate a directly induced emotional state, suggesting that participant experiences are due to an interpretation of the effects of MF exposure.

Plasma ``anti-assistance'' and ``self-assistance'' to high power impulse magnetron sputtering

NASA Astrophysics Data System (ADS)

Anders, André; Yushkov, Georgy Yu.

2009-04-01

A plasma assistance system was investigated with the goal to operate high power impulse magnetron sputtering (HiPIMS) at lower pressure than usual, thereby to enhance the utilization of the ballistic atoms and ions with high kinetic energy in the film growth process. Gas plasma flow from a constricted plasma source was aimed at the magnetron target. Contrary to initial expectations, such plasma assistance turned out to be contraproductive because it led to the extinction of the magnetron discharge. The effect can be explained by gas rarefaction. A better method of reducing the necessary gas pressure is operation at relatively high pulse repetition rates where the afterglow plasma of one pulse assists in the development of the next pulse. Here we show that this method, known from medium-frequency (MF) pulsed sputtering, is also very important at the much lower pulse repetition rates of HiPIMS. A minimum in the possible operational pressure is found in the frequency region between HiPIMS and MF pulsed sputtering.

Magnetic fields from electric toothbrushes promote corrosion in orthodontic stainless steel appliances but not in titanium appliances.

PubMed

Kameda, Takashi; Ohkuma, Kazuo; Oda, Hirotake; Sano, Natsuki; Batbayar, Nomintsetseg; Terashima, Yukari; Sato, Soh; Terada, Kazuto

2013-01-01

Electric toothbrushes are widely used, and their electric motors have been reported to produce low-frequency electromagnetic fields that induced electric currents in metallic objects worn by the users. In this study, we showed that electric toothbrushes generated low-frequency magnetic fields (MFs) and induced electric currents in orthodontic appliances in artificial saliva (AS), which accelerated corrosion in stainless steel (SUS) appliances, but not in titanium (Ti) appliances; the corrosion was evaluated by using an inductively coupled plasma-optical emission spectrometer and a three-dimensional laser confocal microscope. The pH of AS used for appliance immersion did not change during or after MF exposure. These results suggested that MF-induced currents from electric toothbrushes could erode SUS appliances, but not Ti appliances, because of their high corrosion potentials. Further studies are required to clarify the mechanisms of metallic corrosion by induced currents in dental fields, which may trigger metal allergies in patients.

A Hybrid Approach for Efficient Modeling of Medium-Frequency Propagation in Coal Mines

PubMed Central

Brocker, Donovan E.; Sieber, Peter E.; Waynert, Joseph A.; Li, Jingcheng; Werner, Pingjuan L.; Werner, Douglas H.

2015-01-01

An efficient procedure for modeling medium frequency (MF) communications in coal mines is introduced. In particular, a hybrid approach is formulated and demonstrated utilizing ideal transmission line equations to model MF propagation in combination with full-wave sections used for accurate simulation of local antenna-line coupling and other near-field effects. This work confirms that the hybrid method accurately models signal propagation from a source to a load for various system geometries and material compositions, while significantly reducing computation time. With such dramatic improvement to solution times, it becomes feasible to perform large-scale optimizations with the primary motivation of improving communications in coal mines both for daily operations and emergency response. Furthermore, it is demonstrated that the hybrid approach is suitable for modeling and optimizing large communication networks in coal mines that may otherwise be intractable to simulate using traditional full-wave techniques such as moment methods or finite-element analysis. PMID:26478686

Estimating the delay-Doppler of target echo in a high clutter underwater environment using wideband linear chirp signals: Evaluation of performance with experimental data.

PubMed

Yu, Ge; Yang, T C; Piao, Shengchun

2017-10-01

A chirp signal is a signal with linearly varying instantaneous frequency over the signal bandwidth, also known as a linear frequency modulated (LFM) signal. It is widely used in communication, radar, active sonar, and other applications due to its Doppler tolerance property in signal detection using the matched filter (MF) processing. Modern sonar uses high-gain, wideband signals to improve the signal to reverberation ratio. High gain implies a high product of the signal bandwidth and duration. However, wideband and/or long duration LFM signals are no longer Doppler tolerant. The shortcoming of the standard MF processing is loss of performance, and bias in range estimation. This paper uses the wideband ambiguity function and the fractional Fourier transform method to estimate the target velocity and restore the performance. Target velocity or Doppler provides a clue for differentiating the target from the background reverberation and clutter. The methods are applied to simulated and experimental data.

Inherited and environmentally induced differences in mutation frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

PubMed

Lamb, B C; Saleem, M; Scott, W; Thapa, N; Nevo, E

1998-05-01

We have studied whether there is natural genetic variation for mutation frequencies, and whether any such variation is environment-related. Mutation frequencies differed significantly between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. Strains from the harsher, drier, south-facing slope had higher frequencies of new spontaneous mutations and of accumulated mutations than strains from the milder, lusher, north-facing slope. Collective total mutation frequencies over many loci for ascospore pigmentation were 2.3, 3.5 and 4.4% for three strains from the south-facing slope, and 0.9, 1.1, 1.2, 1.3 and 1.3% for five strains from the north-facing slope. Some of this between-slope difference was inherited through two generations of selfing, with average spontaneous mutation frequencies of 1.9% for south-facing slope strains and 0.8% for north-facing slope strains. The remainder was caused by different frequencies of mutations arising in the original environments. There was also significant heritable genetic variation in mutation frequencies within slopes. Similar between-slope differences were found for ascospore germination-resistance to acriflavine, with much higher frequencies in strains from the south-facing slope. Such inherited variation provides a basis for natural selection for optimum mutation rates in each environment.

Inherited and environmentally induced differences in mutation frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

PubMed Central

Lamb, B C; Saleem, M; Scott, W; Thapa, N; Nevo, E

1998-01-01

We have studied whether there is natural genetic variation for mutation frequencies, and whether any such variation is environment-related. Mutation frequencies differed significantly between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. Strains from the harsher, drier, south-facing slope had higher frequencies of new spontaneous mutations and of accumulated mutations than strains from the milder, lusher, north-facing slope. Collective total mutation frequencies over many loci for ascospore pigmentation were 2.3, 3.5 and 4.4% for three strains from the south-facing slope, and 0.9, 1.1, 1.2, 1.3 and 1.3% for five strains from the north-facing slope. Some of this between-slope difference was inherited through two generations of selfing, with average spontaneous mutation frequencies of 1.9% for south-facing slope strains and 0.8% for north-facing slope strains. The remainder was caused by different frequencies of mutations arising in the original environments. There was also significant heritable genetic variation in mutation frequencies within slopes. Similar between-slope differences were found for ascospore germination-resistance to acriflavine, with much higher frequencies in strains from the south-facing slope. Such inherited variation provides a basis for natural selection for optimum mutation rates in each environment. PMID:9584088

A pilot study on the reproductive risks of maternal exposure to magnetic fields from electronic article surveillance systems.

PubMed

Khan, Muhammad Waseem; Roivainen, Päivi; Herrala, Mikko; Tiikkaja, Maria; Sallmén, Markku; Hietanen, Maila; Juutilainen, Jukka

2018-02-26

We investigated the feasibility of a large-scale epidemiological study on reproductive effects of intermediate frequency (IF) magnetic field (MF) exposure among cashiers working near electronic article surveillance (EAS) systems. The study cohort included 4157 women who had worked as cashiers in supermarkets with EAS devices (considered as exposed) or grocery stores without EAS devices (considered as unexposed) between 2008 and 2015. 536 births and 38 miscarriages occurred among these women during the study period, based on information from nationwide health registries. Measurements were also performed to characterize the MF exposure of cashiers. Cashiers were found to be exposed to 8.2 MHz MFs only when passing by the gates at short distance. Static fields of about 0.1 mT were observed at cashier's seat. Extremely low frequency MFs were higher at stores without EAS devices. No differences on the risk of miscarriage, reduced birth weight or preterm birth were observed between cashiers in different store types. Any further studies should attempt to include study subjects working near EAS systems that produce stronger IF MFs at kHz frequencies. Exposure to ELF MFs should be assessed as a possible confounding factor.

In Situ Observation of Chymotrypsin Catalytic Activity Change Actuated by Nonheating Low-Frequency Magnetic Field.

PubMed

Efremova, Maria V; Veselov, Maxim M; Barulin, Alexander V; Gribanovsky, Sergey L; Le-Deygen, Irina M; Uporov, Igor V; Kudryashova, Elena V; Sokolsky-Papkov, Marina; Majouga, Alexander G; Golovin, Yuri I; Kabanov, Alexander V; Klyachko, Natalia L

2018-04-24

Magnetomechanical modulation of biochemical processes is a promising instrument for bioengineering and nanomedicine. This work demonstrates two approaches to control activity of an enzyme, α-chymotrypsin immobilized on the surface of gold-coated magnetite magnetic nanoparticles (GM-MNPs) using a nonheating low-frequency magnetic field (LF MF). The measurement of the enzyme reaction rate was carried out in situ during exposure to the magnetic field. The first approach involves α-chymotrypsin-GM-MNPs conjugates, in which the enzyme undergoes mechanical deformations with the reorientation of the MNPs under LF MF (16-410 Hz frequency, 88 mT flux density). Such mechanical deformations result in conformational changes in α-chymotrypsin structure, as confirmed by infrared spectroscopy and molecular modeling, and lead to a 63% decrease of enzyme initial activity. The second approach involves an α-chymotrypsin-GM-MNPs/trypsin inhibitor-GM-MNPs complex, in which the activity of the enzyme is partially inhibited. In this case the reorientation of MNPs in the field leads to disruption of the enzyme-inhibitor complex and an almost 2-fold increase of enzyme activity. The results further demonstrate the utility of magnetomechanical actuation at the nanoscale for the remote modulation of biochemical reactions.

Development of instrumentation with application to sounding rocket electric and magnetic field measurements above thunderstorms

NASA Astrophysics Data System (ADS)

Baker, Steven D.

1999-06-01

The thunderstorm campaigns led by Cornell University in 1981 and 1988 both measured large-amplitude (10 to 40 mV/m), long duration (1 ms) electric-field pulses parallel to the earth's magnetic field. To investigate the mechanism responsible for these pulses, the instrumentation bandwidth was increased from the VLF range to MF frequencies. The design for a Helmholtz coil developed to calibrate magnetometers from DC to 10 MHz is given in Chapter 3. This coil generates a spatially uniform field with for frequencies up to at least 10 MHz with amplitudes of up to 1.1 mA/m. Coincident with the need for higher bandwidth sensors, a burst-memory data acquisition system was developed to intelligently select the 1.25% of the available data to send to the telemetry encoder. This system uses the optical flash of the lightning as a trigger and has a back-up mode to ensure data is transmitted in the event no triggers occur. The higher-frequency instruments allowed the first rocket-borne measurement of nose- whistlers caused by the plasma frequency resonance (as opposed to the more common electron cyclotron frequency resonance), and what may have been the first observation of a TIPP at MF frequencies. Triggered emission from the second campaign, Thunderstorm-II, are identified as lower hybrid emissions. These emissions enhanced the whistler by several decibels in the lower hybrid frequency band and in bands above the emission. No emissions seen above the lower hybrid frequency. The Thunderstorm-III payloads also measured triggered emissions and long-duration pulses. The former were found in several altitude-independent frequency bands for which the source could not be identified. The long duration pulses, while of interest, have not been studied in sufficient depth for inclusion in this work.

Evaluation of Macaca mulatta as a model for genotoxicity studies.

PubMed

Dobrovolsky, Vasily N; Shaddock, Joseph G; Mittelstaedt, Roberta A; Manjanatha, Mugimane G; Miura, Daishiro; Uchikawa, Makoto; Mattison, Donald R; Morris, Suzanne M

2009-02-19

We have investigated the use of peripheral blood from the nonhuman primate (NHP) rhesus monkey (Macaca mulatta) as a model system for mutation detection. The rhesus monkey is metabolically closer to humans than most common laboratory animals, and therefore may be a relevant model for hazard identification and human risk assessment. To validate the model, conditions were determined for in vitro selection and expansion of 6-thioguanine-resistant (6-TGr) HPRT mutant and proaerolysin-resistant (ProAERr) PIG-A mutant lymphocytes from peripheral blood obtained by routine venipuncture. Also, flow cytometric methods were developed for the rapid detection of PIG-A mutant erythrocytes. The flow cytometric analysis of PIG-A mutant erythrocytes was based on enumerating cells deficient in surface markers attached to the cellular membrane via glycosylphosphatidyl inositol (GPI) anchors. Mutant cells were enumerated over an extended period of time in peripheral blood of male monkeys receiving daily doses of the electrolyte replenisher Prangtrade mark (a common carrier for oral delivery of drugs in NHPs), and in the blood of one male monkey treated with a single i.p. dose of 50mg/kg of N-ethyl-N-nitrosourea at approximately 2 years of age and another similar injection at approximately 3.5 years of age. The spontaneous PIG-A and HPRT T-cell mutant frequency (MF) was low in animals receiving Prang (0-8x10(-6)), and treatment with ENU resulted in a clearly detectable increase in the frequency of ProAERr and 6-TGr lymphocytes (up to approximately 28x10(-6) and approximately 30x10(-6), respectively). Also, the ENU-treated animal had higher frequency of GPI-deficient erythrocytes (46.5x10(-6) in the treated animal vs. 7.8+/-4.2x10(-6) in control animals). Our results indicate that the rhesus monkey can be a valuable model for the identification of agents that may impact upon human health as mutagens and that the PIG-A gene can be a useful target for detection of mutation in both white and red blood cells.

Advanced ACTPol Low-Frequency Array: Readout and Characterization of Prototype 27 and 39 GHz Transition Edge Sensors

NASA Astrophysics Data System (ADS)

Koopman, B. J.; Cothard, N. F.; Choi, S. K.; Crowley, K. T.; Duff, S. M.; Henderson, S. W.; Ho, S. P.; Hubmayr, J.; Gallardo, P. A.; Nati, F.; Niemack, M. D.; Simon, S. M.; Staggs, S. T.; Stevens, J. R.; Vavagiakis, E. M.; Wollack, E. J.

2018-05-01

Advanced ACTPol (AdvACT) is a third-generation polarization upgrade to the Atacama Cosmology Telescope, designed to observe the cosmic microwave background (CMB). AdvACT expands on the 90 and 150 GHz transition edge sensor (TES) bolometer arrays of the ACT Polarimeter (ACTPol), adding both high-frequency (HF, 150/230 GHz) and low-frequency (LF, 27/39 GHz) multichroic arrays. The addition of the high- and low-frequency detectors allows for the characterization of synchrotron and spinning dust emission at the low frequencies and foreground emission from galactic dust and dusty star-forming galaxies at the high frequencies. The increased spectral coverage of AdvACT will enable a wide range of CMB science, such as improving constraints on dark energy, the sum of the neutrino masses, and the existence of primordial gravitational waves. The LF array will be the final AdvACT array, replacing one of the MF arrays for a single season. Prior to the fabrication of the final LF detector array, we designed and characterized prototype TES bolometers. Detector geometries in these prototypes are varied in order to inform and optimize the bolometer designs for the LF array, which requires significantly lower noise levels and saturation powers (as low as {˜ } 1 pW) than the higher-frequency detectors. Here we present results from tests of the first LF prototype TES detectors for AdvACT, including measurements of the saturation power, critical temperature, thermal conductance, and time constants. We also describe the modifications to the time-division SQUID readout architecture compared to the MF and HF arrays.

Effect of static and dynamic exercise on heart rate and blood pressure variabilities.

PubMed

González-Camarena, R; Carrasco-Sosa, S; Román-Ramos, R; Gaitán-González, M J; Medina-Bañuelos, V; Azpiroz-Leehan, J

2000-10-01

This study examines the effect of static and dynamic leg exercises on heart rate variability (HRV) and blood pressure variability (BPV) in humans. 10 healthy male subjects were studied at rest, during static exercise performed at 30% of maximal voluntary contraction (SX30), and during dynamic cycling exercises done at 30% of VO2max (DX30) and at 60% of VO2max (DX60). Respiration, heart rate, and blood pressure signals were digitized to analyze temporal and spectral parameters involving short and overall indexes (SD, deltaRANGE, RMSSD, Total power), power of the low (LF), middle (MF), and high (HF) frequency components, and the baroreceptor sensitivity by the alphaMF index. During SX30, indexes of HRV as SD, deltaRANGE, Total power, and MF in absolute units increased in relation with rest values and were significantly higher (P < 0.001) than during DX30 and DX60; HF during SX30, in normalized and absolute units, was not different of the rest condition but was higher (P < 0.001) than HF during DX30 and DX60. Parameters of BPV as SD and deltaRANGE increased (P < 0.001) during both type of exercises, and significant (P < 0.01) increments were observed on MF during SX30 and DX30; systolic HF was attenuated during DX30 (P < 0.05), whereas diastolic HF was augmented during DX60 (P < 0.001). Compared with rest condition, the alphaMF index decreased (P < 0.01) only during dynamic exercises. Because HRV and BPV response is different when induced by static or dynamic exercise, differences in the autonomic activity can be advised. Instead of the vagal withdrawal and sympathetic augmentation observed during dynamic exercise, the increase in the overall HRV and the MF component during static exercise suggest an increased activity of both autonomic branches.

Is the timed loaded standing test a valid measure of back muscle endurance in people with vertebral osteoporosis?

PubMed

Newman, M; Newman, R; Hughes, T; Vadher, K; Barker, K L

2018-04-01

Timed loaded standing (TLS) is a suggested measure of back muscle endurance for people with vertebral osteoporosis. Surface electromyography revealed back muscles work harder and fatigue during TLS. The test end-point and total time were associated with back fatigue. The findings help demonstrate the concurrent validity of the TLS test. The TLS test is suggested as a measure of back muscle endurance for patients with vertebral osteoporosis. However, to date, no study has demonstrated that TLS does measure back extensor or erector spinae (ES) muscle endurance. We used surface electromyography (sEMG) to investigate the performance of the thoracic ES muscles during TLS. Thirty-six people with vertebral osteoporosis with a mean age of 71.6 (range 45-86) years participated. sEMG recordings were made of the ES at T3 and T12 bilaterally during quiet standing (QS) and TLS. The relative (%) change in sEMG amplitude between conditions was compared. Fatigue was evaluated by analysing the change in median frequency (MF) of the sEMG signal during TLS, and the correlation between maximal TLS time and rate of MF decline was examined. Activity in the ES increased significantly during TLS at all electrode locations. During TLS, the MF declined at a mean rate of -24.2% per minute (95% C.I. -26.5 to -21.9%). The MF slope and test time were strongly correlated (r 2  = 0.71), and at test end, the final MF dropped to an average 89% (95% C.I. 85 to 93%) of initial MF. Twenty-eight participants (78%) reported fatigue was the main reason for stopping, and for eight (22%), it was pain. This study demonstrates that TLS challenges the ES muscles in the thoracic region and results in ES fatigue. Endurance time and the point at which the TLS test ends are strongly related to ES fatigue.

Measuring Vocational Preferences: Ranking versus Categorical Rating Procedures.

ERIC Educational Resources Information Center

Carifio, James

1978-01-01

Describes a study to compare the relative validities of ranking v categorical rating procedures for obtaining student vocational preference data in exploratory program assignment situations. Students indicated their vocational program preferences from career clusters, and the frequency of wrong assignments made by each method was analyzed. (MF)

Observation of hectometric auroral radio emissions in Iceland

NASA Astrophysics Data System (ADS)

Sato, Y.; Ono, T.; Iizima, M.; Sato, N.

2006-12-01

The Earth's auroral region is an active radio source at frequencies from a few hertz to several megahertz. In the hectometric range, it was found that Terrestrial Hectometric Radiation (THR) is related to auroras by observations of the Ohzora satellite [Oya et al.(1985)]. In resent research, Shinbori et al. [2003] showed that occurrence of THR follows SC by several minutes using the Akebono satellite data. On the ground, auroral roar and MF burst were discovered by Kellogg and Monson [1979, 1984] and Weatherwax et al. [1994] in the northern Canada, respectively. Because there is not enough physical and geophysical characterization of these radio emissions, the physical mechanism of these phenomena in the auroral ionosphere has not been fully understood yet. We set up new observation system at Husafell station in Iceland in September, 2005 and have started to observe auroral radio emissions. Radio signals, which are received by the cross loop antennas, are converted into left- and right- handed polarized components within the frequency range from 1 MHz to 5 MHz. Based on the calibration of system, it was found that the possibility of occurence would be smaller than expected due to the low sensitivity because average power spectrum densities of auroral roar and MF burst are 50-100 nV/m/Hz^1/2. So, the system was planed to be upgraded in this September, which makes it possible to detect auroral roar and MF burst. It is expected that the detail physical process will be elucidated by clarifying the spectrum, polarization, dependence on the geomagnetic activity, and so on. In this presentation, we will show the improved points of the new system and preliminary observation results. There is a basic question whether auroral roar and MF burst observed on the ground are generated by the same process as THR observed by satellites. By comparing the results from the ground-based observation and the Akebono satellite observation of THR, it becomes possible to obtain a new picture of auroral radio emissions.

Efficacy and safety evaluation of systemic extremely low frequency magnetic fields used in the healing of diabetic foot ulcers--phase II data.

PubMed

Cañedo-Dorantes, Luis; Soenksen, Luis R; García-Sánchez, Clara; Trejo-Núñez, Daphny; Pérez-Chávez, Fernando; Guerrero, Arturo; Cardona-Vicario, Melisa; García-Lara, Carlos; Collí-Magaña, Dianelly; Serrano-Luna, Gregorio; Angeles Chimal, José S; Cabrera, Guillermo

2015-08-01

Cellular and animal models investigating extremely low frequency magnetic fields (ELF-MF) have reported promotion of leukocyte-endothelial interactions, angiogenesis, myofibroblast and keratinocyte proliferation, improvement of peripheral neuropathy and diabetic wound healing. In humans, it has also been reported that systemic exposure to ELF-MF stimulates peripheral blood mononuclear cells, promoting angiogenesis and healing of chronic leg ulcers. The aim of the study was to investigate the effect of exposing different blood volumes to specific ELF-MFs (120 Hz sinusoidal waves of 0.4-0.9 mT RMS) to induce healing of diabetic foot ulcers (DFUs). Twenty six diabetic patients with non-responsive DFUs were divided into two exposure groups to receive treatment and record healing time. The forearm group, exposed to ELF-MF 2 h/day, twice weekly (3.6 l of blood/session); and the thorax group, exposed 25 min/day, 2 times/week (162.5 l of blood/session). Treatment period was 100 days or upon complete healing. Ulcer recurrences and adverse effects were investigated during short-term (<1 year) and long-term (3.4-7.8 years) follow-up. Mean healing time was 61.48 ± 33.08 days in the forearm group and 62.56 ± 29.33 days for the thorax group. No adverse effects or ulcer recurrences in the original ulcer site were reported during treatment, the short-term follow-up period or the long-term follow-up period in both groups. Healing time was independent of the amount of blood exposed to ELF-MF used in this trial. ELF-MFs are effective and safe and could be applied to non-healing DFUs in conjunction with other preventive interventions to reduce DFUs complications. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Quantitative electroencephalography analysis in university students with hazardous alcohol consumption, but not alcohol dependence.

PubMed

Núñez-Jaramillo, Luis; Vega-Perera, Paulo; Ramírez-Lugo, Leticia; Reyes-López, Julián V; Santiago-Rodríguez, Efraín; Herrera-Morales, Wendy V

2015-07-08

Hazardous alcohol consumption is a pattern of consumption that leads to a higher risk of harmful consequences either for the user or for others. This pattern of alcohol consumption has been linked to risky behaviors, accidents, and injuries. Individuals with hazardous alcohol consumption do not necessarily present alcohol dependence; thus, a study of particular neurophysiological correlates of this alcohol consumption pattern needs to be carried out in nondependent individuals. Here, we carried out a quantitative electroencephalography analysis in health sciences university students with hazardous alcohol consumption, but not alcohol dependence (HAC), and control participants without hazardous alcohol consumption or alcohol dependence (NHAC). We analyzed Absolute Power (AP), Relative Power (RP), and Mean Frequency (MF) for beta and theta frequency bands under both eyes closed and eyes open conditions. We found that participants in the HAC group presented higher beta AP at centroparietal region, as well as lower beta MF at frontal and centroparietal regions in the eyes closed condition. Interestingly, participants did not present any change in theta activity (AP, RP, or MF), whereas previous reports indicate an increase in theta AP in alcohol-dependent individuals. Our results partially resemble those found in alcohol-dependent individuals, although are not completely identical, suggesting a possible difference in the underlying neuronal mechanism behind alcohol dependence and hazardous alcohol consumption. Similarities could be explained considering that both hazardous alcohol consumption and alcohol dependence are manifestations of behavioral disinhibition.

Fifty hertz extremely low-frequency magnetic field exposure elicits redox and trophic response in rat-cortical neurons.

PubMed

Di Loreto, Silvia; Falone, Stefano; Caracciolo, Valentina; Sebastiani, Pierluigi; D'Alessandro, Antonella; Mirabilio, Alessandro; Zimmitti, Vincenzo; Amicarelli, Fernanda

2009-05-01

Large research activity has raised around the mechanisms of interaction between extremely low-frequency magnetic fields (ELF-MFs) and biological systems. ELF-MFs may interfere with chemical reactions involving reactive oxygen species (ROS), thus facilitating oxidative damages in living cells. Cortical neurons are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival. The aim of the present work was to investigate the effects of exposures to two different 50 Hz sinusoidal ELF-MFs intensities (0.1 and 1 mT) in maturing rat cortical neurons' major anti-oxidative enzymatic and non-enzymatic cellular protection systems, membrane peroxidative damage, as well as growth factor, and cytokine expression pattern. Briefly, our results showed that ELF-MFs affected positively the cell viability and concomitantly reduced the levels of apoptotic death in rat neuronal primary cultures, with no significant effects on the main anti-oxidative defences. Interestingly, linear regression analysis suggested a positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF-exposed cells. On this basis, our hypothesis is that GSH could play an important role in the antioxidant defence towards the ELF-MF-induced redox challenge. Moreover, the GSH-based cellular response was achieved together with a brain-derived neurotrophic factor over-expression as well as with the interleukin 1beta-dependent regulation of pro-survival signaling pathways after ELF-MF exposure.

COMMERCIAL MARITIME COAST STATIONS and WEATHER NETS

Science.gov Websites

Tsunamis 406 EPIRB's National Weather Service Marine Forecasts COMMERCIAL MARITIME COAST STATIONS and PRODUCTS VIA COMMERCIAL MARITIME COAST STATIONS and WEATHER NETS Commercial maritime coast stations, which ;NETS" operating on commercial marine VHF, MF and HF frequencies, where weather information is

47 CFR 80.913 - Radiotelephone receivers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pursuant to § 80.909 of this part. (c) If a very high frequency radiotelephone installation is provided... radiotelephone installation must have a sensitivity of at least 50 microvolts in the case of MF equipment, and 1... be capable of efficient operation when energized by the reserve source of energy. (g) The sensitivity...

47 CFR 80.913 - Radiotelephone receivers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pursuant to § 80.909 of this part. (c) If a very high frequency radiotelephone installation is provided... radiotelephone installation must have a sensitivity of at least 50 microvolts in the case of MF equipment, and 1... be capable of efficient operation when energized by the reserve source of energy. (g) The sensitivity...

47 CFR 80.913 - Radiotelephone receivers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pursuant to § 80.909 of this part. (c) If a very high frequency radiotelephone installation is provided... radiotelephone installation must have a sensitivity of at least 50 microvolts in the case of MF equipment, and 1... be capable of efficient operation when energized by the reserve source of energy. (g) The sensitivity...

47 CFR 80.913 - Radiotelephone receivers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pursuant to § 80.909 of this part. (c) If a very high frequency radiotelephone installation is provided... radiotelephone installation must have a sensitivity of at least 50 microvolts in the case of MF equipment, and 1... be capable of efficient operation when energized by the reserve source of energy. (g) The sensitivity...

47 CFR 80.913 - Radiotelephone receivers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pursuant to § 80.909 of this part. (c) If a very high frequency radiotelephone installation is provided... radiotelephone installation must have a sensitivity of at least 50 microvolts in the case of MF equipment, and 1... be capable of efficient operation when energized by the reserve source of energy. (g) The sensitivity...

Oral and Cutaneous Lymphomas other than Mycosis Fungoides and Sézary Syndrome in a Mexican Cohort: Recategorization and Evaluation of International Geographical Disparities

PubMed Central

Hernández-Salazar, Amparo; García-Vera, Jorge Andrés; Charli-Joseph, Yann; Ortiz-Pedroza, Guadalupe; Méndez-Flores, Silvia; Orozco-Topete, Rocío; Morales-Leyte, Ana Lilia; Domínguez-Cherit, Judith; Lome-Maldonado, Carmen

2017-01-01

Background: Nonmycosis fungoides/Sézary syndrome (non-MF/SS) primary cutaneous lymphomas (PCL) are currently categorized under the 2005-World Health Organization/European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for PCL. These differ in behavior from secondary cutaneous lymphomas (SCL) and to lymphomas limited to the oral cavity (primary oral lymphomas [POL]) both categorized under the 2016-WHO classification for lymphoid neoplasms. Aims: This study aims to report the first series of non-MF/SS PCL, SCL, and POL in a Mexican cohort, examine the applicability of current classification systems and compare our findings with those from foreign cohorts. Materials and Methods: Eighteen non-MF/SS PCL, four SCL, and two POL with available tissue for morphology and immunophenotypic assessment were reclassified according to the 2005-WHO/EORTC and 2016-WHO classifications. Results: Non-MF/SS PCLs were primarily of T-cell origin (61%) where CD30+ lymphoproliferative disorders predominated, followed by Epstein–Barr virus-induced lymphomas, and peripheral T-cell lymphomas, not otherwise specified. Primary cutaneous B-cell lymphomas (BCL) were primarily of follicle center cell origin followed by postgerminal lymphomas of the diffuse large BCL variety. Conclusions: Most non-MF/SS PCL, SCL, and POL can be adequately categorized according to the 2005-WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically atypical cases. The relative frequencies in our cohort hold closer similarities to Asian registries than from those of Europe/USA, supporting the concept of individual and/or racial susceptibility, and the notion of geographical variances in the rate of lymphomas. In particular, such disparity may arise from viral-induced lymphomas which might show partial geographical restriction. PMID:28400635

Empirical mode decomposition processing to improve multifocal-visual-evoked-potential signal analysis in multiple sclerosis

PubMed Central

2018-01-01

Objective To study the performance of multifocal-visual-evoked-potential (mfVEP) signals filtered using empirical mode decomposition (EMD) in discriminating, based on amplitude, between control and multiple sclerosis (MS) patient groups, and to reduce variability in interocular latency in control subjects. Methods MfVEP signals were obtained from controls, clinically definitive MS and MS-risk progression patients (radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS)). The conventional method of processing mfVEPs consists of using a 1–35 Hz bandpass frequency filter (XDFT). The EMD algorithm was used to decompose the XDFT signals into several intrinsic mode functions (IMFs). This signal processing was assessed by computing the amplitudes and latencies of the XDFT and IMF signals (XEMD). The amplitudes from the full visual field and from ring 5 (9.8–15° eccentricity) were studied. The discrimination index was calculated between controls and patients. Interocular latency values were computed from the XDFT and XEMD signals in a control database to study variability. Results Using the amplitude of the mfVEP signals filtered with EMD (XEMD) obtains higher discrimination index values than the conventional method when control, MS-risk progression (RIS and CIS) and MS subjects are studied. The lowest variability in interocular latency computations from the control patient database was obtained by comparing the XEMD signals with the XDFT signals. Even better results (amplitude discrimination and latency variability) were obtained in ring 5 (9.8–15° eccentricity of the visual field). Conclusions Filtering mfVEP signals using the EMD algorithm will result in better identification of subjects at risk of developing MS and better accuracy in latency studies. This could be applied to assess visual cortex activity in MS diagnosis and evolution studies. PMID:29677200

Indoor transformer stations as predictors of residential ELF magnetic field exposure.

PubMed

Ilonen, K; Markkanen, A; Mezei, G; Juutilainen, Jukka

2008-04-01

Transformer stations in apartment buildings may offer a possibility to conduct epidemiological studies that involve high exposure to extremely low frequency magnetic fields (MF), avoid selection bias and minimize confounding factors. To validate exposure assessment based on transformer stations, measurements were performed in thirty buildings in three Finnish cities. In each building, spot measurements in all rooms and a 24-h recording in a bedroom were performed in one apartment above a transformer station (AAT), in one first floor (FF) reference apartment, and one reference apartment on upper floors (UF). The apartment mean of spot measurements was 0.62 microT in the AATs, 0.21 microT in the FF and 0.11 microT in the UF reference apartments The 24-h apartment mean (estimated from the spot measurements and the bedroom 24-h recording) was 0.2 microT or higher in 29 (97%) AATs, in 7 (25%) FF and in 3 (10 %) UF reference apartments. The corresponding numbers for the 0.4 microT cut-off point were 19 (63%), 4 (14%), and 1 (3.3%). The higher MF level in the FF reference apartments indicates that they should not be considered "unexposed" in epidemiological studies. If such apartments are excluded, a transformer station under the floor predicts 24-h apartment mean MF with a sensitivity of 0.41 (or 0.58) and a specificity of 0.997 (or 0.97), depending on the MF cut-off point (0.2 or 0.4 microT). The results indicate that apartments can be reliably classified as high and low MF field categories based on the known location of transformer stations. (c) 2007 Wiley-Liss, Inc.

Electromagnetic, morphological and structural characterization of microwave absorbers based on POMA/magnetic filament composites

NASA Astrophysics Data System (ADS)

de Souza Pinto, Simone; Machado, João Paulo Barros; Gomes, Newton A. S.; Rezende, Mirabel Cerqueira

2018-03-01

This study aims to combine dielectric and magnetic properties of different materials in an unique composite. For this, poly(o-methoxyaniline), POMA, was chemically synthesized in situ on magnetic metallic filaments (MF). The obtained composite was inserted into an epoxy resin matrix in the proportions of 40, 50 and 70%, in weight (wt%). The samples were characterized by scanning electron microscopy (SEM), X ray diffraction (XRD) and electromagnetic measurements. On the last case, the measurements considered the reflectivity and the complex parameters of electrical permittivity and magnetic permeability in the frequency range of 8.2-12.4 GHz (X-band). Specimens with different thicknesses were evaluated by reflectivity. XRD results show that the filaments are based on Fe-α steel and SEM analyses show the good incorporation of POMA/MF in the epoxy resin composite. The complex parameters show that the real component of permittivity shows the largest variation with the POMA/MF concentration increasing in epoxy resin and the loss tangent indicates that the magnetic losses are preponderant on dielectric ones. The reflectivity measurements show that the 5 mm-specimen with 50 wt% of POMA/MF presents the best result of attenuation (-21.5 dB, i.e. above 99% of attenuation). Already, the sample containing 70 wt% shows the worst performance (up to -9.0 dB). The increase of POMA/MF concentration in epoxy resin confers maximum attenuation values for less thick specimens. The results show that the combination of dielectric and magnetic materials in a composite contributes for the improvement of microwave absorbing performance, and extends the possibilities of RAM processing with different characteristics.

The population genetics of human disease: The case of recessive, lethal mutations

PubMed Central

Gao, Ziyue; Baker, Zachary; Diesel, José Francisco; Simons, Yuval B.; Haque, Imran S.; Pickrell, Joseph; Przeworski, Molly

2017-01-01

Do the frequencies of disease mutations in human populations reflect a simple balance between mutation and purifying selection? What other factors shape the prevalence of disease mutations? To begin to answer these questions, we focused on one of the simplest cases: recessive mutations that alone cause lethal diseases or complete sterility. To this end, we generated a hand-curated set of 417 Mendelian mutations in 32 genes reported to cause a recessive, lethal Mendelian disease. We then considered analytic models of mutation-selection balance in infinite and finite populations of constant sizes and simulations of purifying selection in a more realistic demographic setting, and tested how well these models fit allele frequencies estimated from 33,370 individuals of European ancestry. In doing so, we distinguished between CpG transitions, which occur at a substantially elevated rate, and three other mutation types. Intriguingly, the observed frequency for CpG transitions is slightly higher than expectation but close, whereas the frequencies observed for the three other mutation types are an order of magnitude higher than expected, with a bigger deviation from expectation seen for less mutable types. This discrepancy is even larger when subtle fitness effects in heterozygotes or lethal compound heterozygotes are taken into account. In principle, higher than expected frequencies of disease mutations could be due to widespread errors in reporting causal variants, compensation by other mutations, or balancing selection. It is unclear why these factors would have a greater impact on disease mutations that occur at lower rates, however. We argue instead that the unexpectedly high frequency of disease mutations and the relationship to the mutation rate likely reflect an ascertainment bias: of all the mutations that cause recessive lethal diseases, those that by chance have reached higher frequencies are more likely to have been identified and thus to have been included in this study. Beyond the specific application, this study highlights the parameters likely to be important in shaping the frequencies of Mendelian disease alleles. PMID:28957316

Inhibition of ovarian development by methyl farnesoate in the tadpole shrimp, Triops longicaudatus.

PubMed

Tsukimura, B; Nelson, W K; Linder, C J

2006-06-01

Methyl farnesoate (MF), a putative crustacean hormone, is the immediate precursor of insect juvenile hormone III (JHIII) in the biosynthetic pathway. We examined whether MF, shown to inhibit adult metamorphosis in several crustacean species, is a juvenilizing factor in the tadpole shrimp, Triops longicaudatus. Oocyte production was chosen as a parameter for measuring reproductive development. MF was administered to juveniles by ingestion via biological vector (Artemia nauplii), MF-coated food pellets, and MF liposome food pellets. Artemia were incubated in 30 microl of 5 microg/ml MF. The MF-coated and MF liposome pellets were prepared with MF concentrations ranging between 0.1 microg/g and 10 microg/g MF by weight. Groups of tadpole shrimp were treated with these vectors from the time of hatching for 5 or 10 days in laboratory and field studies. The treatment groups of all the MF vectors showed reductions in oocyte production. Lower concentrations of MF (0.75 microg/g-3.8 microg/g MF) appeared to have a physiological effect on fecundity, but higher concentrations (10 microg/g MF) reduced somatic growth. MF-coated pellets (1 microg/g MF) administered to adults (after 5 days) caused no difference in oocyte production. The observed reductions of fecundity and the disparity of results between MF treatment on juveniles and adults suggest that MF may regulate ovarian development.

MF2KtoMF05UC, a Program To Convert MODFLOW-2000 Files to MODFLOW-2005 and UCODE_2005 Files

USGS Publications Warehouse

Harbaugh, Arlen W.

2007-01-01

The program MF2KtoMF05UC has been developed to convert MODFLOW-2000 input files for use by MODFLOW-2005 and UCODE_2005. MF2KtoMF05UC was written in the Fortran 90 computer language. This report documents the use of MF2KtoMF05UC.

Prevalence and etiology of false normal aEEG recordings in neonatal hypoxic-ischaemic encephalopathy

PubMed Central

2013-01-01

Background Amplitude-integrated electroencephalography (aEEG) is a useful tool to determine the severity of neonatal hypoxic-ischemic encephalopathy (HIE). Our aim was to assess the prevalence and study the origin of false normal aEEG recordings based on 85 aEEG recordings registered before six hours of age. Methods Raw EEG recordings were reevaluated retrospectively with Fourier analysis to identify and describe the frequency patterns of the raw EEG signal, in cases with inconsistent aEEG recordings and clinical symptoms. Power spectral density curves, power (P) and median frequency (MF) were determined using the raw EEG. In 7 patients non-depolarizing muscle relaxant (NDMR) exposure was found. The EEG sections were analyzed and compared before and after NDMR administration. Results The reevaluation found that the aEEG was truly normal in 4 neonates. In 3 neonates, high voltage electrocardiographic (ECG) artifacts were found with flat trace on raw EEG. High frequency component (HFC) was found as a cause of normal appearing aEEG in 10 neonates. HFC disappeared while P and MF decreased significantly upon NDMR administration in each observed case. Conclusion Occurrence of false normal aEEG background pattern is relatively high in neonates with HIE and hypothermia. High frequency EEG artifacts suggestive of shivering were found to be the most common cause of false normal aEEG in hypothermic neonates while high voltage ECG artifacts are less common. PMID:24268061

Infrared spectra of MF2, MF2+, MF4-, MF3, and M2F6 molecules (M = Sc, Y, La) in solid argon.

PubMed

Wang, Xuefeng; Andrews, Lester

2010-02-18

Reactions of laser-ablated Sc, Y and La atoms with F(2) in excess argon gave new absorptions in the M-F stretching region, which are assigned to metal fluoride neutral species MF(2) and MF(3) and ions MF(2)(+) and MF(4)(-). Dibridged MF(3) dimers, M(2)F(6), were also identified through terminal M-F and bridge M-F-M stretching modes. Density functional theory (DFT) calculations substantiated the experimental assignments. Mulliken and natural charge distributions indicate significant electron transfer from metal d orbitals to F ligands that increase from Sc to La, suggesting that strong participation of La 5d orbital hybridization drives the F-La-F bond angle below 120 degrees.

Fibrosis identified in the bone marrow biopsies of patients with essential thrombocythemia: its incidence and significance for the differential diagnostic considerations.

PubMed

Marcinek, J; Plank, L; Szépe, P; Balhárek, T

2008-07-01

Myelofibrosis (MF) may develop in all types of myeloproliferative disorders and its identification is of clinical relevance. Typical bone marrow (BM) morphology of patients with essential thrombocythemia (ET) shows either "normal" amount or "a slight increase" of reticulin fibers, but the published data differ in relation to the applied MF definition and ET diagnostic criterias. The aim of this study was to evaluate retrospectivelly MF in BM biopsies of 30 cases in which the diagnosis of ET was confirmed also clinically by local hematologists. In 7 of the patients not only primary but also sequential biopsy was available. The MF grade and extent were evaluated semiquantitativelly in archival slides stained by Gömöri silver impregnation. The analysis was based on the European clinicopathological criteria 2004 (ECP) defining a) normal bone marrow fibrosis (MF0), b) slight reticulin fibrosis (MF1), c) advanced reticulin and initial collagen fibrosis (MF2) and d) advanced collagen fibrosis (MF3). Generally, in majority of the biopsies MF0 (n = 6) or MF1 (n = 25, 18x focal and 7x diffuse) was found. More advanced MF2 was much less common as it was present in 6 biopsies (5x focal and 1x diffuse). In relation to the actual time of BM biopsy during course of the disease, the introductory biopsies done at the time of diagnosis (n = 18) showed 3x MF0, 14x MF1 and 1x MF2. The biopsies performed after a long time of patients observations (n = 12) showed 3x MF0, 7x MF1 and 2x MF2. In 5 of 7 sequential biopsies the progress of MF was evident, but 4 of these patients were treated by cytoreductive therapy. We conclude that the BM of patients with ET in initial phase shows either MF0 or focal slight increase of reticulin fibers (MF1). In addition, the long course of the disease and/or applied therapy may lead to more developed MF and more advanced MF stages (diffuse MF1 or MF2). Therefore their finding in the BM biopsies examined in the later phases of the disease should not exclude the diagnosis of ET.

Spontaneous mutations in Streptococcus pyogenes isolates from streptococcal toxic shock syndrome patients play roles in virulence

PubMed Central

Ikebe, Tadayoshi; Matsumura, Takayuki; Nihonmatsu, Hisako; Ohya, Hitomi; Okuno, Rumi; Mitsui, Chieko; Kawahara, Ryuji; Kameyama, Mitsuhiro; Sasaki, Mari; Shimada, Naomi; Ato, Manabu; Ohnishi, Makoto

2016-01-01

Streptococcus pyogenes (group A Streptococcus; GAS) is a widespread human pathogen and causes streptococcal toxic shock syndrome (STSS). STSS isolates have been previously shown to have high frequency mutations in the csrS/csrR (covS/covR) and/or rgg (ropB) genes, which are negative regulators of virulence. However, these mutations were found at somewhat low frequencies in emm1-genotyped isolates, the most prevalent STSS genotype. In this study, we sought to detect causal mutations of enhanced virulence in emm1 isolates lacking mutation(s) in the csrS/csrR and rgg genes. Three mutations associated with elevated virulence were found in the sic (a virulence gene) promoter, the csrR promoter, and the rocA gene (a csrR positive regulator). In vivo contribution of the sic promoter and rocA mutations to pathogenicity and lethality was confirmed in a GAS mouse model. Frequency of the sic promoter mutation was significantly higher in STSS emm1 isolates than in non-invasive STSS isolates; the rocA gene mutation frequency was not significantly different among STSS and non-STSS isolates. STSS emm1 isolates possessed a high frequency mutation in the sic promoter. Thus, this mutation may play a role in the dynamics of virulence and STSS pathogenesis. PMID:27349341

Spontaneous mutations in Streptococcus pyogenes isolates from streptococcal toxic shock syndrome patients play roles in virulence.

PubMed

Ikebe, Tadayoshi; Matsumura, Takayuki; Nihonmatsu, Hisako; Ohya, Hitomi; Okuno, Rumi; Mitsui, Chieko; Kawahara, Ryuji; Kameyama, Mitsuhiro; Sasaki, Mari; Shimada, Naomi; Ato, Manabu; Ohnishi, Makoto

2016-06-28

Streptococcus pyogenes (group A Streptococcus; GAS) is a widespread human pathogen and causes streptococcal toxic shock syndrome (STSS). STSS isolates have been previously shown to have high frequency mutations in the csrS/csrR (covS/covR) and/or rgg (ropB) genes, which are negative regulators of virulence. However, these mutations were found at somewhat low frequencies in emm1-genotyped isolates, the most prevalent STSS genotype. In this study, we sought to detect causal mutations of enhanced virulence in emm1 isolates lacking mutation(s) in the csrS/csrR and rgg genes. Three mutations associated with elevated virulence were found in the sic (a virulence gene) promoter, the csrR promoter, and the rocA gene (a csrR positive regulator). In vivo contribution of the sic promoter and rocA mutations to pathogenicity and lethality was confirmed in a GAS mouse model. Frequency of the sic promoter mutation was significantly higher in STSS emm1 isolates than in non-invasive STSS isolates; the rocA gene mutation frequency was not significantly different among STSS and non-STSS isolates. STSS emm1 isolates possessed a high frequency mutation in the sic promoter. Thus, this mutation may play a role in the dynamics of virulence and STSS pathogenesis.

Insertion of rare gas atoms into BF3 and AlF3 molecules: An ab initio investigation

NASA Astrophysics Data System (ADS)

Jayasekharan, T.; Ghanty, T. K.

2006-12-01

The structure, stability, charge redistribution, and harmonic vibrational frequencies of rare gas inserted group III-B fluorides with the general formula F -Rg-MF2 (where M =B and Al; Rg =Ar, Kr, and Xe) have been investigated using ab initio quantum chemical methods. The Rg atom is inserted in one of the M -F bond of MF3 molecules, and the geometries are optimized for ground as well as transition states using the MP2 method. It has been found that Rg inserted F -Rg-M portion is linear in both F -Rg-BF2 and F -Rg-AlF2 species. The binding energies corresponding to the lowest energy fragmentation products MF3+Rg (two-body dissociation) have been computed to be -670.4, -598.8, -530.7, -617.0, -562.1, and -494.0kJ /mol for F -Ar-BF2, F -Kr-BF2, F -Xe-BF2, F -Ar-AlF2, F -Kr-AlF2, and F -Xe-AlF2 species, respectively. The dissociation energies corresponding to MF2+Rg +F fragments (three-body dissociation) are found to be positive with respect to F -Rg-MF2 species, and the computed values are 56.3, 127.8, and 196.0kJ/mol for F -Ar-BF2, F -Kr-BF2, and F -Xe-BF2 species, respectively. The corresponding values for F -Ar-AlF2, F -Kr-AlF2, and F -Xe-AlF2 species are also found to be positive. The decomposition of F -Rg-MF2 species into the MF3+Rg (two-body dissociation) channel typically proceeds via a transition state involving F -Rg-M out-of-plane bending mode. The transition state barrier heights are 35.5, 62.7, 89.8, 22.0, 45.6, and 75.3kJ/mol for F -Ar-BF2, F -Kr-BF2, F -Xe-BF2, F -Ar-AlF2, F -Kr-AlF2, and F -Xe-AlF2 species, respectively. The calculated geometrical parameters and the energy values suggest that these species are metastable and may be prepared and characterized using low temperature matrix isolation techniques, and are possibly the next new candidates for gas phase or matrix experiments.

Estimating Exceptionally Rare Germline and Somatic Mutation Frequencies via Next Generation Sequencing

PubMed Central

Yoon, Song-Ro; Arnheim, Norman; Calabrese, Peter

2016-01-01

We used targeted next generation deep-sequencing (Safe Sequencing System) to measure ultra-rare de novo mutation frequencies in the human male germline by attaching a unique identifier code to each target DNA molecule. Segments from three different human genes (FGFR3, MECP2 and PTPN11) were studied. Regardless of the gene segment, the particular testis donor or the 73 different testis pieces used, the frequencies for any one of the six different mutation types were consistent. Averaging over the C>T/G>A and G>T/C>A mutation types the background mutation frequency was 2.6x10-5 per base pair, while for the four other mutation types the average background frequency was lower at 1.5x10-6 per base pair. These rates far exceed the well documented human genome average frequency per base pair (~10−8) suggesting a non-biological explanation for our data. By computational modeling and a new experimental procedure to distinguish between pre-mutagenic lesion base mismatches and a fully mutated base pair in the original DNA molecule, we argue that most of the base-dependent variation in background frequency is due to a mixture of deamination and oxidation during the first two PCR cycles. Finally, we looked at a previously studied disease mutation in the PTPN11 gene and could easily distinguish true mutations from the SSS background. We also discuss the limits and possibilities of this and other methods to measure exceptionally rare mutation frequencies, and we present calculations for other scientists seeking to design their own such experiments. PMID:27341568

EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII)

PubMed Central

Midha, Anita; Dearden, Simon; McCormack, Rose

2015-01-01

Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small-cell lung cancer (NSCLC), particularly in tumors of adenocarcinoma (ADC) histology (NSCLC/ADC). Robust data exist regarding the prevalence of EGFR mutations in Western and Asian patients with NSCLC/ADC, yet there is a lack of data for patients of other ethnicities. This review collated available data with the aim of creating a complete, global picture of EGFR mutation frequency in patients with NSCLC/ADC by ethnicity. Worldwide literature reporting EGFR mutation frequency in patients with NSCLC/ADC was reviewed, to create a map of the world populated with EGFR mutation frequency by country (a ‘global EGFR mutMap’). A total of 151 worldwide studies (n=33162 patients with NSCLC/ADC, of which 9749 patients had EGFR mutation-positive NSCLC/ADC) were included. There was substantial variation in EGFR mutation frequency between studies, even when grouped by geographic region or individual country. As expected, the Asia-Pacific NSCLC/ADC subgroup had the highest EGFR mutation frequency (47% [5958/12819; 87 studies; range 20%-76%]) and the lowest EGFR mutation frequency occurred in the Oceania NSCLC/ADC subgroup (12% [69/570; 4 studies; range 7%-36%]); however, comparisons between regions were limited due to the varying sizes of the patient populations studied. In all regional (geographic) subgroups where data were available, EGFR mutation frequency in NSCLC/ADC was higher in women compared with men, and in never-compared with ever-smokers. This review provides the foundation for a global map of EGFR mutation frequency in patients with NSCLC/ADC. The substantial lack of data from several large geographic regions of the world, notably Africa, the Middle East, Central Asia, and Central and South America, highlights a potential lack of routine mutation testing and the need for further investigations in these regions. PMID:26609494

THE ROTATION OF THE SOLAR PHOTOSPHERIC MAGNETIC FIELD

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

Xu, J. C.; Gao, P. X., E-mail: jcxu@ynao.ac.cn

2016-12-20

The rotational characteristics of the solar photospheric magnetic field at four flux ranges are investigated together with the total flux of active regions (MF{sub ar}) and quiet regions (MF{sub qr}). The first four ranges (MF{sub 1–4}) are (1.5–2.9) × 10{sup 18}, (2.9–32.0) × 10{sup 18}, (3.20–4.27) × 10{sup 19}, and (4.27–38.01) × 10{sup 19}, respectively (the unit is Mx per element). Daily values of the flux data are extracted from magnetograms of the Michelson Doppler Imager on board the Solar and Heliospheric Observatory . Lomb–Scargle periodograms show that only MF{sub 2}, MF{sub 4}, MF{sub qr}, and MF{sub ar} exhibit rotational periods. The periods of the first three typesmore » of flux are very similar, i.e., 26.20, 26.23, and 26.24 days, respectively, while that of MF{sub ar} is longer, 26.66 days. This indicates that active regions rotate more slowly than quiet regions on average, and strong magnetic fields tend to repress the surface rotation. Sinusoidal function fittings and cross-correlation analyses reveal that MF{sub ar} leads MF{sub 2} and MF{sub 4} by 5 and 1 days, respectively. This is speculated to be related with the decaying of active regions. MF{sub 2} and MF{sub ar} are negatively correlated, while both MF{sub 4} and MF{sub qr} are positively correlated with MF{sub ar}. At the timescale of the solar activity cycle, MF{sub ar} leads (negatively) MF{sub 2} by around one year (350 days), and leads MF{sub 4} by about 3 rotation periods (82 days). The relation between MF{sub 2} and MF{sub ar} may be explained by the possibility that the former mainly comes from a higher latitude, or emerges from the subsurface shear layer. We conjecture that MF{sub 4} may partly come from the magnetic flux of active regions; this verifies previous results that were obtained with indirect solar magnetic indices.« less

Multifrequency Pulsed EPR Studies of Biologically Relevant Manganese(II) Complexes

PubMed Central

Stich, T. A.; Lahiri, S.; Yeagle, G.; Dicus, M.; Brynda, M.; Gunn, A.; Aznar, C.; DeRose, V. J.; Britt, R. D.

2011-01-01

Electron paramagnetic resonance studies at multiple frequencies (MF EPR) can provide detailed electronic structure descriptions of unpaired electrons in organic radicals, inorganic complexes, and metalloenzymes. Analysis of these properties aids in the assignment of the chemical environment surrounding the paramagnet and provides mechanistic insight into the chemical reactions in which these systems take part. Herein, we present results from pulsed EPR studies performed at three different frequencies (9, 31, and 130 GHz) on [Mn(II)(H2O)6]2+, Mn(II) adducts with the nucleotides ATP and GMP, and the Mn(II)-bound form of the hammerhead ribozyme (MnHH). Through line shape analysis and interpretation of the zero-field splitting values derived from successful simulations of the corresponding continuous-wave and field-swept echo-detected spectra, these data are used to exemplify the ability of the MF EPR approach in distinguishing the nature of the first ligand sphere. A survey of recent results from pulsed EPR, as well as pulsed electron-nuclear double resonance and electron spin echo envelope modulation spectroscopic studies applied to Mn(II)-dependent systems, is also presented. PMID:22190766

Transcriptional and functional profiling defines human small intestinal macrophage subsets.

PubMed

Bujko, Anna; Atlasy, Nader; Landsverk, Ole J B; Richter, Lisa; Yaqub, Sheraz; Horneland, Rune; Øyen, Ole; Aandahl, Einar Martin; Aabakken, Lars; Stunnenberg, Hendrik G; Bækkevold, Espen S; Jahnsen, Frode L

2018-02-05

Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos. © 2018 Bujko et al.

Photocatalytic characteristic and photodegradation kinetics of toluene using N-doped TiO2 modified by radio frequency plasma.

PubMed

Shie, Je-Lueng; Lee, Chiu-Hsuan; Chiou, Chyow-San; Chen, Yi-Hung; Chang, Ching-Yuan

2014-01-01

This study investigates the feasibility of applications of the plasma surface modification of photocatalysts and the removal of toluene from indoor environments. N-doped TiO2 is prepared by precipitation methods and calcined using a muffle furnace (MF) and modified by radio frequency plasma (RF) at different temperatures with light sources from a visible light lamp (VLL), a white light-emitting diode (WLED) and an ultraviolet light-emitting diode (UVLED). The operation parameters and influential factors are addressed and prepared for characteristic analysis and photo-decomposition examination. Furthermore, related kinetic models are established and used to simulate the experimental data. The characteristic analysis results show that the RF plasma-calcination method enhanced the Brunauer Emmett Teller surface area of the modified photocatalysts effectively. For the elemental analysis, the mass percentages of N for the RF-modified photocatalyst are larger than those of MF by six times. The aerodynamic diameters of the RF-modifiedphotocatalyst are all smaller than those of MF. Photocatalytic decompositions of toluene are elucidated according to the Langmuir-Hinshelwood model. Decomposition efficiencies (eta) of toluene for RF-calcined methods are all higher than those of commercial TiO2 (P25). Reaction kinetics ofphoto-decomposition reactions using RF-calcined methods with WLED are proposed. A comparison of the simulation results with experimental data is also made and indicates good agreement. All the results provide useful information and design specifications. Thus, this study shows the feasibility and potential use of plasma modification via LED in photocatalysis.

Cloning and characterization of two novel DNases from Streptococcus pyogenes.

PubMed

Hasegawa, Tadao; Torii, Keizo; Hashikawa, Shinnosuke; Iinuma, Yoshitsugu; Ohta, Michio

2002-06-01

The proteins in the culture supernatant (exoproteins) from Streptococcus pyogenes serotype M1 were separated by two-dimensional gel electrophoresis, and their N-terminal amino acid sequences were determined. The amino acid sequences were compared to sequences in the S. pyogenes genome database. The coding sequence showed similarity to sequences of two genes, mf2-v ( mf2 variant) and mf3, which had sequence similarity to genes encoding mitogenic factor (MF); MF has DNase activity. The recombinant genes were expressed in Escherichia coli and the proteins were synthesized. Mf2-v and Mf3 had DNase activity. The activity of Mf2-v was localized to the C-terminal half of the protein. The mf3 gene was shown to be present in most clinically isolated strains of S. pyogenes tested, and the mf2gene was detected in 20% of the isolates. The products of the mf2 and mf3 genes in clinically isolated S. pyogenes strains were thus shown to be DNases.

Modulations of the surface magnetic field on the intra-cycle variability of total solar irradiance

NASA Astrophysics Data System (ADS)

Xu, J. C.; Kong, D. F.; Li, F. Y.

2018-05-01

Solar photospheric magnetic field plays a dominant role in the variability of total solar irradiance (TSI). The modulation of magnetic flux at six specific ranges on TSI is characterized for the first time. The daily flux values of magnetic field at four ranges are extracted from MDI/ SOHO, together with daily flux of active regions (MF_{ar}) and quiet regions (MF_{qr}); the first four ranges (MF_{1-4}) are: 1.5-2.9, 2.9-32.0, 32.0-42.7, and 42.7-380.1 (× 10^{18} Mx per element), respectively. Cross-correlograms show that MF4, MF_{qr}, and MF_{ ar} are positively correlated with TSI, while MF2 is negatively correlated with TSI; the correlations between MF1, MF3 and TSI are insignificant. The bootstrapping tests confirm that the impact of MF4 on TSI is more significant than that of MF_{ar} and MF_{qr}, and MF_{ar} leads TSI by one rotational period. By extracting the rotational variations in the MFs and TSI, the modulations of the former on the latter at the solar rotational timescale are clearly illustrated and compared during solar maximum and minimum times, respectively. Comparison of the relative amplitudes of the long-term variation show that TSI is in good agreement with the variation of MF4 and MF_{ar}; besides, MF2 is in antiphase with TSI, and it lags the latter by about 1.5 years.

Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

PubMed Central

2012-01-01

Background The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from low- and high-risk areas. Methods English articles using MEDLINE access (from 1998 to 2011). Search terms included CDH1, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype. The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded. The method of this study was scheduled in accordance with the "PRISMA statement for reporting systematic reviews and meta-analyses". Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the CDH1 mutation frequency with gastric cancer incidence areas. Results A total of 122 E-cadherin germline mutations have been identified; the majority (87.5%) occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%). We verified a significant association between the mutation frequency and the gastric cancer risk area (p < 0.001: overall identified mutations in low- vs. middle/high-risk areas). Conclusions E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of CDH1 germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the CDH1 genetic screening, geographic variability, alongside the family history should be considered. PMID:22225527

A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India.

PubMed

Kar, Shantanu Kumar; Dwibedi, Bhagirathi; Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

2015-03-01

Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start.

The Role of Microfilaments in Early Meiotic Maturation of Mouse Oocytes

NASA Astrophysics Data System (ADS)

Calarco, Patricia G.

2005-04-01

Mouse oocyte microfilaments (MF) were perturbed by depolymerization (cytochalasin B) or stabilization (jasplakinolide) and correlated meiotic defects examined by confocal microscopy. MF, microtubules, and mitochondria were vitally stained; centrosomes ([gamma]-tubulin), after fixation. MF depolymerization by cytochalasin in culture medium did not affect central migration of centrosomes, mitochondria, or nuclear breakdown (GVBD); some MF signal was localized around the germinal vesicle (GV). In maturation-blocking medium (containing IBMX), central movement was curtailed and cortical MF aggregations made the plasma membrane wavy. Occasional long MF suggested that not all MF were depolymerized. MF stabilization by jasplakinolide led to MF aggregations throughout the cytoplasm. GVBD occurred (unless IBMX was present) but no spindle formed. Over time, most oocytes constricted creating a dumbbell shape with MF concentrated under one-half of the oocyte cortex and on either side of the constriction. In IBMX medium, the MF-containing half of the dumbbell over time sequestered the GV, MF, mitochondria, and one to two large cortical centrosomes; the non-MF half appeared empty. Cumulus processes contacted the oocyte surface (detected by microtubule content) and mirrored MF distribution. Results demonstrated that MF play an essential role in meiosis, primarily through cortically mediated events, including centrosome localization, spindle (or GV) movement to the periphery, activation of (polar body) constriction, and establishment of oocyte polarity. The presence of a cortical “organizing pole” is hypothesized.

[Measures of occupational exposure to time-varying low frequency magnetic fields of non-uniform spatial distribution in the light of international guidelines and electrodynamic exposure effects in the human body].

PubMed

Karpowicz, Jolanta; Zradziński, Patryk; Gryz, Krzysztof

2012-01-01

The aim of study was to analyze by computer simulations the electrodynamic effects of magnetic field (MF) on workers, to harmonize the principles of occupational hazards assessment with international guidelines. Simulations involved 50 Hz MF of various spatial distributions, representing workers' exposure in enterprises. Homogeneous models of sigma = 0.2 S/m conductivity and dimensions of body parts - palm, head and trunk - were located at 50 cm ("hand-distance") or 5 cm (adjacent) from the source (circle conductor of 20 cm or 200 cm in diameter). Parameters of magnetic flux density (B(i)) affecting the models were the exposure measures, and the induced electric field strength (E(in)) was the measure of MF exposure effects. The ratio E(in)/B(i) in the analyzed cases ranged from 2.59 to 479 (V/m)/T. The strongest correlation (p < 0.001) between B(i) and E(in) was found for parameters characterizing MF at the surface of body models. Parameters characterizing the averaged value of the field affecting models (measures of non-uniform field exposure following ICNIRP guidelines), were less correlated with exposure effects (p < 0.005). E(in)(trunk)/E(in) (palm) estimated from E(in) calculations was 3.81-4.56 but estimated from parameters representing B(i) measurement accounted for 3.96-9.74. It is justified to accept 3.96-9.74 times higher exposure to limb than that to trunk. This supports the regulation of labor law in Poland, which provides that the ceiling value for limb exposure to MF below 800 kHz is fivefold higher than that of the trunk. High uncertainty in assessing the effects of non-uniform fields exposure, resulting from a strong dependence of the E(in)/B(i) ratio on the conditions of exposure and its applied measures, requires special caution when defining the permissible MF levels and the principles of exposure assessment at workplace.

Implications from palaeoseismological investigations at the Markgrafneusiedl Fault (Vienna Basin, Austria) for seismic hazard assessment

NASA Astrophysics Data System (ADS)

Hintersberger, Esther; Decker, Kurt; Lomax, Johanna; Lüthgens, Christopher

2018-02-01

Intraplate regions characterized by low rates of seismicity are challenging for seismic hazard assessment, mainly for two reasons. Firstly, evaluation of historic earthquake catalogues may not reveal all active faults that contribute to regional seismic hazard. Secondly, slip rate determination is limited by sparse geomorphic preservation of slowly moving faults. In the Vienna Basin (Austria), moderate historical seismicity (Imax, obs / Mmax, obs = 8/5.2) concentrates along the left-lateral strike-slip Vienna Basin Transfer Fault (VBTF). In contrast, several normal faults branching out from the VBTF show neither historical nor instrumental earthquake records, although geomorphological data indicate Quaternary displacement along those faults. Here, located about 15 km outside of Vienna, the Austrian capital, we present a palaeoseismological dataset of three trenches that cross one of these splay faults, the Markgrafneusiedl Fault (MF), in order to evaluate its seismic potential. Comparing the observations of the different trenches, we found evidence for five to six surface-breaking earthquakes during the last 120 kyr, with the youngest event occurring at around 14 ka. The derived surface displacements lead to magnitude estimates ranging between 6.2 ± 0.5 and 6.8 ± 0.4. Data can be interpreted by two possible slip models, with slip model 1 showing more regular recurrence intervals of about 20-25 kyr between the earthquakes with M ≥ 6.5 and slip model 2 indicating that such earthquakes cluster in two time intervals in the last 120 kyr. Direct correlation between trenches favours slip model 2 as the more plausible option. Trench observations also show that structural and sedimentological records of strong earthquakes with small surface offset have only low preservation potential. Therefore, the earthquake frequency for magnitudes between 6 and 6.5 cannot be constrained by the trenching records. Vertical slip rates of 0.02-0.05 mm a-1 derived from the trenches compare well to geomorphically derived slip rates of 0.02-0.09 mm a-1. Magnitude estimates from fault dimensions suggest that the largest earthquakes observed in the trenches activated the entire fault surface of the MF including the basal detachment that links the normal fault with the VBTF. The most important implications of these palaeoseismological results for seismic hazard assessment are as follows. (1) The MF is an active seismic source, capable of rupturing the surface despite the lack of historical earthquakes. (2) The MF is kinematically and geologically equivalent to a number of other splay faults of the VBTF. It is reasonable to assume that these faults are potential sources of large earthquakes as well. The frequency of strong earthquakes near Vienna is therefore expected to be significantly higher than the earthquake frequency reconstructed for the MF alone. (3) Although rare events, the potential for earthquake magnitudes equal or greater than M = 7.0 in the Vienna Basin should be considered in seismic hazard studies.

The stereoselective sulfate conjugation of 4'-methoxyfenoterol stereoisomers by sulfotransferase enzymes.

PubMed

Iyer, Lalitha V; Ramamoorthy, Anuradha; Rutkowska, Ewelina; Furimsky, Anna M; Tang, Liang; Catz, Paul; Green, Carol E; Jozwiak, Krzysztof; Wainer, Irving W

2012-10-01

The presystemic sulfate conjugation of the stereoisomers of 4'-methoxyfenoterol, (R,R')-MF, (S,S')-MF, (R,S')-MF, and (S,R')-MF, was investigated using commercially available human intestinal S9 fractions, a mixture of sulfotransferase (SULT) enzymes. The results indicate that the sulfation was stereospecific and that an S-configuration at the β-OH carbon of the MF molecule enhanced the maximal formation rates with (S,R')-MF  (S,S')-MF  (R,S')-MF ≈ (R,R')-MF, and competition studies demonstrated that (S,R')-MF is an effective inhibitor of (R,R')-MF sulfation (IC(50) = 60 μM). In addition, the results from a cDNA-expressed human SULT isoform screen indicated that SULT1A1, SULT1A3, and SULT1E1 can mediate the sulfation of all four MF stereoisomers. Previously published molecular models of SULT1A3 and SULT1A1 were used in docking simulations of the MF stereoisomers using Molegro Virtual Docker. The models of the MF-SULT1A3 and MF-SULT1A1 complexes indicate that each of the two chiral centers of MF molecule plays a role in the observed relative stabilities. The observed stereoselectivity is the result of multiple hydrogen bonding interactions and induced conformational changes within the substrate-enzyme complex. In conclusion, the results suggest that a formulation developed from a mixture of (R,R')-MF and (S,R')-MF may increase the oral bioavailability of (R,R')-MF. Copyright © 2012 Wiley Periodicals, Inc.

Molecular characterization of Giardia lamblia in children less than 5 years of age with diarrhoea attending the Bengo General Hospital, Angola

PubMed Central

Gasparinho, Carolina; Ferreira, Filipa S; Mayer, António Carlos; Mirante, Maria Clara; Vaz Nery, Susana; Santos-Reis, Ana; Portugal-Calisto, Daniela; Brito, Miguel

2017-01-01

Abstract Background Giardia lamblia is a pathogenic intestinal protozoan with high prevalence in developing countries, especially among children. Molecular characterization has revealed the existence of eight assemblages, with A and B being more commonly described in human infections. Despite its importance, to our knowledge this is the first published molecular analysis of G. lamblia assemblages in Angola. Methods The present study aimed to identify the assemblages of G. lamblia in children with acute diarrhoea presenting at the Bengo General Hospital, Angola. A stool sample was collected and microscopy and immunochromatographic tests were used. DNA was extracted and assemblage determination was performed through amplification of the gene fragment ssu-rRNA (175 bp) and β-giardin (511 bp) through polymerase chain reaction and DNA sequencing. Results Of the 16 stool samples screened, 12 were successfully sequenced. Eleven isolates were assigned to assemblage B and one to assemblage A. Subassemblage determination was not possible for assemblage B, while the single isolate assigned to assemblage A was identified as belonging to subassemblage A3. Conclusion This study provides information about G. lamblia assemblages in Bengo Province, Angola and may contribute as a first step in understanding the molecular epidemiology of this protozoan in the country. GenBank accession numbers for the ssur-RNA gene: MF479750, MF479751, MF479752, MF479753, MF479754, MF479755, MF479756, MF479757, MF479758, MF479759, MF479760, MF479761. GenBank accession numbers for the β-giardin gene: MF565378, MF565379, MF565380, MF565381. PMID:29438541

[Comparative analysis of real-time quantitative PCR-Sanger sequencing method and TaqMan probe method for detection of KRAS/BRAF mutation in colorectal carcinomas].

PubMed

Zhang, Xun; Wang, Yuehua; Gao, Ning; Wang, Jinfen

2014-02-01

To compare the application values of real-time quantitative PCR-Sanger sequencing and TaqMan probe method in the detection of KRAS and BRAF mutations, and to correlate KRAS/BRAF mutations with the clinicopathological characteristics in colorectal carcinomas. Genomic DNA of the tumor cells was extracted from formalin fixed paraffin embedded (FFPE) tissue samples of 344 colorectal carcinomas by microdissection. Real-time quantitative PCR-Sanger sequencing and TaqMan probe method were performed to detect the KRAS/BRAF mutations. The frequency and types of KRAS/BRAF mutations, clinicopathological characteristics and survival time were analyzed. KRAS mutations were detected in 39.8% (137/344) and 38.7% (133/344) of 344 colorectal carcinomas by using real-time quantitative PCR-Sanger sequencing and TaqMan probe method, respectively. BRAF mutation was detected in 4.7% (16/344) and 4.1% (14/344), respectively. There was no significant correlation between the two methods. The frequency of the KRAS mutation in female was higher than that in male (P < 0.05). The frequency of the BRAF mutation in colon was higher than that in rectum. The frequency of the BRAF mutation in stage III-IV cases was higher than that in stageI-II cases. The frequency of the BRAF mutation in signet ring cell carcinoma was higher than that in mucinous carcinoma and nonspecific adenocarcinoma had the lowest mutation rate. The frequency of the BRAF mutation in grade III cases was higher than that in grade II cases (P < 0.05). The overall concordance for the two methods of KRAS/BRAF mutation detection was 98.8% (kappa = 0.976). There was statistic significance between BRAF and KRAS mutations for the survival time of colorectal carcinomas (P = 0.039). There were no statistic significance between BRAF mutation type and BRAF/KRAS wild type (P = 0.058). (1) Compared with real-time quantitative PCR-Sanger sequencing, TaqMan probe method is better with regard to handling time, efficiency, repeatability, cost and equipment. (2) The frequency of the KRAS mutation is correlated with gender. BRAF mutation is correlated with primary tumor site, TNM stage, histological types and histological grades.(3) BRAF gene mutation is an independent prognostic marker for colorectal carcinomas.

Tissue-specific time courses of spontaneous mutation frequency and deviations in mutation pattern are observed in middle to late adulthood in Big Blue mice.

PubMed

Hill, Kathleen A; Halangoda, Asanga; Heinmoeller, Petra W; Gonzalez, Kelly; Chitaphan, Chaniga; Longmate, Jeffrey; Scaringe, William A; Wang, Ji-Cheng; Sommer, Steve S

2005-06-01

To better define the time course of spontaneous mutation frequency in middle to late adulthood of the mouse, measurements were made at 10, 14, 17, 23, 25, and 30 months of age in samples of adipose tissue, liver, cerebellum (90% neurons), and the male germline (95% germ cells). A total of 46 million plaque-forming units (pfus) were screened at the six time points and 1,450 circular blue plaques were harvested and sequenced. These data improve resolution and confirm the previously observed occurrence of at least two tissue-specific profiles of spontaneous mutation frequency (elevation with age in adipose tissue and liver, and constancy with age in neurons and male germ cells), a low mutation frequency in the male germline, and a mutation pattern unchanged with age within a tissue. These findings appear to extend to very old age (30 months). Additional findings include interanimal variation in spontaneous mutation frequency is larger in adipose tissues and liver compared with neurons and male germ cells, and subtle but significant differences in the mutation pattern among tissues, consistent with a minor effect of tissue-specific metabolism. The presumptive unaltered balance of DNA damage and repair with age in the male germline has evolutionary consequences. It is of particular interest given the controversy over whether or not increasing germline mutation frequency with paternal age underlies the reports associating older males with a higher incidence of some types of genetic disease. These most detailed measurements available to date regarding the time course of spontaneous mutation frequency and pattern in individual tissues help to constrain hypotheses regarding the role of mutational mechanisms in DNA repair and aging.

LF/MF Propagation Modeling for D-Region Ionospheric Remote Sensing

NASA Astrophysics Data System (ADS)

Higginson-Rollins, M. A.; Cohen, M.

2017-12-01

The D-region of the ionosphere is highly inaccessible because it is too high for continuous in-situ measurement techniques and too low for satellite measurements. Very-Low Frequency (VLF) signals have been developed and used as a diagnostic tool for this region of the ionosphere and are favorable because of the low ionospheric attenuation rates, allowing global propagation - but this also creates an ill-posed multi-mode propagation problem. As an alternative, Low-Frequency (LF) and Medium-Frequency (MF) signals could be used as a diagnostic tool of the D-region. These higher frequencies have a higher attenuation rate, and thus only a few modes propagate in the Earth-ionosphere waveguide, creating a much simpler problem to analyze. The United States Coast Guard (USCG) operates a national network of radio transmitters that serve as an enhancement to the Global Positioning System (GPS). This network is termed Differential Global Positioning System (DGPS) and uses fixed reference stations as a method of determining the error in received GPS satellite signals and transmits the correction value using low frequency and medium frequency radio signals between 285 kHz and 385 kHz. Using sensitive receivers, we can detect this signal many hundreds of km away. We present modeling of the propagation of these transmitters' signals for use as a diagnostic tool for characterizing the D-region. The Finite-Difference Time-Domain (FDTD) method is implemented to model the groundwave radiated by the DGPS beacons and account for environmental effects, such as changing soil conductivities and terrain. A full wave numerical solver is used to model the skywave component of the propagating signal and specifically to ascertain the reflection coefficients for various ionospheric conditions. Preliminary results are shown and discussed, and comparisons with collected data are presented.

Predictive factors of the dimensions and location of mental foramen using cone beam computed tomography

PubMed Central

Fernández-Alonso, Ana; Smyth-Chamosa, Ernesto; Suárez-Quintanilla, Juan Antonio; Varela-Mallou, Jesús

2017-01-01

Objective The mental foramen (MF) hosts main neurovascular structures, making it of crucial importance for surgical procedures. This study aimed to analyze the factors influencing the dimensions and location of the MF. Materials and methods Cone beam computed tomography (CBCT) scans of 344 patients were examined for MF dimensions, as well as for the distances from the MF to the alveolar crest (MF-MSB), and to the inferior mandibular border (MF-MIB). Results Gender, mandibular side and presence of accessory mental foramina (AMF) significantly influence MF area. Males, left hemimandibles, and hemimandibles with no AMF had a higher rate of large MF areas (B = − 0.60; p = 0.003, females; B = 0.55; p = 0.005; B = 0.85; p = 0.038). Age, gender and dental status significantly influence MF-MSB distance. The distance decreased as age increased (B = −0.054; p = 0.001), females showed a lower rate of long MF-MSB distances (B = −0.94, p = 0.001), and dentate patients showed a higher rate of long MF-MSB distances (B = 2.27; p = 0.001). Age, gender and emerging angle significantly influenced MF-MIB distance. The distance decreased as age and emerging angle increased (B = −0.01; p = 0.001; B = −0.03; p = 0.001), and females had a lower rate of long MF-MIB distances (B = −1.94, p = 0.001). Conclusions General and local factors influence the dimensions and location of MF. MF dimensions are influenced by gender, mandibular side, anteroposterior position, and the presence of AMF. Distance from MF to alveolar crest is influenced by gender, age and dental status, while the relative MF position is influenced by age and dental status. CBCT images make it possible to analyze the MF in order to avoid complications during surgical procedures. PMID:28817595

Novel exposure units for at-home personalized testing of electromagnetic sensibility.

PubMed

Huss, Anke; Murbach, Manuel; van Moorselaar, Imke; Kuster, Niels; van Strien, Rob; Kromhout, Hans; Vermeulen, Roel; Slottje, Pauline

2016-01-01

Previous experimental studies on electromagnetic hypersensitivity have been criticized regarding inflexibility of choice of exposure and of study locations. We developed and tested novel portable exposure units that can generate different output levels of various extremely low frequency magnetic fields (ELF-MF; 50 Hz field plus harmonics) and radiofrequency electromagnetic fields (RF-EMF). Testing was done with a group of healthy volunteers (n = 25 for 5 ELF-MF and n = 25 for 5 RF-EMF signals) to assess if units were indeed able to produce double-blind exposure conditions. Results substantiated that double-blind conditions were met; on average participants scored 50.6% of conditions correct on the ELF-MF, and 50.0% on the RF-EMF unit, which corresponds to guessing probability. No cues as to exposure conditions were reported. We aim to use these units in a future experiment with subjects who wish to test their personal hypothesis of being able to sense or experience when being exposed to EMF. The new units allow for a high degree of flexibility regarding choice of applied electromagnetic signal, output power level and location (at home or another environment of subjects' choosing). © 2015 Wiley Periodicals, Inc.

Mutation rate evolution in replicator dynamics.

PubMed

Allen, Benjamin; Rosenbloom, Daniel I Scholes

2012-11-01

The mutation rate of an organism is itself evolvable. In stable environments, if faithful replication is costless, theory predicts that mutation rates will evolve to zero. However, positive mutation rates can evolve in novel or fluctuating environments, as analytical and empirical studies have shown. Previous work on this question has focused on environments that fluctuate independently of the evolving population. Here we consider fluctuations that arise from frequency-dependent selection in the evolving population itself. We investigate how the dynamics of competing traits can induce selective pressure on the rates of mutation between these traits. To address this question, we introduce a theoretical framework combining replicator dynamics and adaptive dynamics. We suppose that changes in mutation rates are rare, compared to changes in the traits under direct selection, so that the expected evolutionary trajectories of mutation rates can be obtained from analysis of pairwise competition between strains of different rates. Depending on the nature of frequency-dependent trait dynamics, we demonstrate three possible outcomes of this competition. First, if trait frequencies are at a mutation-selection equilibrium, lower mutation rates can displace higher ones. Second, if trait dynamics converge to a heteroclinic cycle-arising, for example, from "rock-paper-scissors" interactions-mutator strains succeed against non-mutators. Third, in cases where selection alone maintains all traits at positive frequencies, zero and nonzero mutation rates can coexist indefinitely. Our second result suggests that relatively high mutation rates may be observed for traits subject to cyclical frequency-dependent dynamics.

Cystic fibrosis carrier screening in a North American population.

PubMed

Zvereff, Val V; Faruki, Hawazin; Edwards, Marcia; Friedman, Kenneth J

2014-07-01

The aim of this study was to compare the mutation frequency distribution for a 32-mutation panel and a 69-mutation panel used for cystic fibrosis carrier screening. Further aims of the study were to examine the race-specific detection rates provided by both panels and to assess the performance of extended panels in large-scale, population-based cystic fibrosis carrier screening. Although genetic screening for the most common CFTR mutations allows detection of nearly 90% of cystic fibrosis carriers, the large number of other mutations, and their distribution within different ethnic groups, limits the utility of general population screening. Patients referred for cystic fibrosis screening from January 2005 through December 2010 were tested using either a 32-mutation panel (n = 1,601,308 individuals) or a 69-mutation panel (n = 109,830). The carrier frequencies observed for the 69-mutation panel study population (1/36) and Caucasian (1/27) and African-American individuals (1/79) agree well with published cystic fibrosis carrier frequencies; however, a higher carrier frequency was observed for Hispanic-American individuals (1/48) using the 69-mutation panel as compared with the 32-mutation panel (1/69). The 69-mutation panel detected ~20% more mutations than the 32-mutation panel for both African-American and Hispanic-American individuals. Expanded panels using race-specific variants can improve cystic fibrosis carrier detection rates within specific populations. However, it is important that the pathogenicity and the relative frequency of these variants are confirmed.

[The ultrastructure of Sertoli cells and spermatogonia in the rats exposed to radiation under conditions of therapeutic and prophylactic application of low-intensity electromagnetic emission].

PubMed

Korolev, Y N; Bobrovnitskii, I P; Geniatulina, M S; Nikulina, L A; Mikhailik, L V

2018-04-09

it has been demonstrated in various experimental studies that radiation exposure produces a negative impact on the processes of spermatogenesis associated with the disturbances of the microcirculation processes in the testes and the development of cellular and intracellular disintegration expressed as destructive changes in the cells leading to their death. The objective of the present study was to detect the ultrastructural abnormalities in the cells of Sertoli and spermatogonia under conditions of their exposure to radiation and to identify the peculiarities of their regeneration under the influence of the therapeutic and prophylactic application of low-intensity ultra-high frequency (UHF) electromagnetic radiation (EMR) and low-intensity low-frequency magnetic field (MF). The experiments were carried out on 28 non-pedigree mature male rats with the body weight 180-220 g that were divided into four groups. The first study group was comprised of the animals exposed to radiation followed by the application of low-intensity ultra-high frequency UHF electromagnetic radiation EMR. The rats in the second study group experienced effects of radiation and low-intensity low-frequency MF. The animals of the third (control) group were exposed to radiation alone, and those comprising the fourth group 1 (only radiation exposure) were considered to be intact. The studies with the use of electron microscopy showed that the therapeutic and prophylactic application of low-intensity ultra-high frequency (UHF) electromagnetic radiation and low-intensity low-frequency magnetic field caused the decrease in the number and the severity of post-radiation defects in the treated cells together with the increase of the number and size of mitochondria as well as hyperplasia of ribosomes; moreover, it promoted cellular and intracellular regeneration. UHF electromagnetic radiation had a more pronounced stimulating effect on the regeneration processes as compared with low-frequency MF. Particularly active processes of intracellular regeneration evolved in Sertoli cells; they were manifested as the increase in the number and size of mitochondria, enhanced hyperplasia of ribosomes, and formation of polysomes and new membranes of the granular endoplasmic reticulum. In spermatogonia, intracellular regeneration was less pronounced than in the Sertoli cells but was accompanied by enhanced cell regeneration and a greater number of reserve stem/progenitor cells. The results of the present study provide a rationale for the possibility of the application of a low-frequency magnetic field and especially UHF electromagnetic radiation for the further development of the promising therapeutic and preventive technologies with a view to their introduction into routine clinical practice dealing with radiation-induced pathology.

Infant diet differentially affects human electroencephalographic activities in the first year of life

USDA-ARS?s Scientific Manuscript database

The influence of infant diet (milk-based formula [MF], soy-based formula [SF], and breast milk [BF]) on brain EEG activities was studied in infants (20 males and 20 females per group) at 3, 6, 9, and 12 months of age. Power spectra were calculated in five frequency bands for scalp EEG signals record...

Analyses of cocondensation of melamine and urea through formaldehyde with carbon 13 nuclear magnetic resonance spectroscopy

Treesearch

Tomita Bunchiro; Chung-Yun Hse

1995-01-01

The 13C-NMR (carbon 13 nuclear magnetic resonance) spectra of urea-formaldehyde (UF) resins, melamine-formaldehyde (MF) resins, and melamine-urea-formaldehyde (MUF) cocondensed resins synthesized under various conditions were taken with a frequency of 75 MHz. The main purpose was to investigate whether or not the occurrences of cocondensation...

Analysis of cocondensation of melamine and urea through formaldehyde with carbon 13 nuclear magnetic resonance spectroscopy

Treesearch

Bunichiro Tomita; Chung-Yun Hse

1995-01-01

The 13C-NMR (carbon 13 nuclear magnetic resonance) spectra of urea-formaldehyde (UF) resins, melamine-formaldehyde (MF) resins, and melamine-urea-formaldehyde (MUF) cocondensed resins synthesized under various conditions were taken with a frequency of 75 MHz. The main purpose was to investigate whether or not the occurrences of cocondensation...

Parameters affecting frequency of CRISPR/Cas9 mediated targeted mutagenesis in rice.

PubMed

Mikami, Masafumi; Toki, Seiichi; Endo, Masaki

2015-10-01

Frequency of CRISPR/Cas9-mediated targeted mutagenesis varies depending on Cas9 expression level and culture period of rice callus. Recent reports have demonstrated that the CRISPR/Cas9 system can function as a sequence-specific nuclease in various plant species. Induction of mutation in proliferating tissue during embryogenesis or in germline cells is a practical means of generating heritable mutations. In the case of plant species in which cultured cells are used for transformation, non-chimeric plants can be obtained when regeneration occurs from mutated cells. Since plantlets are regenerated from both mutated and non-mutated cells in a random manner, any increment in the proportion of mutated cells in Cas9- and guide RNA (gRNA)-expressing cells will help increase the number of plants containing heritable mutations. In this study, we examined factors affecting mutation frequency in rice calli. Following sequential transformation of rice calli with Cas9- and gRNA- expression constructs, the mutation frequency in independent Cas9 transgenic lines was analyzed. A positive correlation between Cas9 expression level and mutation frequency was found. This positive relationship was observed regardless of whether the transgene or an endogenous gene was used as the target for CRISPR/Cas9-mediated mutagenesis. Furthermore, we found that extending the culture period increased the proportion of mutated cells as well as the variety of mutations obtained. Because mutated and non-mutated cells might proliferate equally, these results suggest that a prolonged tissue culture period increases the chance of inducing de novo mutations in non-mutated cells. This fundamental knowledge will help improve systems for obtaining non-chimeric regenerated plants in many plant species.

Frequency of 8 CFTR gene mutations in cystic fibrosis patients in Minas Gerais, Brazil, diagnosed by neonatal screening.

PubMed

Perone, C; Medeiros, G S; del Castillo, D M; de Aguiar, M J B; Januário, J N

2010-02-01

The nature and frequency of cystic fibrosis mutations in Brazil is not uniform due to the highly varied ethnic composition of the population. The average frequency of the F508del mutation has been reported to be 48.6%. Other common mutations in Brazil are G542X, R1162X, and N1303K. The aim of this study was to analyze the frequency of 8 mutations (F508del, G542X, R1162X, N1303K, W1282X, G85E, 3120+1G>A, and 711+1G>T) in a sample of 111 newborn patients with cystic fibrosis diagnosed by the Cystic Fibrosis Neonatal Screening Program of Minas Gerais State. The mutations were tested by allele-specific oligonucleotide PCR with specially designed primers. An allele frequency of 48.2% was observed for the F508del mutation, and allele frequencies of 5.41, 4.50, 4.05, and 3.60% were found for the R1162X, G542X, 3120+1G>A, and G85E mutations, respectively. The genotypes obtained were in Hardy-Weinberg equilibrium. These data demonstrate that the 8-mutation panel studied here has extensive coverage (68%) for the cystic fibrosis mutations in Minas Gerais. These data improve our knowledge of cystic fibrosis in Brazil, particularly in this region. In addition, this investigation contributed to the establishment of a sensitive and population-specific mutation panel, which can be helpful for molecular diagnosis of cystic fibrosis.

Exonuclease mutations in DNA polymerase epsilon reveal replication strand specific mutation patterns and human origins of replication

PubMed Central

Shinbrot, Eve; Henninger, Erin E.; Weinhold, Nils; Covington, Kyle R.; Göksenin, A. Yasemin; Schultz, Nikolaus; Chao, Hsu; Doddapaneni, HarshaVardhan; Muzny, Donna M.; Gibbs, Richard A.; Sander, Chris; Pursell, Zachary F.

2014-01-01

Tumors with somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) exhibit a novel mutator phenotype, with markedly elevated TCT→TAT and TCG→TTG mutations and overall mutation frequencies often exceeding 100 mutations/Mb. Here, we identify POLE-exo* tumors in numerous cancers and classify them into two groups, A and B, according to their mutational properties. Group A mutants are found only in POLE, whereas Group B mutants are found in POLE and POLD1 and appear to be nonfunctional. In Group A, cell-free polymerase assays confirm that mutations in the exonuclease domain result in high mutation frequencies with a preference for C→A mutation. We describe the patterns of amino acid substitutions caused by POLE-exo* and compare them to other tumor types. The nucleotide preference of POLE-exo* leads to increased frequencies of recurrent nonsense mutations in key tumor suppressors such as TP53, ATM, and PIK3R1. We further demonstrate that strand-specific mutation patterns arise from some of these POLE-exo* mutants during genome duplication. This is the first direct proof of leading strand-specific replication by human POLE, which has only been demonstrated in yeast so far. Taken together, the extremely high mutation frequency and strand specificity of mutations provide a unique identifier of eukaryotic origins of replication. PMID:25228659

Phenotypes in defined genotypes including siblings with Usher syndrome.

PubMed

Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Andréasson, Sten

2011-06-01

To characterize visual function in defined genotypes including siblings with Usher syndrome. Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

Deletion of p66Shc in mice increases the frequency of size-change mutations in the lacZ transgene.

PubMed

Beltrami, Elena; Ruggiero, Antonella; Busuttil, Rita; Migliaccio, Enrica; Pelicci, Pier Giuseppe; Vijg, Jan; Giorgio, Marco

2013-04-01

Upon oxidative challenge the genome accumulates adducts and breaks that activate the DNA damage response to repair, arrest, or eliminate the damaged cell. Thus, reactive oxygen species (ROS) generated by endogenous oxygen metabolism are thought to affect mutation frequency. However, few studies determined the mutation frequency when oxidative stress is reduced. To test whether in vivo spontaneous mutation frequency is altered in mice with reduced oxidative stress and cell death rate, we crossed p66Shc knockout (p66KO) mice, characterized by reduced intracellular concentration of ROS and by impaired apoptosis, with a transgenic line harboring multiple copies of the lacZ mutation reporter gene as part of a plasmid that can be recovered from organs into Escherichia coli to measure mutation rate. Liver and small intestine from 2- to 24-month-old, lacZ (p66Shc+/+) and lacZp66KO mice, were investigated revealing no difference in overall mutation frequency but a significant increase in the frequency of size-change mutations in the intestine of lacZp66KO mice. This difference was further increased upon irradiation of mice with X-ray. In addition, we found that knocking down cyclophilin D, a gene that facilitates mitochondrial apoptosis acting downstream of p66Shc, increased the size-change mutation frequency in small intestine. Size-change mutations also accumulated in death-resistant embryonic fibroblasts from lacZp66KO mice treated with H2 O2 . These results indicate that p66Shc plays a role in the accumulation of DNA rearrangements and suggest that p66Shc functions to clear damaged cells rather than affect DNA metabolism. © 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats

PubMed Central

Marinaro, Mariarosaria; Rezza, Giovanni; Del Giudice, Giuseppe; Colao, Valeriana; Tarsitano, Elvira; Camero, Michele; Losurdo, Michele; Buonavoglia, Canio; Tempesta, Maria

2012-01-01

The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats. PMID:22511971

Sex differences and sexual orientation differences in personality: findings from the BBC Internet survey.

PubMed

Lippa, Richard A

2008-02-01

Analyzing a large international data set generated by a BBC Internet survey, I examined sex differences and sexual orientation differences in six personality traits: extraversion, agreeableness, neuroticism, disagreeable assertiveness, masculine versus feminine occupational preferences (MF-Occ), and self-ascribed masculinity-femininity (Self-MF). Consistent with previous research, sex differences and sexual orientation differences were largest for MF-Occ and for Self-MF. In general, heterosexual-homosexual differences mirrored sex differences in personality, with gay men shifted in female-typical and lesbians in male-typical directions. Bisexual men scored intermediate between heterosexual and gay men on MF-Occ; however, they were slightly more feminine than gay men on Self-MF. Bisexual women scored intermediate between heterosexual women and lesbians on both MF-Occ and Self-MF. Sex differences and sexual orientation differences in MF-Occ, Self-MF, and other personality traits were consistent across five nations/world regions (the UK, USA, Canada, Australia/New Zealand, and Western Europe), thereby suggesting a biological component to these differences.

Integration of membrane separation and Fenton processes for sanitary landfill leachate treatment.

PubMed

Santos, Amanda Vitória; Andrade, Laura Hamdan de; Amaral, Míriam Cristina Santos; Lange, Liséte Celina

2018-04-06

The appropriate treatment of sanitary landfill leachate is one of the greatest challenges nowadays due to the large volumes of solid waste generated. Thus, the aim of this study is to evaluate the performance of different routes involving the integration of advanced oxidation processes based on Fenton's reagents (AOP-Fenton) and microfiltration (MF) and nanofiltration (NF) membrane processes for the treatment of landfill leachate. MF module configuration (submerged or sidestream) and MF and NF recovery rate were evaluated. The combination of AOP-Fenton, MF and NF proved to be an effective treatment for landfill leachate. High removal efficiencies of chemical oxidation demand (94-96%) and colour (96-99%) were obtained. The configuration named route 3, composed of MF of raw landfill leachate (MF1), POA-Fenton-MF2 of the MF1 concentrate and NF of both MF1 and MF2 permeates, showed a higher global water recovery and was responsible for lower waste generation. It was considered the best one in terms of environmental, technical and economical aspects.

Diamond-Based Supercapacitors: Realization and Properties.

PubMed

Gao, Fang; Nebel, Christoph E

2016-10-26

In this Spotlight on Applications, we describe our recent progress on the fabrication of surface-enlarged boron-doped polycrystalline diamond electrodes, and evaluate their performance in supercapacitor applications. We begin with a discussion of the fabrication methods of porous diamond materials. The diamond surface enlargement starts with a top-down plasma etching method. Although the extra surface area provided by surface roughening or nanostructuring provides good outcome for sensing applications, a capacitance value <1 mF cm -2 or a surface-enlargement factor <100 fail to meet the requirement of a practical supercapacitor. Driven by the need for large surface areas, we recently focused on the tempated-growth method. We worked on both supported and free-standing porous diamond materials to enhance the areal capacitance to the "mF cm -2 " range. With our newly developed free-standing diamond paper, areal capacitance can be multiplied by stacking multilayers of the electrode material. Finally, considering the fact that there is no real diamond-based supercapacitor device up to now, we fabricated the first prototype pouch-cell device based on the free-standing diamond paper to evaluate its performance. The results reveal that the diamond paper is suitable for operation in high potential windows (up to 2.5 V) in aqueous electrolyte with a capacitance of 0.688 mF cm -2 per layer of paper (or 0.645 F g -1 ). Impedance spectroscopy revealed that the operation frequency of the device exceeds 30 Hz. Because of the large potential window and the ability to work at high frequency, the specific power of the device reached 1 × 10 5 W kg -1 . In the end, we made estimations on the future target performance of diamond supercapacitors based on the existing information.

Optical coherence tomography angiography-based capillary velocimetry

NASA Astrophysics Data System (ADS)

Wang, Ruikang K.; Zhang, Qinqin; Li, Yuandong; Song, Shaozhen

2017-06-01

Challenge persists in the field of optical coherence tomography (OCT) when it is required to quantify capillary blood flow within tissue beds in vivo. We propose a useful approach to statistically estimate the mean capillary flow velocity using a model-based statistical method of eigendecomposition (ED) analysis of the complex OCT signals obtained with the OCT angiography (OCTA) scanning protocol. ED-based analysis is achieved by the covariance matrix of the ensemble complex OCT signals, upon which the eigenvalues and eigenvectors that represent the subsets of the signal makeup are calculated. From this analysis, the signals due to moving particles can be isolated by employing an adaptive regression filter to remove the eigencomponents that represent static tissue signals. The mean frequency (MF) of moving particles can be estimated by the first lag-one autocorrelation of the corresponding eigenvectors. Three important parameters are introduced, including the blood flow signal power representing the presence of blood flow (i.e., OCTA signals), the MF indicating the mean velocity of blood flow, and the frequency bandwidth describing the temporal flow heterogeneity within a scanned tissue volume. The proposed approach is tested using scattering phantoms, in which microfluidic channels are used to simulate the functional capillary vessels that are perfused with the scattering intralipid solution. The results indicate a linear relationship between the MF and mean flow velocity. In vivo animal experiments are also conducted by imaging mouse brain with distal middle cerebral artery ligation to test the capability of the method to image the changes in capillary flows in response to an ischemic insult, demonstrating the practical usefulness of the proposed method for providing important quantifiable information about capillary tissue beds in the investigations of neurological conditions in vivo.

Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

PubMed Central

Ghiotto, Fabio; Marcatili, Paolo; Tenca, Claudya; Calevo, Maria Grazia; Yan, Xiao-Jie; Albesiano, Emilia; Bagnara, Davide; Colombo, Monica; Cutrona, Giovanna; Chu, Charles C; Morabito, Fortunato; Bruno, Silvia; Ferrarini, Manlio; Tramontano, Anna; Fais, Franco; Chiorazzi, Nicholas

2011-01-01

B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV–diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation. PMID:21785810

Lineage dynamics and mutation-selection balance in non-adapting asexual populations

NASA Astrophysics Data System (ADS)

Pénisson, Sophie; Sniegowski, Paul D.; Colato, Alexandre; Gerrish, Philip J.

2013-02-01

In classical population genetics, mutation-selection balance refers to the equilibrium frequency of a deleterious allele established and maintained under two opposing forces: recurrent mutation, which tends to increase the frequency of the allele; and selection, which tends to decrease its frequency. In a haploid population, if μ denotes the per capita rate of production of the deleterious allele by mutation and s denotes the selective disadvantage of carrying the allele, then the classical mutation-selection balance frequency of the allele is approximated by μ/s. This calculation assumes that lineages carrying the mutant allele in question—the ‘focal allele’—do not accumulate deleterious mutations linked to the focal allele. In principle, indirect selection against the focal allele caused by such additional mutations can decrease the frequency of the focal allele below the classical mutation-selection balance. This effect of indirect selection will be strongest in an asexual population, in which the entire genome is in linkage. Here, we use an approach based on a multitype branching process to investigate this effect, analyzing lineage dynamics under mutation, direct selection, and indirect selection in a non-adapting asexual population. We find that the equilibrium balance between recurrent mutation to the focal allele and the forces of direct and indirect selection against the focal allele is closely approximated by γμ/(s + U) (s = 0 if the focal allele is neutral), where γ ≈ eθθ-(ω+θ)(ω + θ)(Γ(ω + θ) - Γ(ω + θ,θ)), \\theta =U/\\tilde {s}, and \\omega =s/\\tilde {s}; U denotes the genomic deleterious mutation rate and \\tilde {s} denotes the geometric mean selective disadvantage of deleterious mutations elsewhere on the genome. This mutation-selection balance for asexual populations can remain surprisingly invariant over wide ranges of the mutation rate.

Effects on g2/m phase cell cycle distribution and aneuploidy formation of exposure to a 60 Hz electromagnetic field in combination with ionizing radiation or hydrogen peroxide in l132 nontumorigenic human lung epithelial cells.

PubMed

Jin, Hee; Yoon, Hye Eun; Lee, Jae-Seon; Kim, Jae-Kyung; Myung, Sung Ho; Lee, Yun-Sil

2015-03-01

The aim of the present study was to assess whether exposure to the combination of an extremely low frequency magnetic field (ELF-MF; 60 Hz, 1 mT or 2 mT) with a stress factor, such as ionizing radiation (IR) or H2O2, results in genomic instability in non-tumorigenic human lung epithelial L132 cells. To this end, the percentages of G2/M-arrested cells and aneuploid cells were examined. Exposure to 0.5 Gy IR or 0.05 mM H2O2 for 9 h resulted in the highest levels of aneuploidy; however, no cells were observed in the subG1 phase, which indicated the absence of apoptotic cell death. Exposure to an ELF-MF alone (1 mT or 2 mT) did not affect the percentages of G2/M-arrested cells, aneuploid cells, or the populations of cells in the subG1 phase. Moreover, when cells were exposed to a 1 mT or 2 mT ELF-MF in combination with IR (0.5 Gy) or H2O2 (0.05 mM), the ELF-MF did not further increase the percentages of G2/M-arrested cells or aneuploid cells. These results suggest that ELF-MFs alone do not induce either G2/M arrest or aneuploidy, even when administered in combination with different stressors.

Chronic exposure to 50Hz magnetic fields causes a significant weakening of antioxidant defence systems in aged rat brain.

PubMed

Falone, Stefano; Mirabilio, Alessandro; Carbone, Maria Cristina; Zimmitti, Vincenzo; Di Loreto, Silvia; Mariggiò, Maria Addolorata; Mancinelli, Rosa; Di Ilio, Carmine; Amicarelli, Fernanda

2008-01-01

Several studies suggest that extremely low-frequency magnetic fields (ELF-MFs) may enhance the free radical endogenous production. It is also well known that one of the unavoidable consequences of ageing is an overall oxidative stress-based decline in several physiological functions and in the general resistance to stressors. On the basis of these assumptions, the aim of this study was to establish whether the ageing process can increase susceptibility towards widely present ELF-MF-mediated pro-oxidative challenges. To this end, female Sprague-Dawley rats were continuously exposed to a sinusoidal 50 Hz, 0.1 mT magnetic field for 10 days. Treatment-induced changes in the major antioxidant protection systems and in the neurotrophic support were investigated, as a function of the age of the subjects. All analyses were performed in brain cortices, due to the high susceptibility of neuronal cells to oxidative injury. Our results indicated that ELF-MF exposure significantly affects anti-oxidative capability, both in young and aged animals, although in opposite ways. Indeed, exposed young individuals enhanced their neurotrophic signalling and anti-oxidative enzymatic defence against a possible ELF-MF-mediated increase in oxygen radical species. In contrast, aged subjects were not capable of increasing their defences in response to ELF-MF treatment but, on the contrary, they underwent a significant decrease in the major antioxidant enzymatic activities. In conclusion, our data seem to suggest that the exposure to ELF-MFs may act as a risk factor for the occurrence of oxidative stress-based nervous system pathologies associated with ageing.

Longitudinal Detection of Optic Nerve Head Changes by Spectral Domain Optical Coherence Tomography in Early Experimental Glaucoma

PubMed Central

He, Lin; Yang, Hongli; Gardiner, Stuart K.; Williams, Galen; Hardin, Christy; Strouthidis, Nicholas G.; Fortune, Brad; Burgoyne, Claude F.

2014-01-01

Purpose. We determined if the detection of spectral-domain optical coherence tomography (SDOCT) optic nerve head (ONH) change precedes the detection of confocal scanning laser tomography (CSLT) ONH surface, SDOCT retinal nerve fiber layer (RNFL), scanning laser perimetry (SLP), and multifocal electroretinography (mfERG) change in eight experimental glaucoma (EG) eyes. Methods. Both eyes from eight monkeys were tested at least three times at baseline, and then every 2 weeks following laser-induced chronic unilateral IOP elevation. Event and trend-based definitions of onset in the control and EG eyes for 11 SDOCT neural and connective tissue, CSLT surface, SDOCT RNFL, SLP, and mfERG parameters were explored. The frequency and timing of onset for each parameter were compared using a logrank test. Results. Maximum post-laser IOP was 18 to 42 mm Hg in the EG eyes and 12 to 20 mm Hg in the control eyes. For event- and trend-based analyses, onsets were achieved earliest and most frequently within the ONH neural and connective tissues using SDOCT, and at the ONH surface using CSLT. SDOCT ONH neural and connective tissue parameter change preceded or coincided with CSLT ONH surface change in most EG eyes. The SDOCT and SLP measures of RNFL thickness, and mfERG measures of visual function demonstrated similar onset rates, but occurred later than SDOCT ONH and CSLT surface change, and in fewer eyes. Conclusions. SDOCT ONH change detection commonly precedes or coincides with CSLT ONH surface change detection, and consistently precedes RNFLT, SLP, and mfERG change detection in monkey experimental glaucoma. PMID:24255047

Effects of short term exposure of eggs to magnetic field before incubation on hatchability and post-hatch performance of meat chickens.

PubMed

Shafey, T M; Aljumaah, R S; Swillam, S A; Al-Mufarrej, S I; Al-Abdullatif, A A; Ghannam, M M

2011-10-01

The effects of exposing meat-type breeder eggs to magnetic field (MF) before incubation on hatchability traits (percents of hatchability and hatchability failures of eggs), chick weight at hatch, and post-hatch performance (weight gain, feed intake, and feed conversion ratio (FCR)) from 1 to 39 d of age were investigated. Eggs from a Ross flock at 38 weeks of age were exposed to MF of 18 Gauss (1.8 mT) at 50 Hz for 0, 15, 30, 45, 60, and 75 min (MF0, MF15, MF30, MF45, MF60, and MF75) before incubation. Exposing eggs to MF did not influence hatchability of eggs and chick weight at hatch. However, chickens of MF60 and MF75 treatments had lower weight gain and feed intake than those of the non-exposed treatment at 39 d of age. MF exposure of eggs did not influence FCR of chickens between 1 and 21 d of age, but tended to increase FCR, albeit non-significantly, between 22 and 39 d of age. It is concluded that exposing meat-type breeder eggs to MF of 18 Gauss (1.8 mT) at 50 Hz for up to 75 min did not influence hatchability traits and chick weight at hatch. However, MF exposure of eggs for 60 and 75 min reduced body weight gain and feed intake of chickens over the 39-d experimental period.

Pharmacological evaluation of mangiferin herbosomes for antioxidant and hepatoprotection potential against ethanol induced hepatic damage.

PubMed

Jain, Pushpendra Kumar; Kharya, Murlidhar; Gajbhiye, Asmita

2013-11-01

Fatty liver is the first stage of alcoholic damage which is reversible with abstinence from alcohol. Mangiferin (MF) showed potent scavenging activity on diphenyl-1-picrylhydrazyl radicals which stimulate liver regeneration in various liver injuries. Although, MF shows hepatoprotection against various liver disorders but due to rapid clearance and limited solubility in lipoid environment, there is problem of its poor absorption from intestine hence poor bioavailability. Owing to which there is a need to develop MF herbosomes to resolve the problem of poor bioavailability to enhance the therapeutic potential. Successfully prepared MF herbosomes through complexation with phospholipids were characterized by physicochemical, chromatography, spectroscopy (differential scanning calorimetry (DSC), infrared (IR), and nuclear magnetic resonance (NMR)), ex vivo absorption using everted small intestine sac technique and in vivo studies using ethanol inducing hepatotoxicity in albino rats and comparing the results against plain MF. Ex vivo study showed significant increased absorption of MF from prepared MF herbosomes as compared to plain MF. The hepatoprotective potential of MF herbosomes evaluated by in vivo study revealed significantly decreased levels of serum glutamate oxaloacetate transminase (SGOT), serum glutamate pyruvate transminase (SGPT), total bilirubin, and alkaline phosphatase (ALP) in MF herbosomes as compared to plain MF. MF herbosomes also showed significantly decreased level of malonyl dehydrogenase along with increased levels of reduced glutathione, superoxide dismutase (SOD) and catalase as compared to plain MF which was also comparable to the standard drug, silymarin (SL). The above mentioned results showed that hepatoprotective and antioxidant potency of MF enhanced due to the preparation of its herbosomes.

Quantifying the impact of androgen therapy on the female larynx.

PubMed

Damrose, Edward J

2009-02-01

To describe the timing of changes in fundamental frequency of the female voice following androgen therapy during female to male gender reassignment. A 33-year-old female semi-professional singer undergoing gender reassignment and intramuscular androgen injections was examined at monthly intervals to monitor the impact of therapy on the voice. Laryngostroboscopy and acoustic analysis were performed simultaneously to monitor for potential laryngeal pathology. Pretreatment mean fundamental frequency (MF(0)) was 228.45 Hz and ranged from 140.26 Hz to 430.64 Hz. Between month 3 and month 4 of treatment, MF(0) declined to 116.52 Hz and ranged from 90.75 Hz to 201.07 Hz. Shimmer increased from 3.4% to 7.8%. Noise to harmonics ratio (NHR) also increased from 0.12 to 0.17. The patient has continued to sing semi-professionally despite these changes in laryngeal function. Androgen therapy exerted a profound change on mean fundamental frequency between the third and fourth months of treatment. In addition, pitch range was reduced in a commensurate fashion. Patients undergoing androgen therapy may undergo a significant change in speaking voice between the third and fourth months of therapy. Moreover, though these changes may exert a profound impact on the singing voice, patients undergoing gender reassignment may still be able to achieve personal and professional success in their singing careers.

Mutation Spectra of Common Cancer-Associated Genes in Different Phenotypes of Colorectal Carcinoma Without Distant Metastasis.

PubMed

Chang, Shih-Ching; Lin, Pei-Ching; Lin, Jen-Kou; Lin, Chien-Hsing; Yang, Shung-Haur; Liang, Wen-Yi; Chen, Wei-Shone; Jiang, Jeng-Kai

2016-03-01

Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. This study aimed to describe the mutation frequency of 12 genes in different CRC phenotypes. Patients who underwent surgery at the Taipei Veterans General Hospital during 2000-2010 for CRC (n = 1249) were enrolled. The endpoint was overall survival. The prognostic value was determined with the log-rank test and Cox regression analysis. We found 1836 mutations of 12 genes in 997 (79.8%) tumors. Mutations were most frequently in KRAS (485, 38.8%), TP53 (373, 29.9%), APC (363, 29.0%), and PIK3CA (179, 14.3%); 137 (11.0%) cancers had high microsatellite instability (MSI). Women had significantly higher high MSI (14.3%) and BRAF mutation (6.3%) frequencies. The abnormal MSI (21.7%) and KRAS (44.6%), BRAF (8.6%), PIK3CA (19.4%), AKT1 (2.2%), and TGF - βR (9.6%) mutation frequencies were significantly higher in proximal colon cancer. The high MSI (35.6%) and BRAF (20.3%), TGF - βR (18.6%), PTEN (5.1%), and AKT1 (3.4%) mutation frequencies were significantly higher in 59 (4.7%) poorly differentiated tumors. The high MSI (21.3%) and KRAS (51.9%), BRAF (8.3%), PIK3CA (25.0%), AKT1 (4.6%), and SMAD4 (8.3%) mutation frequencies were significantly higher in 108 mucinous tumors. TNM stage, lymphovascular invasion, and mucinous histology were significantly associated with patient outcomes in univariate and multivariate analyses. Only NRAS mutation (hazard ratio 1.59, 95% confidence interval 1.06-2.38) affected patient survival. Mutational spectra differ significantly between CRC subtypes, implying diverse carcinogenetic pathways. The NRAS mutation is important, despite its low frequency.

Mutant calreticulin knockin mice develop thrombocytosis and myelofibrosis without a stem cell self-renewal advantage.

PubMed

Li, Juan; Prins, Daniel; Park, Hyun Jung; Grinfeld, Jacob; Gonzalez-Arias, Carlos; Loughran, Stephen; Dovey, Oliver M; Klampfl, Thorsten; Bennett, Cavan; Hamilton, Tina L; Pask, Dean C; Sneade, Rachel; Williams, Matthew; Aungier, Juliet; Ghevaert, Cedric; Vassiliou, George S; Kent, David G; Green, Anthony R

2018-02-08

Somatic mutations in the endoplasmic reticulum chaperone calreticulin (CALR) are detected in approximately 40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Multiple different mutations have been reported, but all result in a +1-bp frameshift and generate a novel protein C terminus. In this study, we generated a conditional mouse knockin model of the most common CALR mutation, a 52-bp deletion. The mutant novel human C-terminal sequence is integrated into the otherwise intact mouse CALR gene and results in mutant CALR expression under the control of the endogenous mouse locus. CALR del/+ mice develop a transplantable ET-like disease with marked thrombocytosis, which is associated with increased and morphologically abnormal megakaryocytes and increased numbers of phenotypically defined hematopoietic stem cells (HSCs). Homozygous CALR del/del mice developed extreme thrombocytosis accompanied by features of MF, including leukocytosis, reduced hematocrit, splenomegaly, and increased bone marrow reticulin. CALR del/+ HSCs were more proliferative in vitro, but neither CALR del/+ nor CALR del/del displayed a competitive transplantation advantage in primary or secondary recipient mice. These results demonstrate the consequences of heterozygous and homozygous CALR mutations and provide a powerful model for dissecting the pathogenesis of CALR-mutant ET and PMF. © 2018 by The American Society of Hematology.

Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients

PubMed Central

PAPADOPOULOU, EIRINI; TSOULOS, NIKOLAOS; TSIRIGOTI, ANGELIKI; APESSOS, ANGELA; AGIANNITOPOULOS, KONSTANTINOS; METAXA-MARIATOU, VASILIKI; ZAROGOULIDIS, KONSTANTINOS; ZAROGOULIDIS, PAVLOS; KASARAKIS, DIMITRIOS; KAKOLYRIS, STYLIANOS; DAHABREH, JUBRAIL; VLASTOS, FOTIS; ZOUBLIOS, CHARALAMPOS; RAPTI, AGGELIKI; PAPAGEORGIOU, NIKI GEORGATOU; VELDEKIS, DIMITRIOS; GAGA, MINA; ARAVANTINOS, GERASIMOS; KARAVASILIS, VASILEIOS; KARAGIANNIDIS, NAPOLEON; NASIOULAS, GEORGE

2015-01-01

It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18–21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of EGFR mutations. Furthermore, KRAS mutation analysis in patients with a known smoking history revealed no difference in mutation frequency according to smoking status; however, a different mutation spectrum was observed. PMID:26622815

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

PubMed Central

Al-Shamsi, Humaid O.; Jones, Jeremy; Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Abdel-Wahab, Reham; Abousamra, Ahmed O. S.; Shaw, Kenna R.; Xiao, Lianchun; Hassan, Manal M.; Kipp, Benjamin R.; Kopetz, Scott; Soliman, Amr S.; McWilliams, Robert R.; Wolff, Robert A.

2016-01-01

Background The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. Methods Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher’s exact test was used to determine the association between mutation status and clinical features. Results A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. Conclusions This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation. PMID:28078112

Identification of molting fluid carboxypeptidase A (MF-CPA) in Bombyx mori.

PubMed

Ote, Manabu; Mita, Kazuei; Kawasaki, Hideki; Daimon, Takaaki; Kobayashi, Masahiko; Shimada, Toru

2005-07-01

Using microarray analyses, we identified carboxypeptidase A (MF-CPA), which was induced during pupal ecdysis in the wing discs of Bombyx mori. Here, we report the functional characterization of MF-CPA. MF-CPA has amino acid sequence similarities with the proteins in the carboxypeptidase A/B subfamily, from human to nematode. The MF-CPA gene is expressed during the molting periods in the epithelial tissues. MF-CPA is detected in the molting fluid, which fills the space between the old and new cuticle during molting. By Western blot analysis, we show that MF-CPA is secreted as a zymogen and processed in the molting fluid. Recombinant MF-CPA expressed in the insect cells has carboxypeptidase A activity. We propose that MF-CPA degrades the proteins from the old cuticle during the molting periods and contributes to recycling of the amino acids.

Magnetic fluid - a novel approach to treat amyloid-related diseases

NASA Astrophysics Data System (ADS)

Antosova, Andrea; Siposova, Katarina; Koneracka, Martina; Zavisova, Vlasta; Daxnerova, Zuzana; Vavra, Ivo; Fedunova, Diana; Bagelova, Jaroslava; Kopcansky, Peter; Gazova, Zuzana

Protein amyloid aggregates are associated with several human pathologies termed amyloid-related diseases. We have investigated effect of two magnetic fluids (MFs) - electrostatically stabilized Fe3O4 magnetic nanoparticles (MF1) and sterically stabilized Fe3O4 magnetic nanoparticles by sodium oleate with adsorbed BSA (MF2) on amyloid aggregation of two proteins - human insulin and hen egg lysozyme. We have found that both MF1 and MF2 are able to interact with amyloid fibrils in vitro resulting into decreasing of amyloid aggregates. The extent of fibril disruption depends on MF concentration with extensive reduction of amyloid aggregates, 90% for lysozyme and 70% for insulin (ratio protein: MF=1:5). The obtained results suggest that magnetite component of MF play significant role in the process of amyloid fibril depolymerisation. Our findings indicate that MF1 and MF2 have potential to be used for treatment of amyloid diseases.

Diet and gender are important factors modulating low frequency EEG activity during processing of language sounds in 3 month old infants

USDA-ARS?s Scientific Manuscript database

Little is known about how early postnatal diet affects brain processes related to cognitive function in healthy infants. To address this question we examined EEG activity recorded from 3 month old infants [breastfed (BF: n = 104, 55 males), milk-based formula fed (MF: n = 114, 57 males) or soy for...

47 CFR 80.1077 - Frequencies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... System: Alerting: 406.0-406.1 EPIRBs 406.0-406.1 MHz (Earth-to-space).1544-1545 MHz (space-to-Earth). INMARSAT-E EPIRBs 12 1626.5-1645.5 MHz (Earth-to-space). INMARSAT Ship Earth Stations capable of voice and/or direct printing 1626.5-1645.5 MHz (Earth-to-space). VHF DSC Ch. 70 156.525 MHz. 1 MF/HF DSC 2 2187...

Characterization of EEG patterns in brain-injured subjects and controls after a Snoezelen(®) intervention.

PubMed

Gómez, Carlos; Poza, Jesús; Gutiérrez, María T; Prada, Esther; Mendoza, Nuria; Hornero, Roberto

2016-11-01

The aim of this study was to assess the changes induced in electroencephalographic (EEG) activity by a Snoezelen(®) intervention on individuals with brain-injury and control subjects. EEG activity was recorded preceding and following a Snoezelen(®) session in 18 people with cerebral palsy (CP), 18 subjects who have sustained traumatic brain-injury (TBI) and 18 controls. EEG data were analyzed by means of spectral and nonlinear measures: median frequency (MF), individual alpha frequency (IAF), sample entropy (SampEn) and Lempel-Ziv complexity (LZC). Our results showed decreased values for MF, IAF, SampEn and LZC as a consequence of the therapy. The main changes between pre-stimulation and post-stimulation conditions were found in occipital and parietal brain areas. Additionally, these changes are more widespread in controls than in brain-injured subjects, which can be due to cognitive deficits in TBI and CP groups. Our findings support the notion that Snoezelen(®) therapy affects central nervous system, inducing a slowing of oscillatory activity, as well as a decrease of EEG complexity and irregularity. These alterations seem to be related with higher levels of relaxation of the participants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantum bright solitons in a quasi-one-dimensional optical lattice

NASA Astrophysics Data System (ADS)

Barbiero, Luca; Salasnich, Luca

2014-06-01

We study a quasi-one-dimensional attractive Bose gas confined in an optical lattice with a superimposed harmonic potential by analyzing the one-dimensional Bose-Hubbard Hamiltonian of the system. Starting from the three-dimensional many-body quantum Hamiltonian, we derive strong inequalities involving the transverse degrees of freedom under which the one-dimensional Bose-Hubbard Hamiltonian can be safely used. To have a reliable description of the one-dimensional ground state, which we call a quantum bright soliton, we use the density-matrix-renormalization-group (DMRG) technique. By comparing DMRG results with mean-field (MF) ones, we find that beyond-mean-field effects become relevant by increasing the attraction between bosons or by decreasing the frequency of the harmonic confinement. In particular, we find that, contrary to the MF predictions based on the discrete nonlinear Schrödinger equation, average density profiles of quantum bright solitons are not shape-invariant. We also use the time-evolving-block-decimation method to investigate the dynamical properties of bright solitons when the frequency of the harmonic potential is suddenly increased. This quantum quench induces a breathing mode whose period crucially depends on the final strength of the superimposed harmonic confinement.

Relatively high rates of G:C → A:T transitions at CpG sites were observed in certain epithelial tissues including pancreas and submaxillary gland of adult big blue® mice.

PubMed

Prtenjaca, Anita; Tarnowski, Heather E; Marr, Alison M; Heney, Melanie A; Creamer, Laura; Sathiamoorthy, Sarmitha; Hill, Kathleen A

2014-01-01

With few exceptions, spontaneous mutation frequency and pattern are similar across tissue types and relatively constant in young to middle adulthood in wild type mice. Underrepresented in surveys of spontaneous mutations across murine tissues is the diversity of epithelial tissues. For the first time, spontaneous mutations were detected in pancreas and submaxillary gland and compared with kidney, lung, and male germ cells from five adult male Big Blue® mice. Mutation load was assessed quantitatively through measurement of mutant and mutation frequency and qualitatively through identification of mutations and characterization of recurrent mutations, multiple mutations, mutation pattern, and mutation spectrum. A total of 9.6 million plaque forming units were screened, 226 mutants were collected, and 196 independent mutations were identified. Four novel mutations were discovered. Spontaneous mutation frequency was low in pancreas and high in the submaxillary gland. The submaxillary gland had multiple recurrent mutations in each of the mice and one mutant had two independent mutations. Mutation patterns for epithelial tissues differed from that observed in male germ cells with a striking bias for G:C to A:T transitions at CpG sites. A comprehensive review of lacI spontaneous mutation patterns in young adult mice and rats identified additional examples of this mutational bias. An overarching observation about spontaneous mutation frequency in adult tissues of the mouse remains one of stability. A repeated observation in certain epithelial tissues is a higher rate of G:C to A:T transitions at CpG sites and the underlying mechanisms for this bias are not known. Copyright © 2013 Wiley Periodicals, Inc.

Cancer risk and clinicopathological characteristics of thyroid nodules harboring thyroid-stimulating hormone receptor gene mutations.

PubMed

Mon, Sann Y; Riedlinger, Gregory; Abbott, Collette E; Seethala, Raja; Ohori, N Paul; Nikiforova, Marina N; Nikiforov, Yuri E; Hodak, Steven P

2018-05-01

Thyroid-stimulating hormone receptor (TSHR) gene mutations play a critical role in thyroid cell proliferation and function. They are found in 20%-82% of hyperfunctioning nodules, hyperfunctioning follicular thyroid cancers (FTC), and papillary thyroid cancers (PTC). The diagnostic importance of TSHR mutation testing in fine needle aspiration (FNA) specimens remains unstudied. To examine the association of TSHR mutations with the functional status and surgical outcomes of thyroid nodules, we evaluated 703 consecutive thyroid FNA samples with indeterminate cytology for TSHR mutations using next-generation sequencing. Testing for EZH1 mutations was performed in selected cases. The molecular diagnostic testing was done as part of standard of care treatment, and did not require informed consent. TSHR mutations were detected in 31 (4.4%) nodules and were located in exons 281-640, with codon 486 being the most common. Allelic frequency ranged from 3% to 45%. Of 16 cases (12 benign, 3 FTC, 1 PTC) with surgical correlation, 15 had solitary TSHR mutations and 1 PTC had comutation with BRAF V600E. Hyperthyroidism was confirmed in all 3 FTC (2 overt, 1 subclinical). Of 5 nodules with solitary TSHR mutations detected at high allelic frequency, 3 (60%) were FTC. Those at low allelic frequency (3%-22%) were benign. EZH1 mutations were detected in 2 of 4 TSHR-mutant malignant nodules and neither of 2 benign nodules. We report that TSHR mutations occur in ∼5% thyroid nodules in a large consecutive series with indeterminate cytology. TSHR mutations may be associated with an increased cancer risk when present at high allelic frequency, even when the nodule is hyperfunctioning. Benign nodules were however most strongly correlated with TSHR mutations at low allelic frequency. © 2018 Wiley Periodicals, Inc.

Model of myosin recruitment to the cell equator for cytokinesis: feedback mechanisms and dynamical regimes

NASA Astrophysics Data System (ADS)

Veksler, Alexander; Vavylonis, Dimitrios

2011-03-01

The formation and constriction of the contractile ring during cytokinesis, the final step of cell division, depends on the recruitment of motor protein myosin to the cell's equatorial region. During animal cell cytokinesis, cortical myosin filaments (MF) disassemble at the flanking regions and concentrate in the equator. This recruitment depends on myosin motor activity and the Rho proteins that regulate MF assembly and disassembly. Central spindle and astral microtubules help establish a spatial pattern of differential Rho activity. We propose a reaction-diffusion model for the dynamics of MF recruitment to the equatorial region. In the model, the central spindle and mechanical stress promote self-reinforcing MF assembly. Negative feedback is introduced by MF-induced recruitment of inhibitor myosin phosphatase. Our model yields various dynamical regimes and explains both the recruitment of MF to the cleavage furrow and the observed damped MF oscillations in the flanking regions, as well as steady MF assembly. Space and time parameters of MF oscillations are calculated. We predict oscillatory relaxation of cortical MF upon removal of locally-applied external stress.

Gaucher disease: Gene frequencies in the Ashkenazi Jewish population

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

Beutler, E.; West, C.; Gelbart, T.

1993-01-01

DNA from over 2,000 Ashkenazi Jewish subjects has been examined for the four most common Jewish Gaucher disease mutations, which collectively account for about 96% of the disease-producing alleles in Jewish patients. This population survey has made possible the estimation of gene frequencies for these alleles. Eighty-seven of 1,528 individuals were heterozygous for the 1226G (N370S) mutation, and four presumably well persons were homozygous for this mutation. The gene frequency for the 1226G allele was calculated to be .0311, and when these data were pooled with those obtained previously from another 593 Jewish subjects, a gene frequency of .032 withmore » a standard error of .004 was found. Among 2,305 normal subjects, 10 were found to be heterozygous for the 84GG allele, giving a gene frequency of .00217 with a standard error of .00096. No examples of the IVS2(+1) mutation were found among 1,256 samples screened, and no 1448C (L444P) mutations were found among 1,528 samples examined. Examination of the distribution of Gaucher disease gene frequencies in the general population shows that the ratio of 1226G mutations to 84GG mutations is higher than that in the patient population. This is presumed to be due to the fact that homozygotes for the 1226G mutation often have late-onset disease or no significant clinical manifestations at all. To bring the gene frequency in the patient population into conformity with the gene frequency in the general population, nearly two-thirds of persons with a Gaucher disease genotype would be missing from the patient population, presumably because their clinical manifestations were very mild. 10 refs., 3 tabs.« less

Genomewide Scan Reveals Amplification of mdr1 as a Common Denominator of Resistance to Mefloquine, Lumefantrine, and Artemisinin in Plasmodium chabaudi Malaria Parasites▿†‡

PubMed Central

Borges, Sofia; Cravo, Pedro; Creasey, Alison; Fawcett, Richard; Modrzynska, Katarzyna; Rodrigues, Louise; Martinelli, Axel; Hunt, Paul

2011-01-01

Multidrug-resistant Plasmodium falciparum malaria parasites pose a threat to effective drug control, even to artemisinin-based combination therapies (ACTs). Here we used linkage group selection and Solexa whole-genome resequencing to investigate the genetic basis of resistance to component drugs of ACTs. Using the rodent malaria parasite P. chabaudi, we analyzed the uncloned progeny of a genetic backcross between the mefloquine-, lumefantrine-, and artemisinin-resistant mutant AS-15MF and a genetically distinct sensitive clone, AJ, following drug treatment. Genomewide scans of selection showed that parasites surviving each drug treatment bore a duplication of a segment of chromosome 12 (translocated to chromosome 04) present in AS-15MF. Whole-genome resequencing identified the size of the duplicated segment and its position on chromosome 4. The duplicated fragment extends for ∼393 kbp and contains over 100 genes, including mdr1, encoding the multidrug resistance P-glycoprotein homologue 1. We therefore show that resistance to chemically distinct components of ACTs is mediated by the same genetic mutation, highlighting a possible limitation of these therapies. PMID:21709099

Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract.

PubMed

Law, J C; Whiteside, T L; Gollin, S M; Weissfeld, J; El-Ashmawy, L; Srivastava, S; Landreneau, R J; Johnson, J T; Ferrell, R E

1995-07-01

Mutations of the p53 tumor suppressor gene are the most common genetic alterations associated with human cancer. Tumor-associated p53 mutations often show characteristic tissue-specific profiles which may infer environmentally induced mutational mechanisms. The p53 mutational frequency and spectrum were determined for 95 carcinomas of the upper and lower respiratory tract (32 lung and 63 upper respiratory tract). Mutations were identified at a frequency of 30% in upper respiratory tract (URT) tumors and 31% in lung tumors. All 29 identified mutations were single-base substitutions. Comparison of the frequency of specific base substitutions between lung and URT showed a striking difference. Transitions occurred at a frequency of 68% in URT, but only 30% in lung. Mutations involving G:C-->A:T transitions, which are commonly reported in gastric and esophageal tumors, were the most frequently identified alteration in URT (11/19). Mutations involving G:C-->T:A transversions, which were relatively common in lung tumors (3/10) and are representative of tobacco smoke-induced mutations were rare in URT tumors (1/19). Interestingly, G:C-->A:T mutations at CpG sites, which are characteristic of endogenous processes, were observed frequently in URT tumors (9/19) but only rarely in lung tumors (1/10), suggesting that both endogenous and exogenous factors are responsible for the observed differences in mutational spectra between the upper and lower respiratory systems.

Mutation rates among RNA viruses

PubMed Central

Drake, John W.; Holland, John J.

1999-01-01

The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations. The impact of the accumulated load of mutations and the consequences of increasing the mutation rate are important in assessing the genetic health of populations. Mutation frequencies are among the more directly measurable population parameters, although the information needed to convert them into mutation rates is often lacking. A previous analysis of mutation rates in RNA viruses (specifically in riboviruses rather than retroviruses) was constrained by the quality and quantity of available measurements and by the lack of a specific theoretical framework for converting mutation frequencies into mutation rates in this group of organisms. Here, we describe a simple relation between ribovirus mutation frequencies and mutation rates, apply it to the best (albeit far from satisfactory) available data, and observe a central value for the mutation rate per genome per replication of μg ≈ 0.76. (The rate per round of cell infection is twice this value or about 1.5.) This value is so large, and ribovirus genomes are so informationally dense, that even a modest increase extinguishes the population. PMID:10570172

Genotyping non-small cell lung cancer (NSCLC) in Latin America.

PubMed

Arrieta, Oscar; Cardona, Andrés Felipe; Federico Bramuglia, Guillermo; Gallo, Aly; Campos-Parra, Alma D; Serrano, Silvia; Castro, Marcelo; Avilés, Alejandro; Amorin, Edgar; Kirchuk, Ricardo; Cuello, Mauricio; Borbolla, José; Riemersma, Omar; Becerra, Henry; Rosell, Rafael

2011-11-01

Frequency of mutations in EGFR and KRAS in non-small cell lung cancer (NSCLC) is different between ethnic groups; however, there is no information in Latin-American population. A total of 1150 biopsies of NSCLC patients from Latin America (Argentina, Colombia, Peru, and Mexico) were used extracting genomic DNA to perform direct sequencing of EGFR gene (exons 18 and 21) and KRAS gene in 650 samples. In Mexico, Scorpions ARMS was also used to obtain a genetic profile. We report the frequency of mutations in EGFR and KRAS genes in four Latin-American countries (n = 1150). Frequency of EGFR mutations in NSCLC was 33.2% (95% confidence interval [CI] 30.5-35.9) (Argentina 19.3%, Colombia 24.8%, Mexico 31.2%, and Peru 67%). The frequency of KRAS mutations was 16.6% (95% CI 13.8-19.4). EGFR mutations were independently associated with adenocarcinoma histology, older age, nonsmokers, and absence of KRAS mutations. Overall response rate to tyrosine kinase inhibitors in EGFR-mutated patients (n = 56) was 62.5% (95% CI 50-75) with a median overall survival of 16.5 months (95% CI 12.4-20.6). Our findings suggest that the frequency of EGFR mutations in Latin America lies between that of Asian and Caucasian populations and therefore support the genetic heterogeneity of NSCLC around the world.

Healthcare resource utilization, costs of care, and treatment of mycosis fungoides cutaneous T-cell lymphoma patterns in a large managed care population: a retrospective US claims-based analysis.

PubMed

Tsang, Yuen; Gu, Tao; Sharma, Gaurav; Raspa, Susan; Drake, Bill; Tan, Hiangkiat

2018-05-07

To evaluate health care utilization, treatment patterns and costs among patients with mycosis fungoides-cutaneous T-cell lymphoma (MF-CTCL). This retrospective cohort study queried the HealthCore Integrated Research Database to identify patients ≥18 years with ≥2 diagnoses of MF-CTCL (ICD-9-CM code 202.1x, 202.2x) between 07 January 2006 and 07 January 2013. Index date was defined as first MF-CTCL diagnosis. Patients were continuously enrolled ≥6 months before and ≥12 months after index date. Severe MF-CTCL was identified via systemic therapy use postindex. Generalized linear model (GLM) was used to estimate the relationship between MF-CTCL severity and healthcare costs controlling for selected factors. A total of 1981 MF-CTCL patients were evaluated: 493 (24.9%) severe and 1488 (75.1%) with mild to moderate disease. GLM analysis indicated severe MF-CTCL patients incurred higher all-cause healthcare total costs compared to patients with mild-to-moderate MF-CTCL (coefficient estimate: 4.19, p < .0001). About 51% of patients did not receive any MF-CTCL-specific treatment within 60 days after MF-CTCL diagnosis. MF-CTCL severity was associated with greater healthcare resource utilization and costs. These findings suggest that about half of MF-CTCL patients do not receive MF-CTCL-specific treatment within 60 days following initial diagnosis. Future studies are needed to understand reasons for delayed treatment initiation.

The Frequency and Type of K-RAS Mutations in Mexican Patients With Colorectal Cancer: A National Study.

PubMed

Cárdenas-Ramos, Susana G; Alcázar-González, Gregorio; Reyes-Cortés, Luisa M; Torres-Grimaldo, Abdiel A; Calderón-Garcidueñas, Ana L; Morales-Casas, José; Flores-Sánchez, Patricia; De León-Escobedo, Raúl; Gómez-Díaz, Antonio; Moreno-Bringas, Carmen; Sánchez-Guillén, Jorge; Ramos-Salazar, Pedro; González-de León, César; Barrera-Saldaña, Hugo A

2017-06-01

Current metastatic colorectal cancer (mCRC) therapy uses monoclonal antibodies against the epidermal growth factor receptor. This treatment is only useful in the absence of K-RAS gene mutations; therefore the study of such mutations is part of a personalized treatment. The aim of this work is to determine the frequency and type of the most common K-RAS mutations in Mexican patients with metastatic disease by nucleotide sequencing. We studied 888 patients with mCRC from different regions of Mexico. The presence of mutations in exon 2, codons 12 and 13, of the K-RAS gene was determined by nucleotide sequencing. Patients exhibited K-RAS gene mutations in 35% (310/888) of cases. Mutation frequency of codons 12 and 13 was 71% (221/310) and 29% (89/310), respectively. The most common mutation (45.7%) in codon 12 was c.35G>A (p.G12D), whereas the one in codon 13 was c.38G>A (p.G13D) (78.7%). Given the frequency of K-RAS mutations in Mexicans, making a genetic study before deciding to treat mCRC patients with monoclonal antibodies is indispensable.

[Effects of four species of endophytic fungi on the growth and polysaccharide and alkaloid contents of Dendrobium nobile].

PubMed

Chen, Xiao-mei; Guo, Shun-xing

2005-02-01

To study the effects of four species of endophytic fungi on the growth and polysaccharide and alkaloid contents of cultured Dendrobium nobile. Each fungal strain was cultured together with D. nobile, and the plant weight as well as the polysaccharide and alkaloid contents were measured. Compared with the control group, Mycena sp. (MF23) was found to decrease the fresh weight of D. nobile by 24.9% (P < 0.01). All four species of fungi have no effect on the dry weight of this plant. On the other hand, Epulorhiza sp. (MF18) and MF23 could increase the percent of dry weight of seedlings (P < 0.05). Epulorhiza sp. (MF15) and MF24 increased the number of aerial roots by 4.25 times and 4.14 times respectively (P < 0.01). MF23 decreased the numbers of basal roots by 46.5% (P < 0.01). MF15, MF18, MF23 and MF24 were shown to increase the content of polysacchride by 153.4%, 52.1%, 18.5% and 76.7%, respectively. MF23 also increased the content of total alkaloid by 18.3%. Endophytic fungi cultured together with D. nobile could affect the growth of this plant; they also increase total alkaloid and polysaccharide contents.

Dynamic interactions between arterial pressure and sympathetic nerve activity: role of arterial baroreceptors.

PubMed

Julien, Claude; Chapuis, Bruno; Cheng, Yong; Barrès, Christian

2003-10-01

The role of arterial baroreceptors in controlling arterial pressure (AP) variability through changes in sympathetic nerve activity was examined in conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured continuously during 1-h periods in freely behaving rats that had been subjected to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before study (n = 10 in each group). Fast Fourier transform analysis revealed that chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing the so-called Mayer waves, and induced an eightfold increase in MAP power without altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of rats, coherence between RSNA and MAP was maximal in the MF band and was usually weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP showed the characteristics of a second-order low-pass filter containing a fixed time delay ( approximately 0.5 s). These results indicate that arterial baroreceptors are not involved in production of respiratory-related oscillations of RSNA but play a major role in the genesis of synchronous oscillations of MAP and RSNA at the frequency of Mayer waves. The weak coupling between slow fluctuations of RSNA and MAP in sham-operated and SAD rats points to the interference of noise sources unrelated to RSNA affecting MAP and of noise sources unrelated to MAP affecting RSNA.

Treatment and management of myelofibrosis in the era of JAK inhibitors

PubMed Central

Keohane, Clodagh; Radia, Deepti H; Harrison, Claire N

2013-01-01

Myelofibrosis (MF) can present as a primary disorder or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT), the use of cytoreductive agents (ie, hydroxyurea), splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs), androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK) signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment. PMID:23990704

Treatment and management of myelofibrosis in the era of JAK inhibitors.

PubMed

Keohane, Clodagh; Radia, Deepti H; Harrison, Claire N

2013-01-01

Myelofibrosis (MF) can present as a primary disorder or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT), the use of cytoreductive agents (ie, hydroxyurea), splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs), androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK) signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment.

The male to female ratio at birth in the Republic of Ireland and Northern Ireland: influence of societal stress

PubMed Central

2015-01-01

Introduction Male live births occur slightly in excess of female births. The ratio of male divided by total births is referred to as M/F. Many factors reduce M/F including toxins, stress, and privation, with excess male foetal loss. “The Troubles” (1969-1998) of Northern Ireland (NI) and the economic downturn of Republic of Ireland (ROI) from 2007 posed stresses with corresponding controls. This study analysed M/F in NI and ROI. Methods Annual male and female live births in NI and the ROI were compared using chi tests. Results M/F was significantly higher in NI than in ROI. M/F in NI dropped after 1974. M/F rose in ROI up to 1994, then fell. Discussion Violence-related stress may have been the cause for the M/F drop in NI. Economic improvement followed by recession may have caused parallel M/F changes in ROI. These findings agree with the stress hypothesis of M/F. PMID:26668416

HFE gene C282Y, H63D and S65C mutations frequency in the Transylvania region, Romania.

PubMed

Trifa, Adrian P; Popp, Radu A; Militaru, Mariela S; Farcaş, Marius F; Crişan, Tania O; Gana, Ionuţ; Cucuianu, Andrei; Pop, Ioan V

2012-06-01

HFE-associated haemochromatosis is one of the most frequent autosomal recessive disorders in the Caucasian population. Although most of the cases are homozygous individuals for the C282Y mutation, another two mutations, H63D and S65C, have been reported to be associated with milder forms of the disease. This study was a first attempt to evaluate the distribution of these HFE gene mutations in the Transylvania region. Two-hundred and twenty-five healthy, unrelated volunteers originating from the Transylvania region, Romania, were screened for the HFE gene C282Y, H63D and S65C mutations, using molecular genetics assays (Polymerase Chain Reaction-Restriction Fragments Length Polymorphism). For the C282Y mutation, 7 heterozygotes (3.1%) were found, but no homozygous individual. In the case of the H63D mutation, 40 heterozygotes (17.8%) and 4 homozygotes (1.75%) for the mutant allele were evidenced. We found a compound heterozygous genotype (C282Y/H63D) in one individual (0.45%). Thus, the allele frequencies of the C282Y and H63D were 1.75% and 10.9%, respectively. Three individuals (1.3%) were found to harbour the S65C mutation in a heterozygous state, but none in a homozygous state: the allele frequency of the mutant allele was 0.75%. The distribution of the HFE gene C282Y, H63D and S65C mutations found in our group matches the tendencies observed in other European countries: a decreasing gradient from Northern to Southern Europe for the C282Y mutation; high frequency for the H63D mutation, and low frequency for the S65C mutation in most of the countries.

Beta thalassemia in 31,734 cases with HBB gene mutations: Pathogenic and structural analysis of the common mutations; Iran as the crossroads of the Middle East.

PubMed

Mahdieh, Nejat; Rabbani, Bahareh

2016-11-01

Thalassemia is one of the most common single gene disorders worldwide. Nearly 80 to 90 million with minor beta thalassemia and 60-70 thousand affected infants are born annually worldwide. A comprehensive search on several databases including PubMed, InterScience, British Library Direct, and Science Direct was performed extracting papers about mutation detection and frequency of beta thalassemia. All papers reporting on the mutation frequency of beta thalassemia patients were selected to analyze the frequency of mutations in different regions and various ethnicities. Mutations of 31,734 individuals were identified. Twenty common mutations were selected for further analysis. Genotype-phenotype correlation, interactome, and in silico analyses of the mutations were performed using available bioinformatics tools. Secondary structure prediction was achieved for two common mutations with online tools. The mutations were also common among the countries neighboring Iran, which are responsible for 71% to 98% of mutations. Computational analyses could be used in addition to segregation and expression analysis to assess the extent of pathogenicity of the variant. The genetics of beta thalassemia in Iran is more extensively heterogeneous than in neighboring countries. Some common mutations have arisen historically from Iran and moved to other populations due to population migrations. Also, due to genetic drift, the frequencies of some mutations have increased in small populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study

PubMed Central

Boch, Christian; Kollmeier, Jens; Roth, Andreas; Stephan-Falkenau, Susann; Misch, Daniel; Grüning, Wolfram; Bauer, Torsten Thomas; Mairinger, Thomas

2013-01-01

Objectives Owing to novel therapy strategies in epidermal growth factor receptor (EGFR)-mutated patients, molecular analysis of the EGFR and KRAS genome has become crucial for routine diagnostics. Till date these data have been derived mostly from clinical trials, and thus collected in pre-selected populations. We therefore screened ‘allcomers’ with a newly diagnosed non-small cell lung carcinoma (NSCLC) for the frequencies of these mutations. Design A cohort study. Setting Lung cancer centre in a tertiary care hospital. Participants Within 15 months, a total of 552 cases with NSCLC were eligible for analysis. Primary and secondary outcome measures Frequency of scrutinising exons 18, 19 and 21 for the presence of activating EGFR mutation and secondary codon 12 and 13 for activating KRAS mutations. Results Of the 552 patients, 27 (4.9%) showed a mutation of EGFR. 19 of these patients (70%) had deletion E746-A750 in codon 19 or deletion L858R in codon 21. Adenocarcinoma (ACA) was the most frequent histology among patients with EGFR mutations (ACA, 22/254 (8.7%) vs non-ACA, 5/298 (1.7%); p<0.001). Regarding only ACA, the percentage of EGFR mutations was higher in women (16/116 (14%) women vs 6/138 (4.3%) men; p=0.008). Tumours with an activating EGFR mutation were more likely to be from non-smokers (18/27; 67%) rather than smoker (9/27; 33%). KRAS mutation was present in 85 (15%) of all cases. In 73 patients (86%), the mutation was found in exon 12 and in 12 cases (14%) in exon 13. Similarly, ACA had a higher frequency of KRAS mutations than non-ACA (67/254 (26%) vs 18/298 (6.0%); p<0.001). Conclusions We found a lower frequency for EGFR and KRAS mutations in an unselected Caucasian patient cohort as previously published. Taking our results into account, clinical trials may overestimate the mutation frequency for EGFR and KRAS in NSCLC due to important selection biases. PMID:23558737

Indoor transformer stations and ELF magnetic field exposure: use of transformer structural characteristics to improve exposure assessment.

PubMed

Okokon, Enembe Oku; Roivainen, Päivi; Kheifets, Leeka; Mezei, Gabor; Juutilainen, Jukka

2014-01-01

Previous studies have shown that populations of multiapartment buildings with indoor transformer stations may serve as a basis for improved epidemiological studies on the relationship between childhood leukaemia and extremely-low-frequency (ELF) magnetic fields (MFs). This study investigated whether classification based on structural characteristics of the transformer stations would improve ELF MF exposure assessment. The data included MF measurements in apartments directly above transformer stations ("exposed" apartments) in 30 buildings in Finland, and reference apartments in the same buildings. Transformer structural characteristics (type and location of low-voltage conductors) were used to classify exposed apartments into high-exposure (HE) and intermediate-exposure (IE) categories. An exposure gradient was observed: both the time-average MF and time above a threshold (0.4 μT) were highest in the HE apartments and lowest in the reference apartments, showing a statistically significant trend. The differences between HE and IE apartments, however, were not statistically significant. A simulation exercise showed that the three-category classification did not perform better than a two-category classification (exposed and reference apartments) in detecting the existence of an increased risk. However, data on the structural characteristics of transformers is potentially useful for evaluating exposure-response relationship.

Fatigue Analysis Before and After Shaker Exercise: Physiologic Tool for Exercise Design

PubMed Central

White, Kevin T.; Easterling, Caryn; Roberts, Niles; Shaker, Reza

2016-01-01

Recent studies suggest that the Shaker exercise induces fatigue in the upper esophageal sphincter (UES) opening muscles and sternocleidomastoid (SCM), with the SCMs fatiguing earliest. The aim of this study was to measure fatigue induced by the isometric portion of the Shaker exercise by measuring the rate of change in the median frequency (MF rate) of the power spectral density (PSD) function, which is interpreted as proportional to the rate of fatigue, from surface electromyography (EMG) of suprahyoid (SHM), infrahyoid (IHM), and SCM. EMG data compared fatigue-related changes from 20-, 40-, and 60-s isometric hold durations of the Shaker exercise. We found that fatigue-related changes were manifested during the 20-s hold. The findings confirm that the SCM fatigues initially and as fast as or faster than the SHM and IHM. In addition, upon completion of the exercise protocol, the SCM had a decreased MF rate, implying improved fatigue resistance, while the SHM and IHM showed increased MF rates, implying that these muscles increased their fatiguing effort. We conclude that the Shaker exercise initially leads to increased fatigue resistance of the SCM, after which the exercise loads the less fatigue-resistant SHM and IHM, potentiating the therapeutic effect of the Shaker exercise regimen with continued exercise performance. PMID:18369673

The high frequency of GJB2 gene mutation c.313_326del14 suggests its possible origin in ancestors of Lithuanian population.

PubMed

Mikstiene, Violeta; Jakaitiene, Audrone; Byckova, Jekaterina; Gradauskiene, Egle; Preiksaitiene, Egle; Burnyte, Birute; Tumiene, Birute; Matuleviciene, Ausra; Ambrozaityte, Laima; Uktveryte, Ingrida; Domarkiene, Ingrida; Rancelis, Tautvydas; Cimbalistiene, Loreta; Lesinskas, Eugenijus; Kucinskas, Vaidutis; Utkus, Algirdas

2016-02-19

Congenital hearing loss (CHL) is diagnosed in 1 - 2 newborns in 1000, genetic factors contribute to two thirds of CHL cases in industrialised countries. Mutations of the GJB2 gene located in the DFNB1 locus (13q11-12) are a major cause of CHL worldwide. The aim of this cross-sectional study was to assess the contribution of the DFNB1 locus containing the GJB2 and GJB6 genes in the development of early onset hearing loss in the affected group of participants, to determine the population-specific mutational profile and DFNB1-related HL burden in Lithuanian population. Clinical data were obtained from a collection of 158 affected participants (146 unrelated probands) with early onset non-syndromic HL. GJB2 and GJB6 gene sequencing and GJB6 gene deletion testing were performed. The data of GJB2 and GJB6 gene sequencing in 98 participants in group of self-reported healthy Lithuanian inhabitants were analysed. Statistic summary, homogeneity tests, and logistic regression analysis were used for the assessment of genotype-phenotype correlation. Our findings show 57.5% of affected participants with two pathogenic GJB2 gene mutations identified. The most prevalent GJB2 mutations were c.35delG, p. (Gly12Valfs*2) (rs80338939) and c.313_326del14, p. (Lys105Glyfs*5) (rs111033253) with allele frequencies 64.7% and 28.3% respectively. GJB6 gene mutations were not identified in the affected group of participants. The statistical analysis revealed significant differences between GJB2(-) and GJB2(+) groups in disease severity (p = 0.001), and family history (p = 0.01). The probability of identification of GJB2 mutations in patients with various HL characteristics was estimated. The carrier rate of GJB2 gene mutations - 7.1% (~1 in 14) was identified in the group of healthy participants and a high frequency of GJB2-related hearing loss was estimated in our population. The results show a very high proportion of GJB2-positive individuals in the research group affected with sensorineural HL. The allele frequency of c.35delG mutation (64.7 %) is consistent with many previously published studies in groups of affected individuals of Caucasian populations. The high frequency of the c.313_326del14 (28.3 % of pathogenic alleles) mutation in affected group of participants was an unexpected finding in our study suggesting not only a high frequency of carriers of this mutation in our population but also its possible origin in Lithuanian ancestors. The high frequency of carriers of the c.313_326del14 mutation in the entire Lithuanian population is supported by it being identified twice in the ethnic Lithuanian group of healthy participants (a frequency 2.0 % of carriers in the study group). Analysis of the allele frequency of GJB2 gene mutations revealed a high proportion of c. 313_326del14 (rs111033253) mutations in the GJB2-positive group suggesting its possible origin in Lithuanian forebears. The high frequency of carriers of GJB2 gene mutations in the group of healthy participants corresponds to the substantial frequency of GJB2-associated HL in Lithuania. The observations of the study indicate the significant contribution of GJB2 gene mutations to the pathogenesis of the disorder in the Lithuanian population and will contribute to introducing principles to predict the characteristics of the disease in patients.

Developmental effects of magnetic field (50 Hz) in combination with ionizing radiation and chemical teratogens.

PubMed

Pafková, H; Jerábek, J; Tejnorová, I; Bednár, V

1996-11-01

The influence of a 50 Hz magnetic field (MF) on avian and mammalian embryogenesis, the MF level and vector, as well as the effect of exposure to MF (50 Hz, 10 mT) in combination with X-rays has been recently reported [2,3]. No significant alterations of chick or rat embryogenesis were found after repeated exposures to 50 Hz MF at 10 mT or 6 microT or with different vectors. However, X-ray chick embryotoxicity was significantly affected by repeated exposures of developing organisms to MF. A strong dependence of effect on the type of interaction was revealed. A decrease of X-ray induced teratogenicity was observed when MF preceded X-ray exposure (indirect interaction), while MF exposure applied immediately after X-ray radiation (direct interaction) non-significantly potentiated adverse developmental effects of ionizing radiation. This study deals with the effects of MF in combination with insulin or tetracycline. Exposure of chick embryos to MF influenced the sensitivity of embryonic morphogenetic systems to the subsequently administered chemical teratogens, insulin and/or tetracycline. A protective effect of MF was detected similarly as in the case of indirect interaction with ionizing radiation.

Inability of immunomorphometric assessment of angiogenesis to distinguish primary versus secondary myelofibrosis.

PubMed

Sharma, Prashant; Pati, Hara Prasad; Mishra, Pravas Chandra; Dinda, Amit Kumar; Gupta, Ruchika; Sharma, Alok; Jacob, Tony George

2011-08-01

To explore the utility of bone marrow (BM) angiogenesis in differentiating primary myelofibrosis (PMF) from secondary myelofibrosis (MF). CD34 immunostaining was performed on BM biopsies from 21 PMFs, 23 non-PMF myeloproliferative neoplasms (MPN) with associated MF, 20 secondary MF samples, and 10 nonfibrotic controls. Microvessel density (MVD) and microvessel surface area (MSA), along with blood and BM findings were compared between the groups. The post-MPN MF cases included chronic myeloid leukemia-MF and polycythemia vera-MF. Etiologies of secondary MF were metastatic carcinomas, non-MPN hematologic malignancies, tuberculosis, autoimmune MF, and osteopetrosis. Megakaryocytic clustering was the most frequent and intrasinusoidal hematopoiesis the most specific feature of PMF. Higher reticulin grade, collagenization, and osteomyelosclerosis were commoner in PMF. MVD and MSA were significantly increased in fibrotic marrows regardless of etiology. Although mean MVD as well as MSA were highest in PMF, extensive overlaps among groups and marked heterogeneity in the secondary MF group rendered them of limited utility in the differential diagnosis. Enhanced angiogenesis is not entirely specific for PMF. Overlaps with secondary MF limits its differential diagnostic utility. Pathogenetically, our findings suggest that enhanced angiogenesis is a secondary paraneoplastic stromal response shared by various unrelated conditions.

Effects of caffeine ingestion on endurance performance in mentally fatigued individuals.

PubMed

Azevedo, Rafael; Silva-Cavalcante, Marcos David; Gualano, Bruno; Lima-Silva, Adriano E; Bertuzzi, Romulo

2016-12-01

To examine the effects of caffeine ingestion on physiological and perceptual responses in mentally fatigued individuals. Eight male physically active subjects completed four cycling constant-workload tests in four experimental conditions at 80 % of maximal power output: control (C), mental fatigue (MF), mental fatigue plus caffeine ingestion (5 mg/kg) (MF-CAF), and mental fatigue plus placebo (MF-PLA). The mental fatigue was induced by a continuous performance task A-X version (AX-CPT). Before and after the AX-CPT, the profile of mood state (POMS) and blood samples for lactate measurement were collected. Oxygen consumption ([Formula: see text]), rating of perceived exertion (RPE), and electromyography (EMG) activity were measured during the cycling test. The time to exhaustion in C, MF, MF-PLA, and MF-CAF were 251 ± 30, 222 ± 23, 248 ± 28, and 285 ± 42 s, respectively. Delta values (corrected by C condition) were higher in MF-CAF than MF (P = 0.031). MF-CAF reported higher Vigor scores when compared with C (P = 0.046) and MF (P = 0.020). RPE at the first minute was significantly higher in MF-PLA than in C (P = 0.050); at the second minute, RPE was higher in MF-PLA than in C (P = 0.049) and MF-CAF (P = 0.048). EMG activity was not different between the conditions. Caffeine ingestion increased approximately 14 % endurance performance after the induction of mental fatigue. This effect was accompanied by a tendency to improvement in mood state (i.e., vigor). Therefore, caffeine ingestion can promote a beneficial effect on endurance performance in mentally fatigued individuals.

The effects of retinal abnormalities on the multifocal visual evoked potential.

PubMed

Chen, John Y; Hood, Donald C; Odel, Jeffrey G; Behrens, Myles M

2006-10-01

To examine the effects on the amplitude and latency of the multifocal visual evoked potential (mfVEP) in retinal diseases associated with depressed multifocal electroretinograms (mfERG). Static automated perimetry (SAP), mfERGs, and mfVEPs were obtained from 15 individuals seen by neuro-ophthalmologists and diagnosed with retinal disease based on funduscopic examination, visual field, and mfERG. Optic neuropathy was ruled out in all cases. Diagnoses included autoimmune retinopathy (n = 3), branch retinal arterial occlusion (n = 3), branch retinal vein occlusion (n = 1), vitamin A deficiency (n = 1), digoxin/age-related macular degeneration (n = 1), multiple evanescent white dot syndrome (n = 1), and nonspecific retinal disease (n = 5). Patients were selected from a larger group based on abnormal mfERG amplitudes covering a diameter of 20 degrees or greater. Fourteen (93%) of 15 patients showed significant mfVEP delays, as determined by either mean latency or the probability of a cluster of delayed local responses. Thirteen of 15 patients had normal mfVEP amplitudes in regions corresponding to markedly reduced or nonrecordable mfERG responses. These findings can be mimicked in normal individuals by viewing the display through a neutral-density filter. Retinal diseases can result in mfVEPs of relatively normal amplitudes, often with delays, in regions showing decreased mfERG responses and visual field sensitivity loss. Consequently, a retinal problem can be missed, or dismissed as functional, if a diagnosis is based on an mfVEP of normal or near-normal amplitude. Further, in patients with marked mfVEP delays, a retinal problem could be confused with optic neuritis, especially in a patient with a normal appearing fundus.

Self-Managed Exercises, Fitness and Strength Training, and Multifidus Muscle Size in Elite Footballers.

PubMed

Hides, Julie A; Walsh, Jazmin C; Smith, Melinda M Franettovich; Mendis, M Dilani

2017-07-01

  Low back pain (LBP) and lower limb injuries are common among Australian Football League (AFL) players. Smaller size of 1 key trunk muscle, the lumbar multifidus (MF), has been associated with LBP and injuries in footballers. The size of the MF muscle has been shown to be modifiable with supervised motor-control training programs. Among AFL players, supervised motor-control training has also been shown to reduce the incidence of lower limb injuries and was associated with increased player availability for games. However, the effectiveness of a self-managed MF exercise program is unknown.   To investigate the effect of self-managed exercises and fitness and strength training on MF muscle size in AFL players with or without current LBP.   Cross-sectional study.   Professional AFL context.   Complete data were available for 242 players from 6 elite AFL clubs.   Information related to the presence of LBP and history of injury was collected at the start of the preseason. At the end of the preseason, data were collected regarding performance of MF exercises as well as fitness and strength training. Ultrasound imaging of the MF muscle was conducted at the start and end of the preseason.   Size of the MF muscles.   An interaction effect was found between performance of MF exercises and time (F = 13.89, P ≤ .001). Retention of MF muscle size was greatest in players who practiced the MF exercises during the preseason (F = 4.77, P = .03). Increased adherence to fitness and strength training was associated with retained MF muscle size over the preseason (F = 5.35, P = .02).   Increased adherence to a self-administered MF exercise program and to fitness and strength training was effective in maintaining the size of the MF muscle in the preseason.

Modulation and synchronization technique for MF-TDMA system

NASA Technical Reports Server (NTRS)

Faris, Faris; Inukai, Thomas; Sayegh, Soheil

1994-01-01

This report addresses modulation and synchronization techniques for a multi-frequency time division multiple access (MF-TDMA) system with onboard baseband processing. The types of synchronization techniques analyzed are asynchronous (conventional) TDMA, preambleless asynchronous TDMA, bit synchronous timing with a preamble, and preambleless bit synchronous timing. Among these alternatives, preambleless bit synchronous timing simplifies onboard multicarrier demultiplexer/demodulator designs (about 2:1 reduction in mass and power), requires smaller onboard buffers (10:1 to approximately 3:1 reduction in size), and provides better frame efficiency as well as lower onboard processing delay. Analysis and computer simulation illustrate that this technique can support a bit rate of up to 10 Mbit/s (or higher) with proper selection of design parameters. High bit rate transmission may require Doppler compensation and multiple phase error measurements. The recommended modulation technique for bit synchronous timing is coherent QPSK with differential encoding for the uplink and coherent QPSK for the downlink.

EVALUATING EXTREMELY LOW FREQUENCY MAGNETIC FIELDS IN THE REAR SEATS OF THE ELECTRIC VEHICLES.

PubMed

Lin, Jun; Lu, Meng; Wu, Tong; Yang, Lei; Wu, Tongning

2018-03-23

In the electric vehicles (EVs), children can sit on a safety seat installed in the rear seats. Owing to their smaller physical dimensions, their heads, generally, are closer to the underfloor electrical systems where the magnetic field (MF) exposure is the greatest. In this study, the magnetic flux density (B) was measured in the rear seats of 10 different EVs, for different driving sessions. We used the measurement results from different heights corresponding to the locations of the heads of an adult and an infant to calculate the induced electric field (E-field) strength using anatomical human models. The results revealed that measured B fields in the rear seats were far below the reference levels by the International Commission on Non-Ionizing Radiation Protection. Although small children may be exposed to higher MF strength, induced E-field strengths were much lower than that of adults due to their particular physical dimensions.

Effects of subchronic extremely low-frequency electromagnetic field exposure on biochemical parameters in rats.

PubMed

Luo, Xue; Ma, Lingjuan; Gao, Peng; Zhang, Yanwen

2017-04-01

The objective of the present study was to systematically determine the effects of 50 Hertz (Hz) magnetic fields (MFs) on biochemical parameters in rats. Sixty-four adult (5 weeks old, 140-165 g) male Sprague-Dawley rats were randomly divided into four groups: sham, 20 µTesla (µT), 100 µT, and 500 µT 50 Hz MF ( n = 16 in each group). The rats in the MF groups were exposed for 2 h daily for up to 4 weeks. Under these experimental conditions, body weight, organ coefficients, biochemical parameters (blood lipids, myocardial enzymes, liver function, and renal function) were measured. We found that 50 Hz MFs had no significant effects on growth or on the majority of blood biochemical parameters, with the exception of creatinine and cholesterol. However, the changes in creatinine and cholesterol were relatively small and unlikely to be clinically relevant.

SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: frequency and phenotypic variability.

PubMed

Jorge, Alexander A L; Souza, Silvia C; Nishi, Miriam Y; Billerbeck, Ana E; Libório, Débora C C; Kim, Chong A; Arnhold, Ivo J P; Mendonca, Berenice B

2007-01-01

The frequency of SHOX mutations in children with idiopathic short stature (ISS) has been found to be variable. We analysed the SHOX gene in children with ISS and Leri-Weill dyschondrosteosis (LWD) and evaluated the phenotypic variability in patients harbouring SHOX mutations. Sixty-three ISS, nine LWD children and 21 affected relatives. SHOX gene deletion was evaluated by fluorescence in situ hybridization (FISH), Southern blotting and segregation study of polymorphic marker. Point mutations were assessed by direct DNA sequencing. None of the ISS patients presented SHOX deletions, but two (3.2%) presented heterozygous point mutations, including the novel R147H mutation. However, when ISS patients were selected by sitting height : height ratio (SH/H) for age > 2 SD, mutation frequency detection increased to 22%. Eight (89%) LWD patients had SHOX deletions, but none had point mutations. Analysis of the other relatives in the families carrying SHOX mutations identified 14 children and 17 adult patients. A broad phenotypic variability was observed in all families regarding short stature severity and Madelung deformities. However, the presence of disproportional height, assessed by SH/H, was observed in all children and 82% of adult patients, being the most common feature in our patients with SHOX mutations. Patients with SHOX mutations present a broad phenotypic variability. SHOX mutations are very frequent in LWD (89%), in opposition to ISS (3.2%) in our cohort. The use of SH/H SDS as a selection criterion increases the frequency of SHOX mutation detection to 22% and should be used for selecting ISS children to undergo SHOX mutation molecular studies.

Smoking status and self-reported race affect the frequency of clinically relevant oncogenic alterations in non-small-cell lung cancers at a United States-based academic medical practice.

PubMed

Yamaguchi, Norihiro; Vanderlaan, Paul A; Folch, Erik; Boucher, David H; Canepa, Hannah M; Kent, Michael S; Gangadharan, Sidharta P; Majid, Adnan; Kocher, Olivier N; Goldstein, Michael A; Huberman, Mark S; Costa, Daniel B

2013-10-01

The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient-tumor sample pairs. Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient-tumor samples. Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Sealing performance of a magnetic fluid seal for rotary blood pumps.

PubMed

Mitamura, Yoshinori; Takahashi, Sayaka; Kano, Kentaro; Okamoto, Eiji; Murabayashi, Shun; Nishimura, Ikuya; Higuchi, Taka-Aki

2009-09-01

A magnetic fluid (MF) for a rotary blood pump seal enables mechanical contact-free rotation of the shaft and, hence, has excellent durability. The performance of a MF seal, however, has been reported to decrease in liquids. We have developed a MF seal that has a "shield" mechanism and a new MF with a higher magnetization of 47.9 kA/m. The sealing performance of the MF seal installed in a rotary blood pump was studied. Under the condition of continuous flow, the MF seal remained in perfect condition against a pressure of 298 mm Hg (pump flow rate: 3.96 L/min). The seal was also perfect against a pressure of 170 mm Hg in a continuous flow of 3.9 L/min for 275 days. We have developed a MF seal that works in liquid against clinically used pressures. The MF seal is promising as a shaft seal for rotary blood pumps.

Combining magnetic sorting of mother cells and fluctuation tests to analyze genome instability during mitotic cell aging in Saccharomyces cerevisiae.

PubMed

Patterson, Melissa N; Maxwell, Patrick H

2014-10-16

Saccharomyces cerevisiae has been an excellent model system for examining mechanisms and consequences of genome instability. Information gained from this yeast model is relevant to many organisms, including humans, since DNA repair and DNA damage response factors are well conserved across diverse species. However, S. cerevisiae has not yet been used to fully address whether the rate of accumulating mutations changes with increasing replicative (mitotic) age due to technical constraints. For instance, measurements of yeast replicative lifespan through micromanipulation involve very small populations of cells, which prohibit detection of rare mutations. Genetic methods to enrich for mother cells in populations by inducing death of daughter cells have been developed, but population sizes are still limited by the frequency with which random mutations that compromise the selection systems occur. The current protocol takes advantage of magnetic sorting of surface-labeled yeast mother cells to obtain large enough populations of aging mother cells to quantify rare mutations through phenotypic selections. Mutation rates, measured through fluctuation tests, and mutation frequencies are first established for young cells and used to predict the frequency of mutations in mother cells of various replicative ages. Mutation frequencies are then determined for sorted mother cells, and the age of the mother cells is determined using flow cytometry by staining with a fluorescent reagent that detects bud scars formed on their cell surfaces during cell division. Comparison of predicted mutation frequencies based on the number of cell divisions to the frequencies experimentally observed for mother cells of a given replicative age can then identify whether there are age-related changes in the rate of accumulating mutations. Variations of this basic protocol provide the means to investigate the influence of alterations in specific gene functions or specific environmental conditions on mutation accumulation to address mechanisms underlying genome instability during replicative aging.

Methyl farnesoate couples environmental changes to testicular development in the crab Carcinus maenas.

PubMed

Nagaraju, G P C; Borst, D W

2008-09-01

Carcinus maenas males have two major color phases. Green-phase males molt frequently and tend to live in brackish estuaries during the summer. After becoming red-phase males, they molt infrequently, have higher mating success, and live in cooler, deeper water. We found profound differences between these two phases in the way salinity and temperature affect hemolymph levels of methyl farnesoate (MF), a hormone that affects crustacean reproduction. Few green-phase males (<10%) had detectable MF in 33 ppt seawater (SW) at 11 or 18 degrees C. By contrast, about 30% of the red-phase males had detectable MF at either temperature. After transfer to 5 ppt SW, none of the green-phase males had detectable MF at 11 degrees C whereas 100% of green-phase males did at 18 degrees C. By contrast, 100% of the red-phase males had detectable MF in 5 ppt SW at either temperature. At 11 degrees C, green-phase males had detectable MF after eyestalk ablation (ESA), showing that they can produce MF. There was no additional increase in MF levels when ESA animals of either color phase were transferred to 5 ppt SW, suggesting that the eyestalk is the primary regulator of the MF response to low salinity. MF levels of green-phase males were increased by injecting MF, by ESA, or by exposure to 5 ppt SW at 18 degrees C. The testicular index of these treated animals nearly doubled after two weeks. Our results strongly suggest that environmental conditions such as temperature and salinity, affect testicular development in this crab by changing its MF levels.

BcMF26a and BcMF26b Are Duplicated Polygalacturonase Genes with Divergent Expression Patterns and Functions in Pollen Development and Pollen Tube Formation in Brassica campestris

PubMed Central

Lyu, Meiling; Yu, Youjian; Jiang, Jingjing; Song, Limin; Liang, Ying; Ma, Zhiming; Xiong, Xingpeng; Cao, Jiashu

2015-01-01

Polygalacturonase (PG) is one of the cell wall hydrolytic enzymes involving in pectin degradation. A comparison of two highly conserved duplicated PG genes, namely, Brassica campestris Male Fertility 26a (BcMF26a) and BcMF26b, revealed the different features of their expression patterns and functions. We found that these two genes were orthologous genes of At4g33440, and they originated from a chromosomal segmental duplication. Although structurally similar, their regulatory and intron sequences largely diverged. QRT-PCR analysis showed that the expression level of BcMF26b was higher than that of BcMF26a in almost all the tested organs and tissues in Brassica campestris. Promoter activity analysis showed that, at reproductive development stages, BcMF26b promoter was active in tapetum, pollen grains, and pistils, whereas BcMF26a promoter was only active in pistils. In the subcellular localization experiment, BcMF26a and BcMF26b proteins could be localized to the cell wall. When the two genes were co-inhibited, pollen intine was formed abnormally and pollen tubes could not grow or stretch. Moreover, the knockout mutants of At4g33440 delayed the growth of pollen tubes. Therefore, BcMF26a/b can participate in the construction of pollen wall by modulating intine information and BcMF26b may play a major role in co-inhibiting transformed plants. PMID:26153985

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

PubMed Central

Stroup, Bridget M.; Sawin, Emily A.; Murali, Sangita G.; Binkley, Neil; Hansen, Karen E.

2017-01-01

Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258. PMID:28546877

Hydrogen bond docking preference in furans: Osbnd H ⋯ π vs. Osbnd H ⋯ O

NASA Astrophysics Data System (ADS)

Jiang, Xiaotong; Tsona, Narcisse T.; Tang, Shanshan; Du, Lin

2018-02-01

The docking sites of hydrogen bonds in complexes formed between 2,2,2-trifluoroethanol (TFE), furan (Fu), and 2-methyl furan (MF) have been investigated. Using density functional theory (DFT) calculations, gas phase and matrix isolation FTIR spectroscopies, the strengths of Osbnd H ⋯ O and Osbnd H ⋯ π hydrogen bonds in the complexes were compared to find the docking preference. Calculations suggest that the hydrogen bond donor, TFE, is more likely to dock onto the oxygen atom of the aromatic furans ring, and consequently, the Osbnd H ⋯ O type hydrogen bond is relatively stronger than the Osbnd H ⋯ π type. The FTIR spectrum in the OH-stretching fundamental range obtained at room temperatures has been compared with that obtained at extremely low temperatures in the matrix. The fundamental and the red shifts of OH-stretching vibrations were observed in both FTIR spectra, confirming the formation of hydrogen bonded complexes. By assessing the ability of furan and MF to participate in the formation of Osbnd H ⋯ O hydrogen bond, the effect of ring methylation has been highlighted. From the calculated geometric and thermodynamic parameters as well as the frequency shift of the OH-stretching vibrations in complexes, TFE-MF is found to be more stable than TFE-Fu, which suggests that the strength of the Osbnd H ⋯ O hydrogen bond in TFE-MF originates from the high activity of the furan molecule caused by the methylation of the aromatic ring. The present study furthers the knowledge of docking preference in heteroaromatic molecules and is helpful to understand the nature of intermolecular interactions between hydrogen bond donors and acceptors, including both electron-deficient atoms and π cloud.

Alkylating agent (MNU)-induced mutation in space environment

NASA Astrophysics Data System (ADS)

Ohnishi, T.; Takahashi, A.; Ohnishi, K.; Takahashi, S.; Masukawa, M.; Sekikawa, K.; Amano, T.; Nakano, T.; Nagaoka, S.

2001-01-01

In recent years, some contradictory data about the effects of microgravity on radiation-induced biological responses in space experiments have been reported. We prepared a damaged template DNA produced with an alkylating agent (N-methyl-N-nitroso urea; MNU) to measure incorrect base-incorporation during DNA replication in microgravity. We examined whether mutation frequency is affected by microgravity during DNA replication for a DNA template damaged by an alkylating agent. Using an in vitro enzymatic reaction system, DNA synthesis by Taq polymerase or polymerase III was done during a US space shuttle mission (Discovery, STS-91). After the flight, DNA replication and mutation frequencies were measured. We found that there was almost no effect of microgravity on DNA replication and mutation frequency. It is suggested that microgravity might not affect at the stage of substrate incorporation in induced-mutation frequency.

Postadjustment polishing of CAD-CAM ceramic with luminescence diamond gel.

PubMed

Finger, W J; Noack, M D

2000-02-01

(1) to investigate by SEM and profilometry the effectiveness of Luminescence diamond polishing gel on machinable ceramic after adjustment grinding with different grit diamond finishing burs, and (2) to define a simple, time-saving ceramic finishing and polishing technique for clinically satisfactory results. Discs, 3 mm thick, were cut from Vita Mark II CAD-CAM ceramic and ground to a uniform surface finish on 600 grit wet SiC paper. Five specimens in each of the seven groups below were finished unidirectionally by a sweeping mode with the following Two Striper MFS diamond burs: 1. MF1 (45 microm); 2. MF2 (25 microm); 3. MF3 (10 microm); 4. MF1 + MF2; 5. MF1 + MF3; 6. MF2 + MF3; 7. MF1 + MF2 + MF3. Then, Luminescence diamond polishing gel was dispensed on a mandrel-mounted felt applicator and applied at 10,000 rpm for 60 s, and after dipping in water for another 60-s sequence. Surface roughness was determined for each step with a stylus-fitted surface analyzer. On each specimen five parallel tracings (evaluation length 4.0 mm and cut-off length 0.8 mm) were made 1 mm apart. Ra and Rz values were recorded as roughness parameters. Data was subjected to one-way ANOVA and Tukey's multiple comparison test at a significance level of alpha = 0.05. One additional sample for each grinding and polishing step in each of the seven groups was produced for SEM analysis. Diamond polishing after MF1 finishing reduced Ra and Rz significantly from 1.75 to 0.79, and from 10.0 to 4.09 microm, respectively, whereas the Ra and Rz reduction after MF3 finishing and diamond polishing were from 0.64 to 0.49 and from 4.31 to 1.81 microm. The polished surface roughness of specimens prefinished with MF2 or MF3 burs alone or as the final step after preceding grinding with coarser grits was not significantly different. The average Ra and Rz values were 0.42 microm and 1.73 microm. SEM photographs confirmed the uniformity of the surface finish in these groups. The second polishing sequence did not significantly improve the smoothness obtained with the first cycle.

Tomato TILLING Technology: Development of a Reverse Genetics Tool for the Efficient Isolation of Mutants from Micro-Tom Mutant Libraries

PubMed Central

Okabe, Yoshihiro; Asamizu, Erika; Saito, Takeshi; Matsukura, Chiaki; Ariizumi, Tohru; Brès, Cécile; Rothan, Christophe; Mizoguchi, Tsuyoshi; Ezura, Hiroshi

2011-01-01

To accelerate functional genomic research in tomato, we developed a Micro-Tom TILLING (Targeting Induced Local Lesions In Genomes) platform. DNA pools were constructed from 3,052 ethyl methanesulfonate (EMS) mutant lines treated with 0.5 or 1.0% EMS. The mutation frequency was calculated by screening 10 genes. The 0.5% EMS population had a mild mutation frequency of one mutation per 1,710 kb, whereas the 1.0% EMS population had a frequency of one mutation per 737 kb, a frequency suitable for producing an allelic series of mutations in the target genes. The overall mutation frequency was one mutation per 1,237 kb, which affected an average of three alleles per kilobase screened. To assess whether a Micro-Tom TILLING platform could be used for efficient mutant isolation, six ethylene receptor genes in tomato (SlETR1–SlETR6) were screened. Two allelic mutants of SlETR1 (Sletr1-1 and Sletr1-2) that resulted in reduced ethylene responses were identified, indicating that our Micro-Tom TILLING platform provides a powerful tool for the rapid detection of mutations in an EMS mutant library. This work provides a practical and publicly accessible tool for the study of fruit biology and for obtaining novel genetic material that can be used to improve important agronomic traits in tomato. PMID:21965606

Tomato TILLING technology: development of a reverse genetics tool for the efficient isolation of mutants from Micro-Tom mutant libraries.

PubMed

Okabe, Yoshihiro; Asamizu, Erika; Saito, Takeshi; Matsukura, Chiaki; Ariizumi, Tohru; Brès, Cécile; Rothan, Christophe; Mizoguchi, Tsuyoshi; Ezura, Hiroshi

2011-11-01

To accelerate functional genomic research in tomato, we developed a Micro-Tom TILLING (Targeting Induced Local Lesions In Genomes) platform. DNA pools were constructed from 3,052 ethyl methanesulfonate (EMS) mutant lines treated with 0.5 or 1.0% EMS. The mutation frequency was calculated by screening 10 genes. The 0.5% EMS population had a mild mutation frequency of one mutation per 1,710 kb, whereas the 1.0% EMS population had a frequency of one mutation per 737 kb, a frequency suitable for producing an allelic series of mutations in the target genes. The overall mutation frequency was one mutation per 1,237 kb, which affected an average of three alleles per kilobase screened. To assess whether a Micro-Tom TILLING platform could be used for efficient mutant isolation, six ethylene receptor genes in tomato (SlETR1-SlETR6) were screened. Two allelic mutants of SlETR1 (Sletr1-1 and Sletr1-2) that resulted in reduced ethylene responses were identified, indicating that our Micro-Tom TILLING platform provides a powerful tool for the rapid detection of mutations in an EMS mutant library. This work provides a practical and publicly accessible tool for the study of fruit biology and for obtaining novel genetic material that can be used to improve important agronomic traits in tomato.

Frequency-dependent selection can lead to evolution of high mutation rates.

PubMed

Rosenbloom, Daniel I S; Allen, Benjamin

2014-05-01

Theoretical and experimental studies have shown that high mutation rates can be advantageous, especially in novel or fluctuating environments. Here we examine how frequency-dependent competition may lead to fluctuations in trait frequencies that exert upward selective pressure on mutation rates. We use a mathematical model to show that cyclical trait dynamics generated by "rock-paper-scissors" competition can cause the mutation rate in a population to converge to a high evolutionarily stable mutation rate, reflecting a trade-off between generating novelty and reproducing past success. Introducing recombination lowers the evolutionarily stable mutation rate but allows stable coexistence between mutation rates above and below the evolutionarily stable rate. Even considering strong mutational load and ignoring the costs of faithful replication, evolution favors positive mutation rates if the selective advantage of prevailing in competition exceeds the ratio of recombining to nonrecombining offspring. We discuss a number of genomic mechanisms that may meet our theoretical requirements for the adaptive evolution of mutation. Overall, our results suggest that local mutation rates may be higher on genes influencing cyclical competition and that global mutation rates in asexual species may be higher in populations subject to strong cyclical competition.

Locating the Source of Long-Distance Radio Distress Signals from the Southern Ocean

DTIC Science & Technology

1988-03-01

fomZwaic ad e(91) Ref t ~) areshown -39 - ERL-0449-SD 30 EQU IV ALE N T GEOGRAPHIC LATITUDE (DEG), S. j ~jj5"f RN HEMISPHERE, AT LONGITUDE OF ADELAIDE...45 - ERL-0449-SD AST = 48 ASB = 61 - 0.5(Kp - i) ANB = 73 - 1.0(Kp- ) ANT = 76 - 1.25(Kp - j ) where A represents invariant latitude, the subscripts T ...frequency (MF) maritime band (410-512 kHz) for long-distance commun- cation in telegraphy (Morse code) at a frequency which was returned t the earth by

Use of cold microfiltration retentates produced with polymeric membranes for standardization of milks for manufacture of pizza cheese.

PubMed

Govindasamy-Lucey, S; Jaeggi, J J; Johnson, M E; Wang, T; Lucey, J A

2007-10-01

Pizza cheese was manufactured with milk (12.1% total solids, 3.1% casein, 3.1% fat) standardized with microfiltered (MF) and diafiltered retentates. Polymeric, spiral-wound MF membranes were used to process cold (<7 degrees C) skim milk, and diafiltration of MF retentates resulted in at least 36% removal of serum protein on a true protein basis. Cheese milks were obtained by blending the MF retentate (16.4% total solids, 11.0% casein, 0.4% fat) with whole milk (12.1% total solids, 2.4% casein, 3.4% fat). Control cheese was made with part-skim milk (10.9% total solids, 2.4% casein, 2.4% fat). Initial trials with MF standardized milk resulted in cheese with approximately 2 to 3% lower moisture (45%) than control cheese ( approximately 47 to 48%). Cheese-making procedures (cutting conditions) were then altered to obtain a similar moisture content in all cheeses by using a lower setting temperature, increasing the curd size, and lowering the wash water temperature during manufacture of the MF cheeses. Two types of MF standardized cheeses were produced, one with preacidification of milk to pH 6.4 (pH6.4MF) and another made from milk preacidified to pH 6.3 (pH6.3MF). Cheese functionality was assessed by dynamic low-amplitude oscillatory rheology, University of Wisconsin MeltProfiler, and performance on pizza. Nitrogen recoveries were significantly higher in MF standardized cheeses. Fat recoveries were higher in the pH6.3MF cheese than the control or pH6.4MF cheese. Moisture-adjusted cheese yield was significantly higher in the 2 MF-fortified cheeses compared with the control cheese. Maximum loss tangent (LT(max)) values were not significantly different among the 3 cheeses, suggesting that these cheeses had similar meltability. The LT(max) values increased during ripening. The temperature at which the LT(max) was observed was highest in control cheese and was lower in the pH6.3MF cheese than in the pH6.4MF cheese. The temperature of the LT(max) decreased with age for all 3 cheeses. Values of 12% trichloroacetic acid soluble nitrogen levels were similar in all cheeses. Performance on pizza was similar for all cheeses. The use of MF retentates derived with polymeric membranes was successful in increasing cheese yield, and cheese quality was similar in the control and MF standardized cheeses.

Amyotrophic lateral sclerosis

PubMed Central

Wijesekera, Lokesh C; Leigh, P Nigel

2009-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio~1.5:1). Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in degenerating lower motor neurones. Signs of upper motor neurone and lower motor neurone damage not explained by any other disease process are suggestive of ALS. The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival. PMID:19192301

Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

PubMed Central

Christofferson, Austin; Aldrich, Jessica; Jewell, Scott; Kittles, Rick A.; Derome, Mary; Craig, David Wesley; Carpten, John D.

2017-01-01

Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups. Of interest, BCL7A, BRWD3, and AUTS2 demonstrate significantly higher mutation frequencies among AA cases. These genes are all involved in translocations in B-cell malignancies. Moreover, we detected a significant difference in mutation frequency of TP53 and IRF4 with frequencies higher among CA cases. Our study provides rationale for interrogating diverse tumor cohorts to best understand tumor genomics across populations. PMID:29166413

Motor fitness and preschooler children obesity status.

PubMed

Silva-Santos, Sandra; Santos, Amanda; Vale, Susana; Mota, Jorge

2017-09-01

The aim of this study was to examine the association between motor fitness (MF) and obesity status in preschool children. The sample comprised 467 children aged 3-6 years. Preschool children body mass index was classified according to International Obesity Task Force and categorised into three levels, normal, overweight and obesity. Total physical activity was assessed by accelerometer and MF test was assessed through two MF tests 10 × 5m shuttle run test (SRT) and a 7 m jumping distance on 2 feet test (J2F). Low MF was considered for MF if SD above 1. A single variable with three categories was created: low MF medium MF and high MF. The prevalence of normal weight, overweight and obesity was 67.6%, 22.7% and 9.7%, respectively. The prevalence of SD > 1 for SRT was 13.7% and 14.4% for J2F, for single variable was 19.2%. Multinomial logistic regression analysis showed that obese preschoolers were more likely six times classified as having low MF level than their non-overweight counterparts (OR: 6.4; IC: 1.3-36.6). This study showed a considerable prevalence of overweight and obesity among preschoolers. Obesity has already been associated with lower MF. Further longitudinal studies are needed to confirm this data.

Multifractal detrended cross-correlations between the CSI 300 index futures and the spot markets based on high-frequency data

NASA Astrophysics Data System (ADS)

Cao, Guangxi; Han, Yan; Cui, Weijun; Guo, Yu

2014-11-01

The cross-correlation between the China Securities Index 300 (CSI 300) index futures and the spot markets based on high-frequency data is discussed in this paper. We empirically analyze the cross-correlation by using the multifractal detrended cross-correlation analysis (MF-DCCA), and investigate further the characteristics of asymmetry, frequency difference, and transmission direction of the cross-correlation. The results indicate that the cross-correlation between the two markets is significant and multifractal. Meanwhile, weak asymmetries exist in the cross-correlation, and higher data frequency results in a lower multifractality degree of the cross-correlation. The causal relationship between the two markets is bidirectional, but the CSI 300 index futures market has greater impact on the spot market.

Estimated frequency of the canine hyperuricosuria mutation in different dog breeds.

PubMed

Karmi, N; Brown, E A; Hughes, S S; McLaughlin, B; Mellersh, C S; Biourge, V; Bannasch, D L

2010-01-01

Hyperuricosuria is a condition that predisposes dogs to urate urolithiasis. A mutation that causes canine hyperuricosuria was previously identified in 3 unrelated dog breeds. The occurrence of the mutation in additional breeds was not determined. Identify additional breeds that have the hyperuricosuria mutation and estimate the mutant allele frequency in those breeds. Three thousand five hundred and thirty dogs from 127 different breeds were screened for the hyperuricosuria mutation. DNA samples were genotyped by pyrosequencing and allele-specific polymerase chain reaction methods. Mutant allele frequencies that range from 0.001 to 0.15 were identified in the American Staffordshire Terrier, Australian Shepherd, German Shepherd Dog, Giant Schnauzer, Parson (Jack) Russell Terrier, Labrador Retriever, Large Munsterlander, Pomeranian, South African Boerboel, and Weimaraner breeds. The hyperuricosuria mutation has been identified in several unrelated dog breeds. The mutant allele frequencies vary among breeds and can be used to determine an appropriate breeding plan for each breed. A DNA test is available and may be used by breeders to decrease the mutant allele frequency in breeds that carry the mutation. In addition, veterinarians may use the test as a diagnostic tool to identify the cause of urate urolithiasis. Copyright © 2010 by the American College of Veterinary Internal Medicine.

No correlation between germline mutation at repeat DNA and meiotic crossover in male mice exposed to X-rays or cisplatin.

PubMed

Barber, R; Plumb, M; Smith, A G; Cesar, C E; Boulton, E; Jeffreys, A J; Dubrova, Y E

2000-12-20

To test the hypothesis that mouse germline expanded simple tandem repeat (ESTR) mutations are associated with recombination events during spermatogenesis, crossover frequencies were compared with germline mutation rates at ESTR loci in male mice acutely exposed to 1Gy of X-rays or to 10mg/kg of the anticancer drug cisplatin. Ionising radiation resulted in a highly significant 2.7-3.6-fold increase in ESTR mutation rate in males mated 4, 5 and 6 weeks after exposure, but not 3 weeks after exposure. In contrast, irradiation had no effect on meiotic crossover frequencies assayed on six chromosomes using 25 polymorphic microsatellite loci spaced at approximately 20cM intervals and covering 421cM of the mouse genome. Paternal exposure to cisplatin did not affect either ESTR mutation rates or crossover frequencies, despite a report that cisplatin can increase crossover frequency in mice. Correlation analysis did not reveal any associations between the paternal ESTR mutation rate and crossover frequency in unexposed males and in those exposed to X-rays or cisplatin. This study does not, therefore, support the hypothesis that mutation induction at mouse ESTR loci results from a general genome-wide increase in meiotic recombination rate.

Detection of MPLW515L/K Mutations and Determination of Allele Frequencies with a Single-Tube PCR Assay

PubMed Central

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner. PMID:25144224

Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

PubMed

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

Echolocation in the Risso's dolphin, Grampus griseus.

PubMed

Philips, Jennifer D; Nachtigall, Paul E; Au, Whitlow W L; Pawloski, Jeffrey L; Roitblat, Herbert L

2003-01-01

The Risso's dolphin (Grampus griseus) is an exclusively cephalopod-consuming delphinid with a distinctive vertical indentation along its forehead. To investigate whether or not the species echolocates, a female Risso's dolphin was trained to discriminate an aluminum cylinder from a nylon sphere (experiment 1) or an aluminum sphere (experiment 2) while wearing eyecups and free swimming in an open-water pen in Kaneohe Bay, Hawaii. The dolphin completed the task with little difficulty despite being blindfolded. Clicks emitted by the dolphin were acquired at average amplitudes of 192.6 dB re 1 microPa, with estimated sources levels up to 216 dB re 1 microPa-1 m. Clicks were acquired with peak frequencies as high as 104.7 kHz (Mf(p) = 47.9 kHz), center frequencies as high as 85.7 kHz (Mf(0) = 56.5 kHz), 3-dB bandwidths up to 94.1 kHz (M(BW) = 39.7 kHz), and root-mean-square bandwidths up to 32.8 kHz (M(RMS) = 23.3 kHz). Click durations were between 40 and 70 micros. The data establish that the Risso's dolphin echolocates, and that, aside from slightly lower amplitudes and frequencies, the clicks emitted by the dolphin were similar to those emitted by other echolocating odontocetes. The particular acoustic and behavioral findings in the study are discussed with respect to the possible direction of the sonar transmission beam of the species.

The digestive system of the stony coral Stylophora pistillata.

PubMed

Raz-Bahat, M; Douek, J; Moiseeva, E; Peters, E C; Rinkevich, B

2017-05-01

Because hermatypic species use symbiotic algal photosynthesis, most of the literature in this field focuses on this autotrophic mode and very little research has studied the morphology of the coral's digestive system or the digestion process of particulate food. Using histology and histochemestry, our research reveals that Stylophora pistillata's digestive system is concentrated at the corals' peristome, actinopharynx and mesenterial filaments (MF). We used in-situ hybridization (ISH) of the RNA transcript of the gene that codes for the S. pistillata digestive enzyme, chymotrypsinogen, to shed light on the functionality of the digestive system. Both the histochemistry and the ISH pointed to the MF being specialized digestive organs, equipped with large numbers of acidophilic and basophilic granular gland cells, as well as acidophilic non-granular gland cells, some of which produce chymotrypsinogen. We identified two types of MF: short, trilobed MF and unilobed, long and convoluted MF. Each S. pistillata polyp harbors two long convoluted MF and 10 short MF. While the short MF have neither secreting nor stinging cells, each of the convoluted MF display gradual cytological changes along their longitudinal axis, alternating between stinging and secreting cells and three distinctive types of secretory cells. These observations indicate the important digestive role of the long convoluted MF. They also indicate the existence of novel feeding compartments in the gastric cavity of the polyp, primarily in the nutritionally active peristome, in the actinopharynx and in three regions of the MF that differ from each other in their cellular components, general morphology and chymotrypsinogen excretion.

Comparison between Malassezia Folliculitis and Non-Malassezia Folliculitis

PubMed Central

Song, Hyo Sang; Kim, Sue Kyung

2014-01-01

Background Among the various types of folliculitis, differentiation of Malassezia folliculitis (MF) from other forms of folliculitis is important because it is usually treated with antifungal agents. Objective We attempted to find a method to enhance the detection rate of MF, and examined the differences in the clinical manifestation between MF and non-MF (NMF). Methods We performed a retrospective study involving patients with folliculitis who were previously diagnosed with MF or NMF on the basis of serial tissue sectioning and diastase-Periodic acid-Schiff (d-PAS) staining findings. The clinical features of MF and NMF were compared. Results Among a total of 100 folliculitis patients, 20 were diagnosed with MF and 80 with NMF. Tissues from the 80 patients with NMF were sectioned serially into 10 slices and stained with hematoxylin and eosin stain; among these, 10 had many round-to-oval yeast organisms in the hair follicles that confirmed MF. Finally, d-PAS staining was used to detect the presence of yeast in the NMF slides. Notably, among the 70 d-PAS-stained samples, yeast organisms were found in 6 samples, confirming MF. As a result, the diagnosis of 16 patients changed from NMF to MF. Compared with NMF, MF showed major involvement of the trunk and low involvement of the face and legs as well as male predilection. Conclusion Physicians should consider serial sectioning and/or d-PAS staining of folliculitis lesions, particularly of those on the trunk of male patients, even if no yeast organisms are detected initially. PMID:25324652

An integrated approach to conjunctive-use analysis with the one-water hydrologic flow model, MODFLOW-OWHM

USGS Publications Warehouse

Boyce, Scott E.; Hanson, Randall T.

2015-01-01

The MODFLOW-2005 (MF) family of hydrologic simulators has diverged into multiple versions designed for specific needs, thus limiting their use to their respective designs. The One-Water Hydrologic Flow Model (MF-OWHM v1.0) is an integrated hydrologic flow model that is an enhanced fusion of multiple MF versions. While maintaining compatibility with existing MF versions, MF-OWHM includes: linkages for coupled heads, flows, and deformation; facilitation of self-updating models, additional observation and parameter options for higher-order calibrations; and redesigned code for faster simulations. This first release of MF-OWHM incorporates MODFLOW-2005 and the Farm Process (MF-FMP2), with new features (FMP3), combined with Local Grid Refinement (MF-LGR), Streamflow Routing (SFR), Surfacewater Routing Process (SWR), Seawater Intrusion (SWI), Riparian Evapotranspiration (RIP-ET), the Newton Formulation (MF-NWT), and more. MF-OWHM represents a complete integrated hydrologic model that fully links the movement and use of groundwater, surface water, and imported water for consumption by agriculture and natural vegetation on the landscape, and for potable and other uses. By retaining and keeping track of the water during simulation of the hydrosphere, MF-OWHM accounts for “all of the water everywhere and all of the time.” This provides the foundation needed to address integrated hydrologic problems such as evaluation of conjunctive-use alternatives and sustainability analysis, including potential adaptation and mitigation strategies, and best management practices.

ACTION OF MUTAGENIC AGENTS ON AUXOTROPHIC STRAINS OF STREPTOMYCES

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

Jarai, M.

1962-01-01

The mutagenic effect on Streptomyces auxotrophs of uv and x irradiation and of some chemical agerts was studied. From the observed reverse mutations it was concluded that uv and probably x irradiation have an optimal mutagenic dose. With nine auxotrophic strains it was shown that under the same conditions different gene loci reacted differently to the same mutagenic agent. With uy radiation, mutations occurred most frequently at doses falling within the range of 3500 to 4000 erg/mm/sup 2/. With such doses, the average mutation frequency for singly deficient mutants was 0.8 x 10/sup -6/, for doubly deficient mutants 8.4 xmore » 10/sup -8/. An analysis of the number of mutations as compared to the number of survivors in two biochemical mutants (N-4 and N-11) showed that with N- 4 the highest number of mutations was obtained at doses of 3500 to 4500 erg/mm/ sup 2/, namely, 12 to 15 per 10 surviving conidia, and with strain N-11, the highest frequency was obtained in the same dose range, namely, three to four mutations per 10/sup 6/ surviving conidia. The optimal dose of irradiation corresponds to 90 to 97% lethality. It was shown that, unlike the results with uv irradiation, with x rays no such definite relation existed between optimal dose and frequency of mutations. The highest mutation frequency occurred at doses of 20,000 to 25,000 r, which corresponded to 85 to 91% lethality. Of the chemical substances examined, a definite mutagenic action was exerted by acridine orange, streptomycin, hydroxylamine, phenyl, isocyannte, and 8-quinolinol. The maximum mutagenic frequency for survivors was 41.4 x 10/sup -6/ after uv irradiation (biochemical mutant arg 3-; frequency of sportaneous back mutation, 0.041 x 10/sup -6/). With x irradiation the maximum mutagenic frequency was 3.42 x 10/sup -6/ (biochemical mutant meth 1-; frequency of spontaneous back mutation, 0.28 X 10/sup -6/). With chemical agents the maximum mutation frequencies for the initial conidia number were as follows: acridine orange, 3.65 x 10/sup -6/ (biochemical mutant arg 3-); streptomycin, 2.05 x 10/sup -6/ (biochemical mutant arg 3-); hydroxylamine, 5.81 x 10/sup -6/ (biochemical mutant meth 1/sup -/); phenyl isocyanate, 6.11 x 10/sup -6/ (biochemical mutant meth 1/sup -/); 8- quinolinol, 1.02 x 10/sup -6/ (biochemical mutant meth 1/sup -/). (BBB)« less

The molecular epidemiology of Huntington disease is related to intermediate allele frequency and haplotype in the general population.

PubMed

Kay, Chris; Collins, Jennifer A; Wright, Galen E B; Baine, Fiona; Miedzybrodzka, Zosia; Aminkeng, Folefac; Semaka, Alicia J; McDonald, Cassandra; Davidson, Mark; Madore, Steven J; Gordon, Erynn S; Gerry, Norman P; Cornejo-Olivas, Mario; Squitieri, Ferdinando; Tishkoff, Sarah; Greenberg, Jacquie L; Krause, Amanda; Hayden, Michael R

2018-04-01

Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD-associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries. © 2018 Wiley Periodicals, Inc.

Cardiovascular Benefits of Moderate Exercise Training in Marfan Syndrome: Insights From an Animal Model.

PubMed

Mas-Stachurska, Aleksandra; Siegert, Anna-Maria; Batlle, Monsterrat; Gorbenko Del Blanco, Darya; Meirelles, Thayna; Rubies, Cira; Bonorino, Fabio; Serra-Peinado, Carla; Bijnens, Bart; Baudin, Julio; Sitges, Marta; Mont, Lluís; Guasch, Eduard; Egea, Gustavo

2017-09-25

Marfan syndrome (MF) leads to aortic root dilatation and a predisposition to aortic dissection, mitral valve prolapse, and primary and secondary cardiomyopathy. Overall, regular physical exercise is recommended for a healthy lifestyle, but dynamic sports are strongly discouraged in MF patients. Nonetheless, evidence supporting this recommendation is lacking. Therefore, we studied the role of long-term dynamic exercise of moderate intensity on the MF cardiovascular phenotype. In a transgenic mouse model of MF ( Fbn1 C1039G/+ ), 4-month-old wild-type and MF mice were subjected to training on a treadmill for 5 months; sedentary littermates served as controls for each group. Aortic and cardiac remodeling was assessed by echocardiography and histology. The 4-month-old MF mice showed aortic root dilatation, elastic lamina rupture, and tunica media fibrosis, as well as cardiac hypertrophy, left ventricular fibrosis, and intramyocardial vessel remodeling. Over the 5-month experimental period, aortic root dilation rate was significantly greater in the sedentary MF group, compared with the wild-type group (∆mm, 0.27±0.07 versus 0.13±0.02, respectively). Exercise significantly blunted the aortic root dilation rate in MF mice compared with sedentary MF littermates (∆mm, 0.10±0.04 versus 0.27±0.07, respectively). However, these 2 groups were indistinguishable by aortic root stiffness, tunica media fibrosis, and elastic lamina ruptures. In MF mice, exercise also produced cardiac hypertrophy regression without changes in left ventricular fibrosis. Our results in a transgenic mouse model of MF indicate that moderate dynamic exercise mitigates the progression of the MF cardiovascular phenotype. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Selective breeding of dogs for segregation of limb edema from microfilaremia as clinical manifestations of Brugia infections.

PubMed

Miller, S; Snowden, K; Schreuer, D; Hammerberg, B

1990-11-01

Three generations of beagles were monitored for microfilaremia (mf) and clinical disease during repeated infection with Brugia pahangi and were selectively bred for offspring manifesting limb edema and low or amicrofilaremia. A high microfilaremic female mated to a high microfilaremic male produced 7 pups, 6 of which maintained mf greater than 1,000/ml for greater than 2 years after 5 monthly infections of 10 infective larvae each. An uninfected female mated to another high mf male produced 5 pups, 4 of which did not exceed 1,000 mf/ml 7 months after initiation of the repeating infection regimen; 1 of these remained amicrofilaremic after 2 additional challenges. Neither the parents nor the offspring from these matings manifested chronic limb edema. Two matings were conducted with offspring from the microfilaremic female by breeding siblings with the lowest mf and breeding siblings with the highest mf. The high mf siblings produced 4/5 offspring manifesting chronic limb edema (greater than or equal to 7 months duration) and either no mf (in 2 dogs) or less than 100 mf/ml after the repeating infection regimen. The lower mf siblings produced 5 offspring, all with greater than 1,000 mf/ml 6 months after the initiation of the repeating infection regimen; none manifested edema. Comparisons of IgG antibody levels, specific for extracts of adult worms, showed no consistent differences between these 2 litters of dogs that could be associated with limb edema or mf when monitored for 16 months; however, the onset of lymph node enlargement was much earlier in the group of dogs manifesting limb edema than in the other litter.

Optimal Adherence to a Mediterranean Diet and High Muscular Fitness Are Associated with a Healthier Cardiometabolic Profile in Collegiate Students

PubMed Central

Correa-Bautista, Jorge Enrique; Ojeda-Pardo, Mónica Liliana; Sandoval-Cuellar, Carolina; González-Ruíz, Katherine; Prieto-Benavides, Daniel Humberto; Tordecilla-Sanders, Alejandra; Martinkėnas, Arvydas

2018-01-01

The aim of the study was to investigate the combined association of adherence to a Mediterranean diet (MedDiet) and muscular fitness (MF) with cardiometabolic health in collegiate students. The present cross-sectional analysis consisted of 1248 (714 females) healthy collegiate students (20.1 ± 2.7 years old). Adherence to a MedDiet was assessed by a KIDMED (Mediterranean Diet Quality Index) questionnaire. Standing broad jump, standing vertical jump, and isometric handgrip dynamometry were used as indicators of MF. The cardiometabolic profile was assessed using the following components: triglycerides, blood pressure, triglycerides, high-density lipoprotein (HDL)-cholesterol, glucose, and waist circumference. Analysis of covariance shows a significant difference in the cardiometabolic profile of both genders between the high MF/low MedDiet and high MF/optimal MedDiet groups, and the low MF/low MedDiet and low MF/optimal MedDiet groups (p < 0.001). No difference was found on cardiometabolic profile between high MF/optimal MedDiet and high MF/low MedDiet, both in males and females. Additionally, logistic regression shows that both female (odds ratio (OR) = 2.01; 95% confidence interval (CI): (1.8–3.7); p = 0.02) and male (OR = 3.38; 95% CI: (1.9–5.8); p < 0.001) participants in the optimal MedDiet/high MF group had the highest odds of expressing a healthier cardiometabolic profile as compared to those in the low MF/low MedDiet group. In conclusion, a combination of high MF levels and optimal adherence to a MedDiet is associated with a healthier cardiometabolic profile; however, high MF levels seem to circumvent the deleterious effects of having a low adherence to a MedDiet. PMID:29677099

Optimal Adherence to a Mediterranean Diet and High Muscular Fitness Are Associated with a Healthier Cardiometabolic Profile in Collegiate Students.

PubMed

Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Ojeda-Pardo, Mónica Liliana; Sandoval-Cuellar, Carolina; García-Hermoso, Antonio; Carrillo, Hugo Alejandro; González-Ruíz, Katherine; Prieto-Benavides, Daniel Humberto; Tordecilla-Sanders, Alejandra; Martinkėnas, Arvydas; Agostinis-Sobrinho, César

2018-04-20

The aim of the study was to investigate the combined association of adherence to a Mediterranean diet (MedDiet) and muscular fitness (MF) with cardiometabolic health in collegiate students. The present cross-sectional analysis consisted of 1248 (714 females) healthy collegiate students (20.1 ± 2.7 years old). Adherence to a MedDiet was assessed by a KIDMED (Mediterranean Diet Quality Index) questionnaire. Standing broad jump, standing vertical jump, and isometric handgrip dynamometry were used as indicators of MF. The cardiometabolic profile was assessed using the following components: triglycerides, blood pressure, triglycerides, high-density lipoprotein (HDL)-cholesterol, glucose, and waist circumference. Analysis of covariance shows a significant difference in the cardiometabolic profile of both genders between the high MF/low MedDiet and high MF/optimal MedDiet groups, and the low MF/low MedDiet and low MF/optimal MedDiet groups ( p < 0.001). No difference was found on cardiometabolic profile between high MF/optimal MedDiet and high MF/low MedDiet, both in males and females. Additionally, logistic regression shows that both female (odds ratio (OR) = 2.01; 95% confidence interval (CI): (1.8⁻3.7); p = 0.02) and male (OR = 3.38; 95% CI: (1.9⁻5.8); p < 0.001) participants in the optimal MedDiet/high MF group had the highest odds of expressing a healthier cardiometabolic profile as compared to those in the low MF/low MedDiet group. In conclusion, a combination of high MF levels and optimal adherence to a MedDiet is associated with a healthier cardiometabolic profile; however, high MF levels seem to circumvent the deleterious effects of having a low adherence to a MedDiet.

Factors Associated with Wuchereria bancrofti Microfilaremia in an Endemic Area of Mali.

PubMed

Dolo, Housseini; Coulibaly, Yaya Ibrahim; Kelly-Hope, Louise; Konate, Siaka; Dembele, Benoit; Coulibaly, Siaka Yamoussa; Sanogo, Dramane; Soumaoro, Lamine; Coulibaly, Michel Emmanuel; Doumbia, Salif Seriba; Diallo, Abdallah Amadou; Traore, Sekou Fantamady; Colebunders, Robert; Nutman, Thomas B; Klion, Amy D

2018-04-30

Although Wuchereria bancrofti (Wb), the causative agent of lymphatic filariasis, is endemic throughout Mali, the prevalence of Wb microfilaremia (Mf) can vary widely between villages despite similar prevalence of infection as assessed by circulating antigen. To examine this variation, cross-sectional data obtained during screening prior to an interventional study in two neighboring villages in Mali were analyzed. The overall prevalence of Wb, as assessed by Wb Cag (circulating antigen), was 50.3% among 373 participants, aged 14-65. Wb Mf-positive and negative individuals appeared randomly distributed across the two villages (Moran's I spatial statistic = -0.01, Z score = 0.1, P > 0.05). Among the 187 subjects positive for Wb CAg, 117 (62.5%) had detectable Mansonella perstans microfilaremia (Mp Mf) and 64(34.2%) had detectable Wb microfilaremia. The prevalence of Mp microfilaremia was 73.4% in the Wb Mf-positive group (as compared to 56.9% in the Wb Mf-negative group; p=0.01), and median Wb Mf load was increased in co-infected subjects (267 Mf/ml vs 100 Mf/ml; p < 0.001). In multivariate analysis, village of residence, Mp Mf positivity and gender were significantly associated with Wb Mf positivity. After controlling for age, gender and village of residence, the odds of being Wb Mf positive was 2.67 times higher in Mp positive individuals (95% CI [1.42-5.01]). Given the geographical overlap between Mp and Wb in Africa, a better understanding of the distribution and prevalence of Mp could assist national LF control programs in predicting areas of high Wb mf prevalence that may require closer surveillance.

Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma

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

Burmer, G.C.; Rabinovitch, P.S.; Loeb, L.A.

1991-06-01

Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum ofmore » mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.« less

Association between serum adiponectin levels and muscular fitness in Portuguese adolescents: LabMed Physical Activity Study.

PubMed

Agostinis-Sobrinho, C; Santos, R; Moreira, C; Abreu, S; Lopes, L; Oliveira-Santos, J; Rosário, R; Póvoas, S; Mota, J

2016-06-01

Paradoxically, recent investigations have showed that adiponectin levels are inversely associated with muscle strength. However, to date, there is a lack of knowledge on the relationship between muscular fitness (MF) and adiponectin levels in adolescents. We aimed to examine the independent associations between MF and adiponectin levels in adolescents, controlling for several potential confounders. This is a cross-sectional analysis with 529 Portuguese adolescents aged 12-18 years. A MF score was computed as the mean of the handgrip strength and standing long jump standardized values by age and gender. We measured fasting glucose, insulin, HDL-cholesterol, C-reactive protein and adiponectin. Linear regression analysis showed a significant inverse association between adiponectin (Z-score by age and sex) and MF score, after adjustments for age, sex, pubertal stage, socioeconomic status, adherence to the Mediterranean diet, body mass index, HOMA-IR, HDL-cholesterol, C-reactive protein and cardiorespiratory fitness (unstandardized β = -0.176; p < 0.005). Analysis of covariance showed a significant difference between the Low MF/Non-overweight group and the High MF/Non-overweight Group (p < 0.05) and between the Low MF/Non-overweight and High MF/Overweight Group (p < 0.05) (F (5, 523) = 2.262, p = 0.047). Adiponectin circulating levels are inversely and independently associated with MF. In non-overweight adolescents, those with high levels of MF presented lower levels of adiponectin compared to those with Low MF. Likewise, overweight adolescents with High MF presented lower levels of serum adiponectin than non-overweight adolescents with Low MF. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Magnetic Fluids Have Ability to Decrease Amyloid Aggregation Associated with Amyloid-Related Diseases

NASA Astrophysics Data System (ADS)

Antosova, Andrea; Koneracka, Martina; Siposova, Katarina; Zavisova, Vlasta; Daxnerova, Zuzana; Vavra, Ivo; Fabian, Martin; Kopcansky, Peter; Gazova, Zuzana

2010-12-01

At least twenty human proteins can fold abnormally to form pathological deposits that are associated with several amyloid-related diseases. We have investigated the effect of four magnetic fluids (MFs)—electrostatically stabilized Fe3O4 magnetic nanoparticles (MF1) and sterically stabilized Fe3O4 magnetic nanoparticles by sodium oleate (MF2, MF3 and MF4) with adsorbed BSA (MF2) or dextran (MF4)—on amyloid aggregation of two proteins, human insulin and chicken egg lysozyme. The morphology, particle size and size distribution of the prepared magnetic fluids were characterized. We have found that MFs are able to decrease amyloid aggregation of both studied proteins and the extent of depolymerization depended on the MF properties. The most effective reduction was observed for MF4 as 90% decrease of amyloids was detected for insulin and lysozyme amyloid aggregates. Our findings indicate that MFs have potential to be used for treatment of amyloid diseases.

Evaluating the genotoxicity of topoisomerase-targeted antibiotics

PubMed Central

Smart, Daniel J.; Lynch, Anthony M.

2012-01-01

Antibiotics like fluoroquinolones (FQs) that target bacterial type II topoisomerases pose a potential genotoxic risk due to interactions with mammalian topoisomerase II (TOPO II) counterparts. Inhibition of TOPO II can lead to the generation of clastogenic DNA double-strand breaks (DSBs) that can in turn manifest in mutagenesis. Thus, methods that allow early identification of drugs that present the greatest hazard are warranted. A rapid, medium-throughput and predictive genotoxicity screen that can be applied to bacterial type II topoisomerase inhibitors is described herein. Maximal induction of the DSB biomarker serine139-phosphorylated histone H2AX (γH2AX) in L5178Y cells was quantified via flow cytometry and correlated with data derived from the mouse lymphoma screen (MLS), a default assay used to rank genotoxic potential. When applied to a class of novel bacterial type II topoisomerase inhibitors (NBTIs) in lead-optimisation, maximal γH2AX induction >1.4-fold (relative to controls) identified 22/27 NBTIs that induced >6-fold relative mutation frequency (MF) in MLS. Moreover, response signatures comprising of γH2AX induction and G2M cell cycle arrest elucidated using this approach suggested that these NBTIs, primarily of the H class, operated via a TOPO II poison-like mechanism of action (MoA) similar to FQs. NBTIs that induced ≤6-fold relative MF, which were mainly A class-derived, had less impact on γH2AX (≤1.4-fold) and also evoked G1 arrest, indicating that their cytotoxic effects were likely mediated through a non-poison MoA. Concordance between assays was 86% (54/63) when 1.4- and 6-fold ‘cut offs’ were applied. These findings were corroborated through inspection of human TOPO IIα IC50 data as NBTIs exhibiting equivalent inhibitory capacities had differing genotoxic potencies. Deployed in an early screening capacity, the γH2AX by flow assay coupled with structure–activity relationship evaluation can provide insight into MoA and impact medicinal chemistry efforts, ultimately leading to the production of inherently safer molecules. PMID:22155972

Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification.

PubMed

De Brouwer, Sara; De Preter, Katleen; Kumps, Candy; Zabrocki, Piotr; Porcu, Michaël; Westerhout, Ellen M; Lakeman, Arjan; Vandesompele, Jo; Hoebeeck, Jasmien; Van Maerken, Tom; De Paepe, Anne; Laureys, Geneviève; Schulte, Johannes H; Schramm, Alexander; Van Den Broecke, Caroline; Vermeulen, Joëlle; Van Roy, Nadine; Beiske, Klaus; Renard, Marleen; Noguera, Rosa; Delattre, Olivier; Janoueix-Lerosey, Isabelle; Kogner, Per; Martinsson, Tommy; Nakagawara, Akira; Ohira, Miki; Caron, Huib; Eggert, Angelika; Cools, Jan; Versteeg, Rogier; Speleman, Frank

2010-09-01

Activating mutations of the anaplastic lymphoma kinase (ALK) were recently described in neuroblastoma. We carried out a meta-analysis of 709 neuroblastoma tumors to determine their frequency and mutation spectrum in relation to genomic and clinical parameters, and studied the prognostic significance of ALK copy number and expression. The frequency and type of ALK mutations, copy number gain, and expression were analyzed in a new series of 254 neuroblastoma tumors. Data from 455 published cases were used for further in-depth analysis. ALK mutations were present in 6.9% of 709 investigated tumors, and mutations were found in similar frequencies in favorable [International Neuroblastoma Staging System (INSS) 1, 2, and 4S; 5.7%] and unfavorable (INSS 3 and 4; 7.5%) neuroblastomas (P = 0.087). Two hotspot mutations, at positions R1275 and F1174, were observed (49% and 34.7% of the mutated cases, respectively). Interestingly, the F1174 mutations occurred in a high proportion of MYCN-amplified cases (P = 0.001), and this combined occurrence was associated with a particular poor outcome, suggesting a positive cooperative effect between both aberrations. Furthermore, the F1174L mutant was characterized by a higher degree of autophosphorylation and a more potent transforming capacity as compared with the R1275Q mutant. Chromosome 2p gains, including the ALK locus (91.8%), were associated with a significantly increased ALK expression, which was also correlated with poor survival. ALK mutations occur in equal frequencies across all genomic subtypes, but F1174L mutants are observed in a higher frequency of MYCN-amplified tumors and show increased transforming capacity as compared with the R1275Q mutants.

Impact of a static magnetic field on the electricity production of Shewanella-inoculated microbial fuel cells.

PubMed

Li, Wen-Wei; Sheng, Guo-Ping; Liu, Xian-Wei; Cai, Pei-Jie; Sun, Min; Xiao, Xiang; Wang, Yun-Kun; Tong, Zhong-Hua; Dong, Fang; Yu, Han-Qing

2011-06-15

The electricity production of Shewanella-inoculated microbial fuel cells (MFCs) under magnetic field (MF) exposure was investigated in different reactor systems. The persistency of the MF effect and the influences of MF intensity and direction on MFC performance were also studied. Application of a 100-mT static MF to the MFCs improved electricity production considerably, with an increase in the maximum voltage by 20-27% in both single- and two-chamber MFCs, while a more conspicuous improvement in the electricity generation was observed in a three-electrode cell. The MF effects were found to be immediate and reversible, and adverse effects seemed to occur when the MF was suddenly removed. The medium components analysis demonstrated that the application of MF led to an enhanced bioelectrochemical activity of Shewanella, and no significant promotion in mediator secretion was found. The improvement in the electricity production of MFCs under MF was mainly attributed to the enhanced bioelectrochemical activity, possibly through the oxidative stress mechanism. An accelerated cell growth under MF might also contribute to the enhanced substrate degradation and power generation. Copyright © 2010 Elsevier B.V. All rights reserved.

Group 4 transition metal CH2=MF2, CHF=MF2, and HC/MF3 complexes formed by C-F activation and alpha-fluorine transfer.

PubMed

Lyon, Jonathan T; Andrews, Lester

2007-06-11

Group 4 transition metal methylidene difluoride complexes (CH2=MF2) are formed by the reaction of methylene fluoride with laser-ablated metal atoms and are isolated in an argon matrix. Isotopic substitution of the CH2F2 precursor and theoretical computations (B3LYP and CCSD) confirm product identifications and assignments. Our calculations indicate that the CH2=MF2 complexes have near C2v symmetry and are considerably more stable than other possible products (CH2(mu-F)MF and CHF=MHF). The primary reaction exothermicity provides more than enough energy to activate the initial bridge-bonded CH2(mu-F)MF products on the triplet potential energy surface to complete an alpha-F transfer to form the very stable CH2=MF2 products. Analogous experiments with CHF3 produce CHF=TiF2, which is not distorted at the C-H bond, whereas the heavier group 4 metals form lower-energy triplet HC/MF3 complexes, which contain weak degenerate C(p)-M(d) pi-bonding interactions. Comparisons are made with the CH2=MHF methylidene species, which showed considerable agostic distortions.

Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone.

PubMed

Koroma, Joseph B; Sesay, Santigie; Conteh, Abdul; Koudou, Benjamin; Paye, Jusufu; Bah, Mohamed; Sonnie, Mustapha; Hodges, Mary H; Zhang, Yaobi; Bockarie, Moses J

2018-04-06

Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone. Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict. Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution. In total, 39 sentinel villages from hyper- and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010. Results were analyzed and compared with the baseline data from the same 39 villages. The average microfilaridermia (MF) prevalence across 39 sentinel villages was 53.10% at baseline. The MF prevalence was higher in older age groups, with the lowest in the age group of 1-9 years (11.00%) and the highest in the age group of 40-49 years (82.31%). Overall mean MF density among the positives was 28.87 microfilariae (mf)/snip, increasing with age with the lowest in the age group of 1-9 years and the highest in the age group of 40-49 years. Males had higher MF prevalence and density than females. In 2010 after five rounds of mass drug administration, the overall MF prevalence decreased by 60.26% from 53.10% to 21.10%; the overall mean MF density among the positives decreased by 71.29% from 28.87 mf/snip to 8.29 mf/snip; and the overall mean MF density among all persons examined decreased by 88.58% from 15.33 mf/snip to 1.75 mf/snip. Ten of 12 endemic districts had > 50% reduction in MF prevalence. Eleven of 12 districts had ≥50% reduction in mean MF density among the positives. A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage. The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025. Annual MDA with ivermectin should continue in all 12 districts and further evaluations are needed across the country to assist the NTDP with programme decision making.

Frequency and Distribution of Tuberculosis Resistance-Associated Mutations between Mumbai, Moldova, and Eastern Cape

PubMed Central

Seifert, M.; Catanzaro, D.; Garfein, R. S.; Valafar, F.; Crudu, V.; Rodrigues, C.; Victor, T. C.; Catanzaro, A.; Rodwell, T. C.

2016-01-01

Molecular diagnostic assays, with their ability to rapidly detect resistance-associated mutations in bacterial genes, are promising technologies to control the spread of drug-resistant tuberculosis (DR-TB). Sequencing assays provide detailed information for specific gene regions and can help diagnostic assay developers prioritize mutations for inclusion in their assays. We performed pyrosequencing of seven Mycobacterium tuberculosis gene regions (katG, inhA, ahpC, rpoB, gyrA, rrs, and eis) for 1,128 clinical specimens from India, Moldova, and South Africa. We determined the frequencies of each mutation among drug-resistant and -susceptible specimens based on phenotypic drug susceptibility testing results and examined mutation distributions by country. The most common mutation among isoniazid-resistant (INHr) specimens was the katG 315ACC mutation (87%). However, in the Eastern Cape, INHr specimens had a lower frequency of katG mutations (44%) and higher frequencies of inhA (47%) and ahpC (10%) promoter mutations. The most common mutation among rifampin-resistant (RIFr) specimens was the rpoB 531TTG mutation (80%). The mutation was common in RIFr specimens in Mumbai (83%) and Moldova (84%) but not the Eastern Cape (17%), where the 516GTC mutation appeared more frequently (57%). The most common mutation among fluoroquinolone-resistant specimens was the gyrA 94GGC mutation (44%). The rrs 1401G mutation was found in 84%, 84%, and 50% of amikacin-resistant, capreomycin-resistant, and kanamycin (KAN)-resistant (KANr) specimens, respectively. The eis promoter mutation −12T was found in 26% of KANr and 4% of KAN-susceptible (KANs) specimens. Inclusion of the ahpC and eis promoter gene regions was critical for optimal test sensitivity for the detection of INH resistance in the Eastern Cape and KAN resistance in Moldova. (This study has been registered at ClinicalTrials.gov under registration number NCT02170441.) PMID:27090176

The ABCA4 2588G>C Stargardt mutation: single origin and increasing frequency from South-West to North-East Europe.

PubMed

Maugeri, Alessandra; Flothmann, Kris; Hemmrich, Nadine; Ingvast, Sofie; Jorge, Paula; Paloma, Eva; Patel, Reshma; Rozet, Jean-Michel; Tammur, Jaana; Testa, Francesco; Balcells, Susana; Bird, Alan C; Brunner, Han G; Hoyng, Carel B; Metspalu, Andres; Simonelli, Francesca; Allikmets, Rando; Bhattacharya, Shomi S; D'Urso, Michele; Gonzàlez-Duarte, Roser; Kaplan, Josseline; te Meerman, Gerard J; Santos, Rosário; Schwartz, Marianne; Van Camp, Guy; Wadelius, Claes; Weber, Bernhard H F; Cremers, Frans P M

2002-03-01

Inherited retinal dystrophies represent the most important cause of vision impairment in adolescence, affecting approximately 1 out of 3000 individuals. Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of retinal dystrophy. A number of mutations have been repeatedly reported for this gene, notably the 2588G>C mutation which is frequent in both patients and controls. Here we ascertained the frequency of the 2588G>C mutation in a total of 2343 unrelated random control individuals from 11 European countries and 241 control individuals from the US, as well as in 614 patients with STGD both from Europe and the US. We found an overall carrier frequency of 1 out of 54 in Europe, compared with 1 out of 121 in the US, confirming that the 2588G>C ABCA4 mutation is one of the most frequent autosomal recessive mutations in the European population. Carrier frequencies show an increasing gradient in Europe from South-West to North-East. The lowest carrier frequency, 0 out of 199 (0%), was found in Portugal; the highest, 11 out of 197 (5.5%), was found in Sweden. Haplotype analysis in 16 families segregating the 2588G>C mutation showed four intragenic polymorphisms invariably present in all 16 disease chromosomes and sharing of the same allele for several markers flanking the ABCA4 locus in most of the disease chromosomes. These results indicate a single origin of the 2588G>C mutation which, to our best estimate, occurred between 2400 and 3000 years ago.

A magnetic fluid seal for rotary blood pumps: effects of seal structure on long-term performance in liquid.

PubMed

Mitamura, Yoshinori; Takahashi, Sayaka; Amari, Shuichi; Okamoto, Eiji; Murabayashi, Shun; Nishimura, Ikuya

2011-03-01

A magnetic fluid (MF) seal enables mechanical contact-free rotation of the shaft and hence has excellent durability. The performance of an MF seal, however, has been reported to decrease in liquids. We developed an MF seal that has a "shield" mechanism, and a new MF with a higher magnetization of 47.9 kA/m. The sealing performance of the MF seal installed in a rotary blood pump was studied. Three types of MF seals were used. Seal A was a conventional seal without a shield. Seal B had the same structure as that of Seal A, but the seal was installed at 1 mm below liquid level. Seal C was a seal with a shield and the MF was set at 1 mm below liquid level. Seal A failed after 6 and 11 days. Seal B showed better results (20 and 73 days). Seal C showed long-term durability (217 and 275 days). The reason for different results in different seal structures was considered to be different flow conditions near the magnetic fluid. Fluid dynamics near the MF in the pump were analyzed using computational fluid dynamics (CFD) software. We have developed an MF seal with a shield that works in liquid for >275 days. The MF seal is promising as a shaft seal for rotary blood pumps.

Characterization of BcMF23a and BcMF23b, two putative pectin methylesterase genes related to pollen development in Brassica campestris ssp. chinensis.

PubMed

Lin, Sue; Huang, Li; Yu, Xiaolin; Xiong, Xingpeng; Yue, Xiaoyan; Liu, Tingting; Liang, Ying; Lv, Meiling; Cao, Jiashu

2017-02-01

Two homologous genes, Brassica campestris Male Fertility 23a (BcMF23a) and Brassica campestris Male Fertility 23b (BcMF23b), encoding putative pectin methylesterases (PMEs) were isolated from Brassica campestris ssp. chinensis (syn. Brassica rapa ssp. chinensis). These two genes sharing high sequence identity with each other were highly expressed in the fertile flower buds but silenced in the sterile ones of genic male sterile line system ('Bcajh97-01A/B'). Results of RT-PCR and in situ hybridization suggested that BcMF23a and BcMF23b were pollen-expressed genes, whose transcripts were first detected at the binucleate pollen and maintained throughout to the mature pollen grains. Western blot indicated that both of the putative BcMF23a and BcMF23b proteins are approximately 40 kDa, which exhibited extracellular localization revealed by transient expression analysis in the onion epidermal cells. The promoter of BcMF23a was active specifically in pollen during the late pollen developmental stages, while, in addition to the pollen, BcMF23b promoter drove an extra gene expression in the valve margins, abscission layer at the base of the first true leaves, taproot and lateral roots in seedlings.

Investigation of Rubidium Hyperfine Structure Frequency Stabilization Mechanisms.

DTIC Science & Technology

1984-08-01

Frueholtz, and C. H. Volk, Phys. Rev. A 27, 1914 (1983). 4. C. Cohen-Tannoudji, Metrologia 13, 161 (1977). 5. W. Happer, and A. C. Tam, Phys. Rev. A 16, 1877...w U C) ED W mF w c M0 -0 Dm U(i2 DOW V) ZivF 00. LA *I U-(JL OLLIAJ - (I 0 7 a I I ~w..-..- ~ * * ~ -~.’,** ~-, .*h4w.’.-* .- ,-~-. . .- * 8

Preferential flows and soil moistures on a Benggang slope: Determined by the water and temperature co-monitoring

NASA Astrophysics Data System (ADS)

Tao, Yu; He, Yangbo; Duan, Xiaoqian; Zou, Ziqiang; Lin, Lirong; Chen, Jiazhou

2017-10-01

Soil preferential flow (PF) has important effects on rainfall infiltration, moisture distribution, and hydrological and ecological process; but it is very difficult to monitor and characterize on a slope. In this paper, soil water and soil temperature at 20, 40, 60, 80 cm depths in six positions were simultaneously monitored at high frequency to confirm the occurrence of PF at a typical Benggang slope underlain granite residual deposits, and to determine the interaction of soil moisture distribution and Benggang erosion. In the presence of PF, the soil temperature was first (half to one hour) governed by the rainwater temperature, then (more than one hour) governed by the upper soil temperature; in the absence of PF (only matrix flow, MF), the soil temperature was initially governed by the upper soil temperature, then by the rainwater temperature. The results confirmed the water replacement phenomenon in MF, thus it can be distinguished from PF by additional temperature monitoring. It indicates that high frequency moisture and temperature monitoring can determine the occurrence of PF and reveal the soil water movement. The distribution of soil water content and PF on the different positions of the slope showed that a higher frequency of PF resulted in a higher variation of average of water content. The frequency of PF at the lower position can be three times as that of the upper position, therefore, the variation coefficient of soil water content increased from 4.67% to 12.68% at the upper position to 8.18%-33.12% at the lower position, where the Benggang erosion (soil collapse) was more possible. The results suggest strong relationships between PF, soil water variation, and collapse activation near the Benggang wall.

Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort.

PubMed

De Rienzo, Francesca; Mellone, Simona; Bellone, Simonetta; Babu, Deepak; Fusco, Ileana; Prodam, Flavia; Petri, Antonella; Muniswamy, Ranjith; De Luca, Filippo; Salerno, Mariacarolina; Momigliano-Richardi, Patricia; Bona, Gianni; Giordano, Mara

2015-12-01

Combined pituitary hormonal deficiency (CPHD) can result from mutations within genes that encode transcription factors. This study evaluated the frequency of mutations in these genes in a cohort of 144 unrelated Italian patients with CPHD and estimated the overall prevalence of mutations across different populations using a systematic literature review. A multicentre study of adult and paediatric patients with CPHD was performed. The PROP1, POU1F1, HESX1, LHX3 and LHX4 genes were analysed for the presence of mutations using direct sequencing. We systematically searched PubMed with no date restrictions for studies that reported genetic screening of CPHD cohorts. We only considered genetic screenings with at least 10 individuals. Data extraction was conducted in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Global mutation frequency in Italian patients with CPHD was 2·9% (4/136) in sporadic cases and 12·5% (1/8) in familial cases. The worldwide mutation frequency for the five genes calculated from 21 studies was 12·4%, which ranged from 11·2% in sporadic to 63% in familial cases. PROP1 was the most frequently mutated gene in sporadic (6·7%) and familial cases (48·5%). The frequency of defects in genes encoding pituitary transcription factors is quite low in Italian patients with CPHD and other western European countries, especially in sporadic patients. The decision of which genes should be tested and in which order should be guided by hormonal and imaging phenotype, the presence of extrapituitary abnormalities and the frequency of mutation for each gene in the patient-referring population. © 2015 John Wiley & Sons Ltd.

Mutagenic frequencies of site-specifically located O6-methylguanine in wild-type Escherichia coli and in a strain deficient in ada-methyltransferase.

PubMed

Rossi, S C; Topal, M D

1991-02-01

The adaptive response of Escherichia coli involves protection of the cells against the toxic and mutagenic consequences of exposure to high doses of a methylating agent by prior exposure to low doses of the agent. Ada protein, a major repair activity for O6-methylguanine, is activated to positively control the adaptive response; O6-methylguanine is one of the major mutagenic lesions produced by methylating agents. We investigated the mutation frequency of wild-type Escherichia coli and strains containing the ada-5 mutation in response to site-specifically synthesized O6-methylguanine under conditions in which the adaptive response was not induced. Site-directed mutagenesis and oligonucleotide self-selection techniques were used to isolate the progeny of M13mp18 DNAs constructed to contain O6-methylguanine at any of eight different positions. The progeny were isolated from E. coli strains isogeneic except for deficiency in Ada-methyltransferase repair, UvrABC excision repair, or both. The resulting O6-methylguanine mutation levels at each position were determined by using differential oligonucleotide hybridization. We found that the wild type had up to a 2.6-fold higher mutation frequency than ada-5 mutants. In addition, the mutation frequency varied with the position of the O6-methylguanine in the DNA in the wild type but not in ada-5 mutants; O6-methylguanine lesions at the 5' ends of runs of consecutive guanines gave the highest mutation frequencies. Determination of the mutation frequency of O6-methylguanine in wild-type and mutS cells showed that mismatch repair can affect O6-methylguanine mutation levels.

[Frequency of the most common mutations of the CFTR gene in peruvian patients with cystic fibrosis using the ARMS-PCR technique].

PubMed

Aquino, Ruth; Protzel, Ana; Rivera, Juan; Abarca, Hugo; Dueñas, Milagros; Nestarez, Cecilia; Purizaga, Nestor; Diringer, Benoit

2017-01-01

To determine the frequency of the ten most common mutations of the CFTR gene reported in Latin Americausing amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) in patients with cystic fibrosis (CF) in two referral hospitals in Peru during the year 2014. The frequency of the ten most common mutations of the CFTR gene was assessed in patients of the Hospital Nacional Edgardo Rebagliati Martins and the Instituto Nacional de Salud del Niño, both located in Lima, Peru. Blood samples were collected from 36 patients with CF, and the ARMS-PCR technique was used to determine the presence of these mutations. The study group included 73.5% of patients with a known diagnosis of CF in the country when the study was carried out. ARMS-PCR allowed three of the mutations to be identified in a combined 30.6% of the alleles from patients with CF, and 64.9% of the mutated alleles were not identified. The mutations found were p.Phe508del (22,2%), p.Gly542* (6,9%), and p.Arg1162* (1,4%). There is significant variability in both the frequency and type of mutations present in our study population and in what has been reported in other Latin American countries. It is necessary to perform studies that use complete sequencing technology for the CFTR gene to identify other mutations present in our population.

The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect

PubMed Central

Tiemann-Boege, Irene; Navidi, William; Grewal, Raji; Cohn, Dan; Eskenazi, Brenda; Wyrobek, Andrew J.; Arnheim, Norman

2002-01-01

The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g., achondroplasia) increase in incidence with the age of the father is consistent with this idea. Although it is assumed that the paternal age effect is the result of an increasing frequency of mutant sperm as a man grows older, no direct molecular measurement of the germ-line mutation frequency has been made to confirm this hypothesis. Using sperm DNA from donors of different ages, we determined the frequency of the nucleotide substitution in the fibroblast growth factor receptor 3 (FGFR3) gene that causes achondroplasia. Surprisingly, the magnitude of the increase in mutation frequency with age appears insufficient to explain why older fathers have a greater chance of having a child with this condition. A number of alternatives may explain this discrepancy, including selection for sperm that carry the mutation or an age-dependent increase in premutagenic lesions that remain unrepaired in sperm and are inefficiently detected by the PCR assay. PMID:12397172

Edge-Oriented Graphene on Carbon Nanofiber for High-Frequency Supercapacitors

NASA Astrophysics Data System (ADS)

Islam, Nazifah; Warzywoda, Juliusz; Fan, Zhaoyang

2018-03-01

High-frequency supercapacitors are being studied with the aim to replace the bulky electrolytic capacitors for current ripple filtering and other functions used in power systems. Here, 3D edge-oriented graphene (EOG) was grown encircling carbon nanofiber (CNF) framework to form a highly conductive electrode with a large surface area. Such EOG/CNF electrodes were tested in aqueous and organic electrolytes for high-frequency supercapacitor development. For the aqueous and the organic cell, the characteristic frequency at - 45° phase angle was found to be as high as 22 and 8.5 kHz, respectively. At 120 Hz, the electrode capacitance density was 0.37 and 0.16 mF cm-2 for the two cells. In particular, the 3 V high-frequency organic cell was successfully tested as filtering capacitor used in AC/DC converter, suggesting the promising potential of this technology for compact power supply design and other applications. [Figure not available: see fulltext.

Novel DNA variants and mutation frequencies of hMLH1 and hMSH2 genes in colorectal cancer in the Northeast China population.

PubMed

Hu, Fulan; Li, Dandan; Wang, Yibaina; Yao, Xiaoping; Zhang, Wencui; Liang, Jing; Lin, Chunqing; Ren, Jiaojiao; Zhu, Lin; Wu, Zhiwei; Li, Shuying; Li, Ye; Zhao, Xiaojuan; Cui, Binbin; Dong, Xinshu; Tian, Suli; Zhao, Yashuang

2013-01-01

Research on hMLH1 and hMSH2 mutations tend to focus on Lynch syndrome (LS) and LS-like colorectal cancer (CRC). No studies to date have assessed the role of hMLH1 and hMSH2 genes in mass sporadic CRC (without preselection by MSI or early age of onset). We aimed to identify novel hMLH1 and hMSH2 DNA variants, to determine the mutation frequencies and sites in both sporadic and LS CRC and their relationships with clinicopathological characteristics of CRC in Northeast of China. 452 sporadic and 21 LS CRC patients were screened for germline and somatic mutations in hMLH1 and hMSH2 genes with PCR-SSCP sequencing. We identified 11 hMLH1 and seven hMSH2 DNA variants in our study cohort. Six of them were novel: four in hMLH1 gene (IVS8-16 A>T, c.644 GAT>GTT, c.1529 CAG>CGG and c.1831 ATT>TTT) and two in hMSH2 gene (-39 C>T, insertion AACAACA at c.1127 and deletion AAG at c.1129). In sporadic CRC, germline and somatic mutation frequencies of hMLH1/hMSH2 gene were 15.59% and 17.54%, respectively (p = 0.52). Germline mutations present in hMLH1 and hMSH2 genes were 5.28% and 10.78%, respectively (p<0.01). Somatic mutations in hMLH1 and hMSH2 genes were 6.73% and 11.70%, respectively (p = 0.02). In LS CRC, both germline and somatic mutation frequencies of hMLH1/hMSH2 gene were 28.57%. The most prevalent germline mutation site in hMSH2 gene was c.1168 CTT>TTT (3.90%), a polymorphism. Somatic mutation frequency of hMLH1/hMSH2 gene was significantly different in proximal, distal colon and rectal cancer (p = 0.03). Our findings elucidate the mutation spectrum and frequency of hMLH1 and hMSH2 genes in sporadic and LS CRC, and their relationships with clinicopathological characteristics of CRC.

Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure.

PubMed

Wilsey, Laura; Gowrisankaran, Sowjanya; Cull, Grant; Hardin, Christy; Burgoyne, Claude F; Fortune, Brad

2017-04-01

To compare diagnostic performance and structure-function correlations of multifocal electroretinogram (mfERG), full-field flash ERG (ff-ERG) photopic negative response (PhNR) and transient pattern-reversal ERG (PERG) in a non-human primate (NHP) model of experimental glaucoma (EG). At baseline and after induction of chronic unilateral IOP elevation, 43 NHP had alternating weekly recordings of retinal nerve fiber layer thickness (RNFLT) by spectral domain OCT (Spectralis) and retinal function by mfERG (7F slow-sequence stimulus, VERIS), ff-ERG (red 0.42 log cd-s/m 2 flashes on blue 30 scotopic cd/m 2 background, LKC UTAS-E3000), and PERG (0.8° checks, 99% contrast, 100 cd/m 2 mean, 5 reversals/s, VERIS). All NHP were followed at least until HRT-confirmed optic nerve head posterior deformation, most to later stages. mfERG responses were filtered into low- and high-frequency components (LFC, HFC, >75 Hz). Peak-to-trough amplitudes of LFC features (N1, P1, N2) and HFC RMS amplitudes were measured and ratios calculated for HFC:P1 and N2:P1. ff-ERG parameters included A-wave (at 10 ms), B-wave (trough-to-peak) and PhNR (baseline-to-trough) amplitudes as well as PhNR:B-wave ratio. PERG parameters included P50 and N95 amplitudes as well as N95:P50 ratio and N95 slope. Diagnostic performance of retinal function parameters was compared using the area under the receiver operating characteristic curve (A-ROC) to discriminate between EG and control eyes. Correlations to RNFLT were compared using Steiger's test. Study duration was 15 ± 8 months. At final follow-up, structural damage in EG eyes measured by RNFLT ranged from 9% above baseline (BL) to 58% below BL; 29/43 EG eyes (67%) and 0/43 of the fellow control eyes exhibited significant (>7%) loss of RNFLT from BL. Using raw parameter values, the largest A-ROC findings for mfERG were: HFC (0.82) and HFC:P1 (0.90); for ff-ERG: PhNR (0.90) and PhNR:B-wave (0.88) and for PERG: P50 (0.64) and N95 (0.61). A-ROC increased when data were expressed as % change from BL, but the pattern of results persisted. At 95% specificity, the diagnostic sensitivity of mfERG HFC:P1 ratio was best, followed by PhNR and PERG. The correlation to RNFLT was stronger for mfERG HFC (R = 0.65) than for PhNR (R = 0.59) or PERG N95 (R = 0.36), (p = 0.20, p = 0.0006, respectively). The PhNR flagged a few EG eyes at the final time point that had not been flagged by mfERG HFC or PERG. Diagnostic performance and structure-function correlation were strongest for mfERG HFC as compared with ff-ERG PhNR or PERG in NHP EG.

On the incidence and sex ratio of transsexualism in Sweden, 1972-2002.

PubMed

Olsson, Stig-Eric; Möller, Anders R

2003-08-01

The purpose of this study was to investigate whether the incidence of transsexualism in Sweden has been stable over the period of the three decades sex reassignment has been permitted by law in Sweden and whether there has been a change over time in the sex ratio of those requesting sex reassignment surgery (SRS). The incidence and sex ratio of transsexualism were calculated on the basis of the total number of applications for sex reassignment submitted to the National Board of Health and Welfare between July 1972 and June 2002. The frequency data were then analyzed in relation to the number of SRSs performed, age at the time SRS was requested, and the proportion of applicants of foreign origin. The results showed that the incidence of transsexualism was not stable during the study period of three decades. The sex ratio changed from almost 1:1 in the late 1960s to almost 2:1 in favor of male-to-female (MF) transsexuals in the 1990s. The number of SRSs performed rose considerably after the mid- 1980s. On average, MF transsexuals are now 6 years older than female-to-male (FM) transsexuals when they apply for SRS, and MF transsexuals are currently about 8 years older at the time of application than they were 20 years ago. The proportion of applications from applicants of foreign origin increased during the 1990s.

The dynamics of genetic draft in rapidly adapting populations.

PubMed

Kosheleva, Katya; Desai, Michael M

2013-11-01

The accumulation of beneficial mutations on competing genetic backgrounds in rapidly adapting populations has a striking impact on evolutionary dynamics. This effect, known as clonal interference, causes erratic fluctuations in the frequencies of observed mutations, randomizes the fixation times of successful mutations, and leaves distinct signatures on patterns of genetic variation. Here, we show how this form of "genetic draft" affects the forward-time dynamics of site frequencies in rapidly adapting asexual populations. We calculate the probability that mutations at individual sites shift in frequency over a characteristic timescale, extending Gillespie's original model of draft to the case where many strongly selected beneficial mutations segregate simultaneously. We then derive the sojourn time of mutant alleles, the expected fixation time of successful mutants, and the site frequency spectrum of beneficial and neutral mutations. Finally, we show how this form of draft affects inferences in the McDonald-Kreitman test and how it relates to recent observations that some aspects of genetic diversity are described by the Bolthausen-Sznitman coalescent in the limit of very rapid adaptation.

Methyl farnesoate levels in male spider crabs exhibiting active reproductive behavior.

PubMed

Sagi, A; Ahl, J S; Danaee, H; Laufer, H

1994-09-01

The concentration of methyl farnesoate (MF) in the hemolymph and its synthesis by the mandibular organs (MOs) were investigated to determine whether this compound is related to the differences in the size of the reproductive system and the mating behavior among male morphotypes of the spider crab, Libinia emarginata. Large-claw abraded males displayed mating behavior under competitive conditions. They have the largest reproductive systems, their MOs synthesize large amounts of MF in vitro, and the concentration of MF in their hemolymph is high. Small-claw abraded males displayed mating behavior with receptive females only when isolated. These smaller crabs have intermediate-sized reproductive systems, their MOs synthesize the most MF, and they have the highest circulating level of MF relative to their body size. The unabraded males did not display mating behavior; their reproductive systems are smaller; their MO activity is low, as is their circulating level of MF. The strong relationship between MF levels and the intensity of reproductive behavior suggests that MF may be one of the driving forces behind mating behavior in Crustacea.

Effect of static magnetic field on trichloroethylene removal in a biotrickling filter.

PubMed

Quan, Yue; Wu, Hao; Yin, Zhenhao; Fang, Yingyu; Yin, Chengri

2017-09-01

A laboratory-scale biotrickling filter combined with a magnetic field (MF-BTF) and a single BTF (S-BTF) were set up to treat trichloroethylene (TCE) gas. The influences of phenol alone and NaAc-phenol as co-substrates and different MF intensities were investigated. At low MF intensity, MF-BTF displayed better performance with 0.20g/L of phenol, 53.6-337.1mg/m 3 of TCE, and empty bed residence times of 202.5s. The performances followed the order MF-BTF (60.0mT)>MF-BTF (30.0mT)>S-BTF (0mT)>MF-BTF (130.0mT), and the removal efficiencies (REs) and maximum elimination capacities (ECs) corresponded to: 92.2%-45.5%, 2656.8mg/m 3 h; 89.8%-37.2%, 2169.1mg/m 3 h; 89.8%-29.8%, 1967.7mg/m 3 h; 76.0%-20.8%, 1697.1mg/m 3 h, respectively. High-throughput sequencing indicated that the bacterial diversity was lower, whereas the relative abundances of Acinetobacter, Chryseobacterium, and Acidovorax were higher in MF-BTF. Results confirmed that a proper MF could improve TCE removal performance in BTF. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of magnetic fields exposure on relative permittivity of saline solutions measured by a high resolution SPR system

PubMed Central

Jiang, Li; Zhao, Xinyuan; Fei, Yue; Yu, Dongdong; Qian, Jun; Tong, Jinguang; Chen, Guangdi; He, Sailing

2016-01-01

A measurement system for the relative permittivity of a physiological solution under 50 Hz magnetic fields (MF) is presented. It is based on a phase-sensitive surface plasmon resonance (SPR) system. Relative permittivity was analyzed for different solute concentrations of sodium chloride under various MF exposure parameters. We found that MF exposure at 0.2–4.0 mT step-wise decreased significantly the SPR phase signal of a 0.9% sodium chloride solution while 0.1 mT of MF exposure did not. The decreases in the SPR phase signal depended on the duration of MF exposure, and the signal reached a plateau after 15 min of exposure. Interestingly, the decreased SPR phase signal showed a gradual increase and approached the background level when the exposure was drawn off. In addition, we found that the response of the sodium chloride solution to MF also depended on its concentration. In brief, the relative permittivity of sodium chloride in solutions appears to be practically affected by 50 Hz MF exposure. Our data indicates that the relative permittivity of the saline solution influenced by MF exposure should be considered when investigating the biological effects of MF exposure on organisms in experimental study. PMID:27121618

The mitochondrial plasmid of the true slime mold Physarum polycephalum bypasses uniparental inheritance by promoting mitochondrial fusion.

PubMed

Sakurai, Rakusa; Nomura, Hideo; Moriyam, Yohsuke; Kawano, Shigeyuki

2004-08-01

Mitochondrial DNA (mtDNA) is inherited maternally in most eukaryotes. Linear mitochondrial plasmids in higher plants and fungi are also transmitted from the maternal parent to the progeny. However, mF, which is a mitochondrial linear plasmid of Physarum polycephalum, evades uniparental mitochondrial inheritance. We examined 36 myxamoebal strains of Physarum and isolated three novel mF+ strains (JE8, TU111, NG111) that harbored free mF plasmids. These strains were mated with the mF- strain KM88. Of the three mF- x mF+ crosses, only KM88 x JE8 displayed complete uniparental inheritance. However, in KM88 x TU111 and KM88 x NG111, the mtDNA of KM88 and mF of TU111 and NG111 were inherited by the plasmodia and showed recombination. For example, although the mtDNA of TU111 was eliminated, the mF of TU111 persisted and became inserted into the mtDNA of KM88, such that recombinant mtDNA represented 80% of the total mtDNA. The parental mitochondria fused to yield giant mitochondria with two or more mitochondrial nucleoids. The mF appears to exchange mitochondria from the recipient (paternal) to the donor (maternal) by promoting mitochondrial fusion.

Highly Prevalent LIPH Founder Mutations Causing Autosomal Recessive Woolly Hair/Hypotrichosis in Japan and the Genotype/Phenotype Correlations

PubMed Central

Kono, Michihiro; Takama, Hiromichi; Hamajima, Nobuyuki; Akiyama, Masashi

2014-01-01

Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH), and the 2 missense mutations c.736T>A (p.Cys246Ser) and c.742C>A (p.His248Asn) are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016), and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024). In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH. PMID:24586639

Identification and expression analysis of BoMF25, a novel polygalacturonase gene involved in pollen development of Brassica oleracea.

PubMed

Lyu, Meiling; Liang, Ying; Yu, Youjian; Ma, Zhiming; Song, Limin; Yue, Xiaoyan; Cao, Jiashu

2015-06-01

BoMF25 acts on pollen wall. Polygalacturonase (PG) is a pectin-digesting enzyme involved in numerous plant developmental processes and is described to be of critical importance for pollen wall development. In the present study, a PG gene, BoMF25, was isolated from Brassica oleracea. BoMF25 is the homologous gene of At4g35670, a PG gene in Arabidopsis thaliana with a high expression level at the tricellular pollen stage. Collinear analysis revealed that the orthologous gene of BoMF25 in Brassica campestris (syn. B. rapa) genome was probably lost because of genome deletion and reshuffling. Sequence analysis indicated that BoMF25 contained four classical conserved domains (I, II, III, and IV) of PG protein. Homology and phylogenetic analyses showed that BoMF25 was clustered in Clade F. The putative promoter sequence, containing classical cis-acting elements and pollen-specific motifs, could drive green fluorescence protein expression in onion epidermal cells. Quantitative RT-PCR analysis suggested that BoMF25 was mainly expressed in the anther at the late stage of pollen development. In situ hybridization analysis also indicated that the strong and specific expression signal of BoMF25 existed in pollen grains at the mature pollen stage. Subcellular localization showed that the fluorescence signal was observed in the cell wall of onion epidermal cells, which suggested that BoMF25 may be a secreted protein localized in the pollen wall.

Oily wastewater treatment by adsorption-membrane filtration hybrid process using powdered activated carbon, natural zeolite powder and low cost ceramic membranes.

PubMed

Rasouli, Yaser; Abbasi, Mohsen; Hashemifard, Seyed Abdollatif

2017-08-01

In this research, four types of low cost and high performance ceramic microfiltration (MF) membranes have been employed in an in-line adsorption-MF process for oily wastewater treatment. Mullite, mullite-alumina, mullite-alumina-zeolite and mullite-zeolite membranes were fabricated as ceramic MF membranes by low cost kaolin clay, natural zeolite and α-alumina powder. Powdered activated carbon (PAC) and natural zeolite powder in concentrations of 100-800 mg L -1 were used as adsorbent agent in the in-line adsorption-MF process. Performance of the hybrid adsorption-MF process for each concentration of PAC and natural zeolite powder was investigated by comparing quantity of permeation flux (PF) and total organic carbon (TOC) rejection during oily wastewater treatment. Results showed that by application of 400 mg L -1 PAC in the adsorption-MF process with mullite and mullite-alumina membranes, TOC rejection was enhanced up to 99.5% in comparison to the MF only process. An increasing trend was observed in PF by application of 100-800 mg L -1 PAC. Also, results demonstrated that the adsorption-MF process with natural zeolite powder has higher performance in comparison to the MF process for all membranes except mullite-alumina membranes in terms of PF. In fact, significant enhancement of PF and TOC rejection up to 99.9% were achieved by employing natural zeolite powder in the in-line adsorption-MF hybrid process.

A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation?

PubMed

Lucotte, Gérard; Dieterlen, Florent

2003-01-01

The aim of this new meta-analysis (to the end of 2002) is to compile the Y allele frequencies of the C282Y mutation of hereditary hemochromatosis (HFE gene) for 63 European populations, representing a total of 10,708 unrelated people concerning control samples. A new allele map of C282Y frequencies in Europe was constructed. The highest European frequencies are observed in the Celtic populations in Ireland, in the United Kingdom, and in France, but elevated frequencies are also observed in Scandinavia.

TransRapid TR-07 maglev-spectrum magnetic field effects on daily pineal indoleamine metabolic rhythms in rodents

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

Groh, K.R.

This study examined the effects on pineal function of magnetic field (MF) exposures (ac and dc components) similar to those produced by the TransRapid TR-07 and other electromagnetic maglev systems (EMS). Rats were entrained to a light-dark cycle and then exposed to a continuous, or to an inverted, intermittent (on = 45 s, off = 15 s, induced current = 267 G/s) simulated multifrequency ac and dc magnetic field (MF) at 1 or 7 times the TR-07 maglev vehicle MF intensity for 2 hr. Other groups of rats were exposed to only the ac or the dc-component of the maglevmore » MF. For comparison, one group was exposed to an inverted, intermittent 60-Hz MF. Each group was compared to an unexposed group of rats for changes in pineal melatonin and serotonin-N-acetyltransferase (NAT). MF exposures at an intensity equivalent to that produced by the TR-07 vehicle had no effect on melatonin or NAT compared with sham-exposed animals under any of the conditions examined. However, 7X TR-07-level continuous 2-h MF exposures significantly depressed pineal NAT by 45%. Pineal melatonin was also depressed 33--43% by a continuous 7X TR-07 MF exposure and 28% by an intermittent 60-Hz 850-mG MF, but the results were not statically significant. This study demonstrates that intermittent, combined ac and dc MFs similar to those produced by the TR-07 EMS maglev vehicle alter the normal circadian rhythm of pineal indoleamine metabolism. The pineal regulatory enzyme NAT was more sensitive to MF exposure than melatonin and may be a more desirable measure of the biological effects of MF exposure.« less

Evaluation of conventional and alternative monitoring methods for a recreational marine beach with nonpoint source of fecal contamination.

PubMed

Shibata, Tomoyuki; Solo-Gabriele, Helena M; Sinigalliano, Christopher D; Gidley, Maribeth L; Plano, Lisa R W; Fleisher, Jay M; Wang, John D; Elmir, Samir M; He, Guoqing; Wright, Mary E; Abdelzaher, Amir M; Ortega, Cristina; Wanless, David; Garza, Anna C; Kish, Jonathan; Scott, Troy; Hollenbeck, Julie; Backer, Lorraine C; Fleming, Lora E

2010-11-01

The objectives of this work were to compare enterococci (ENT) measurements based on the membrane filter, ENT(MF) with alternatives that can provide faster results including alternative enterococci methods (e.g., chromogenic substrate (CS), and quantitative polymerase chain reaction (qPCR)), and results from regression models based upon environmental parameters that can be measured in real-time. ENT(MF) were also compared to source tracking markers (Staphylococcus aureus, Bacteroidales human and dog markers, and Catellicoccus gull marker) in an effort to interpret the variability of the signal. Results showed that concentrations of enterococci based upon MF (<2 to 3320 CFU/100 mL) were significantly different from the CS and qPCR methods (p < 0.01). The correlations between MF and CS (r = 0.58, p < 0.01) were stronger than between MF and qPCR (r ≤ 0.36, p < 0.01). Enterococci levels by MF, CS, and qPCR methods were positively correlated with turbidity and tidal height. Enterococci by MF and CS were also inversely correlated with solar radiation but enterococci by qPCR was not. The regression model based on environmental variables provided fair qualitative predictions of enterococci by MF in real-time, for daily geometric mean levels, but not for individual samples. Overall, ENT(MF) was not significantly correlated with source tracking markers with the exception of samples collected during one storm event. The inability of the regression model to predict ENT(MF) levels for individual samples is likely due to the different sources of ENT impacting the beach at any given time, making it particularly difficult to to predict short-term variability of ENT(MF) for environmental parameters.

The Rotation of the Solar Photospheric Magnetic Field

NASA Astrophysics Data System (ADS)

Xu, J. C.; Gao, P. X.

2016-12-01

The rotational characteristics of the solar photospheric magnetic field at four flux ranges are investigated together with the total flux of active regions (MFar) and quiet regions (MFqr). The first four ranges (MF1-4) are (1.5-2.9) × 1018, (2.9-32.0) × 1018, (3.20-4.27) × 1019, and (4.27-38.01) × 1019, respectively (the unit is Mx per element). Daily values of the flux data are extracted from magnetograms of the Michelson Doppler Imager on board the Solar and Heliospheric Observatory. Lomb-Scargle periodograms show that only MF2, MF4, MFqr, and MFar exhibit rotational periods. The periods of the first three types of flux are very similar, I.e., 26.20, 26.23, and 26.24 days, respectively, while that of MFar is longer, 26.66 days. This indicates that active regions rotate more slowly than quiet regions on average, and strong magnetic fields tend to repress the surface rotation. Sinusoidal function fittings and cross-correlation analyses reveal that MFar leads MF2 and MF4 by 5 and 1 days, respectively. This is speculated to be related with the decaying of active regions. MF2 and MFar are negatively correlated, while both MF4 and MFqr are positively correlated with MFar. At the timescale of the solar activity cycle, MFar leads (negatively) MF2 by around one year (350 days), and leads MF4 by about 3 rotation periods (82 days). The relation between MF2 and MFar may be explained by the possibility that the former mainly comes from a higher latitude, or emerges from the subsurface shear layer. We conjecture that MF4 may partly come from the magnetic flux of active regions; this verifies previous results that were obtained with indirect solar magnetic indices.

Dichoptic stimulation improves detection of glaucoma with multifocal visual evoked potentials.

PubMed

Arvind, Hemamalini; Klistorner, Alexander; Graham, Stuart; Grigg, John; Goldberg, Ivan; Klistorner, Asya; Billson, Frank A

2007-10-01

To determine whether simultaneous binocular (dichoptic) stimulation for multifocal visual evoked potentials (mfVEP) detects glaucomatous defects and decreases intereye variability. Twenty-eight patients with glaucoma and 30 healthy subjects underwent mfVEP on monocular and dichoptic stimulation. Dichoptic stimulation was presented with the use of virtual reality goggles (recording time, 7 minutes). Monocular mfVEPs were recorded sequentially for each eye (recording time, 10 minutes). Comparison of mean relative asymmetry coefficient (RAC; calculated as difference in amplitudes between eyes/sum of amplitudes of both eyes at each segment) on monocular and dichoptic mfVEP revealed significantly lower RAC on dichoptic (0.003 +/- 0.03) compared with monocular testing (-0.02 +/- 0.04; P = 0.002). In all 28 patients, dichoptic mfVEP identified defects with excellent topographic correspondence. Of 56 hemifields (28 eyes), 33 had Humphrey visual field (HFA) scotomas, all of which were detected by dichoptic mfVEP. Among 23 hemifields with normal HFA, two were abnormal on monocular and dichoptic mfVEP. Five hemifields (five patients) normal on HFA and monocular mfVEP were abnormal on dichoptic mfVEP. In all five patients, corresponding rim changes were observed on disc photographs. Mean RAC of glaucomatous eyes was significantly higher on dichoptic (0.283 +/- 0.18) compared with monocular (0.199 +/- 0.12) tests (P = 0.0006). Dichoptic mfVEP not only detects HFA losses, it may identify early defects in areas unaffected on HFA and monocular mfVEP while reducing testing time by 30%. Asymmetry was tighter among healthy subjects but wider in patients with glaucoma on simultaneous binocular stimulation, which is potentially a new tool in the early detection of glaucoma.

Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis.

PubMed

Zou, Zhang-Yu; Zhou, Zhi-Rui; Che, Chun-Hui; Liu, Chang-Yun; He, Rao-Li; Huang, Hua-Pin

2017-07-01

Genetic studies have shown that C9orf72 , SOD1 , TARDBP and FUS are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS. We performed an extensive literature research to identify all original articles reporting frequencies of C9orf72 , SOD1 , TARDBP and FUS mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis. 111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the C9orf72 repeat expansions (FALS 33.7%, SALS 5.1%), followed by SOD1 (FALS 14.8%, SALS 1.2%), TARDBP (FALS 4.2%, SALS 0.8%) and FUS mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were SOD1 mutations (FALS 30.0%, SALS 1.5%), followed by FUS (FALS 6.4%, SALS 0.9%), C9orf72 (FALS 2.3%, SALS 0.3%) and TARDBP (FALS 1.5%, SALS 0.2%) mutations. These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

gamma-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver.

PubMed

Obrador, Elena; Carretero, Julian; Ortega, Angel; Medina, Ignacio; Rodilla, Vicente; Pellicer, José A; Estrela, José M

2002-01-01

B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and high metastatic activity in the liver in vivo. gamma-Glutamyl transpeptidase (GGT)-mediated extracellular GSH cleavage and intracellular GSH synthesis were studied in vitro in B16M cells with high (F10) and low (F1) metastatic potential. GGT activity was modified by transfection with the human GGT gene (B16MF1/Tet-GGT cells) or by acivicin-induced inhibition. B16MF1/Tet-GGT and B16MF10 cells exhibited higher GSH content (35 +/- 6 and 40 +/- 5 nmol/10(6) cells, respectively) and GGT activity (89 +/- 9 and 37 +/- 7 mU/10(6) cells, respectively) as compared (P <.05) with B16MF1 cells (10 +/- 3 nmol GSH and 4 mU GGT/10(6) cells). Metastasis (number of foci/100 mm(3) of liver) increased in B16MF1 cells pretreated with GSH ester ( approximately 3-fold, P <.01), and decreased in B16MF1/Tet-GGT and B16MF10 cells pretreated with the GSH synthesis inhibitor L-buthionine (S,R)-sulphoximine ( approximately 5-fold and 2-fold, respectively, P <.01). Liver, kidney, brain, lung, and erythrocyte GSH content in B16MF1/Tet-GGT- or B16MF10-bearing mice decreased as compared with B16MF1- and non-tumor-bearing mice. Organic anion transporting polypeptide 1-independent sinusoidal GSH efflux from hepatocytes increased in B16MF1/Tet-GGT- or B16MF10-bearing mice ( approximately 2-fold, P <.01) as compared with non-tumor-bearing mice. Our results indicate that tumor GGT activity and an intertissue flow of GSH can regulate GSH content of melanoma cells and their metastatic growth in the liver.

Delineating distinct heme-scavenging and -binding functions of domains in MF6p/helminth defense molecule (HDM) proteins from parasitic flatworms.

PubMed

Martínez-Sernández, Victoria; Mezo, Mercedes; González-Warleta, Marta; Perteguer, María J; Gárate, Teresa; Romarís, Fernanda; Ubeira, Florencio M

2017-05-26

MF6p/FhHDM-1 is a small protein secreted by the parasitic flatworm (trematode) Fasciola hepatica that belongs to a broad family of heme-binding proteins (MF6p/helminth defense molecules (HDMs)). MF6p/HDMs are of interest for understanding heme homeostasis in trematodes and as potential targets for the development of new flukicides. Moreover, interest in these molecules has also increased because of their immunomodulatory properties. Here we have extended our previous findings on the mechanism of MF6p/HDM-heme interactions and mapped the protein regions required for heme binding and for other biological functions. Our data revealed that MF6p/FhHDM-1 forms high-molecular-weight complexes when associated with heme and that these complexes are reorganized by a stacking procedure to form fibril-like and granular nanostructures. Furthermore, we showed that MF6p/FhHDM-1 is a transitory heme-binding protein as protein·heme complexes can be disrupted by contact with an apoprotein ( e.g. apomyoglobin) with higher affinity for heme. We also demonstrated that (i) the heme-binding region is located in the MF6p/FhHDM-1 C-terminal moiety, which also inhibits the peroxidase-like activity of heme, and (ii) MF6p/HDMs from other trematodes, such as Opisthorchis viverrini and Paragonimus westermani , also bind heme. Finally, we observed that the N-terminal, but not the C-terminal, moiety of MF6p/HDMs has a predicted structural analogy with cell-penetrating peptides and that both the entire protein and the peptide corresponding to the N-terminal moiety of MF6p/FhHDM-1 interact in vitro with cell membranes in hemin-preconditioned erythrocytes. Our findings suggest that MF6p/HDMs can transport heme in trematodes and thereby shield the parasite from the harmful effects of heme. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of recording duration on the diagnostic performance of multifocal visual-evoked potentials in high-risk ocular hypertension and early glaucoma.

PubMed

Fortune, Brad; Zhang, Xian; Hood, Donald C; Demirel, Shaban; Patterson, Emily; Jamil, Annisa; Mansberger, Steven L; Cioffi, George A; Johnson, Chris A

2008-01-01

To evaluate the effect on diagnostic performance of reducing multifocal visual-evoked potential (mfVEP) recording duration from 16 to 8 minutes per eye. Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were studied. Two 8-minute mfVEP recordings were obtained for each eye in an ABBA order using VERIS. The first recording for each eye was compared against single run (1-Run) mfVEP normative data; the average of both recordings for each eye was compared against 2-Run normative data. Visual fields (VFs) were obtained by standard automated perimetry (SAP) within 22.3+/-27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph images were obtained together, within 24.8+/-50.4 days of the mfVEP and 33.1+/-62.9 days of SAP. Masked experts graded disc photographs as either glaucomatous optic neuropathy or normal. The overall Moorfields Regression Analysis result from the Heidelberg Retina Tomograph was used as a separate diagnostic classification. Thus, 4 diagnostic standards were applied in total, 2 based on optic disc structure alone and 2 others based on disc structure and SAP. Agreement between the 1-Run and 2-Run mfVEP was 90%. Diagnostic performance of the 1-Run mfVEP was similar to that of the 2-Run mfVEP for all 4 diagnostic standards. Sensitivity was slightly higher for the 2-Run mfVEP, whereas specificity was slightly higher for the 1-Run mfVEP. If higher sensitivity is sought, the 2-Run mfVEP will provide better discrimination between groups of eyes with relatively high signal-to-noise ratio (eg, early glaucoma or high-risk suspects). But if higher specificity is a more important goal, the 1-Run mfVEP provides adequate sensitivity and requires only half the test time. Considered alongside prior studies, the present results suggest that the 1-Run mfVEP is an efficient way to confirm (or refute) the extent of VF loss in patients with moderate or advanced glaucoma, particularly in those with unreliable VFs, including malingering or other "functional" forms of VF loss.

Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

PubMed Central

Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

2015-01-01

Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–<3, 3–8, and 9–17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–<3 and 3–8 y cohorts. Among children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

[Effect of fentanyl on expression of mu-receptor and beta-arrestin 2 in periaqueductal gray of rats tolerant to morphine].

PubMed

Liu, Ruo-shan; Sun, Li; Liu, Xiao-yan; Li, Xuan-ying; Xu, Lei

2009-05-19

To investigate the effect of fentanyl upon the expression of mu-receptor and beta-arrestin 2 in peri-aqueductal gray of morphine-tolerant rats. Forty male SD rats weighing (230 +/- 20) g were randomly divided into 5 groups of eight animals each: group NS, group M, group MF1, group MF2 and group MF3. Rats in group NS received only subcutaneous normal saline 1 ml/kg twice a day for 9 consecutive days; group M received subcutaneous morphine 10 mg/kg followed by NS 1 ml/kg twice a day for 9 consecutive days; In groups MF1, MF2 and MF3, morphine 10 mg x kg(-1) was injected subcutaneously followed by fentanyl 3, 6, 12 microg/kg respectively. All animals were sacrificed at Day 9 after measurement of pain threshold. Periaqueductal gray was removed for determination of the expression of mRNA (RT-PCR) and protein (Western-blot) of mu-receptor and beta-arrestin 2. Compared with group NS, TFL of group M was significantly elevated after the first morphine injection (P < 0.01). But TFL of group M returned to the baseline value after chronic morphine treatment. Compared with group M, TFL increased in groups MF2 and MF3 at Days 7 and 9 (P < 0.05 or 0.01). However, TFL of group MF1 was negative (P > 0.05). The expression of mu-receptor mRNA and protein was significantly lower in group M than in group NS (P < 0.01). Compared with group M, the expressions of mu-receptor mRNA and protein were significantly elevated in group MF2 and MF3 (P < 0.05 or 0.01) but there was no significant change in group MF1 (P > 0.05). The expression of beta-arrestin 2 mRNA and protein significantly decreased in group M as compared with group NS (P < 0.01). Compared with group M, the expressions of beta-arrestin 2 mRNA and protein were significantly elevated in group MF2 and MF3 (P < 0.05 or 0.01), but there was no significant change in group MF1 (P > 0.05). Fentanyl at 6 and 12 microg/kg can partly inhibit morphine tolerance through an increased expression of mu-receptor and beta-arrestin 2 in periaqueductal gray of morphine-tolerant rats.

ACE: an efficient and sensitive tool to detect insecticide resistance-associated mutations in insect acetylcholinesterase from RNA-Seq data.

PubMed

Guo, Dianhao; Luo, Jiapeng; Zhou, Yuenan; Xiao, Huamei; He, Kang; Yin, Chuanlin; Xu, Jianhua; Li, Fei

2017-07-10

Insecticide resistance is a substantial problem in controlling agricultural and medical pests. Detecting target site mutations is crucial to manage insecticide resistance. Though PCR-based methods have been widely used in this field, they are time-consuming and inefficient, and typically have a high false positive rate. Acetylcholinesterases (Ace) is the neural target of the widely used organophosphate (OP) and carbamate insecticides. However, there is not any software available to detect insecticide resistance associated mutations in RNA-Seq data at present. A computational pipeline ACE was developed to detect resistance mutations of ace in insect RNA-Seq data. Known ace resistance mutations were collected and used as a reference. We constructed a Web server for ACE, and the standalone software in both Linux and Windows versions is available for download. ACE was used to analyse 971 RNA-Seq data from 136 studies in 7 insect pests. The mutation frequency of each RNA-Seq dataset was calculated. The results indicated that the resistance frequency was 30%-44% in an eastern Ugandan Anopheles population, thus suggesting this resistance-conferring mutation has reached high frequency in these mosquitoes in Uganda. Analyses of RNA-Seq data from the diamondback moth Plutella xylostella indicated that the G227A mutation was positively related with resistance levels to organophosphate or carbamate insecticides. The wasp Nasonia vitripennis had a low frequency of resistant reads (<5%), but the agricultural pests Chilo suppressalis and Bemisia tabaci had a high resistance frequency. All ace reads in the 30 B. tabaci RNA-Seq data were resistant reads, suggesting that insecticide resistance has spread to very high frequency in B. tabaci. To the best of our knowledge, the ACE pipeline is the first tool to detect resistance mutations from RNA-Seq data, and it facilitates the full utilization of large-scale genetic data obtained by using next-generation sequencing.

FSensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions and cell free DNA of breast cancer patients

PubMed Central

Wang, Peilu; Bahreini, Amir; Gyanchandani, Rekha; Lucas, Peter C.; Hartmaier, Ryan J.; Watters, Rebecca J.; Jonnalagadda, Amruth R.; Trejo Bittar, Humberto E.; Berg, Aaron; Hamilton, Ronald L.; Kurland, Brenda F.; Weiss, Kurt R.; Mathew, Aju; Leone, Jose Pablo; Davidson, Nancy E; Nikiforova, Marina N.; Brufsky, Adam M.; Ambros, Tadeu F.; Stern, Andrew M.; Puhalla, Shannon L.; Lee, Adrian V.; Oesterreich, Steffi

2015-01-01

Purpose Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell free DNA (cfDNA). Patients and Methods Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n=43), bone (n=12) and brain metastases (n=38), and cfDNA (n=29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed. Results ESR1 mutations were detected for D538G (n=13), Y537S (n=3) and Y537C (n=1), and not for K303R, S463P or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3 to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n=5), mutations were detected in both (n=3) or in cfDNA only (n=2). Treatment was associated with changes in ESR1 mutation detection and allele frequency. Conclusions ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1 mutant clones are enriched by endocrine therapy. Further studies should address if sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. PMID:26500237

Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients.

PubMed

Wang, Peilu; Bahreini, Amir; Gyanchandani, Rekha; Lucas, Peter C; Hartmaier, Ryan J; Watters, Rebecca J; Jonnalagadda, Amruth R; Trejo Bittar, Humberto E; Berg, Aaron; Hamilton, Ronald L; Kurland, Brenda F; Weiss, Kurt R; Mathew, Aju; Leone, Jose Pablo; Davidson, Nancy E; Nikiforova, Marina N; Brufsky, Adam M; Ambros, Tadeu F; Stern, Andrew M; Puhalla, Shannon L; Lee, Adrian V; Oesterreich, Steffi

2016-03-01

Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell-free DNA (cfDNA). Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n = 43), bone (n = 12) and brain metastases (n = 38), and cfDNA (n = 29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed. ESR1 mutations were detected for D538G (n = 13), Y537S (n = 3), and Y537C (n = 1), and not for K303R, S463P, or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3% to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n = 5), mutations were detected in both (n = 3) or in cfDNA only (n = 2). Treatment was associated with changes in ESR1 mutation detection and allele frequency. ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1-mutant clones are enriched by endocrine therapy. Further studies should address whether sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. See related commentary by Gu and Fuqua, p. 1034. ©2015 American Association for Cancer Research.

Two common low density lipoprotein receptor gene mutations cause familial hypercholesterolemia in Afrikaners.

PubMed

Leitersdorf, E; Van der Westhuyzen, D R; Coetzee, G A; Hobbs, H H

1989-09-01

Familial hypercholesterolemia (FH), an autosomal dominant disease caused by mutations in the LDL receptor gene, is five times more frequent in the Afrikaner population of South Africa than it is in the population of the United States and Europe. It has been proposed that the high frequency is due to a founder effect. In this paper, we characterized 24 mutant LDL receptor alleles from 12 Afrikaner individuals homozygous for FH. We identified two mutations that together makeup greater than 95% of the mutant LDL receptor genes represented in our sample. Both mutations were basepair substitutions that result in single-amino acid changes. Each mutation can be detected readily with the polymerase chain reaction and restriction analysis. The finding of two common LDL receptor mutations in the Afrikaner FH homozygotes predicts that these mutations will predominate in the Afrikaner population and that the high frequency of FH is due to a founder effect. The increased incidence of ischemic heart disease in the Afrikaner population may in part be due to the high frequency of these two mutations in the LDL receptor gene.

Two common low density lipoprotein receptor gene mutations cause familial hypercholesterolemia in Afrikaners.

PubMed Central

Leitersdorf, E; Van der Westhuyzen, D R; Coetzee, G A; Hobbs, H H

1989-01-01

Familial hypercholesterolemia (FH), an autosomal dominant disease caused by mutations in the LDL receptor gene, is five times more frequent in the Afrikaner population of South Africa than it is in the population of the United States and Europe. It has been proposed that the high frequency is due to a founder effect. In this paper, we characterized 24 mutant LDL receptor alleles from 12 Afrikaner individuals homozygous for FH. We identified two mutations that together makeup greater than 95% of the mutant LDL receptor genes represented in our sample. Both mutations were basepair substitutions that result in single-amino acid changes. Each mutation can be detected readily with the polymerase chain reaction and restriction analysis. The finding of two common LDL receptor mutations in the Afrikaner FH homozygotes predicts that these mutations will predominate in the Afrikaner population and that the high frequency of FH is due to a founder effect. The increased incidence of ischemic heart disease in the Afrikaner population may in part be due to the high frequency of these two mutations in the LDL receptor gene. Images PMID:2569482

Mutational effects of γ-rays and carbon ion beams on Arabidopsis seedlings

PubMed Central

Yoshihara, Ryouhei; Nozawa, Shigeki; Hase, Yoshihiro; Narumi, Issay; Hidema, Jun; Sakamoto, Ayako N.

2013-01-01

To assess the mutational effects of radiation on vigorously proliferating plant tissue, the mutation spectrum was analyzed with Arabidopsis seedlings using the plasmid-rescue method. Transgenic plants containing the Escherichia coli rpsL gene were irradiated with γ-rays and carbon ion beams (320-MeV 12C6+), and mutations in the rpsL gene were analyzed. Mutant frequency increased significantly following irradiation by γ-rays, but not by 320-MeV 12C6+. Mutation spectra showed that both radiations increased the frequency of frameshifts and other mutations, including deletions and insertions, but only γ-rays increased the frequency of total base substitutions. These results suggest that the type of DNA lesions which cause base substitutions were less often induced by 320-MeV 12C6+ than by γ-rays in Arabidopsis seedlings. Furthermore, γ-rays never increased the frequencies of G:C to T:A or A:T to C:G transversions, which are caused by oxidized guanine; 320-MeV 12C6+, however, produced a slight increase in both transversions. Instead, γ-rays produced a significant increase in the frequency of G:C to A:T transitions. These results suggest that 8-oxoguanine has little effect on mutagenesis in Arabidopsis cells. PMID:23728320

Distinct tumor protein p53 mutants in breast cancer subgroups.

PubMed

Dumay, Anne; Feugeas, Jean-Paul; Wittmer, Evelyne; Lehmann-Che, Jacqueline; Bertheau, Philippe; Espié, Marc; Plassa, Louis-François; Cottu, Paul; Marty, Michel; André, Fabrice; Sotiriou, Christos; Pusztai, Lajos; de Thé, Hugues

2013-03-01

Tumor protein p53 (TP53) is mutated in approximately 30% of breast cancers, but this frequency fluctuates widely between subclasses. We investigated the p53 mutation status in 572 breast tumors, classified into luminal, basal and molecular apocrine subgroups. As expected, the lowest mutation frequency was observed in luminal (26%), and the highest in basal (88%) tumors. Luminal tumors showed significantly higher frequency of substitutions (82 vs. 65%), notably A/T to G/C transitions (31 vs. 15%), whereas molecular apocrine and basal tumors presented much higher frequencies of complex mutations (deletions/insertions) (36 and 33%, respectively, vs. 18%). Accordingly, missense mutations were significantly more frequent in luminal tumors (75 vs. 54%), whereas basal tumors displayed significantly increased rates of TP53 truncations (43 vs. 25%), resulting in loss of function and/or expression. Interestingly, as basal tumors, molecular apocrine tumors presented with a high rate of complex mutations, but paradoxically, these were not associated with increased frequency of p53 truncation. As in luminal tumors, this could reflect a selective pressure for p53 gain of function, possibly through P63/P73 inactivation. Collectively, these observations point not only to different mechanisms of TP53 alterations, but also to different functional consequences in the different breast cancer subtypes. Copyright © 2012 UICC.

Theoretical study of the electron affinities of MF6 and MF - 6 (M=Cr, Mo, and W) using a model potential method

NASA Astrophysics Data System (ADS)

Sakai, Yoshiko; Miyoshi, Eisaku

1987-09-01

Electronic structures of MF6, MF-6, and MF2-6 (M=Cr, Mo, and W) were calculated using a model potential method in the Hartree-Fock-Roothaan scheme. Major relativistic effects were taken into account for the calculations on MoFq6 and WFq6 (q=0, -1, and -2). It is shown that the calculated electron affinities (EAs) are extremely high for all the MF6 molecules, and that the CrF-6 and MoF-6 anions also have positive EAs, whereas the WF-6 anion has a slightly negative EA. The behaviors of the EAs are interpreted with reference to the electronic structures of the MFq6 systems.

Novel mutations and mutation combinations of ryanodine receptor in a chlorantraniliprole resistant population of Plutella xylostella (L.)

PubMed Central

Guo, Lei; Liang, Pei; Zhou, Xuguo; Gao, Xiwu

2014-01-01

A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three new mutations showed a high frequency of 100%, while the G4946E had a frequency of 20%. Furthermore, the florescent ligand binding assay revealed that the RyR containing multiple mutations displayed a significantly lower affinity to the chlorantraniliprole. The combined results suggested that the co-existence of different combinations of the four mutations was involved in the chlorantraniliprole resistance. An allele-specific PCR based method was developed for the diagnosis of the four mutations in the field populations of P. xylostella. PMID:25377064

Mutation frequencies of the cytochrome CYP2D6 gene in Parkinson disease patients and in families

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

Lucotte, G.; Turpin, J.C.; Gerard, N.

1996-07-26

The frequencies of five mutations of the debrisoquine 4-hydroxylase (CYP2D6) gene (mutations D6-A, B, C, D, and T), corresponding to poor metabolizer (PM) phenotypes, were determined by restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) in 47 patients with Parkinson disease, and compared with the findings in 47 healthy controls. These mutant alleles were about twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.12 (95% confidence interval, 1.41-2.62). There seem to be no significant differences in frequencies of mutant genotypes in patients among gender and modalities of response with levodopa therapy;more » but frequency of the mutations was slightly enhanced after age-at-onset of 60 years. Mutations D6-B, D, and T were detected in 7 patients belonging to 10 Parkinson pedigrees. 25 refs., 1 fig., 2 tabs.« less

Plasticity of lifelong calorie-restricted C57BL/6J mice in adapting to a medium-fat diet intervention at old age.

PubMed

Rusli, Fenni; Boekschoten, Mark V; Borelli, Vincenzo; Sun, Chen; Lute, Carolien; Menke, Aswin L; van den Heuvel, Joost; Salvioli, Stefano; Franceschi, Claudio; Müller, Michael; Steegenga, Wilma T

2018-04-01

Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine-week-old C57BL/6J mice were exposed either to a control, CR, or MF diet. At the age of 24 months, a subset of mice of the CR group was transferred to ad libitumMF feeding (CR-MF). The mice were sacrificed at the age of 28 months, and then, biochemical and molecular analyses were performed. Our results showed that, despite the long-term exposure to the CR regimen, mice in the CR-MF group displayed hyperphagia, rapid weight gain, and hepatic steatosis. However, no hepatic fibrosis/injury or alteration in CR-improved survival was observed in the diet switch group. The liver transcriptomic profile of CR-MF mice largely shifted to a profile similar to the MF-fed animals but leaving ~22% of the 1,578 differentially regulated genes between the CR and MF diet groups comparable with the expression of the lifelong CR group. Therefore, although the diet switch was performed at an old age, the CR-MF-exposed mice showed plasticity in coping with the challenge of a MF diet without developing severe liver pathologies. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Germline stem cell competition, mutation hot spots, genetic disorders and older dads

PubMed Central

Arnheim, Norman; Calabrese, Peter

2016-01-01

Some de novo human mutations arise at frequencies far exceeding the genome average mutation rate. Examples are the common mutations at one or a few sites in the genes causing achondroplasia, Noonan syndrome, multiple endocrine neoplasia 2B and Apert syndrome. These mutations are recurrent, provide a gain of function, are paternally derived and are more likely transmitted as the father ages. Recent experiments tested whether the high mutation frequencies are due to an elevated mutation rate per cell division, as expected, or an advantage of the mutant spermatogonial stem cells over wild-type stem cells. The evidence, which includes the surprising discovery of testis mutation clusters, rejects the former model but not the latter. We propose how the mutations might alter spermatogonial stem cell function and discuss how germline selection contributes to the paternal age effect, the human mutational load and adaptive evolution. PMID:27070266

[Ultrastructural changes of myelinated fibers in the brain in continuous and attack-like paranoid schizophrenia].

PubMed

Uranova, N A; Kolomeets, N S; Vikhreva, O V; Zimina, I S; Rakhmanova, V I; Orlovskaya, D D

Previously the authors have reported the ultrastructural pathology of myelinated fibers (MF) in the brain in schizophrenia. The aim of the present study was to compare the effect of disease course on ultrastructural changes of MF. Postmortem electron microscopic morphometric study of MF was performed in the prefrontal cortex, caudate nucleus and hippocampus in 19 cases of paranoid schizophrenia. Fourteen cases of continuous schizophrenia, 5 cases of attack-like schizophrenia and 25 normal matched control cases were studied. The proportion (percentage) of pathological MF was estimated in the prefrontal cortex, layer 5, CA3 area of hippocampus, pyramidal layer, and in the head of the caudate nucleus. The percentage of MF having axonal atrophy and swelling of periaxonal oligodendrocyte process was significantly higher in both continuous and attack-like schizophrenia in all brain structures studied as compared to the control group. In the hippocampus and caudate nucleus, this parameter was increased significantly in attack-like schizophrenia as compared to continuous schizophrenia. In the prefrontal cortex. The percentage of the pathological MF having signs of deformation and destruction of myelin sheaths increased significantly only in continuous schizophrenia as compared to the control group. MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.

Simple synthesis of nitrogen-rich polymer network and its further amination with PEI for CO2 adsorption

NASA Astrophysics Data System (ADS)

Yin, Fengqin; Zhuang, Linzhou; Luo, Xianyong; Chen, Shuixia

2018-03-01

The nitrogen-rich polymer network (MF/PAM) was synthesized through interpenetration between the molecular chains of melamine-formaldehyde resin(MF) and polyacrylamide (PAM), to which the polyethylene imine (PEI) was grafted to obtain solid amine adsorbent (MF/PAM-g-PEI). Compared with MF, the swelling capacity of MF/PAM was greatly enhanced, it could swell rapidly and directly in water. Although the interpenetration of PAM into MF may reduce the porosity of MF/PAM, the CO2 capture capacity of the solid amine adsorbents (MF/PAM-g-PEI) could still reach 2.8 mmol/g at 273 K. The adsorbents also exhibited promising adsorption kinetics and regeneration performances. The kinetics observation showed that the Avrami model could better descript the CO2 adsorption process compared with the pseudo-first-order model and pseudo-second-order model. Meanwhile, the Avrami kinetic orders (na) range from 1.21 to 1.56, displaying that the both physisorption and chemisorption exist in the adsorption process and the PEI have successfully grafted onto the polymer network, which also can be confirmed by the adsorption activation energy value. After 18 adsorption-desorption recycles, the MF/PAM-g-PEI could preserve its initial capacity without any decrease. Our work provides a new method to achieve promising solid amine adsorbents with higher adsorption capacity and better regeneration performance.

The Frequency of c.550delA Mutation of the CANP3 Gene in the Polish LGMD2A Population.

PubMed

Dorobek, Małgorzata; Ryniewicz, Barbara; Kabzińska, Dagmara; Fidziańska, Anna; Styczyńska, Maria; Hausmanowa-Petrusewicz, Irena

2015-11-01

Limb girdle muscular dystrophy 2A (LGMD2A) is the most frequent LGMD variant in the European population, representing about 40% of LGMD. The c.550delA mutation in the CANP3 (calcium activated neutral protease 3) gene is the most commonly reported mutation in LGMD2A. Prevalence of this mutation in the Polish population has not been previously investigated. The aim of this study was to identify and estimate the frequency of the c.550delA mutation in Polish LGMD2A patients. Polymerase chain reaction-sequencing analysis, restriction fragment length polymorphism polymerase chain reaction method. We analyzed 76 families affected with LGMD and identified 62 probands with mutations in the CANP3 gene. C.550delA was the most common mutation identified, being found in 78% of the LGMD2A families. The remaining mutations observed multiple times were as follows: c.598-612del15ntd; c.2242C>T; c.418dupC; c.1356insT, listed in terms of decreasing frequency. Two novel variants in the CANP3 gene, that is, c.700G>A Gly234Arg and c.661G>A Gly221Ser were also characterized. Overall, mutations in the LGMD2A gene were estimated to be present in 81% of patients with the LGMD phenotype who were without sarcoglycans and dysferlin deficiency on immunocytochemical analysis. The frequency of the heterozygous c.550delA mutation in the healthy Polish population was estimated at 1/124. The c.550delA is the most frequent CANP3 mutation in the Polish population, thus sequencing of exon 4 of this gene could identify the majority of LGMD2A patients in Poland.

Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6.

PubMed

Hegan, Denise Campisi; Narayanan, Latha; Jirik, Frank R; Edelmann, Winfried; Liskay, R Michael; Glazer, Peter M

2006-12-01

Defects in genes associated with DNA mismatch repair (MMR) have been linked to hereditary colon cancer. Because the MMR pathway includes multiple factors with both overlapping and divergent functions, we sought to compare the impact of deficiencies in each of several MMR genes on genetic instability using a collection of knock-out mouse models. We investigated mutation frequencies and patterns in MMR-deficient mice using two transgenic reporter genes, supFG1 and cII, in the context of mice deficient for Pms2, Mlh1, Msh2, Msh3 or Msh6 or both Msh2 and Msh3 or both Msh3 and Msh6. We found that the mean mutation frequencies of all of the MMR-deficient mice were significantly higher than the mean mutation frequencies of wild-type mice. Mlh1-deficient mice and Msh2-deficient mice had the highest mutation frequencies in a comparison of the single nullizygous mice. Of all the mice studied, mice nullizygous for both Msh2 and Msh3 and those nullizygous for both Msh3 and Msh6 displayed the greatest overall increases in mutation frequencies compared with wild-type mice. Sequence analysis of the mutated reporter genes revealed significant differences between the individual groups of MMR-deficient mice. Taken together, our results further characterize the functions of the MMR factors in mutation avoidance and provide in vivo correlation to biochemical models of the MMR pathway.

Effect of Chitin Isolated from Crustaceans and Cephalopods on Denaturation of Fish Myofibrillar Protein and the State of Water during Frozen Storage

NASA Astrophysics Data System (ADS)

Yamashita, Yasumitsu; Zhang, Nong; Nozaki, Yukinori

The effect of chitin hydrolysate made from shell of crustaceans and cartilage of cephalopods on the denaturation and the state of water of lizard fish myofibrillar protein (Mf) during frozen storage at -250°C for 120 days were investigated. 5.0% chitin hydrolysate (dried matter) added Mf samples were frozen at -25°C and storage for 120 days, and the change of inactivation of Mf Ca-ATPase and the change of unfrozen water in Mf were examined during the frozen storage. The decrease of Mf Ca-ATPase during frozen storage were slow by addition of chitin hydrolysate. The amount of unfrozen water in Mf were increased by addition of chitin hydrolysate, and decreaced gradually during frozen storage. On the other hand, the amount of unfrozen water of the control were decreaced suddenly during frozen storage. Above results suggest that chitin hydrolysate has cryoprotective effect on Mf. It is guessed that the mechanism of cryoprotective effect of chitin hydrolysate may be caused by an interaction between hydration sphere of Mf and equatorial OH groups in the molecular structure of chitin hydrolysate.

Gauging Variational Inference

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

Chertkov, Michael; Ahn, Sungsoo; Shin, Jinwoo

Computing partition function is the most important statistical inference task arising in applications of Graphical Models (GM). Since it is computationally intractable, approximate methods have been used to resolve the issue in practice, where meanfield (MF) and belief propagation (BP) are arguably the most popular and successful approaches of a variational type. In this paper, we propose two new variational schemes, coined Gauged-MF (G-MF) and Gauged-BP (G-BP), improving MF and BP, respectively. Both provide lower bounds for the partition function by utilizing the so-called gauge transformation which modifies factors of GM while keeping the partition function invariant. Moreover, we provemore » that both G-MF and G-BP are exact for GMs with a single loop of a special structure, even though the bare MF and BP perform badly in this case. Our extensive experiments, on complete GMs of relatively small size and on large GM (up-to 300 variables) confirm that the newly proposed algorithms outperform and generalize MF and BP.« less

The effects of fundus photography on the multifocal electroretinogram.

PubMed

Suresh, Sandip; Tienor, Brian J; Smith, Scott D; Lee, Michael S

2016-02-01

To determine the effect of flash fundus photography (FFP) on the multifocal electroretinogram (mfERG). Ten subjects underwent mfERG testing on three separate dates. Subjects received either mfERG without FFP, mfERG at 5 and 15 min after FFP, or mfERG at 30 and 45 min after FFP on each date. The FFP groups received 10 fundus photographs followed by mfERG testing, first of the right eye then of the left eye 10 min later. Data were averaged and analyzed in six concentric rings at each time point. Average amplitude and implicit times of the N1, P1, and N2 peaks for each concentric ring at each time point after FFP were compared to baseline. Flash fundus photography did not lead to a significant change of amplitude or implicit times of N1, P1, or N2 at 5 min after light exposure. These findings suggest that it is acceptable to perform mfERG testing without delay after performance of FFP.

Low diversity and high host preference of ectomycorrhizal fungi in western Amazonia, a neotropical biodiversity hotspot.

PubMed

Tedersoo, Leho; Sadam, Ave; Zambrano, Milton; Valencia, Renato; Bahram, Mohammad

2010-04-01

Information about the diversity of tropical microbes, including fungi is relatively scarce. This study addresses the diversity, spatial distribution and host preference of ectomycorrhizal fungi (EcMF) in a neotropical rainforest site in North East Ecuador. DNA sequence analysis of both symbionts revealed relatively low richness of EcMF as compared with the richness of temperate regions that contrasts with high plant (including host) diversity. EcMF community was positively autocorrelated up to 8.5+/-1.0-m distance-roughly corresponding to the canopy and potentially rooting area of host individuals. Coccoloba (Polygonaceae), Guapira and Neea (Nyctaginaceae) differed by their most frequent EcMF. Two-thirds of these EcMF preferred one of the host genera, a feature uncommon in boreal forests. Scattered distribution of hosts probably accounts for the low EcMF richness. This study demonstrates that the diversity of plants and their mycorrhizal fungi is not always related and host preference among EcMF can be substantial outside the temperate zone.

Enhancement of in vitro high-density polyethylene (HDPE) degradation by physical, chemical, and biological treatments.

PubMed

Balasubramanian, V; Natarajan, K; Rajeshkannan, V; Perumal, P

2014-11-01

Partially degraded high-density polyethylene (HDPE) was collected from plastic waste dump yard for biodegradation using fungi. Of various fungi screened, strain MF12 was found efficient in degrading HDPE by weight loss and Fourier transform infrared (FT-IR) spectrophotometric analysis. Strain MF12 was selected as efficient HDPE degraders for further studies, and their growth medium composition was optimized. Among those different media used, basal minimal medium (BMM) was suitable for the HDPE degradation by strain MF12. Strain MF12 was subjected to 28S rRNA sequence analysis and identified as Aspergillus terreus MF12. HDPE degradation was carried out using combinatorial physical and chemical treatments in conjunction to biological treatment. The high level of HDPE degradation was observed in ultraviolet (UV) and KMnO4/HCl with A. terreus MF12 treatment, i.e., FT10. The abiotic physical and chemical factors enhance the biodegradation of HDPE using A. terreus MF12.

High performance multi-finger MOSFET on SOI for RF amplifiers

NASA Astrophysics Data System (ADS)

Adhikari, M. Singh; Singh, Y.

2017-10-01

In this paper, we propose structural modifications in the conventional planar metal-oxide-semiconductor field-effect transistor (MOSFET) on silicon-on-insulator by utilizing trenches in the epitaxial layer. The proposed multi-finger MOSFET (MF-MOSFET) has dual vertical-gates placed in separate trenches to form multiple channels in the p-base which carry the drain current in parallel. The proposed device uses TaN as gate electrode and SiO2 as gate dielectric. Simultaneous conduction of multiple channels enhances the drain current (ID) and provides higher transconductance (gm) leading to significant improvement in cut-off frequency (ft). Two-dimensional simulations are performed to evaluate and compare the performance of the MF-MOSFET with the conventional MOSFET. At a gate length of 60 nm, the proposed device provides 4 times higher ID, 3 times improvement in gm and 1.25 times increase in ft with better control over the short channel effects as compared with the conventional device.

Efficacy of kinesiology tape versus postural correction exercises on neck disability and axioscapular muscles fatigue in mechanical neck dysfunction: A randomized blinded clinical trial.

PubMed

El-Abd, Aliaa M; Ibrahim, Abeer R; El-Hafez, Haytham M

2017-04-01

Mechanical neck dysfunction (MND), with axioscapular muscles fatigue, is highly prevalent worldwide. While postural correction is commonly used for its treatment, efficacy of kinesiology tape (KT) has received considerable attention. To determine the effectiveness of KT versus correction exercises on neck disability, and axioscapular muscles fatigue in MND patients. 46 MND patients were randomly assigned into 1 of 2 groups receiving 4 weeks treatment of either KT or correction exercises. Neck disability and axioscapular muscles fatigue as median frequency of electromyography (EMG-MF) were measured pre and post treatment. Group-by-time interaction was not significant in the multivariable test. Post hoc tests revealed that KT produced more disability reduction than the postural exercises. However, there was no significant interaction for EMG-MF. KT has been found to be more effective than postural exercises to reduce neck disability. However, both modalities have similar effects to reduce axioscapular muscles fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Obstruction of adaptation in diploids by recessive, strongly deleterious alleles.

PubMed

Assaf, Zoe June; Petrov, Dmitri A; Blundell, Jamie R

2015-05-19

Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a "staggered sweep." It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila.

Effects of dietary fucoidan on the blood constituents, anti-oxidation and innate immunity of juvenile yellow catfish (Pelteobagrus fulvidraco).

PubMed

Yang, Qing; Yang, Rui; Li, Ming; Zhou, Qicun; Liang, Xiongpei; Elmada, Zacharia Cassian

2014-12-01

This experiment was conducted to investigate the effects of fucoidan on the blood constituents, anti-oxidation and innate immunity of juvenile yellow catfish, Pelteobagrus fulvidraco. Totally 420 individuals of juvenile yellow catfish were randomly allocated to 7 groups with 3 replicates per group and 20 fishes per replicate. The same experimental fish were randomly subjected to one of the following 7 treatments for 12 weeks: The basal diet was applied as control group, the experimental groups were fed on fucoidan extracted from Sargassum horneri (SF) and commodity fucoidan purchased from the market (MF), and the effective dosages were 0.05%, 0.1% and 0.2% per kilogram feed (the groups were respectively marked as SF1, SF2, SF3, MF1, MF2 and MF3). The capabilities of anti-oxidation and innate immunity were detected by the blood characters, serum enzyme activities, serum MDA content, respiratory burst activity and phagocytic index of head-kidney macrophages. Challenge test was conducted also. The results indicated that the triglyceride (TG) and total cholesterol (TC) values of the yellow catfish were significantly decreased when dietary with SF and MF, while there was no significant difference between the MF1 and the control group. Fish fed on SF and MF diets had a lower high density lipoprotein-cholesterol (HDL-C) level than those fed on basal diet except SF2 group. The low density lipoprotein-cholesterol (LDL-C) and glucose (GUL) levels of the fish were significantly decreased at the 0.2% dietary fucoidan level, and there were no significant differences between the other groups. The activities of serum superoxide dismutase (SOD) significantly increased and the contents of malondialdehyde (MDA) significantly decreased when the fish fed dietary SF and MF. The CAT activities of SF groups were higher than that of control groups, while these values were not significantly changed in MF1 and MF3 groups. The maximum of catalase (CAT) activities of the fish fed on two kind fucoidan were obtained in the SF2 and MF2 groups (fucoidan = 0.1%) respectively. The serum lysozyme (LZM) activities of the yellow catfish fed on SF and MF were significantly higher than the control ones except SF3, MF2 and MF3 group. Phagocytosis index (PI) and the respiratory burst (RB) activity of head-kidney were significantly influenced by dietary fucoidan, PI values of the fish fed on SF2, MF1 and MF2 were higher than those fed on basal diet. RB activity of the yellow catfishes were significantly increased when they were fed on fucoidan except the SF3 and MF3 groups. The challenge experiment with Aeromonas hydrophilalala revealed that the fish fed on fucoidan had no significant effect on mortality rate of the yellow catfish. These results suggested that fucoidan significantly influences the blood characters, antioxidant status, non-specific immune responses in juvenile yellow catfish. Copyright © 2014 Elsevier Ltd. All rights reserved.

[In Vitro Evaluation of the Optical Quality of Segmental Refractive Multifocal Intraocular Lenses].

PubMed

Yildirim, Timur Mert; Auffarth, Gerd Uwe; Tandogan, Tamer; Liebing, Stephanie; Labuz, Grzegorz; Choi, Chul Young; Khoramnia, Ramin

2017-11-08

In customised patient care, it is important to know the optical quality of different intraocular lenses (IOL). In this study, the optical quality of three segmental intraocular lenses were compared. The LENTIS Comfort LS-313 MF15, LENTIS Mplus X LS-313 MF30 and LENTIS High Add IOL LS-313 MF80 (Oculentis, Berlin, Germany) with a far power of + 21 D were analysed at the optical bench OptiSpheric IOL PRO (Trioptics GmbH, Wedel, Germany). The lenses have almost the same optical design but differ in the power of the near segment. The MF15 has a + 1.5 D addition to improve vision in intermediate distances, the MF30 has a near addition of + 3 D and the MF80 has a near addition of + 8 D. The modulation transfer function area (MTFa) and the Strehl ratio were examined for apertures of 3 mm (photopic) and 4.5 mm (mesopic). The MTFa values for the far focus are 33.34/30.80/51.53 (MF15/MF30/MF80) with an aperture of 3 mm and 25.38/22.52/43.15 for 4.5 mm. The MTFa values for the intermediate focus are 29.85/16.21/6.25 for a 3 mm aperture and 23.92/8.05/3.08 for 4.5 mm. The MTFa values for the near focus are 9.75/21.49/33.12 for an aperture of 3 mm and 4.95/22.70/31.68 for 4.5 mm. The Strehl ratio of the far focus is 0.34/0.30/0.52 for an aperture of 3 mm and 0.24/0.22/0.43 for 4.5 mm. For the intermediate focus, the Strehl ratio is 0.30/0.17/0.07 for an aperture of 3 mm and 0.24/0.08/0.03 for 4.5 mm. The Strehl ratio of the near focus is 0.10/0.22/0.33 for an aperture of 3 mm and 0.05/0.23/0.32 for 4.5 mm. We confirmed that the addition influences the optical quality of segmental bifocal intraocular lenses. For the far focus, the results of the MF15 and MF30 are similar. In intermediate distances, the MF15 achieves the best results. For near distances, the MF30 achieves better optical values than the MF15. The lens MF80, which has been designed for patients with maculopathies, achieves good results for far and near distances. Georg Thieme Verlag KG Stuttgart · New York.

Prevalence of glucocerebrosidase mutations in the Israeli Ashkenazi Jewish population.

PubMed

Horowitz, M; Pasmanik-Chor, M; Borochowitz, Z; Falik-Zaccai, T; Heldmann, K; Carmi, R; Parvari, R; Beit-Or, H; Goldman, B; Peleg, L; Levy-Lahad, E; Renbaum, P; Legum, S; Shomrat, R; Yeger, H; Benbenisti, D; Navon, R; Dror, V; Shohat, M; Magal, N; Navot, N; Eyal, N

1998-01-01

Gaucher disease is the most prevalent inherited disease among Ashkenazi Jews. It is very heterogeneous due to a large number of mutations within the glucocerebrosidase gene, whose impaired activity is the cause for this disease. Aiming at determining Gaucher carrier frequency among the Ashkenazi Jewish population in Israel, 1,208 individuals were molecularly diagnosed for six mutations known to occur among Ashkenazi Jewish Gaucher patients, using the newly developed Pronto Gaucher kit. The following mutations were tested: N370S, 84GG, IVS2+1, D409H, L444P, and V394L. Molecular testing of these mutations also allows identification of the recTL allele. The results indicated that Gaucher carrier frequency is 1:17 within the tested population. The prevalence of N370S carriers is 1:17.5. This implies that approximately 1:1225 Ashkenazi Jews will be homozygous for the N370S mutation. Actually, in our study of 1,208 individuals one was found to be homozygous for the N370S mutation. The actual number of known Ashkenazi Jewish Gaucher patients with this genotype is much lower than that expected according to the frequency of the N370S mutation, suggesting a low penetrance of this mutation. Results of loading experiments in cells homozygous for the N370S mutation, as well as cells homozygous for the L444P and the D409H mutations, exemplified this phenomenon.

Effect of Recording Duration on the Diagnostic Performance of Multifocal Visual-evoked Potentials in High-risk Ocular Hypertension and Early Glaucoma

PubMed Central

Fortune, Brad; Zhang, Xian; Hood, Donald C.; Demirel, Shaban; Patterson, Emily; Jamil, Annisa; Mansberger, Steven L.; Cioffi, George A.; Johnson, Chris A.

2010-01-01

Purpose To evaluate the effect on diagnostic performance of reducing multifocal visual-evoked potential (mfVEP) recording duration from 16 to 8 minutes per eye. Methods Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were studied. Two 8-minute mfVEP recordings were obtained for each eye in an ABBA order using VERIS. The first recording for each eye was compared against single run (1-Run) mfVEP normative data; the average of both recordings for each eye was compared against 2-Run normative data. Visual fields (VFs) were obtained by standard automated perimetry (SAP) within 22.3±27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph images were obtained together, within 24.8±50.4 days of the mfVEP and 33.1±62.9 days of SAP. Masked experts graded disc photographs as either glaucomatous optic neuropathy or normal. The overall Moorfields Regression Analysis result from the Heidelberg Retina Tomograph was used as a separate diagnostic classification. Thus, 4 diagnostic standards were applied in total, 2 based on optic disc structure alone and 2 others based on disc structure and SAP. Results Agreement between the 1-Run and 2-Run mfVEP was 90%. Diagnostic performance of the 1-Run mfVEP was similar to that of the 2-Run mfVEP for all 4 diagnostic standards. Sensitivity was slightly higher for the 2-Run mfVEP, whereas specificity was slightly higher for the 1-Run mfVEP. Conclusions If higher sensitivity is sought, the 2-Run mfVEP will provide better discrimination between groups of eyes with relatively high signal-to-noise ratio (eg, early glaucoma or high-risk suspects). But if higher specificity is a more important goal, the 1-Run mfVEP provides adequate sensitivity and requires only half the test time. Considered alongside prior studies, the present results suggest that the 1-Run mfVEP is an efficient way to confirm (or refute) the extent of VF loss in patients with moderate or advanced glaucoma, particularly in those with unreliable VFs, including malingering or other “functional” forms of VF loss. PMID:18414101

Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs

PubMed Central

Sørensen, Nina Buus; Christiansen, Anders Tolstrup; Kjær, Troels Wesenberg; Klemp, Kristian; la Cour, Morten; Kiilgaard, Jens Folke

2017-01-01

Purpose The time-dependent effect of anesthetics on the retinal function is debated. We hypothesize that in anesthetized animals there is a time-dependent decline that requires optimized multifocal electroretinogram (mfERG) recording procedures. Methods Conventional and four-frame global-flash mfERG recordings were obtained approximately 15, 60, and 150 minutes after the induction of propofol anesthesia (20 pigs) and isoflurane anesthesia (nine pigs). In six of the propofol-anesthetized pigs, the mfERG recordings were split in 3-minute segments. Two to 4 weeks after initial recordings, an intraocular injection of tetrodotoxin (TTX) was given and the mfERG was rerecorded as described above. Data were analyzed using mixed models in SAS statistical software. Results Propofol significantly decreases the conventional and global-flash amplitudes over time. The only significant effect of isoflurane is a decrease in the global-flash amplitudes. At 15 minutes after TTX injection several of the mfERG amplitudes are significantly decreased. There is a linear correlation between the conventional P1 and the global-flash DR mfERG-amplitude (R2 = 0.82, slope = 0.72, P < 0.0001). There is no significant difference between the 3-minute and the prolonged mfERG recordings for conventional amplitudes and the global-flash direct response. The global flash–induced component significantly decreases with prolonged mfERG recordings. Conclusions A 3-minute mfERG recording and a single stimulation protocol is sufficient in anesthetized pigs. Recordings should be obtained immediately after the induction of anesthesia. The effect of TTX is significant 15 minutes after injection, but is contaminated by the effect of anesthesia 90 minutes after injection. Therefore, the quality of mfERG recordings can be further improved by determining the necessary time-of-delay from intraocular injection of a drug to full effect. Translational Relevance General anesthesia is a possible source of error in mfERG recordings. Therefore, it is important to investigate the translational relevance of the results to mfERG recordings in children in general anesthesia. PMID:28377845

Dual-Gated Motion-Frozen Cardiac PET with Flurpiridaz F 18.

PubMed

Slomka, Piotr J; Rubeaux, Mathieu; Le Meunier, Ludovic; Dey, Damini; Lazewatsky, Joel L; Pan, Tinsu; Dweck, Marc R; Newby, David E; Germano, Guido; Berman, Daniel S

2015-12-01

A novel PET radiotracer, Flurpiridaz F 18, has undergone phase II clinical trial evaluation as a high-resolution PET cardiac perfusion imaging agent. In a subgroup of patients imaged with this agent, we assessed the feasibility and benefit of simultaneous correction of respiratory and cardiac motion. In 16 patients, PET imaging was performed on a 4-ring scanner in dual cardiac and respiratory gating mode. Four sets of data were reconstructed with high-definition reconstruction (HD•PET): ungated and 8-bin electrocardiography-gated images using 5-min acquisition, optimal respiratory gating (ORG)-as developed for oncologic imaging-using a narrow range of breathing amplitude around end-expiration level with 35% of the counts in a 7-min acquisition, and 4-bin respiration-gated and 8-bin electrocardiography-gated images (32 bins in total) using the 7-min acquisition (dual-gating, using all data). Motion-frozen (MF) registration algorithms were applied to electrocardiography-gated and dual-gated data, creating cardiac-MF and dual-MF images. We computed wall thickness, wall/cavity contrast, and contrast-to-noise ratio for standard, ORG, cardiac-MF, and dual-MF images to assess image quality. The wall/cavity contrast was similar for ungated (9.3 ± 2.9) and ORG (9.5 ± 3.2) images and improved for cardiac-MF (10.8 ± 3.6) and dual-MF images (14.8 ± 8.0) (P < 0.05). The contrast-to-noise ratio was 22.2 ± 9.1 with ungated, 24.7 ± 12.2 with ORG, 35.5 ± 12.8 with cardiac-MF, and 42.1 ± 13.2 with dual-MF images (all P < 0.05). The wall thickness was significantly decreased (P < 0.05) with dual-MF (11.6 ± 1.9 mm) compared with ungated (13.9 ± 2.8 mm), ORG (13.1 ± 2.9 mm), and cardiac-MF images (12.1 ± 2.7 mm). Dual (respiratory/cardiac)-gated perfusion imaging with Flurpiridaz F 18 is feasible and improves image resolution, contrast, and contrast-to-noise ratio when MF registration methods are applied. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Antidepressant, anticonvulsant and antinociceptive effects of 3'-methoxy-6-methylflavone and 3'-hydroxy-6-methylflavone may involve GABAergic mechanisms.

PubMed

Karim, Nasiara; Khan, Imran; Ahmad, Naveed; Umar, Muhammad Naveed; Gavande, Navnath

2017-10-01

GABA A receptors have been implicated in the pathophysiology of depression, epilepsy and pain disorders. The purpose of this study was to investigate two novel synthetic flavones, 3'-methoxy-6-methylflavone (3'-MeO6MF) and 3'-hydroxy-6-methylflavone (3'-OH6MF), for their effect on GABA A receptors and subsequently investigate their antidepressant, anticonvulsant and antinociceptive effects. Recombinant GABA A receptor subunits were expressed in Xenopus oocytes and a two electrode voltage clamp technique was used for electrophysiological studies. The antidepressant and anticonvulsant activities were determined using forced swim (FST) and tail suspension tests (TST) and bicuculline (BIC)-induced seizures respectively. Furthermore, the antinociceptive activity was determined using tail immersion and hot plate tests. 3'-MeO6MF and 3'-OH6MF potentiated GABA-induced currents through ternary α1-2β1-3γ2L and binary α1β2 receptors indicating that the positive modulation by these flavonoids is not dependent on the γ subunit. In behavioral studies, 3'-MeO6MF and 3'-OH6MF (10-100mg/kg, ip) exerted significant antidepressant like effects in the FST and TST. 3'-MeO6MF (10-100mg/kg) and 3'-OH6MF (30 and 100mg/kg) also exhibited significant anticonvulsant effects in BIC-induced seizures, and antinociceptive activity in tail immersion and hot plate tests (*p<0.05, **p<0.01, ***p<0.001). Furthermore, the antidepressant and antinociceptive activities of 3'-MeO6MF and 3'-OH6MF were partially ameliorated by co-administration of BIC (3mg/kg) suggesting the involvement of GABAergic mechanisms. The findings of this study suggest that 3'-MeO6MF and 3'-OH6MF exhibited significant antidepressant, anticonvulsant and antinociceptive effects mediated via interactions with GABA A receptors. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Analysis of cis and trans 3-Methylfentanyl by Liquid Chromatography High Resolution Mass Spectrometry and Findings in Forensic Toxicology Casework.

PubMed

Fogarty, Melissa F; Papsun, Donna M; Logan, Barry K

2018-05-25

3-Methylfentanyl (3-MF), N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide, has reappeared in the United States illicit drug market since its disappearance after a series of overdose deaths in 1988.3-MF presents an analytical challenge, due to presence of cis and trans stereoisomers, each with different potencies, and ultimately very low concentrations in the blood after use. A method was developed using liquid chromatography time-of-flight mass spectrometry for the analysis of (±)-cis-3-MF and (±)-trans-3-MF in blood specimens after solid phase extraction. The linear dynamic range of this method was 0.1-10 ng/mL. Blood samples from 25 postmortem cases and 2 human performance case involving 3-MF were submitted for quantitative analysis. The mean and median concentration for the (±)-cis-3-MF were 0.84 ng/mL (±0.81) and 0.66 ng/mL, respectively, range 0.14-3.43 ng/mL. The resulting (±)-trans-3-MF mean concentration was 0.46 ng/mL (±0.38) and the median concentration was 0.37 ng/mL with a range of 0.11-1.90 ng/mL. The resulting (±)-cis-3-MF and (±)-trans-3-MF concentrations were summed to give the total amount of 3-MF present in the case with the resulting average concentration at 1.28 ng/mL (±1.16), median at 1 ng/mL and range 0.18-5.18. As the estimated dose of this compound is approximately 0.1-0.5 mg with the resulting concentrations in the sub-nanogram range, it is necessary for forensic toxicology laboratories to obtain instruments sensitive enough to detect these substances in driving under the influence of drugs and postmortem cases. Quantitation of 3-MF with separation of (±)-cis and (±)-trans-3-MF provides additional detail for more specific toxicological interpretation. This article is protected by copyright. All rights reserved.

Amazonian onchocerciasis: parasitological profiles by host-age, sex, and endemicity in southern Venezuela.

PubMed

Vivas-Martínez, S; Basáñez, M G; Botto, C; Rojas, S; García, M; Pacheco, M; Curtis, C F

2000-11-01

This paper describes, for the human onchocerciasis focus of southern Venezuela, the age profiles of Onchocerca volvulus microfilarial (mf) and nodule prevalence, mf intensity, and mf aggregation for the whole examined population (836 Yanomami people) living in 20 villages, and for these communities classified according to endemicity levels (hypoendemic: < or = 20 %; mesoendemic: 21-59 %; hyperendemic: < or = 60 % infected). Mf prevalence and intensity increased with age, particularly in the hyperendemic areas, and there were no marked differences between the sexes. The prevalence of nodules followed the same age pattern. Fifty percent mf prevalence was reached in the 15-19 year age-class when the population was taken as a whole; nearly in the 10 to 14-year-olds for the hyperendemic level, in those aged 20-29 years in mesoendemic areas, and not reached at all in hypoendemic villages. The degree of mf aggregation was measured by the k value of the negative binomial distribution and by the variance to mean ratio (VMR). The relationship between the standard deviation (S.D.) of mf counts and the mean mf density was also explored. These 3 indices (k, VMR, and S.D.) showed a tendency to increase with both mean mf load and host age. Since infection intensity and host age were themselves positively related, it was not possible to draw definite conclusions about age-specific changes of parasite aggregation. There was not a significant decrease of mf intensity after an earlier peak neither was there a shift towards younger ages of the maximum no. of mf/mg reached as the endemicity level increased. These results are discussed in relation to detection of density dependence in the human host, selection of an indicator age-group for rapid epidemiological assessment (REA) methods, and strategies of ivermectin distribution in the Amazonian focus. It is recommended that, for the Amazonian onchocerciasis focus, the indicator group for REA consists of all those aged 15 years and over.

Polar Motion Constraints on Models of the Fortnightly Tide

NASA Technical Reports Server (NTRS)

Ray, Richard D.; Egbert, G. D.; Smith, David E. (Technical Monitor)

2002-01-01

Estimates of the near-fortnightly Mf ocean tide from Topex/Poseidon satellite altimetry and from numerical solutions to the shallow water equations agree reasonably well, at least in their basin-scale features. For example, both show that the Pacific Ocean tide lags the Atlantic tide by roughly 30 degrees. There are hints of finer scale agreements in the elevation fields, but noise levels are high. In contrast, estimates of Mf currents are only weakly constrained by the TP data, because high-wavenumber Rossby waves (with intense currents) are associated with relatively small perturbations in surface elevation. As a result, a wide range of Mf current fields are consistent with both the TP data and the hydrodynamic equations within a priori plausible misfit bounds. We find that a useful constraint on the Mf currents is provided by independent estimates of the Earth's polar motion. At the Mf period polar motion shows a weak signal (both prograde and retrograde) which must be almost entirely caused by the ocean tide. We have estimated this signal from the SPACE2000 time series, after applying a broad-band correction for atmospheric angular momentum. Although the polar motion estimates have relatively large uncertainties, they are sufficiently precise to fix optimum data weights in a global ocean inverse model of Mf. These weights control the tradeoff between fitting a prior hydrodynamic model of Mf and fitting the relatively noisy T/P measurements of Mf. The predicted polar motion from the final inverse model agrees remarkably well with the Mf polar motion observations. The preferred model is also consistent with noise levels suggested by island gauges, and it is marginally consistent with differences observed by subsetting the altimetry (to the small extent that this is possible). In turn, this new model of the Mf ocean tide allows the ocean component to be removed from Mf estimates of length of day, thus yielding estimates of complex Love numbers less contaminated by oceanic effects than has hitherto been possible.

Cloning and expression analysis of the ATP-binding cassette transporter gene MFABC1 and the alternative oxidase gene MfAOX1 from Monilinia fructicola.

PubMed

Schnabel, Guido; Dait, Qun; Paradkar, Manjiri R

2003-10-01

Brown rot, caused by Moniliniafructicola (G Wint) Honey, is a serious disease of peach in all commercial peach production areas in the USA, including South Carolina where it has been primarily controlled by pre-harvest application of 14-alpha demethylation (DMI) fungicides for more than 15 years. Recently, the Qo fungicide azoxystrobin was registered for brown rot control and is currently being investigated for its potential as a DMI fungicide rotation partner because of its different mode of action. In an effort to investigate molecular mechanisms of DMI and Qo fungicide resistance in M fructicola, the ABC transporter gene MfABC1 and the alternative oxidase gene MfAOX1 were cloned to study their potential role in conferring fungicide resistance. The MfABC1 gene was 4380 bp in length and contained one intron of 71 bp. The gene revealed high amino acid homologies with atrB from Aspergillus nidulans (Eidam) Winter, an ABC transporter conferring resistance to many fungicides, including DMI fungicides. MfABC1 gene expression was induced after myclobutanil and propiconazole treatment in isolates with low sensitivity to the same fungicides, and in an isolate with high sensitivity to propiconazole. The results suggest that the MfABC1 gene may be a DMI fungicide resistance determinant in M fructicola. The alternative oxidase gene MfAOX1 from M fructicola was cloned and gene expression was analyzed. The MfAOX1 gene was 1077 bp in length and contained two introns of 54 and 67 bp. The amino acid sequence was 63.8, 63.8 and 57.7% identical to alternative oxidases from Venturia inaequalis (Cooke) Winter, Aspergillus niger van Teighem and A nidulans, respectively. MfAOX1 expression in some but not all M fructicola isolates was induced in mycelia treated with azoxystrobin. Azoxystrobin at 2 microg ml(-1) significantly induced MfAOX1 expression in isolates with low MfAOX1 constitutive expression levels.

Fanconi anemia: correlating central nervous system malformations and genetic complementation groups.

PubMed

Johnson-Tesch, Benjamin A; Gawande, Rakhee S; Zhang, Lei; MacMillan, Margaret L; Nascene, David R

2017-06-01

Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.

PubMed

Gauthier, Julie; Bonnel, Anna; St-Onge, Judith; Karemera, Liliane; Laurent, Sandra; Mottron, Laurent; Fombonne, Eric; Joober, Ridha; Rouleau, Guy A

2005-01-05

Jamain [2003: Nat Genet 34:27-29] recently reported mutations in two neuroligin genes in sib-pairs affected with autism. In order to confirm these causative mutations in our autistic population and to determine their frequency we screened 96 individuals affected with autism. We found no mutations in these X-linked genes. These results indicate that mutations in NLGN3 and NLGN4 genes are responsible for at most a small fraction of autism cases and additional screenings in other autistic populations are needed to better determine the frequency with which mutations in NLGN3 and NLGN4 occur in autism. Copyright 2004 Wiley-Liss, Inc.

Impact of low concentration factor microfiltration on milk component recovery and Cheddar cheese yield.

PubMed

Neocleous, M; Barbano, D M; Rudan, M A

2002-10-01

The effect of microfiltration (MF) on the composition of Cheddar cheese, fat, crude protein (CP), calcium, total solids recovery, and Cheddar cheese yield efficiency (i.e., composition adjusted yield divided by theoretical yield) was determined. Raw skim milk was microfiltered twofold using a 0.1-microm ceramic membrane at 50 degrees C. Four vats of cheese were made in one day using milk at lx, 1.26x, 1.51x, and 1.82x concentration factor (CF). An appropriate amount of cream was added to achieve a constant casein (CN)-to-fat ratio across treatments. Cheese manufacture was repeated on four different days using a randomized complete block design. The composition of the cheese was affected by MF. Moisture content of the cheese decreased with increasing MF CF. Standardization of milk to a constant CN-to-fat ratio did not eliminate the effect of MF on cheese moisture content. Fat recovery in cheese was not changed by MF. Separation of cream prior to MF, followed by the recombination of skim or MF retentate with cream resulted in lower fat recovery in cheese for control and all treatments and higher fat loss in whey when compared to previous yield experiments, when control Cheddar cheese was made from unseparated milk. Crude protein, calcium, and total solids recovery in cheese increased with increasing MF CF, due to partial removal of these components prior to cheese making. Calcium and calcium as a percentage of protein increased in the cheese, suggesting an increase in calcium retention in the cheese with increasing CF. While the actual and composition adjusted cheese yields increased with increasing MF CF, as expected, there was no effect of MF CF on cheese yield efficiency.

Diagnostic performance of labial minor salivary gland flow measurement for assessment of xerostomia.

PubMed

Satoh-Kuriwada, Shizuko; Iikubo, Masahiro; Shoji, Noriaki; Sakamoto, Maya; Sasano, Takashi

2012-08-01

Minor salivary gland flow rate (MF) has been proposed as a key feature of xerostomia (subjective feeling of dry mouth). To assess its diagnostic performance, MF was compared in xerostomia and control subjects. Sixty-six subjects with xerostomia and 30 controls were enrolled. MF was measured in the lower labial mucosa using the iodine-starch filter paper method. Stimulated whole salivary flow rates were also measured using the gum test (stimulated-WF). Both labial-MF and stimulated-WF were significantly lower in xerostomia subjects than in controls. There was a positive correlation between labial-MF and stimulated-WF in control but not xerostomia subjects. In xerostomia subjects compared to controls, there was a significantly larger reduction in labial-MF than in stimulated-WF. Xerostomia was most accurately diagnosed using a labial-MF cutoff value of 0.25 μL/cm(2)/min. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy at this cutoff value were 1.00, 0.87, 0.93, 1.00, and 0.96, respectively. Compared to respective values of 0.64, 1.00, 1.00, 0.56, and 0.75 for stimulated-WF at the traditional cutoff of 1.0 mL/min, these data indicate the higher sensitivity, negative predictive value, and diagnostic accuracy of labial-MF. Xerostomia was more strongly related to reduction of labial-MF than to that of stimulated-WF. Xerostomia was most likely triggered at a labial-MF cut-off value of 0.25 μL/cm(2)/min based on results from the iodine-starch method. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maps Showing Locations of Damaging Landslides Caused by El Nino Rainstorms, Winter Season 1997-98, San Francisco Bay Region, California

USGS Publications Warehouse

Godt, Jonathan W.

1999-01-01

Heavy rainfall associated with a strong El Nino caused over $150 million in landslide damage in the 10-county San Francisco Bay region during the winter and spring of 1998. Reports of landsliding began in early January 1998 and continued throughout the winter and spring. On February 9, President Clinton declared all 10 counties eligible for Federal Emergency Management Agency (FEMA) disaster assistance. In April and May of 1998, personnel from the U.S. Geological Survey (USGS) conducted a field reconnaissance in the area to provide a general overview of landslide damage resulting from the 1997-98 sequence of El Nino-related storms. Seven scientists from the USGS Landslide Hazards Program based in Reston, Virginia; Golden, Colorado; and Menlo Park, California; and five scientists from the USGS Geologic Mapping Program?s San Francisco Bay Mapping Team based in Menlo Park, California, cooperated in the landslide-damage assessments. The assessments were done for 10 counties in the Bay area: Alameda, Contra Costa, Marin, Napa, San Francisco, Santa Clara, Santa Cruz, San Mateo, Solano, and Sonoma. USGS Maps in this series include: MF-2325-A (Napa County), MF-2325-B (Alameda County), MF-2325-C (Marin County), MF-2325-D (Santa Cruz County), MF-2325-E (Contra Costa County), MF-2325-F (Sonoma County), MF-2325-G (San Francisco City and County), MF-2325-H (San Mateo County), MF-2325-I (Solano County), MF-2325-J (Santa Clara County). In addition to USGS scientists providing data from the field evaluation, each of the counties, many consultants, and others cooperated fully in providing the landslide-damage information compiled here.

Clinical use of multifocal visual-evoked potentials in a glaucoma practice: a prospective study

PubMed Central

Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2012-01-01

Purpose To test a framework that describes how the multifocal visual-evoked potential (mfVEP) technique is used in a particular glaucoma practice. Methods In this prospective, descriptive study, glaucoma suspects, ocular hypertensives and glaucoma patients were referred for mfVEP testing by a single glaucoma specialist over a 2-year period. All patients underwent standard automated perimetry (SAP) and mfVEP testing within 3 months. Two hundred and ten patients (420 eyes) were referred for mfVEP testing for the following reasons: (1) normal SAP tests suspected of early functional loss (ocular hypertensives, n = 43; and glaucoma suspects on the basis of suspicious optic disks, n = 52); (2) normal-tension glaucoma patients with suspected central SAP defects (n = 33); and (3) SAP abnormalities needing confirmation (n = 82). Results All the glaucoma suspects with normal SAP and mfVEP results remained untreated. Of those with abnormal mfVEP results, 68 % (15/22) were treated because the abnormal regions on the mfVEP were consistent with the abnormal regions seen during clinical examination of the optic disk. The mfVEP was abnormal in 86 % (69/80) of eyes with glaucomatous optic neuropathy and SAP damage, even though it did not result in an altered treatment regimen. In NTG patients, the mfVEP showed central defects in 44 % (12 of 27) of the eyes with apparently normal central fields and confirmed central scotomata in 92 % (36 of 39), leading to more rigorous surveillance of these patients. Conclusions In a clinical practice, the mfVEP was used when clinical examination and subjective visual fields provided insufficient or conflicting information. This information influenced clinical management. PMID:22476612

Clinical use of multifocal visual-evoked potentials in a glaucoma practice: a prospective study.

PubMed

De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2012-08-01

To test a framework that describes how the multifocal visual-evoked potential (mfVEP) technique is used in a particular glaucoma practice. In this prospective, descriptive study, glaucoma suspects, ocular hypertensives and glaucoma patients were referred for mfVEP testing by a single glaucoma specialist over a 2-year period. All patients underwent standard automated perimetry (SAP) and mfVEP testing within 3 months. Two hundred and ten patients (420 eyes) were referred for mfVEP testing for the following reasons: (1) normal SAP tests suspected of early functional loss (ocular hypertensives, n = 43; and glaucoma suspects on the basis of suspicious optic disks, n = 52); (2) normal-tension glaucoma patients with suspected central SAP defects (n = 33); and (3) SAP abnormalities needing confirmation (n = 82). All the glaucoma suspects with normal SAP and mfVEP results remained untreated. Of those with abnormal mfVEP results, 68 % (15/22) were treated because the abnormal regions on the mfVEP were consistent with the abnormal regions seen during clinical examination of the optic disk. The mfVEP was abnormal in 86 % (69/80) of eyes with glaucomatous optic neuropathy and SAP damage, even though it did not result in an altered treatment regimen. In NTG patients, the mfVEP showed central defects in 44 % (12 of 27) of the eyes with apparently normal central fields and confirmed central scotomata in 92 % (36 of 39), leading to more rigorous surveillance of these patients. In a clinical practice, the mfVEP was used when clinical examination and subjective visual fields provided insufficient or conflicting information. This information influenced clinical management.

Mangiferin Mitigates Gastric Ulcer in Ischemia/ Reperfused Rats: Involvement of PPAR-γ, NF-κB and Nrf2/HO-1 Signaling Pathways

PubMed Central

Mahmoud-Awny, Magdy; Attia, Ahmed S.; Abd-Ellah, Mohamed F.; El-Abhar, Hanan Salah

2015-01-01

Mangiferin (MF), a xanthonoid from Mangifera indica, has been proved to have antisecretory and antioxidant gastroprotective effects against different gastric ulcer models; however, its molecular mechanism has not been previously elucidated. Therefore, the aim of this study was to test its modulatory effect on several signaling pathways using the ischemia/reperfusion model for the first time. Animals were treated with MF, omeprazole (OMP), and the vehicle. The mechanistic studies revealed that MF mediated its gastroprotective effect partly via inducing the expression of Nrf2, HO-1 and PPAR-γ along with downregulating that of NF-κB. Surprisingly, the effect of MF, especially the high dose, exceeded that mediated by OMP except for Nrf2. The molecular results were reflected on the biomarkers measured, where the antioxidant effect of MF was manifested by increasing total antioxidant capacity and glutathione, besides normalizing malondialdehyde level. Additionally, MF decreased the I/R-induced nitric oxide elevation, an effect that was better than that of OMP. In the serum, MF, dose dependently, enhanced endothelial nitric oxide synthase, while reduced the inducible isoform. Regarding the anti-inflammatory effect of MF, it reduced serum level of IL-1β and sE-selectin, effects that were mirrored on the tissue level of myeloperoxidase, the neutrophil infiltration marker. In addition, MF possessed an antiapoptotic character evidenced by elevating Bcl-2 level and reducing that of caspase-3 in a dose related order. As a conclusion, the intimated gastroprotective mechanisms of MF are mediated, partially, by modulation of oxidative stress, inflammation and apoptosis possibly via the Nrf2/HO-1, PPAR-γ/NF-κB signaling pathways. PMID:26196679

A new image segmentation method based on multifractal detrended moving average analysis

NASA Astrophysics Data System (ADS)

Shi, Wen; Zou, Rui-biao; Wang, Fang; Su, Le

2015-08-01

In order to segment and delineate some regions of interest in an image, we propose a novel algorithm based on the multifractal detrended moving average analysis (MF-DMA). In this method, the generalized Hurst exponent h(q) is calculated for every pixel firstly and considered as the local feature of a surface. And then a multifractal detrended moving average spectrum (MF-DMS) D(h(q)) is defined by the idea of box-counting dimension method. Therefore, we call the new image segmentation method MF-DMS-based algorithm. The performance of the MF-DMS-based method is tested by two image segmentation experiments of rapeseed leaf image of potassium deficiency and magnesium deficiency under three cases, namely, backward (θ = 0), centered (θ = 0.5) and forward (θ = 1) with different q values. The comparison experiments are conducted between the MF-DMS method and other two multifractal segmentation methods, namely, the popular MFS-based and latest MF-DFS-based methods. The results show that our MF-DMS-based method is superior to the latter two methods. The best segmentation result for the rapeseed leaf image of potassium deficiency and magnesium deficiency is from the same parameter combination of θ = 0.5 and D(h(- 10)) when using the MF-DMS-based method. An interesting finding is that the D(h(- 10)) outperforms other parameters for both the MF-DMS-based method with centered case and MF-DFS-based algorithms. By comparing the multifractal nature between nutrient deficiency and non-nutrient deficiency areas determined by the segmentation results, an important finding is that the gray value's fluctuation in nutrient deficiency area is much severer than that in non-nutrient deficiency area.

Characterization of plasma membrane domains of mouse EL4 lymphoma cells obtained by affinity chromatography on concanavalin A-Sepharose.

PubMed

Szamel, M; Goppelt, M; Resch, K

1985-12-19

Purified plasma membranes of mouse EL4 lymphoma cells were fractionated by means of affinity chromatography on concanavalin A-Sepharose into two subfractions; one (MF1) eluted freely from the affinity column, the second (MF2) adhered specifically to Con A-Sepharose. Both membrane subfractions proved to be of plasma membrane origin, as evidenced by the following criteria. (i) The ratio of cholesterol to phospholipid was nearly identical in plasma membrane and both subfractions. (ii) When isolated plasma membranes were labelled with tritiated NaBH4, both subfractions exhibited identical specific radioactivities. (iii) After enzymatic radioiodination of the cells, the total content of labelled proteins was very similar in isolated plasma membranes and in both subfractions. (iv) Some plasma membrane marker enzymes exhibited nearly identical specific activities in plasma membranes, MF1 or MF2 including gamma-glutamyl transpeptidase, 5'-nucleotidase and Mg2+-ATPase. Both subfractions exhibited characteristic differences. Thus the specific activities of (Na+ + K+)-ATPase, Ca2+-ATPase and lysophosphatidylcholine acyltransferase were several-fold enriched in MF2 compared to MF1. SDS-polyacrylamide gel electrophoresis revealed a different polypeptide composition of the two subfractions. Polypeptides of apparent molecular mass of 116, 95, 42, 39, 30 and 28 kDa were highly enriched in MF2, whereas MF1 contained another set of proteins, of apparent molecular mass of 70, 55 and 24 kDa. The phospholipid fatty acid composition of the subfractions proved to be different, as well, MF2 contained more saturated fatty acids than MF1. The data suggest the existence of plasma membrane domains in the plasma membranes of the mouse EL4 lymphoma cells, containing a set of polypeptides, among others membrane bound enzymes, embedded in a different phospholipid milieu.

Evidence for Hitchhiking of Deleterious Mutations within the Human Genome

PubMed Central

Chun, Sung; Fay, Justin C.

2011-01-01

Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles. PMID:21901107

Frequency of the S65C mutation in the hemochromatosis gene in Brazil.

PubMed

Oliveira, V C; Caxito, F A; Gomes, K B; Castro, A M; Pardini, V C; Ferreira, A C S

2009-07-14

Development of hereditary hemochromatosis is associated with the C282Y, H63D or S65C mutations in the hemochromatosis gene. Though there is extensive knowledge about the former two, there is little information on the mechanism of action and the allelic frequency of the S65C mutation. We examined the prevalence of the S65C mutation of the hemochromatosis gene in Brazilians with clinical suspicion of hereditary hemochromatosis. Genotyping for this mutation was carried out in 633 individuals with clinical suspicion of hereditary hemochromatosis, using the polymerase chain reaction, followed by enzymatic digestion. The sample comprised 77.1% men and 22.9% women, giving a ratio of approximately 3:1; the mean age was 48.8 +/- 13.8 years. More than half (57.3%) of the individuals in the sample were 41 to 60 years old. The frequency of heterozygotes for this mutation was 0.016; no homozygous mutant patients were found. This is the first analysis of the S65C mutation in individuals suspected of having hereditary hemochromatosis in Brazil.

Decreased mutation frequencies among immunoglobulin G variable region genes during viremic HIV-1 infection.

PubMed

Bowers, Elisabeth; Scamurra, Ronald W; Asrani, Anil; Beniguel, Lydie; MaWhinney, Samantha; Keays, Kathryne M; Thurn, Joseph R; Janoff, Edward N

2014-01-01

HIV-1 infection is complicated by high rates of opportunistic infections against which specific antibodies contribute to immune defense. Antibody function depends on somatic hypermutation (SHM) of variable regions of immunoglobulin heavy chain genes (VH-D-J). We characterized the frequency of SHM in expressed IgG mRNA immunoglobulin transcripts from control and HIV-1-infected patients. We compared utilization of genes in the most prominent VH family (VH3) and mutation frequencies and patterns of cDNA from VH3-IgG genes from 10 seronegative control subjects and 21 patients with HIV-1 infection (6 without and 15 patients with detectable plasma viremia). Unique IgG VH3 family cDNA sequences (n = 1,565) were PCR amplified, cloned, and sequenced from blood. Sequences were analyzed using online (Vbase) and in-house immunoglobulin alignment resources. Mutation frequencies in the antigen-binding hypervariable complementarity determining regions (CDR1/2) of IgG class-switched B cells were lower among viremic HIV-1-infected patients vs. controls for nucleotides (CDR1/2: 10±5% vs. 13.5±6%, p = 0.03) and amino acids (CDR: 20%±10 vs. 25%±12, p = 0.02) and in structural framework regions. Mutation patterns were similar among groups. The most common VH3 gene, VH3-23, was utilized less frequently among viremic HIV-1-infected patients (p = 0.03), and overall, mutation frequencies were decreased in nearly all VH3 genes compared with controls. B cells from HIV-1-infected patients show decreased mutation frequencies, especially in antigen-binding VH3 CDR genes, and selective defects in gene utilization. Similar mutation patterns suggest defects in the quantity, but not quality, of mutator activity. Lower levels of SHM in IgG class-switched B cells from HIV-1-infected patients may contribute to the increased risk of opportunistic infections and impaired humoral responses to preventative vaccines.

Mutator dynamics in sexual and asexual experimental populations of yeast.

PubMed

Raynes, Yevgeniy; Gazzara, Matthew R; Sniegowski, Paul D

2011-06-07

In asexual populations, mutators may be expected to hitchhike with associated beneficial mutations. In sexual populations, recombination is predicted to erode such associations, inhibiting mutator hitchhiking. To investigate the effect of recombination on mutators experimentally, we compared the frequency dynamics of a mutator allele (msh2Δ) in sexual and asexual populations of Saccharomyces cerevisiae. Mutator strains increased in frequency at the expense of wild-type strains in all asexual diploid populations, with some approaching fixation in 150 generations of propagation. Over the same period of time, mutators declined toward loss in all corresponding sexual diploid populations as well as in haploid populations propagated asexually. We report the first experimental investigation of mutator dynamics in sexual populations. We show that a strong mutator quickly declines in sexual populations while hitchhiking to high frequency in asexual diploid populations, as predicted by theory. We also show that the msh2Δ mutator has a high and immediate realized cost that is alone sufficient to explain its decline in sexual populations. We postulate that this cost is indirect; namely, that it is due to a very high rate of recessive lethal or strongly deleterious mutation. However, we cannot rule out the possibility that msh2Δ also has unknown directly deleterious effects on fitness, and that these effects may differ between haploid asexual and sexual populations. Despite these reservations, our results prompt us to speculate that the short-term cost of highly deleterious recessive mutations can be as important as recombination in preventing mutator hitchhiking in sexual populations.

Comparison of multifocal visual evoked potential, standard automated perimetry and optical coherence tomography in assessing visual pathway in multiple sclerosis patients

PubMed Central

Laron, Michal; Cheng, Han; Zhang, Bin; Schiffman, Jade S.; Tang, Rosa A.; Frishman, Laura J.

2010-01-01

Background Multifocal visual evoked potentials (mfVEP) measure local response amplitude and latency in the field of vision Objective To compare the sensitivity of mfVEP, Humphrey visual field (HVF) and optical coherence tomography (OCT) in detecting visual abnormality in multiple sclerosis (MS) patients. Methods MfVEP, HVF, and OCT (retinal nerve fiber layer [RNFL]) were performed in 47 MS-ON eyes (last optic neuritis (ON) attack ≥ 6 months prior) and 65 MS-no-ON eyes without ON history. Criteria to define an eye as abnormal were: mfVEP 1) amplitude/latency: either amplitude or latency probability plots meeting cluster criteria with 95% specificity 2) amplitude or latency alone (specificity: 97% and 98%, respectively); HVF and OCT, mean deviation and RNFL thickness meeting p < 0.05, respectively. Results MfVEP (amplitude/latency) identified more abnormality in MS-ON eyes (89%) than HVF (72%), OCT (62%), mfVEP amplitude (66%) or latency (67%) alone. 18% of MS-no-ON eyes were abnormal for both mfVEP (amplitude/latency) and HVF compared to 8% with OCT. Agreement between tests ranged from 60% to 79%. MfVEP (amplitude/latency) categorized an additional 15% of MS-ON eyes as abnormal compared to HVF and OCT combined. Conclusions MfVEP, which detects both demyelination (increased latency) and neural degeneration (reduced amplitude) revealed more abnormality than HVF or OCT in MS patients. PMID:20207786

BcMF11, a novel non-coding RNA gene from Brassica campestris, is required for pollen development and male fertility.

PubMed

Song, Jiang-Hua; Cao, Jia-Shu; Wang, Cheng-Gang

2013-01-01

KEY MESSAGE : BcMF11 as a non-coding RNA gene has an essential role in pollen development, and might be useful for regulating the pollen fertility of crops by antisense RNA technology. We previously identified a 828-bp full-length cDNA of BcMF11, a novel pollen-specific non-coding mRNA-like gene from Chinese cabbage (Brassica campestris L. ssp. chinensis Makino). However, little information is known about the function of BcMF11 in pollen development. To investigate its exact biological roles in pollen development, the BcMF11 cDNA was antisense inhibited in transgenic Chinese cabbage under the control of a tapetum-specific promoter BcA9 and a constitutive promoter CaMV 35S. Antisense RNA transgenic plants displayed decreasing expression of BcMF11 and showed distinct morphological defects. Pollen germination test in vitro and in vivo of the transgenic plants suggested that inhibition of BcMF11 decreased pollen germination efficiency and delayed the pollen tubes' extension in the style. Under scanning electron microscopy, many shrunken and collapsed pollen grains were detected in the antisense BcMF11 transgenic Chinese cabbage. Further cytological observation revealed abnormal pollen development process in transgenic plants, including delayed degradation of tapetum, asynchronous separation of microspore, and aborted development of pollen grain. These results suggest that BcMF11, as a non-coding RNA, plays an essential role in pollen development and male fertility.

Some news from the unknown soldier, the Peyer's patch macrophage.

PubMed

Wagner, Camille; Bonnardel, Johnny; Da Silva, Clément; Martens, Liesbet; Gorvel, Jean-Pierre; Lelouard, Hugues

2018-01-31

In mammals, macrophages (MF) are present in virtually all tissues where they serve many different functions linked primarily to the maintenance of homeostasis, innate defense against pathogens, tissue repair and metabolism. Although some of these functions appear common to all tissues, others are specific to the homing tissue. Thus, MF become adapted to perform particular functions in a given tissue. Accordingly, MF express common markers but also sets of tissue-specific markers linked to dedicated functions. One of the largest pool of MF in the body lines up the wall of the gut. Located in the small intestine, Peyer's patches (PP) are primary antigen sampling and mucosal immune response inductive sites. Surprisingly, although markers of intestinal MF, such as F4/80, have been identified more than 30 years ago, MF of PP escaped any kind of phenotypic description and remained "unknown" for decades. In absence of MF identification, the characterization of the PP mononuclear phagocyte system (MPS) functions has been impaired. However, taking into account that PP are privileged sites of entry for pathogens, it is important to understand how the latter are handled by and/or escape the PP MPS, especially MF, which role in killing invaders is well known. This review focuses on recent advances on the PP MPS, which have allowed, through new criteria of PP phagocyte subset identification, the characterization of PP MF origin, diversity, specificity, location and functions. Copyright © 2018 Elsevier Inc. All rights reserved.

Wealth, justice and freedom: Objective and subjective measures predicting poor mental health in a study across eight countries.

PubMed

Scholten, Saskia; Velten, Julia; Neher, Torsten; Margraf, Jürgen

2017-12-01

Macro-level factors (MF) such as wealth, justice and freedom measured with objective country-level indicators (objective MF), for instance the Gross Domestic Product (GDP), have been investigated in relation to health and well-being, but rarely in connection with depression, anxiety and stress subsumed as poor mental health. Also, a combination of different objective MF and of how individuals perceive those MF (subjective MF) has not been taken into consideration. In the present study, we combined subjective and objective measures of wealth, justice and freedom and examined their relationship with poor mental health. Population-based interviews were conducted in France, Germany, Poland, Russia, Spain, Sweden, U.K. and U.S.A. (n ≈ 1000 per country). GDP, GINI coefficient, Justice Index and Freedom Index were used as objective MF, whereas subjective MF were perceived wealth, justice and freedom measured at the individual level. Poor mental health was assessed as a combination of symptoms of depression, anxiety and stress. In a random-intercept-model, GINI coefficient and Freedom Index were significant positive country-level, and perceived wealth, justice, and freedom significant negative individual-level predictors of symptoms of poor mental health. Multiple subjective and objective MF should be combined to assess the macrosystem's relationship with poor mental health more precisely. The relationship between MF and poor mental health indicates that the macrosystem should be taken into account as relevant context for mental health problems, too.

Declining male births in Germany before and after reunification.

PubMed

Grech, Victor

2013-01-01

Male births occur 3% in excess of female births in mammals in a ratio (M/F) of 0.515. Many factors have been shown to influence this, including socioeconomic deprivation. This paper reviews live birth data for Germany over the period 1946-2009, and identifies secular trends in M/F pre- and post-reunification. The null hypothesis is that there were no differences between East and West Germany, geographically or temporally, before and after reunification. Annual data on male and female live births were obtained from the Human Mortality Database and analyzed with contingency tables. These data were available separately for East and West Germany (1950-1989). There was a significant decline in M/F in both German Republics overall and before reunification (p<0.0001). No decline was present after. Pre-reunification, West Germany had a lower overall M/F than East Germany (p=0.001). In conclusion, a declining M/F has been shown in many countries over the past decades. The two German Republics' M/F fell prior to reunification and the economic collapse of East Germany. Contracting societies that offer poor socioeconomic conditions (such as the communist former East Germany) may result in a decrease in M/F, but this is not reflected in the data, which show that M/F in West Germany prior to reunification was lower than in East Germany. This is not explicable with the contracting economies hypothesis; other and as yet unknown influences may have modified M/F trends anticipated by known variables.

Multifocal blue-on-yellow visual evoked potentials in early glaucoma.

PubMed

Klistorner, Alexander; Graham, Stuart L; Martins, Alessandra; Grigg, John R; Arvind, Hemamalini; Kumar, Rajesh S; James, Andrew C; Billson, Francis A

2007-09-01

To determine the sensitivity and specificity of blue-on-yellow multifocal visual evoked potentials (mfVEPs) in early glaucoma. Cross-sectional study. Fifty patients with a confirmed diagnosis of early glaucoma and 60 normal participants. Black-and-white mfVEPs and blue-on-yellow mfVEPs were recorded using the Accumap version 2.0 (ObjectiVision Pty. Ltd., Sydney, Australia). All patients also underwent achromatic standard automated perimetry (SAP). Multifocal VEP amplitude and latency values in glaucoma patients were analyzed and compared with those of the normal controls. Based on the definition of visual field defect, in the group of glaucomatous eyes with SAP defects, amplitude of blue-on-yellow mfVEP was abnormal in all 64 cases (100% sensitivity), whereas black-and-white mfVEP missed 5 cases (92.2% sensitivity). Generally, larger scotomata were noted on blue-on-yellow mfVEP compared with black-and-white mfVEP for the same eyes. There was high topographic correspondence between SAP and amplitude of blue-on-yellow mfVEP and significant (P<0.0001) correlation between them (correlation coefficient, 0.73). Abnormal amplitude was detected in 3 of 60 eyes of control subjects (95% specificity). There was, however, no correlation between visual field defect and latency delay in glaucoma patients. Although there was a significant difference between averaged latency of control and glaucoma eyes, values considerably overlapped. The blue-on-yellow mfVEP is a sensitive and specific tool for detecting early glaucoma based on amplitude analysis.

Functional assessment of the visual pathway with multifocal visual evoked potentials, and their relationship with disability in patients with multiple sclerosis.

PubMed

Blanco, Román; Pérez-Rico, Consuelo; Puertas-Muñoz, Inmaculada; Ayuso-Peralta, Lucía; Boquete, Luciano; Arévalo-Serrano, Juan

2014-02-01

To objectively evaluate the visual function, and the relationship between disability and optic nerve dysfunction, in patients with multiple sclerosis (MS) and optic neuritis (ON), using multifocal visual evoked potentials (mfVEP). This observational, cross-sectional study assessed 28 consecutive patients with clinically definite MS, according to the McDonald criteria, and 19 age-matched healthy subjects. Disability was recorded using the Expanded Disability Status Scale (EDSS) score. The patients' mfVEP were compared to their clinical, psychophysical (Humphrey perimetry) and structural (optic coherence tomography (OCT)) diagnostic test data. We observed a significant agreement between mfVEP amplitude and Humphrey perimetry/OCT in MS-ON eyes, and between mfVEP amplitude and OCT in MS but non-ON eyes. We found significant differences in EDSS score between patients with abnormal and normal mfVEP amplitudes. Abnormal mfVEP amplitude defects (from interocular and monocular probability analysis) were found in 67.9% and 73.7% of the MS-ON and MS-non-ON group eyes, respectively. Delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 70.3% and 73.7% of the MS-ON and MS-non-ON groups, respectively. We found a significant relationship between mfVEP amplitude and disease severity, as measured by EDSS score, that suggested there is a role for mfVEP amplitude as a functional biomarker of axonal loss in MS.

Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans

PubMed Central

Pritchard, Jonathan K.

2016-01-01

The site frequency spectrum (SFS) has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the “phylogenetically-conditioned SFS” or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC), combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans. PMID:27977673

High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma.

PubMed

Oda, Katsutoshi; Stokoe, David; Taketani, Yuji; McCormick, Frank

2005-12-01

The phosphatidylinositol 3'-kinase (PI3K) pathway is activated in many human cancers. In addition to inactivation of the PTEN tumor suppressor gene, mutations or amplifications of the catalytic subunit alpha of PI3K (PIK3CA) have been reported. However, the coexistence of mutations in these two genes seems exceedingly rare. As PTEN mutations occur at high frequency in endometrial carcinoma, we screened 66 primary endometrial carcinomas for mutations in the helical and catalytic domains of PIK3CA. We identified a total of 24 (36%) mutations in this gene and coexistence of PIK3CA/PTEN mutations at high frequency (26%). PIK3CA mutations were more common in tumors with PTEN mutations (17 of 37, 46%) compared with those without PTEN mutations (7 of 29, 24%). Array comparative genomic hybridization detected 3q24-qter amplification, which covers the PIK3CA gene (3q26.3), in one of nine tumors. Knocking down PTEN expression in the HEC-1B cell line, which possesses both K-Ras and PIK3CA mutations, further enhances phosphorylation of Akt (Ser473), indicating that double mutation of PIK3CA and PTEN has an additive effect on PI3K activation. Our data suggest that the PI3K pathway is extensively activated in endometrial carcinomas, and that combination of PIK3CA/PTEN alterations might play an important role in development of these tumors.

Identification of constrained cancer driver genes based on mutation timing.

PubMed

Sakoparnig, Thomas; Fried, Patrick; Beerenwinkel, Niko

2015-01-01

Cancer drivers are genomic alterations that provide cells containing them with a selective advantage over their local competitors, whereas neutral passengers do not change the somatic fitness of cells. Cancer-driving mutations are usually discriminated from passenger mutations by their higher degree of recurrence in tumor samples. However, there is increasing evidence that many additional driver mutations may exist that occur at very low frequencies among tumors. This observation has prompted alternative methods for driver detection, including finding groups of mutually exclusive mutations and incorporating prior biological knowledge about gene function or network structure. Dependencies among drivers due to epistatic interactions can also result in low mutation frequencies, but this effect has been ignored in driver detection so far. Here, we present a new computational approach for identifying genomic alterations that occur at low frequencies because they depend on other events. Unlike passengers, these constrained mutations display punctuated patterns of occurrence in time. We test this driver-passenger discrimination approach based on mutation timing in extensive simulation studies, and we apply it to cross-sectional copy number alteration (CNA) data from ovarian cancer, CNA and single-nucleotide variant (SNV) data from breast tumors and SNV data from colorectal cancer. Among the top ranked predicted drivers, we find low-frequency genes that have already been shown to be involved in carcinogenesis, as well as many new candidate drivers. The mutation timing approach is orthogonal and complementary to existing driver prediction methods. It will help identifying from cancer genome data the alterations that drive tumor progression.

Identification of Constrained Cancer Driver Genes Based on Mutation Timing

PubMed Central

Sakoparnig, Thomas; Fried, Patrick; Beerenwinkel, Niko

2015-01-01

Cancer drivers are genomic alterations that provide cells containing them with a selective advantage over their local competitors, whereas neutral passengers do not change the somatic fitness of cells. Cancer-driving mutations are usually discriminated from passenger mutations by their higher degree of recurrence in tumor samples. However, there is increasing evidence that many additional driver mutations may exist that occur at very low frequencies among tumors. This observation has prompted alternative methods for driver detection, including finding groups of mutually exclusive mutations and incorporating prior biological knowledge about gene function or network structure. Dependencies among drivers due to epistatic interactions can also result in low mutation frequencies, but this effect has been ignored in driver detection so far. Here, we present a new computational approach for identifying genomic alterations that occur at low frequencies because they depend on other events. Unlike passengers, these constrained mutations display punctuated patterns of occurrence in time. We test this driver–passenger discrimination approach based on mutation timing in extensive simulation studies, and we apply it to cross-sectional copy number alteration (CNA) data from ovarian cancer, CNA and single-nucleotide variant (SNV) data from breast tumors and SNV data from colorectal cancer. Among the top ranked predicted drivers, we find low-frequency genes that have already been shown to be involved in carcinogenesis, as well as many new candidate drivers. The mutation timing approach is orthogonal and complementary to existing driver prediction methods. It will help identifying from cancer genome data the alterations that drive tumor progression. PMID:25569148

Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients.

PubMed

Gimbrone, Nicholas T; Sarcar, Bhaswati; Gordian, Edna R; Rivera, Jason I; Lopez, Christian; Yoder, Sean J; Teer, Jamie K; Welsh, Eric A; Chiappori, Alberto A; Schabath, Matthew B; Reuther, Gary W; Dutil, Julie; Garcia, Miosotis; Ventosilla-Villanueva, Ronald; Vera-Valdivia, Luis; Yabar-Berrocal, Alejandro; Motta-Guerrero, Rodrigo; Santiago-Cardona, Pedro G; Muñoz-Antonia, Teresita; Cress, W Douglas

2017-12-01

To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from H/L patients. This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, serine/threonine kinase 11 gene [STK11], and tumor protein p53 gene [TP53]) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and correlated with ancestry, sex, smoking status, and tumor histologic type. Of the adenocarcinomas in the H/L cohort (n = 120), 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% versus 38% [p = 0.002]) and STK11 (8% versus 16% [p = 0.065]) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% versus 40% [p = 0.355]) in H/L and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p = 0.009) and may have influenced the rate of EGFR, KRAS, and STK11 mutations. Driver mutations in H/L patients with lung adenocarcinoma differ in frequency from those in NHW patients associated with their indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya.

PubMed

de Laurent, Zaydah R; Chebon, Lorna J; Ingasia, Luicer A; Akala, Hoseah M; Andagalu, Ben; Ochola-Oyier, Lynette Isabella; Kamau, Edwin

2018-05-01

The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller domain have been useful in identifying ART resistance in SEA. ART combination therapy (ACT) remains highly efficacious in the treatment of uncomplicated malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of ACT is closely monitored. Toward this effort, this study profiled the prevalence of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and in different time periods, before (pre) and after (post) the introduction of ACT as the first-line treatment of malaria. Nineteen nonsynonymous mutations were present in the pre-ACT samples ( N = 64) compared with 22 in the post-ACT samples ( N = 251). Eight of these mutations were present in both pre- and post-ACT parasites. Interestingly, seven of the shared single-nucleotide polymorphisms were at higher frequencies in the pre-ACT than the post-ACT parasites. The A578S mutation reported in SSA and the V568G mutation reported in SEA were found in both pre- and post-ACT parasites, with their frequencies declining post-ACT. D584Y and R539K mutations were found only in post-ACT parasites; changes in these codons have also been reported in SEA with different amino acids. The N585K mutation described for the first time in this study was present only in post-ACT parasites, and it was the most prevalent mutation at a frequency of 5.2%. This study showed the type, prevalence, and frequency of K13 mutations that varied based on the malaria ecological zones and also between the pre- and post-ACT time periods.

Multi-service small-cell cloud wired/wireless access network based on tunable optical frequency comb

NASA Astrophysics Data System (ADS)

Xiang, Yu; Zhou, Kun; Yang, Liu; Pan, Lei; Liao, Zhen-wan; Zhang, Qiang

2015-11-01

In this paper, we demonstrate a novel multi-service wired/wireless integrated access architecture of cloud radio access network (C-RAN) based on radio-over-fiber passive optical network (RoF-PON) system, which utilizes scalable multiple- frequency millimeter-wave (MF-MMW) generation based on tunable optical frequency comb (TOFC). In the baseband unit (BBU) pool, the generated optical comb lines are modulated into wired, RoF and WiFi/WiMAX signals, respectively. The multi-frequency RoF signals are generated by beating the optical comb line pairs in the small cell. The WiFi/WiMAX signals are demodulated after passing through the band pass filter (BPF) and band stop filter (BSF), respectively, whereas the wired signal can be received directly. The feasibility and scalability of the proposed multi-service wired/wireless integrated C-RAN are confirmed by the simulations.

Cloning and expression analysis of a new anther-specific gene CaMF4 in Capsicum annuum.

PubMed

Hao, Xuefeng; Chen, Changming; Chen, Guoju; Cao, Bihao; Lei, Jianjun

2017-03-01

Our previous study on the genic male sterile-fertile line 114AB of Capsicum annuum indicated a diversity of differentially expressed cDNA fragments in fertile and sterile lines. In this study, a transcript-derived fragment (TDF), male fertile 4 (CaMF4) was chosen for further investigation to observe that this specific fragment accumulates in the flower buds of the fertile line. The full genomic DNA sequence of CaMF4 was 894 bp in length, containing two exons and one intron, and the complete coding sequence encoded a putative 11.53 kDa protein of 109 amino acids. The derived protein of CaMF4 shared similarity with the members of PGPS/D3 protein family. The expression of CaMF4 was detected in both the flower buds at stage 8 and open flowers of the male fertile line. In contrast to this observation, expression of CaMF4 was not detected in any organs of the male sterile line. Further analysis revealed that CaMF4 was expressed particularly in anthers of the fertile line. Our results suggest that CaMF4 is an anther-specific gene and might be indispensable for anther or pollen development in C. annuum.

Frequency and type of inheritable mutations induced by γ rays in rice as revealed by whole genome sequencing.

PubMed

Li, Shan; Zheng, Yun-Chao; Cui, Hai-Rui; Fu, Hao-Wei; Shu, Qing-Yao; Huang, Jian-Zhong

Mutation breeding is based on the induction of genetic variations; hence knowledge of the frequency and type of induced mutations is of paramount importance for the design and implementation of a mutation breeding program. Although γ ray irradiation has been widely used since the 1960s in the breeding of about 200 economically important plant species, molecular elucidation of its genetic effects has so far been achieved largely by analysis of target genes or genomic regions. In the present study, the whole genomes of six γ-irradiated M 2 rice plants were sequenced; a total of 144-188 million high-quality (Q>20) reads were generated for each M 2 plant, resulting in genome coverage of >45 times for each plant. Single base substitution (SBS) and short insertion/deletion (Indel) mutations were detected at the average frequency of 7.5×10 -6 -9.8×10 -6 in the six M 2 rice plants (SBS being about 4 times more frequent than Indels). Structural and copy number variations, though less frequent than SBS and Indel, were also identified and validated. The mutations were scattered in all genomic regions across 12 rice chromosomes without apparent hotspots. The present study is the first genome-wide single-nucleotide resolution study on the feature and frequency of γ irradiation-induced mutations in a seed propagated crop; the findings are of practical importance for mutation breeding of rice and other crop species.

47 CFR 2.101 - Frequency and wavelength bands.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Myriametric waves B.Mam 5 LF 30 to 300 kHz Kilometric waves B.km 6 MF 300 to 3 000 kHz Hectometric waves B.hm 7 HF 3 to 30 MHz Decametric waves B.dam 8 VHF 30 to 300 MHz Metric waves B.m 9 UHF 300 to 3 000 MHz Decimetric waves B.dm 10 SHF 3 to 30 GHz Centimetric waves B.cm 11 EHF 30 to 300 GHz Millimetric waves B.mm...

47 CFR 2.101 - Frequency and wavelength bands.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Metric abbreviations for the bands 4 VLF 3 to 30 kHz Myriametric waves B.Mam 5 LF 30 to 300 kHz Kilometric waves B.km 6 MF 300 to 3 000 kHz Hectometric waves B.hm 7 HF 3 to 30 MHz Decametric waves B.dam 8 VHF 30 to 300 MHz Metric waves B.m 9 UHF 300 to 3 000 MHz Decimetric waves B.dm 10 SHF 3 to 30 GHz...

47 CFR 2.101 - Frequency and wavelength bands.

Code of Federal Regulations, 2011 CFR

2011-10-01

... kHz Myriametric waves B.Mam 5 LF 30 to 300 kHz Kilometric waves B.km 6 MF 300 to 3 000 kHz Hectometric waves B.hm 7 HF 3 to 30 MHz Decametric waves B.dam 8 VHF 30 to 300 MHz Metric waves B.m 9 UHF 300 to 3 000 MHz Decimetric waves B.dm 10 SHF 3 to 30 GHz Centimetric waves B.cm 11 EHF 30 to 300 GHz...

47 CFR 2.101 - Frequency and wavelength bands.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Myriametric waves B.Mam 5 LF 30 to 300 kHz Kilometric waves B.km 6 MF 300 to 3 000 kHz Hectometric waves B.hm 7 HF 3 to 30 MHz Decametric waves B.dam 8 VHF 30 to 300 MHz Metric waves B.m 9 UHF 300 to 3 000 MHz Decimetric waves B.dm 10 SHF 3 to 30 GHz Centimetric waves B.cm 11 EHF 30 to 300 GHz Millimetric waves B.mm...