tbuckley/cabot-search huggingface dataset:
The Platypus Is in Its Place: Nuclear Genes and Indels Confirm the Sister Group Relation of Monotremes and Therians
Authors: Teun van Rheede, Trijntje Bastiaans, David N. Boone, S. Blair Hedges, Wilfried W. de Jong, Ole Madsen
Journal: Molecular Biology and Evolution (2005)

Morphological data supports monotremes as the sister group of Theria (extant marsupials + eutherians), but phylogenetic analyses of 12 mitochondrial protein-coding genes have strongly supported the grouping of monotremes with marsupials: the Marsupionta hypothesis. Various nuclear genes tend to support Theria, but a comprehensive study of long concatenated sequences and broad taxon sampling is lacking. We therefore determined sequences from six nuclear genes and obtained additional sequences from the databases to create two large and independent nuclear data sets. One (data set I) emphasized taxon sampling and comprised five genes, with a concatenated length of 2,793 bp, from 21 species (two monotremes, six marsupials, nine placentals, and four outgroups). The other (data set II) emphasized gene sampling and comprised eight genes and three proteins, with a concatenated length of 10,773 bp or 3,669 amino acids, from five taxa (a monotreme, a marsupial, a rodent, human, and chicken). Both data sets were analyzed by parsimony, minimum evolution, maximum likelihood, and Bayesian methods using various models and data partitions. Data set I gave bootstrap support values for Theria between 55% and 100%, while support for Marsupionta was at most 12.3%. Taking base compositional bias into account generally increased the support for Theria. Data set II exclusively supported Theria, with the highest possible values and significantly rejected Marsupionta. Independent phylogenetic evidence in support of Theria was obtained from two single amino acid deletions and one insertion, while no supporting insertions and deletions were found for Marsupionta. On the basis of our data sets, the time of divergence between Monotremata and Theria was estimated at 231–217 MYA and between Marsupialia and Eutheria at 193–186 MYA. The morphological evidence for a basal position of Monotremata, well separated from Theria, is thus fully supported by the available molecular data from nuclear genes.
Guidelines for Exposure Assessment in Health Risk Studies Following a Nuclear Reactor Accident
Authors: André Bouville, Martha S. Linet, Maureen Hatch, Kiyohiko Mabuchi, Steven L. Simon
Journal: Environmental Health Perspectives (2013)

Worldwide concerns regarding health effects after the Chernobyl and Fukushima nuclear power plant accidents indicate a clear need to identify short- and long-term health impacts that might result from accidents in the future. Fundamental to addressing this problem are reliable and accurate radiation dose estimates for the affected populations. The available guidance for activities following nuclear accidents is limited with regard to strategies for dose assessment in health risk studies.Here we propose a comprehensive systematic approach to estimating radiation doses for the evaluation of health risks resulting from a nuclear power plant accident, reflected in a set of seven guidelines.Four major nuclear reactor accidents have occurred during the history of nuclear power production. The circumstances leading to these accidents were varied, as were the magnitude of the releases of radioactive materials, the pathways by which persons were exposed, the data collected afterward, and the lifestyle factors and dietary consumption that played an important role in the associated radiation exposure of the affected populations. Accidents involving nuclear reactors may occur in the future under a variety of conditions. The guidelines we recommend here are intended to facilitate obtaining reliable dose estimations for a range of different exposure conditions. We recognize that full implementation of the proposed approach may not always be feasible because of other priorities during the nuclear accident emergency and because of limited resources in manpower and equipment.The proposed approach can serve as a basis to optimize the value of radiation dose reconstruction following a nuclear reactor accident.
Glutamine in parenteral nutrition: more food for thought
Authors: M ELIA
Journal: Gut (1999)

See article on page 82 

Until recently glutamine had not been included in commercial parenteral nutrition solutions. This is because of concerns about its spontaneous degradation, which results in the formation of pyroglutamic acid and ammonia. However, the degradation rate is slower than previously thought, especially in dextrose containing parenteral nutrition solutions.1 2 Therefore, parenteral nutrition solutions containing free glutamine can be stored at 4°C for at least a few days before clinical use. The study by Powell-Tuck et al (see page 82) is one of a handful of studies that has included free glutamine in parenteral nutrition solutions. Stable synthetic glutamine containing dipeptides are also available as an alternative source of glutamine. In considering how much glutamine should be added to parenteral nutrition solutions it is useful to refer to the normal dietary intake. Surprisingly, the quantities of glutamine in normal diets are not accurately known because food tables usually report glutamine and glutamate in combination (glutamine is liberated during hydrolysis of proteins and is converted to glutamate). However, it is estimated that roughly 5 g glutamine are ingested daily by healthy people, and a similar amount is probably delivered by enteral tube feeds. In Powell-Tuck et al ’s study 20 g glutamine was …
High prevalence of osteoarthritis 14 years after an anterior cruciate ligament tear in male soccer players: a study of radiographic and patient relevant outcomes
Authors: A von Porat, E M Roos, H Roos
Journal: British Journal of Sports Medicine (2004)

Objective: To identify the consequences of an anterior cruciate ligament (ACL) tear in a cohort of male soccer players 14 years after the initial injury with respect to radiographic knee osteoarthritis and patient relevant outcomes.

Methods: Of 219 male soccer players with an …
Maternal Glucose Tolerance in Pregnancy Affects Fetal Insulin Sensitivity
Authors: Zhong-Cheng Luo, Edgard Delvin, William D. Fraser, Francois Audibert, Cheri I. Deal, Pierre Julien, Isabelle Girard, Roberta Shear, Emile Levy, Anne-Monique Nuyt
Journal: Diabetes Care (2010)

OBJECTIVE Offspring of mothers with impaired glucose tolerance are far more likely to develop type 2 diabetes. We tested the hypothesis that maternal glucose tolerance in pregnancy affects fetal insulin sensitivity or β-cell function. RESEARCH DESIGN AND METHODS In a prospective singleton pregnancy cohort study, we analyzed glucose, insulin, and proinsulin concentrations in maternal blood at the 50-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation and in venous cord blood (n = 248). The cord blood glucose-to-insulin ratio and proinsulin concentration were used as indicators of fetal insulin sensitivity and the proinsulin-to-insulin ratio was used as an indicator of fetal β-cell function. RESULTS Higher OGTT blood glucose levels were associated with significantly lower cord plasma glucose-to-insulin ratios (r = −0.31, P &amp;lt; 0.001) and higher proinsulin concentrations (r = 0.31, P &amp;lt; 0.001) but not with proinsulin-to-insulin ratios. In a comparison of gestational diabetic (n = 26) versus euglycemic pregnancy, cord blood glucose-to-insulin ratios were substantially lower (geometric mean 10.1 vs. 20.0 mg/dl/μU/ml; P &amp;lt; 0.001), whereas proinsulin concentrations were much higher (24.4 vs. 13.8 pmol/l; P &amp;lt; 0.001), despite similar cord blood glucose concentrations indicating adequate management of diabetes. The differences remained significant after controlling for prepregnancy and fetal adiposity, family history of diabetes, gestational age, and other potential confounders. Significant changes in the glucose-to-insulin ratio and proinsulin concentration were also observed in obese (n = 31) mothers, but the differences became not statistically significant after adjustment for maternal glucose tolerance and fetal adiposity. CONCLUSIONS Maternal glucose intolerance may impair fetal insulin sensitivity (but not β-cell function) and consequently “program” the susceptibility to type 2 diabetes.
Elucidating the Function of Secreted Maspin: Inhibiting Cathepsin D–Mediated Matrix Degradation
Authors: Zhila Khalkhali-Ellis, Mary J.C. Hendrix
Journal: Cancer Research (2007)

Abstract Cellular interaction with the extracellular milieu plays a significant role in normal biological and pathologic processes. Excessive degradation of basement membrane matrix by proteolytic enzymes is a hallmark of tumor invasion and metastasis, and aspartyl proteinase cathepsin D is implicated as a major contributor to this process. Maspin, a non-inhibitory serpin, plays an important role in mammary gland development and remodeling. Expression of Maspin is decreased in primary tumors and lost in metastatic lesions. Maspin is mostly cytoplasmic and is partially secreted; however, the fate and function of secreted Maspin has remained mostly unexplored. We hypothesized that secreted Maspin is incorporated into the matrix deposited by normal mammary epithelial cells and thus could play a critical role in cathepsin D–mediated matrix degradation and remodeling of mammary tissue. In the absence of Maspin, as is the case with most cancer cells, matrix degradation proceeds unrestricted, thus facilitating the progression to metastasis. To test this, we employed an in vitro model where gels containing both types I and IV collagen were preconditioned with normal mammary epithelial cells to allow the incorporation of secreted Maspin. This conditioned matrix was used to examine cathepsin D–mediated collagen degradation by human breast cancer cell lines. Our results indicate that secretion of Maspin and its deposition into the extracellular milieu play an important role in matrix degradation. In this capacity, Maspin could potentially regulate mammary tissue remodeling occurring under normal and pathologic conditions. In addition, these findings could have a potential effect on future therapeutic intervention strategies for breast cancer. [Cancer Res 2007;67(8):3535–9]
THE RELATIONSHIP BETWEEN FORMAL AND INFORMAL PHYSICAL ACTIVITY AND THE BODY MASS INDEX
Authors: M Peralta, A Marques
Journal: British Journal of Sports Medicine (2013)

We analysed the relationship between formal and informal physical activity (PA) and the body mass index (BMI) in children. The participants of this study were 1369 boys (14±3 y) and 1297 girls (13±3 y), with ages between 10 and 19 years old. Data was collected by the application of a questionnaire about formal and informal PA. Weight and height were self-reported by the subjects and used to calculate the BMI. For data analyses <i>t test</i>, to independents samples, and <i>X</i><sup>2</sup> were used. 64% of the boys and 49% of the girls reported participation in formal PA (<i>X</i><sup>2</sup>(1)=67.217, <i>p</i>&lt;0.001). Regarding the informal PA, 57% of the boys and 42% of the girls reported participation (<i>X</i><sup>2</sup>(1)=61.338, <i>p</i>&lt;0.001). The mean value of BMI for boys was 21 while girls were 20. Boys who reported participation in formal PA had a lower value of BMI than boys that did not (20.3 vs. 21.0: <i>t</i>(1136)=2.718, <i>p</i>=0.007), the same was verified for girls (19.7 vs. 20.3: <i>t</i>(1059)=3.376, <i>p</i>=0.001). On the other hand, significant differences between informal PA and BMI were not found in both genders. A relationship between formal PA and BMI was verified. However, the same did not happen to informal PA and BMI. These results suggests that formal PA must be encouraged for children, as it could be a strategy to fight pre-obesity and obesity.
Granulomatous synovialitis with erosions in the shoulder joint: a rare case of polyarthritis caused by Mycobacterium kansasii
Authors: K Loddenkemper
Journal: Annals of the Rheumatic Diseases (2005)

We cannot, however, rule out the possibility that an association with other SNPs exists in these genes.Furthermore, we also acknowledge that because our sample size is limited we are unlikely to detect small differences in allele frequencies.
Cross-sectional association between smoking depictions in films and adolescent tobacco use nested in a British cohort study
Authors: A. E. Waylen, S. D. Leary, A. R. Ness, S. E. Tanski, J. D. Sargent
Journal: Thorax (2011)

<h3>Objective</h3> To assess associations between exposure to smoking depictions in films and adolescent tobacco use in a British population cohort. <h3>Methods</h3> Data on exposure to smoking in films and smoking behaviour were collected from 5166 15-year-old adolescents in the UK. Main outcome measures were smoking initiation (ever tried a cigarette) and current smoking status. Social, family and behavioural factors were adjusted for, together with alcohol use and peer smoking as potential mediators. Data from all existing cross-sectional studies examining the effects of exposure to smoking in films were summarised in a meta-analysis. <h3>Results</h3> Higher exposure to smoking in films was associated with a dose-response increase in the risk of smoking initiation even after adjusting for confounders. Adolescents in the highest exposure quartile were 1.73 (95% CI 1.55 to 1.93) times (RR) more likely to initiate smoking than those in the lowest quartile. They were more likely to report current smoking after adjusting for social and familial factors (RR 1.47 (95% CI 1.07 to 2.02)), but the association attenuated after including behavioural factors (RR 1.34 (95% CI 0.95 to 1.87)). The meta-analysis shows that, after aggregation of all relevant data, viewing smoking in films increases the risk of smoking onset by over 100% (combined RR 2.13 (95% CI 1.76 to 2.57)) and the risk of current or established smoking behaviour by 68% (combined RR 1.68 (95% CI 0.40 to 2.01)). <h3>Conclusions</h3> This study provides evidence that adolescents in the UK and elsewhere who are exposed to smoking depictions in films are more likely to initiate smoking. Given the association between smoking and poor health outcomes, these data justify a review of film ratings.
Gene expression analysis reveals<i>HBP1</i>as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22
Authors: E V A Raine, N Wreglesworth, A W Dodd, L N Reynard, J Loughlin
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> An osteoarthritis (OA) susceptibility locus has been mapped to chromosome 7q22, to a region of high-linkage disequilibrium encompassing six genes: <i>PRKAR2B, HBP1, COG5, GPR22, DUS4L</i> and <i>BCAP29</i>. The authors assessed whether these genes were subject to <i>cis</i>-acting regulatory polymorphisms that are active in joint tissues and which could contribute to the association signal. <h3>Methods</h3> Using joint tissues from 156 patients with OA, and control cartilage from 25 patients who had neck of the femur fractures, the authors measured the overall gene expression by quantitative PCR and the allelic expression of the genes, using an assay that can distinguish mRNA output from each allele of a transcript single nucleotide polymorphism. <h3>Results</h3> Five of the genes were expressed in joint tissues, the exception being <i>GPR22</i>, which the authors could not detect. In OA cartilage compared with control cartilage, significantly reduced expression levels were observed for these five genes. Carriers of the OA-associated alleles showed a significant reduction in expression of <i>HBP1</i> in cartilage (p=0.0002) and synovium (p=0.02), and of <i>DUS4L</i> in fat pad (p=0.04). <i>HBP1</i> and <i>DUS4L</i> also demonstrated allelic expression imbalance across a range of different joint tissues, with carriers of the associated allele showing an <i>HBP1</i> allelic expression imbalance profile that was significantly different from non-carriers (p=0.008). <h3>Conclusion</h3> <i>Cis</i>-acting regulatory polymorphisms acting on <i>HBP1</i> contribute to the OA association signal at chromosome 7q22. <i>HBP1</i> codes for a transcription factor and studies by the authors have enabled them to prioritise this gene for further investigation.
Bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improve ex vivo peritoneal macrophage TNFalpha secretion.
Authors: R K MacKenzie, C J Holmes, A Moseley, J P Jenkins, J D Williams, G A Coles, D Faict, N Topley
Journal: Journal of the American Society of Nephrology (1998)

Peritoneal macrophage (PMO) function was examined ex vivo after their in vivo exposure to either acidic, lactate-buffered solutions (PD4; 40 mM lactate, pH 5.2), bicarbonate/lactate-buffered solution (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3), or bicarbonate-buffered solution (TB; 38 mM bicarbonate, pH 7.3), containing either 1.36 or 3.86% glucose. Initial experiments demonstrated that tumor necrosis factor-alpha (TNFalpha) release (assessed by TNF-direct immunoassay [DIA]) from PMO isolated from the peritoneal cavities of patients exposed to conventional fluid (PD4 1.36% glucose) was lowest after 30 min of intraperitoneal dwell (3591+/-1200 versus 28,946+/-9359 for 240-min dwell [pg/ml], n=5, P < 0.05). Five patients were exposed on 3 successive days to PD4, TBL, and TB for 30-min acute dwells containing 1.36% glucose in the first week and 3.86% glucose during the second. PMO TNFalpha release was assessed after ex vitro exposure to lipopolysaccharide (LPS). Exposure of PMO to TBL or TB (1.36% glucose) resulted in a significant increase in the generation of TNFalpha (pg/2 X 10(6) PMO) compared with PD4. TBL: 68,659+/-35,633, TB: 53,682+/-26,536 versus PD4 17,107+/-8996 (LPS 1.0 ng/ml, n=5 patients, P=0.043 versus PD4 for both). PMO that were recovered from PD4 and TB dwells (3.86% glucose) showed no significant difference in TNFalpha secretion (21,661+/-6934 and 23,923+/-9147, respectively). In contrast, exposure to TBL resulted in a significant increase (41,846+/-11,471) compared with PD4 (LPS 1.0 ng/ml, n=5 patients, P=0.043). These data demonstrate enhanced PMO function after in vivo exposure to bicarbonate- and bicarbonate/lactate-buffered solutions. This response was sustained in TBL alone at the highest glucose concentrations. These results suggest that the newer solutions, and particularly bicarbonate/lactate, might improve host defense status in peritoneal dialysis patients.
Emergence of hepatitis B virus S gene mutants in patients experiencing hepatitis B surface antigen seroconversion after peginterferon therapy
Authors: Chao-Wei Hsu, Chau-Ting Yeh
Journal: Hepatology (2011)

Abstract: With anti–hepatitis B virus (anti-HBV) therapy using peginterferon, the seroconversion of hepatitis B surface antigen (HBsAg), which is considered a cure of the disease, can be achieved in a small percentage of patients. Eight of 245 consecutive patients (3.27%) with chronic hepatitis B who received peginterferon therapy at our center achieved HBsAg seroclearance. Surprisingly, two of the eight patients remained viremic according to standard HBV DNA assays. The coding regions of the HBV pre-S/S gene, which were derived from serial serum samples, were analyzed. Site-directed mutagenesis experimentation was performed to verify the phenotypic alterations in Huh-7 cells. In patient 1, an sT125A mutant developed during the HBsAg-negative stage and constituted 11.2% of the viral population. The HBV DNA level was 2.73 × 10 4 IU/mL at the time of detection. This mutant was not detectable in the HBsAg-positive stages. A phenotypic study of Huh-7 cells showed a significant reduction of antigenicity. In patient 2, an sW74* truncation mutation was found during the HBsAg-negative stage and constituted 83.1% of the viral population. The HBV DNA level was 4.12 × 10 4 IU/mL at the time of detection. A phenotypic study of Huh-7 cells showed a complete loss of antigenicity. Patient 2 subsequently experienced an episode of hepatitis relapse 7 months after the end of treatment and was negative for HBsAg throughout the hepatitis flare. Conclusion: During antiviral therapy with peginterferon, the achievement of HBsAg seroconversion does not necessarily indicate viral eradication. The emergence of S gene mutants is another possibility, and a relapse with HBsAg-negative hepatitis can occur. (Hepatology 2011;)
Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease
Authors: Douglas C. Dean, Beth A. Jerskey, Kewei Chen, Hillary Protas, Pradeep Thiyyagura, Auttawat Roontiva, Jonathan O'Muircheartaigh, Holly Dirks, Nicole Waskiewicz, Katie Lehman, Ashley L. Siniard, Mari N. Turk, Xue Hua, Sarah K. Madsen, Paul M. Thompson, Adam S. Fleisher, Matthew J. Huentelman, Sean C. L. Deoni, Eric M. Reiman
Journal: JAMA Neurology (2013)

Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons). Infant ε4 carriers also exhibited an attenuated relationship between MWF and age in posterior white matter regions. While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies.