tbuckley/cabot-search huggingface dataset:
Predictors of sustained response to alpha interferon therapy in chronic hepatitis C
Authors: Michèle Martinot-Peignoux, Nathalie Boyer, Michèle Pouteau, Corinne Castelnau, Nathalie Giuily, Véronique Duchatelle, Anne Aupérin, Claude Degott, Jean-Pierre Benhamou, Serge Erlinger, Patrick Marcellin
Journal: Journal of Hepatology (1998)
Identifying G-protein Coupled Receptors Using Weighted Levenshtein Distance and Nearest Neighbor Method
Authors: Jian-Hua Xu
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract G-protein coupled receptors (GPCRs) are a class of seven-helix transmembrane proteins that have been used in bioinformatics as the targets to facilitate drug discovery for human diseases. Although thousands of GPCR sequences have been collected, the ligand specificity of many GPCRs is still unknown and only one crystal structure of the rhodopsin-like family has been solved. Therefore, identifying GPCR types only from sequence data has become an important research issue. In this study, a novel technique for identifying GPCR types based on the weighted Levenshtein distance between two receptor sequences and the nearest neighbor method (NNM) is introduced, which can deal with receptor sequences with different lengths directly. In our experiments for classifying four classes (acetylcholine, adrenoceptor, dopamine, and serotonin) of the rhodopsin-like family of GPCRs, the error rates from the leave-one-out procedure and the leave-half-out procedure were 0.62% and 1.24%, respectively. These results are prior to those of the covariant discriminant algorithm, the support vector machine method, and the NNM with Euclidean distance.
Lessons from Mouse Mutants of Epithelial Sodium Channel and Its Regulatory Proteins
Authors: Edith Hummler, Volker Vallon
Journal: Journal of the American Society of Nephrology (2005)

The use of gene-modified mouse models allows the experimental in vivo analysis of specific gene defects at the level of target cells. With respect to the epithelial sodium channel and some of its regulatory proteins, gene-modified models that control gene defects in a time- and tissue-dependent conditional or constitutive manner have been generated. The combination of molecular and physiologic approaches in these mouse models increases the understanding of the complex regulation and the cell signaling cascades involved in Na(+) transport in target cells and may ultimately provide new insights into the pathophysiology of renal Na(+) retention and BP regulation. This review summarizes and discusses the gene-targeting approaches that have been applied to the epithelial sodium channel and its regulatory proteins.
Activation of B lymphocytes by monovalent anti-Lyb-2 antibodies.
Authors: B Subbarao, D E Mosier
Journal: The Journal of Experimental Medicine (1984)

Although activation of B lymphocytes by antigen or anti-Ig antibody has been shown to require cross-linking of surface Ig molecules, cross-linking is not necessary for B cell activation by anti-Lyb-2 monoclonal antibody (MAb). Monovalent Fab' fragments of anti-Lyb-2 MAb are as effective as the intact antibody in inducing blast cell transformation of small B cells and B cell proliferation in the apparent absence of T cells and adherent cells. In the presence of factors from T cells, B cells activated by Fab' fragments of anti-Lyb-2 MAb were induced to mature into Ig-secreting cells. Since monovalent Fab' fragments probably cannot induce receptor aggregation, it appears that receptor occupancy is sufficient to induce B cell activation with anti-Lyb-2 MAb.
Adolescent Depressive Symptoms as Predictors of Adult Depression: Moodiness or Mood Disorder?
Authors: Daniel S. Pine, Elizabeth Cohen, Patricia Cohen, Judith Brook
Journal: American Journal of Psychiatry (1999)

The authors' goal was to examine the relationship between subclinical depressive symptoms in adolescence and major depressive episodes in adulthood.An epidemiologic sample of 776 young people received psychiatric assessments in 1983, 1985, and 1992. Among adolescents not meeting criteria for major depression, the authors estimated the magnitude of the association between subclinical adolescent depressive symptoms and adult major depression.Symptoms of major depression in adolescence strongly predicted an adult episode of major depression: having depressive symptoms more than two-standard-deviations above the mean in number predicted a two-fold to three-fold greater risk for an adult major depressive episode.Symptoms of depression in adolescence strongly predict an episode of major depression in adulthood, even among adolescents without major depression.
Baroreceptor function and changes in strain sensitivity in normotensive and spontaneously hypertensive rats.
Authors: M C Andresen, S Kuraoka, A M Brown
Journal: Circulation Research (1980)

Baroreceptor resetting during hypertension has been attributed to a reduction in the distensibility of the vessel wall in which the receptors are located.According to this hypothesis, a simple increase in pressure is all that is required to overcome the increase in vessel wall stiffness.However, previous work from our laboratory suggested a more complicated situation.Measurements of both vessel wall mechanical properties and baroreceptor discharge characteristics in spontaneously hypertensive rats (SHR) showed that distortion thresholds for the receptors also undergo changes.Here we have examined the time course of resetting, measuring both aortic distensibility and baroreceptor properties in SHR and mormotensive Wistar-Kyoto rats (WKY) from 5 to 30 weeks in age.An in vitro aortic arch-aortic nerve preparation was used.We found that for a given pressure the aortic radii of WKY were increasing much more rapidly than the aortic radii for SHR and, beyond 5 weeks of age, were much more distensible.The lower distensibility in SHR was accompanied by increased wall thickness.The discharge characteristics of single baroreceptors were expressed in terms of both pressure and distortion or circumferential wall strain.The change in distensibility of WKY aortas from 5 to 30 weeks was suitably matched by an increase in the strain threshold for discharge of WKY baroreceptors resulting in a constant pressure threshold for discharge.The lower distensibility of SHR aortas was accompanied by lower threshold strains in SHR baroreceptors, but the changes were not suitably matched, and progressive resetting of SHR baroreceptors to higher threshold pressures occurred.The two sets of receptors appear to be different as early as 5 weeks of age when blood pressures are similar and, futhermore, these differences are accentuated by age and hypertension.CircRes 47: [821][822][823][824][825][826][827][828] 1980 ARTERIAL baroreceptor function is abnormal in all forms of established hypertension; greater distending pressures are required to activate the receptors, and the suprathreshold sensitivity to pressure changes is reduced (McCubbin et al., 1956).Since distensibility of the vessel wall in which the receptors are located is reduced at this time, the resetting of baroreceptor function to higher operating pressures has been attributed to the confinement or "splinting" of receptors within a stiffer vessel (Angell-James, 1973;Nosaka and Wang, 1972;Sapru and Wang, 1976; Kedzi, 1976;Jones, 1977).Investigations of the time course of baroreflex resetting during experimental renal hypertension indicate that the threshold pressure and/or sensitivity for reflex activation can shift within hours to days of the onset of hypertension (Krieger, 1970; Jones and Floras, in press).These changes are
Waking hallucinations could correspond to a mild form of dreaming sleep stage hallucinatory activity
Authors: Claude Gottesmann
Journal: Behavioral and Brain Sciences (2005)

There are strong resemblances between the neurobiological characteristics of hallucinations occurring in the particular case of schizophrenia and the hallucinatory activity observed during the rapid-eye-movement (dreaming) sleep stage: the same prefrontal dorsolateral deactivation; forebrain disconnectivity and disinhibition; sensory deprivation; and acetylcholine, monoamine, and glutamate modifications.
Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis
Authors: Judith M. de Bont, Johan M. Kros, Monique M.C.J. Passier, Roel E. Reddingius, Peter A.E. Sillevis Smitt, Theo M. Luider, Monique L. den Boer, Rob Pieters
Journal: Neuro-Oncology (2008)

The objective of this study was to identify differentially expressed and prognostically important genes in pediatric medulloblastoma and pediatric ependymoma by Affymetrix microarray analysis. Among the most discriminative genes, three members of the SOX transcription factor family were differentially expressed. Both SOX4 and SOX11 were significantly overexpressed in medulloblastoma (median, 11-fold and 5-fold, respectively) compared with ependymoma and normal cerebellum. SOX9 had greater expression in ependymoma (median, 16-fold) compared with normal cerebellum and medulloblastoma (p<0.001 for all comparisons). The differential expression of the SOX genes was confirmed at the protein level by immunohistochemical analysis. Survival analysis of the most discriminative probe sets for each subgroup showed that 35 and 13 probe sets were predictive of survival in patients with medulloblastoma and ependymoma, respectively. There was a trend toward better survival with increasing SOX4 expression in medulloblastoma. SOX9 expression was predictive for favorable outcome in ependymoma. The mRNA levels of BCAT1, a mediator of amino acid breakdown, were higher (median, 15-fold) in medulloblastoma patients with metastases compared with those without metastasized disease (p<0.01). However, the correlation between BCAT1 expression and metastatic medulloblastoma could not be confirmed at the protein level. The potential prognostic effect of the genes associated with outcome should be evaluated in ongoing studies using larger groups of patients. Furthermore, our findings support further analysis of the functional properties of the selected genes, especially SOX4 and BCAT1 for medulloblastoma and SOX9 for ependymoma, to evaluate the use of these genes as potential tumor markers, prognostic markers, and drug targets in pediatric brain tumors.
Evidence for an Alzheimer Disease Susceptibility Locus on Chromosome 12 and for Further Locus Heterogeneity
Authors: Ekaterina Rogaeva, Smita Premkumar, Youqiang Song, Sandro Sorbi, Nicholas Brindle, Andrew Paterson, Ranjan Duara, Georges Levesque, Gang Yu, Masaki Nishimura, Masaki Ikeda, Colleen O'Toole, Toshitaka Kawarai, Ricardo Jorge, Daniel Vilarino, Amalia C. Bruni, Lindsay A. Farrer, Peter H. St. George-Hyslop
Journal: JAMA (1998)

Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, and a recent study has suggested a locus on chromosome 12.To confirm or refute the existence of a familial AD susceptibility locus on chromosome 12 in an independent sample of familial AD cases.Retrospective cohort study. DNA data for 6 chromosome 12 genetic markers were evaluated using parametric lod score and nonparametric linkage methods and linkage heterogeneity tests. The latter include the admixture test of homogeneity in the total group of families and the predivided sample test in families stratified by the presence or absence of an apolipoprotein E (APOE) epsilon4 allele among affected members. Parametric analyses were repeated assuming autosomal dominant inheritance of AD and either age- and sex-dependent penetrance or zero penetrance for the analysis of unaffected relatives.Clinical populations in the continental United States, Canada, Argentina, and Italy.Fifty-three white families composed of multiple members affected with AD, from whom DNA samples were obtained from 173 patients with AD whose conditions were diagnosed using established criteria and from 146 nondemented relatives.Presence of an APOE epsilon4 allele among affected family members.Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families. However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1). The estimated proportion of linked families within the 53 families examined varied between 0.40 and 0.65, depending on the genetic model assumed and APOE status. The precise location of the AD gene could not be determined, but includes the entire region suggested previously. Nonparametric linkage analysis confirmed linkage to chromosome 12 with the strongest evidence at D12S96 (P<.001).Our data provide independent confirmation of the existence of an AD susceptibility locus on chromosome 12 and suggest the existence of AD susceptibility genes on other chromosomes. Screening a larger set of families with additional chromosome markers will be necessary for identifying the chromosome 12 AD gene.
AMSSM: leaders in primary care sports and exercise medicine
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2012)

Obama, Lincoln, Elizabeth I, Merkel, Sarkozy, Streep/Thatcher, Papandreou, Berlusconi, Gadaffi, Henry VIII. Leadership is in the news and leadership influences outcomes. Primary care sports and exercise medicine has benefitted from transformational leadership in certain countries. Building a national primary care sports and exercise medicine body with 1500 or more members requires a guiding coalition1 to focus on the common, compelling goal.2 It takes a community and it takes a professional lifetime. If quasi-leaders cannot subvert their personal ambition to genuinely support each other to benefit, the collective things go awry.3 Underperformance has many faces.

The American Medical Society for Sports Medicine (AMSSM) has benefitted from 21 years of transformational leadership. The result is a brilliantly supportive milieu for American primary care physicians and fellows which means better outcomes for patients. Lives saved. AMSSM is a jewel in the global primary care sports and exercise medicine crown. In a free, very competitive, market, US primary care physicians vote with their feet for AMSSM. Membership is accelerating, conference attendance climbs year over year and balance sheets point to sustainability. The organisation may serve as a role model, a ‘success story’ for some, and as a result AMSSM is now able to offer terrific value for international physicians who wish to join. More on that over the page.

1. Facebook effect – 845 million people cannot be wrong. People join Facebook to share common interests – it provides a forum. That 2000+ year old Roman word, forum, highlights the need to gather. No woman or man is an island. AMSSM is the nationwide sports and exercise medicine interest group exclusively dedicated to US primary care sports physicians. No need to get primary care on the agenda. Primary care sports and exercise medicine …
Gas exchange at extreme altitude: results from the British 40th Anniversary Everest Expedition
Authors: AJ Peacock, PL Jones
Journal: European Respiratory Journal (1997)

Since Messner and Habeler climbed to the summit of Mount Everest (8,848 m) without oxygen in 1978, there has been controversy between scientists trying to explain this feat. Field studies have suggested better respiratory performance than that found during a simulated climb in a hypobaric chamber, but the lack of data at extreme altitude has hampered the debate. We measured arterial oxygen saturation (Sa,O2) and alveolar partial pressure of oxygen (PA,O2) in nine subjects as they climbed from 3,500 to 8,000 m. Four of the climbers reached 8,000 m and one reached the summit. We also tested the effects of breathing supplementary oxygen on Sa,O2 at 6,550 and 8,000 m. At all altitudes tested, we found that both PA,O2 and Sa,O2 were higher than expected from low pressure chamber studies. We also found that standard rates of supplementary oxygen (2 L x min(-1)) were insufficient to restore Sa,O2 above 90% at 8,000 m. The respiratory performance of climbers at extreme altitude is better than expected from sea-level chamber studies, which may, in part, explain why humans can reach the summit (8,848 m) without added oxygen. The better performance is likely to be due to more appropriate acclimatization.
Genome Expansion and Differential Expression of Amino Acid Transporters at the Aphid/Buchnera Symbiotic Interface
Authors: D. R. G. Price, R. P. Duncan, S. Shigenobu, A. C. C. Wilson
Journal: Molecular Biology and Evolution (2011)

In insects, some of the most ecologically important symbioses are nutritional symbioses that provide hosts with novel traits and thereby facilitate exploitation of otherwise inaccessible niches. One such symbiosis is the ancient obligate intracellular symbiosis of aphids with the γ-proteobacteria, Buchnera aphidicola. Although the nutritional basis of the aphid/Buchnera symbiosis is well understood, the processes and structures that mediate the intimate interactions of symbiotic partners remain uncharacterized. Here, using a de novo approach, we characterize the complement of 40 amino acid polyamine organocation (APC) superfamily member amino acid transporters (AATs) encoded in the genome of the pea aphid, Acyrthosiphon pisum. We find that the A. pisum APC superfamily is characterized by extensive gene duplications such that A. pisum has more APC superfamily transporters than other fully sequenced insects, including a ten paralog aphid-specific expansion of the APC transporter slimfast. Detailed expression analysis of 17 transporters selected on the basis of their phylogenetic relationship to five AATs identified in an earlier bacteriocyte expressed sequence tag study distinguished a subset of eight transporters that have been recruited for amino acid transport in bacteriocyte cells at the symbiotic interface. These eight transporters include transporters that are highly expressed and/or highly enriched in bacteriocytes and intriguingly, the four AATs that show bacteriocyte-enriched expression are all members of gene family expansions, whereas three of the four that are highly expressed but not enriched in bacteriocytes retain one-to-one orthology with transporters in other genomes. Finally, analysis of evolutionary rates within the large A. pisum slimfast expansion demonstrated increased rates of molecular evolution coinciding with two major shifts in expression: 1) a loss of gut expression and possibly a gain of bacteriocyte expression and 2) loss of expression in all surveyed tissues in asexual females. Taken together, our characterization of nutrient AATs at the aphid/Buchnera symbiotic interface provides the first examination of the processes and structures operating at the interface of an obligate intracellular insect nutritional symbiosis, offering unique insight into the types of genomic change that likely facilitated evolutionary maintenance of the symbiosis.
Milk and mortality: the potential effects of modern milk production
Authors: S. Sundar
Journal: BMJ (2014)

Modern industrial scale milk production involves administration of various synthetic substances to dairy cows to enhance production.The milk contains residues of these synthetic substances such as hormones, antibiotics, and analgesics. 1 Sadly, Michaëlsson and colleagues did not discuss these negative aspects of mass produced milk. 2 For instance, cohorts were recruited to the study between 1987 and 1997.But until the European-wide ban in 2000, recombinant bovine somatotropin was used to enhance milk production.This hormone can affect hormonal and metabolic growth factors, including human serum insulin-like growth factors (IGF), which in turn can increase the risk of cancer. 3 4A large European cross sectional study showed that intake of dairy products was an important dietary determinant of serum IGF-1. 5 Analysis of milk for the presence of these substances would have provided a more plausible explanation for the effect on mortality.
Transinhibition of C1 inhibitor synthesis in type I hereditary angioneurotic edema.
Authors: J Kramer, F S Rosen, H R Colten, K Rajczy, R C Strunk
Journal: Journal of Clinical Investigation (1993)

To ascertain the mechanism for decreased synthesis of C1 inhibitor (C1 INH) in certain patients with the autosomal dominant disorder hereditary angioneurotic edema, we studied expression of C1 INH in fibroblasts in which the mutant and wild type mRNA and protein could be distinguished because of deletion of exon 7 (delta Ex7). In the HANE delta Ex7 cells, the amount of wild type mRNA (2.1 kb) was expressed at 52 +/- 2% (n = 5) of normal, whereas the mutant mRNA was 17 +/- 1% (n = 5) of normal. Rates of synthesis of both wild type and mutant proteins (11 +/- 3 and 3 +/- 1% of normal, respectively) were lower than predicted from the mRNA levels. There was no evidence of increased C1 INH protein catabolism. These data indicate that there are multiple levels of control of C1 INH synthesis in type I hereditary angioneurotic edema. Pretranslational regulation results in < 50% of the mutant truncated 1.9-kb mRNA. In addition, translational regulation results in decreased synthesis of both wild type and mutatn C1 INH proteins. These data suggest a transinhibition of wild type C1 INH translation by mutant mRNA and/or protein.
Relations between cystatin C plasma concentration and cardiovascular complications in patients with obstructive sleep apnoea (OSA)
Authors: Anna Czyzak-Gradkowska, Adam Nowinski, Robert Plywaczewski, Luiza Jonczak, Monika Targowska, Pawel Sliwinski, Dorota Gorecka
Journal: European Respiratory Journal (2012)

Cystatin C (Cys C) is a protease inhibitor synthetized in all nucleated cells. Lately it has been proposed as an indicator of early dysfunction in glomerular filtration rate. NT-proBNP is a hormone secreted by ventricles in response to heart overload.  The aim of this study was to assess Cys C plasma level in patients with OSA and its relationships with OSA-associated cardiovascular diseases. Cys C and NT-proBNP were also compared as predictors of cardiac abnormalities.  We studied 238 consecutive patients with OSA: mean age=56.87±9.97yrs, BMI=33.5±5.84kg/m 2 , mean AHI=38.97±21.71, mean ODI= 44.85±27.85. Elevated level of cystatin C (under 50yrs: CysC  Logistic regression analysis (LRA) revealed that CAD (OR=2.56; 95%CI=1.31-4.98, p=0.005) and HF (OR=6.2; 95%CI=1.9-19.9, p=0.001) were associated with increased CysC level. Association of increased NT-proBNP level with cardiac disorders in OSA pts was also confirmed (for CAD OR=2.5, 95%CI=1.1-5.3, p=0.01, for HF OR=4.9, 95%CI=1.6-14.9, p=0.004).  Conclusions: Increased Cys C level is strongly assosiated with cardiac diseases in pts with OSA. Cys C seems to be a better indicator of HF than NT-proBNP in OSA pts.