tbuckley/cabot-search huggingface dataset:
A Phylogenetic Mixture Model for the Evolution of Gene Expression
Authors: Kevin H. Eng, Héctor Corrada Bravo, Sündüz Keleş
Journal: Molecular Biology and Evolution (2009)

Microarray platforms are used increasingly to make comparative inferences through genome-wide surveys of gene expression. Although recent studies focus on describing the evidence for natural selection using estimates of the within- and between-taxa mutational variances, these methods do not explicitly or flexibly account for predicted nonindependence due to phylogenetic associations between measurements. In the interest of parsing the effects of selection: we introduce a mixture model for the comparative analysis of variation in gene expression across multiple taxa. This class of models isolates the phylogenetic signal from the nonphylogenetic and the heritable signal from the nonheritable while measuring the proper amount of correction. As a result, the mixture model resolves outstanding differences between existing models, relates different ways to estimate the across taxa variance, and induces a likelihood ratio test for selection. We investigate by simulation and application the feasibility and utility of estimation of the required parameters and the power of the proposed test. We illustrate analysis under this mixture model with a gene duplication family data set.
Discovery of biological networks from diverse functional genomic data.
Authors: Chad L Myers, Drew Robson, Adam Wible, Matthew A Hibbs, Camelia Chiriac, Chandra L Theesfeld, Kara Dolinski, Olga G Troyanskaya
Journal: Genome biology (2005)

Abstract We have developed a general probabilistic system for query-based discovery of pathway-specific networks through integration of diverse genome-wide data. This framework was validated by accurately recovering known networks for 31 biological processes in Saccharomyces cerevisiae and experimentally verifying predictions for the process of chromosomal segregation. Our system, bioPIXIE, a public, comprehensive system for integration, analysis, and visualization of biological network predictions for S. cerevisiae , is freely accessible over the worldwide web.
Serologic Antienzyme Rate of Epstein-Barr Virus DNase-Specific Neutralizing Antibody Segregates TNM Classification in Nasopharyngeal Carcinoma
Authors: Jie Xu, Xiang-Bo Wan, Xue-Fei Huang, K.C. Allen Chan, Ming-Huang Hong, Li-Hui Wang, Zi-Jie Long, Qing Liu, Min Yan, Y.M. Dennis Lo, Yi-Xin Zeng, Quentin Liu
Journal: Journal of Clinical Oncology (2010)

We investigate the value of pretreatment serologic antienzyme rate (AER) of Epstein-Barr virus (EBV) DNase-specific neutralizing antibody complementing TNM staging in prognostication of nasopharyngeal carcinoma (NPC).Pretreatment serum samples from 1,303 patients with untreated NPC were collected and examined for AER. After a 10-year follow-up period, the prognoses of the patients, classified by their clinical stage with AER, were assessed by multivariate analysis. Of the 1,303 patients, 600 patients were randomly assigned to a training set to generate an AER cutoff point by receiver operating characteristic (ROC) curve analysis. AER levels were then analyzed with overall survival (OS), progression-free survival (PFS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS) in a testing set (703 patients). Another independent cohort of 464 patients was studied in a validating set.In the training set, the ROC analysis-generated AER cutoff point for OS was 58.0%, which was used as the cutoff point in the testing set. The subset of low AER levels predicted a significant survival advantage over the subset of high AER levels for OS, PFS, LFFS, and DMFS in the testing set. Moreover, two distinguished subgroups were segregated by an AER level of 58.0% within each clinical stage comparing prognostication of OS, PFS, LFFS, and DMFS. Importantly, AER level was revealed as the only significant independent prognostic factor for death, recurrence, and distant metastasis in the validating set.Pretreatment serologic AER of EBV DNase-specific neutralizing antibody serves as an independent prognostic marker complementing TNM stage in NPC. Supplementing pretreatment AER with TNM staging leads to more accurate risk definition in patient subgroups.
Effective Nasal Symptom Relief and Improvement in Health-Related Quality of Life in Subjects with Perennial Allergic Rhinitis Following 6-Week Once-Daily Treatment with Beclomethasone Dipropionate Hydrofluoroalkane Nasal Aerosol
Authors: W. Carr, E.O. Meltzer, A. Finn, P.M. Dorinsky, L. Kelley, S.A. Dunbar, S.K. Tantry
Journal: Journal of Allergy and Clinical Immunology (2012)
Leisure-Time Physical Activity, Body Size, and Colon Cancer in Women
Authors: M. E. Martinez, E. Giovannucci, D. Spiegelman, W. C. Willett, D. J. Hunter, G. A. Colditz
Journal: JNCI Journal of the National Cancer Institute (1997)

Physical inactivity and high body mass index (weight in kilograms divided by height in square meters) have been linked to increased risk of colon cancer. However, none of the few prospective studies in women has shown a statistically significant reduction in colon cancer incidence or mortality associated with increased leisure-time physical activity.In this prospective study, we asked whether leisure-time physical activity, body mass index, or body fat distribution could significantly influence the risk of colon cancer in women.The participants in this study were enrolled in the Nurses' Health Study, which began in 1976. Every 2 years, the women provided additional personal information and information on medical risk factors and major medical events. The time spent per week at a variety of leisure-time physical activities was determined, and the time spent at each activity was multiplied by its typical energy expenditure, expressed in terms of metabolic equivalents or METs. The resulting values for each woman were added to yield an MET-hours-per-week score. Reported diagnoses of colon cancer were confirmed by review of hospital records and pathology reports. Relative risks and associated 95% confidence intervals were calculated.In multivariate analyses that included body mass index, women who expended more than 21 MET-hours per week on leisure-time physical activity had a relative risk of colon cancer of 0.54 (95% confidence interval [CI] = 0.33-0.90) in comparison with women who expended less than 2 MET-hours per week. Women who had a body mass index greater than 29 kg/m2 had a relative risk of colon cancer of 1.45 (95% CI = 1.02-2.07) in comparison with women who had a body mass index less than 21 kg/m2. A tendency toward higher colon cancer risk was observed for increasing waist-to-hip ratio (relative risk = 1.48 [95% CI = 0.88-2.49] for comparison of the highest quintile ratio [>0.833] to the lowest [<0.728]).The significant inverse association between leisure-time physical activity and incidence of colon cancer in women in this study is consistent with what has been found in men. Recommendations to increase physical activity and maintain lean body weight should receive greater emphasis as part of a feasible approach to the prevention of colon cancer.
The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration
Authors: Ilya Bezprozvanny, Peter Hiesinger
Journal: Molecular Neurodegeneration (2013)

Most neurons are born with the potential to live for the entire lifespan of the organism. In addition, neurons are highly polarized cells with often long axons, extensively branched dendritic trees and many synaptic contacts. Longevity together with morphological complexity results in a formidable challenge to maintain synapses healthy and functional. This challenge is often evoked to explain adult-onset degeneration in numerous neurodegenerative disorders that result from otherwise divergent causes. However, comparably little is known about the basic cell biological mechanisms that keep normal synapses alive and functional in the first place. How the basic maintenance mechanisms are related to slow adult-onset degeneration in different diseasesis largely unclear. In this review we focus on two basic and interconnected cell biological mechanisms that are required for synaptic maintenance: endomembrane recycling and calcium (Ca2+) homeostasis. We propose that subtle defects in these homeostatic processes can lead to late onset synaptic degeneration. Moreover, the same basic mechanisms are hijacked, impaired or overstimulated in numerous neurodegenerative disorders. Understanding the pathogenesis of these disorders requires an understanding of both the initial cause of the disease and the on-going changes in basic maintenance mechanisms. Here we discuss the mechanisms that keep synapses functional over long periods of time with the emphasis on their role in slow adult-onset neurodegeneration.
Recovery of Anoikis in Src-Transformed Cells and Human Breast Carcinoma Cells by Restoration of the SIRPα1/SHP-2 Signaling System
Authors: Kazuo Hara, Takeshi Senga, Md. Helal Uddin Biswas, Hitoki Hasegawa, Satoko Ito, Toshinori Hyodo, Yoshiki Hirooka, Yasumasa Niwa, Hidemi Goto, Michinari Hamaguchi
Journal: Cancer Research (2010)

Abstract Src kinase dysregulation contributes to cancer progression but mechanistic understanding for this contribution remains incomplete. Signal regulatory protein α1 (SIRPα1) is a tumor suppressor that is constitutively suppressed in v-Src-transformed cells, where restoration of SIRPα1 expression inhibits anchorage-independent growth. In this study, we investigated the role of the protein tyrosine phosphatase-2 (SHP-2) in SIRPα1 activity. SHP-2 suppression resulted in a blockade of SIRPα1-mediated inhibition of anchorage-independent growth. Notably, we found that SIRPα1 did not act in v-Src-transformed cells by triggering cell growth arrest but by eliciting a suspension-selective apoptosis (anoikis), and that SHP-2 was required for this effect. Furthermore, we found that SHP-2 was crucial for recovery of stress fiber and focal contact formation by SIRPα1 in v-Src-transformed cells. Finally, we found that SIRPα1/SHP-2 signaling regulates anoikis in human breast carcinoma cells with activated c-Src. Taken together, our findings define SHP-2 as an essential component of tumor suppression and anoikis mediated by SIRPα1 in human breast carcinoma cells as well as in v-Src-transformed cells. Cancer Res; 71(4); 1229–34. ©2010 AACR.
Saulo Klahr Was as Good as It Gets
Authors: Neal Bricker
Journal: Journal of the American Society of Nephrology (2010)

Saulo Klahr was a brilliant, cultured man; a physician who excelled in both clinical and basic medical research.

He was born in 1935 and raised in the small town of Santendar, Colombia. When Saulo was still in high school, he shared an experience with many of us. He read Microbe Hunters , and from that point on, medicine and medical research would be his chosen fields. Graduating from the Universidad National de Colombia School of Medicine at the top of his class, he remained in Colombia for 3 years of clinical training and then embarked on what proved to be a life-changing event. Saulo decided to become a nephrologist and moved to the United States, where, being a graduate of a foreign medical school and speaking less than perfect English, his hopes for a career in academic medicine had to be regarded as a long shot.

In 1966, he visited me at Washington University in St. Louis hoping for a fellowship. This was a moment when nephrology was a new field …
Regional fMRI Hypoactivation and Altered Functional Connectivity During Emotion Processing in Nonmedicated Depressed Patients With Bipolar II Disorder
Authors: Nathalie Vizueta, Jeffrey D. Rudie, Jennifer D. Townsend, Salvatore Torrisi, Teena D. Moody, Susan Y. Bookheimer, Lori L. Altshuler
Journal: American Journal of Psychiatry (2012)

Although the amygdala and ventrolateral prefrontal cortex have been implicated in the pathophysiology of bipolar I disorder, the neural mechanisms underlying bipolar II disorder remain unknown. The authors examined neural activity in response to negative emotional faces during an emotion perception task that reliably activates emotion regulatory regions.Twenty-one nonmedicated depressed bipolar II patients and 21 healthy comparison subjects underwent functional MRI (fMRI) while performing an emotional face-matching task. Within- and between-group whole-brain fMRI activation and seed-based connectivity analyses were conducted.In depressed bipolar II patients, random-effects between-group fMRI analyses revealed a significant reduction in activation in several regions, including the left and right ventrolateral prefrontal cortices (Brodmann's area [BA] 47) and the right amygdala, a priori regions of interest. Additionally, bipolar patients exhibited significantly reduced negative functional connectivity between the right amygdala and the right orbitofrontal cortex (BA 10) as well as the right dorsolateral prefrontal cortex (BA 46) relative to healthy comparison subjects.These findings suggest that bipolar II depression is characterized by reduced regional orbitofrontal and limbic activation and altered connectivity in a fronto-temporal circuit implicated in working memory and emotional learning. While the amygdala hypoactivation observed in bipolar II depression is opposite to the direction seen in bipolar I mania and may therefore be state dependent, the observed orbitofrontal cortex hypoactivation is consistent with findings in bipolar I depression, mania, and euthymia, suggesting a physiologic trait marker of the disorder.
Exon 3 -catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome
Authors: V Johnson
Journal: Gut (2005)

Activating beta-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that beta-catenin mutations occur more often in microsatellite unstable (MSI+) colorectal carcinomas, including hereditary non-polyposis colorectal cancer (HNPCC), as a consequence of defective DNA mismatch repair. We have analysed 337 colorectal carcinomas and adenomas, from both sporadic cases and HNPCC families, to provide an accurate assessment of beta-catenin mutation frequency in each tumour type.Direct sequencing of exon 3 of beta-catenin.Mutations were rare in sporadic (1/83, 1.2%) and HNPCC adenomas (1/37, 2.7%). Most of the sporadic adenomas analysed (80%) were small (<1 cm), and our data therefore differ from a previous report of a much higher mutation frequency in small adenomas. No oncogenic beta-catenin mutations were identified in 34 MSI+ and 78 microsatellite stable (MSI-) sporadic colorectal cancers but a raised mutation frequency (8/44, 18.2%) was found in HNPCC cancers; this frequency was significantly higher than that in HNPCC adenomas (p=0.035) and in both MSI- (p<0.0001) and MSI+ (p=0.008) sporadic cancers. Mutations were more common in higher stage (Dukes' stages C and D) cancers (p=0.001).Exon 3 beta-catenin mutations are associated specifically with malignant colorectal tumours in HNPCC; mutations appear not to result directly from deficient mismatch repair. Our data provide evidence that the genetic pathways of sporadic MSI+ and HNPCC cancers may be divergent, and indicate that mutations in the HNPCC pathway of colorectal tumorigenesis may be determined by selection, not simply by hypermutation.
Bacterial cell wall-induced hepatic granulomas. An in vivo model of T cell-dependent fibrosis.
Authors: S M Wahl, D A Hunt, J B Allen, R L Wilder, L Paglia, A R Hand
Journal: The Journal of Experimental Medicine (1986)

In vitro studies implicate a molecular link between inflammatory mononuclear cells and alterations in fibroblast growth and function. We have extended these observations in an experimental animal model in which we document the T cell-dependence of fibrosis that occurs after activation of the cell-mediated immune system by specific antigen. Chronic granulomatous lesions were induced in the livers of susceptible rats by the intraperitoneal injection of group A streptococcal cell walls (SCW). The development of granulomas that are composed primarily of lymphocytes and macrophages was associated with the recruitment and proliferation of connective tissue cells. Furthermore, this expanded population of fibroblasts generated a collagenous structure consisting primarily of types I and III collagen around the granuloma. The progression of these chronic inflammatory lesions leads to the formation of fibrotic nodules throughout the livers of the treated animals. Intact granulomas, as well as mononuclear cells derived from the granulomas, spontaneously elaborated a soluble factor(s) that stimulates fibroblast proliferation. Physicochemical analysis revealed that the primary granuloma-derived peak of fibroblast growth activity corresponded to an apparent Mr of 40,000, which is consistent with a previously described T lymphocyte--derived fibroblast-activating factor (FAF) in guinea pig and human. Furthermore, the fibrosis that occurs in the granuloma is apparently T cell--dependent, since no fibrotic lesions developed in SCW-injected athymic nude rats nor in SCW-injected animals treated with the T cell inhibitor, cyclosporin A (CsA). Mononuclear cells from neither of these functionally T cell--deficient animals could generate FAF activity. These data show a role for T lymphocyte--derived cytokines in the development of hepatic fibrosis in SCW-injected rats.
Sex, Age, and the Diagnosis of Hysteria (Briquet's Syndrome)
Authors: SAMUEL B. GUZE, ROBERT A. WOODRUFF, PAULA J. CLAYTON
Journal: American Journal of Psychiatry (1972)

A study of hysteria (Briquet's syndrome) in 500 psychiatric clinic patients showed that men and women differ with regard to the number of symptoms reported and to the distribution of symptoms by age. Young women reported a disproportionately greater number of symptoms than men or older women. The authors conclude that a diagnosis of hysteria, which is based upon a polysymptomatic disorder beginning early in life, is more likely to be made in women than in men.
Activated neutrophils induce an hMSH2-dependent G2/M checkpoint arrest and replication errors at a (CA)13-repeat in colon epithelial cells
Authors: C Campregher, M G Luciani, C Gasche
Journal: Gut (2008)

Chronic inflammation in ulcerative colitis is associated with increased risk for colorectal cancer. Its molecular pathway of cancer development is poorly understood. We investigated the role of neutrophil-derived cellular stress in an in vitro model of neutrophils as effectors and colon epithelial cells as targets, and tested for changes in cell cycle distribution and the appearance of replication errors.
Effect of Galla chinensis on the In Vitro Remineralization of Advanced Enamel Lesions
Authors: Lei Cheng, Jacob M ten Cate
Journal: International Journal of Oral Science (2010)

The effect of Galla chinensis on de-/re-mineralization of advanced enamel lesions was investigated by using micro-CT in a prolonged in vitro experiment.Baseline mineral contents of sound enamels were first analyzed. Then lesions were produced in an acidic buffer solution (2.2 m mol x L(-1) Ca(NO3)2, 2.2 mmol x L(-1) KH2PO4, and pH = 4.5) for 21 days, with thrice daily three-minute treatments, divided into four groups: Group A, 4 000 ppm crude aqueous extract of Galla chinensis (GCE); Group B, 4000 ppm gallic acid; Group C, 1000 ppm F aq. (as NaF, positive control); Group D, deionized water (negative control). Next, the blocks were immersed in a remineralization solution (1.5 mmol x L(-1) CaCl2, 0.9 mmol x L(-1) KH2PO4, 0.1 ppm F, and pH = 7.0) for 200 days. Mineral loss (ML) in each region of interest (ROI) and integrated mineral loss (IML) of the lesions were calculated (comparing with baseline mineral content of sound enamel) at different time points.After 21 days demineralization, fluoride treatment showed a statistically significant demineralization-inhibiting effect among the four groups, and after 200 days of remineralization, mineral content recovery was ordered (lowest to highest) as A = C < B < D.GCE could slow down the remineralization of enamel in the surface layer and thereby facilitate ion transport into the lesion body. The mechanism of Galla chinensis in enhancing the remineralization of dental caries is different from fluoride.
Peritumor Lymphatics Induced by Vascular Endothelial Growth Factor-C Exhibit Abnormal Function
Authors: Naohide Isaka, Timothy P. Padera, Jeroen Hagendoorn, Dai Fukumura, Rakesh K. Jain
Journal: Cancer Research (2004)

Abstract Vascular endothelial growth factor (VEGF)-C is known to induce hyperplasia in normal murine lymphatics and in peritumor lymphatics. Here, we examine the function of these hyperplastic peritumor lymphatics. Microlymphangiography of B16F10 melanomas growing in the murine dorsal skinfold chamber showed that the number of functional, draining lymphatics in the peritumor tissue of VEGF-C-overexpressing tumors was significantly greater than that in mock-transduced tumors (9.5 ± 1.0 versus 6.3 ± 0.4; n = 6; P &amp;lt; 0.05). Forty percent of functional lymphatics associated with VEGF-C-overexpressing tumors contained proliferating lymphatic endothelial cells. Surprisingly, these new, functional lymphatic vessels displayed a retrograde draining pattern, which indicates possible dysfunction of the intraluminal valves of these vessels.
Growth Inhibition of Estrogen-Dependent and Estrogen-Independent MXT Mammary Cancers in Mice by the Bombesin and Gastrin-Releasing Peptide Antagonist RC-3095
Authors: Karoly Szepeshazi, Andrew V. Schally, Gabor Halmos, Kate Groot, Sinisa Radulovic
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Growth Inhibition of Estrogen-Dependent and Estrogen-Independent MXT Mammary Cancers in Mice by the Bombesin and Gastrin-Releasing Peptide Antagonist RC-3095 Get access Karoly Szepeshazi, Karoly Szepeshazi Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrew V. Schally, Andrew V. Schally Search for other works by this author on: Oxford Academic PubMed Google Scholar Gabor Halmos, Gabor Halmos Search for other works by this author on: Oxford Academic PubMed Google Scholar Kate Groot, Kate Groot Search for other works by this author on: Oxford Academic PubMed Google Scholar Sinisa Radulovic Sinisa Radulovic Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 24, 16 December 1992, Pages 1915–1922, https://doi.org/10.1093/jnci/84.24.1915 Published: 16 December 1992 Article history Received: 19 September 1991 Revision received: 19 August 1992 Accepted: 25 September 1992 Published: 16 December 1992