tbuckley/cabot-search huggingface dataset:
Pregnancy-related changes in the maternal gut microbiota are dependent upon the mother's periconceptional diet
Authors: Wajiha Gohir, Fiona J Whelan, Michael G Surette, Caroline Moore, Jonathan D Schertzer, Deborah M Sloboda
Journal: Gut Microbes (2015)

Shifts in the maternal gut microbiome have been implicated in metabolic adaptations to pregnancy. We investigated how pregnancy and diet interact to influence the composition of the maternal gut microbiota. Female C57BL/6 mice were fed either a control or a high fat diet for 8 weeks prior to mating. After confirmation of pregnancy, maternal weight gain and food intake were recorded. Fecal pellets were collected at 2 timepoints prior to mating (at the beginning of the experiment, and after 6 weeks of the specified diet) and at 4 timepoints during pregnancy (gestation day 0.5, 5.5, 10.5, and 15.5). The microbial composition and predicted metabolic functionality of the non-pregnant and pregnant gut was determined via sequencing of the variable 3 region of the 16S rRNA gene. Upon conception, differences in gut microbial communities were observed in both control and high fat-fed mice, including an increase in mucin-degrading bacteria. Control versus high fat-fed pregnant mice possessed the most profound changes to their maternal gut microbiota as indicated by statistically significant taxonomic differences. High fat-fed pregnant mice, when compared to control-fed animals, were found to be significantly enriched in microbes involved in metabolic pathways favoring fatty acid, ketone, vitamin, and bile synthesis. We show that pregnancy-induced changes in the female gut microbiota occur immediately at the onset of pregnancy, are vulnerable to modulation by diet, but are not dependent upon increases in maternal weight gain during pregnancy. High fat diet intake before and during pregnancy results in distinctive shifts in the pregnant gut microbiota in a gestational-age dependent manner and these shifts predict significant differences in the abundance of genes that favor lipid metabolism, glycolysis and gluconeogenic metabolic pathways over the course of pregnancy.
<i>LATS2</i> Is a Tumor Suppressor Gene of Malignant Mesothelioma
Authors: Hideki Murakami, Tetsuya Mizuno, Tetsuo Taniguchi, Makiko Fujii, Futoshi Ishiguro, Takayuki Fukui, Shinya Akatsuka, Yoshitsugu Horio, Toyoaki Hida, Yutaka Kondo, Shinya Toyokuni, Hirotaka Osada, Yoshitaka Sekido
Journal: Cancer Research (2011)

Malignant mesothelioma (MM) is an aggressive neoplasm associated with asbestos exposure. We carried out genome-wide array-based comparative genomic hybridization analysis with 14 MM cell lines. Three cell lines showed overlapping homozygous deletion at chromosome 13q12, which harbored the LATS2 (large tumor suppressor homolog 2) gene. With 6 other MM cell lines and 25 MM tumors, we found 10 inactivating homozygous deletions or mutations of LATS2 among 45 MMs. LATS2 encodes a serine/threonine kinase, a component of the Hippo tumor-suppressive signaling pathway, and we transduced LATS2 in MM cells with its mutation. Transduction of LATS2 inactivated oncoprotein YAP, a transcriptional coactivator, via phosphorylation, and inhibited MM cell growth. We also analyzed LATS2 immunohistochemically and found that 13 of 45 MM tumors had low expression of LATS2. Because NF2 is genetically mutated in 40% to 50% of MM, our data indicate that Hippo pathway dysregulation is frequent in MM cells with inactivation of LATS2 or an upstream regulator of this pathway, Merlin, which is encoded by NF2. Thus, our results suggest that the inactivation of LATS2 is one of the key mechanisms for constitutive activation of YAP, which induces deregulation of MM cell proliferation.
Trafficking of the Membrane Type-1 Matrix Metalloproteinase in Ischemia and Reperfusion
Authors: Anne M. Deschamps, William M. Yarbrough, Christina E. Squires, Rebecca A. Allen, David M. McClister, Kathryn B. Dowdy, Julie E. McLean, Joseph T. Mingoia, Jeffrey A. Sample, Rupak Mukherjee, Francis G. Spinale
Journal: Circulation (2005)

Background— The matrix metalloproteinases (MMPs) contribute to regional remodeling after prolonged periods of ischemia and reperfusion (I/R), but specific MMP types activated during this process remain poorly understood. A novel class, the membrane-type MMPs (MT-MMPs), has been identified in the myocardium, but activity of these MMP types has not been assessed in vivo, particularly during I/R. Methods and Results— Pigs (30 kg, n=8) were instrumented with microdialysis catheters to measure MT1-MMP activity in both ischemic and nonischemic (remote) myocardium. A validated MT1-MMP fluorogenic substrate was infused through the microdialysis system, and changes in fluorescence were reflective of MT1-MMP activity at steady state, during ischemia (90 minutes), and during reperfusion (120 minutes). At peak ischemia, MT1-MMP activity was increased by &gt;40% in the ischemic region, with no change in the remote region, which persisted with reperfusion ( P &lt;0.05). After I/R, MT1-MMP abundance was increased by &gt;50% ( P &lt;0.05). Differential centrifugation revealed that the endosomal fraction (which contains subcellular organelles) within the ischemic myocardium was associated with a &gt;135% increase in MT1-MMP ( P &lt;0.05). Furthermore, in an isolated left ventricular myocyte model of I/R, hypoxia (simulated ischemia) induced a &gt;70% increase in MT1-MMP abundance in myocytes, and confocal microscopy revealed MT1-MMP internalization during this time period and reemergence to the membrane with reperfusion. Conclusions— These unique results demonstrate that a specific MMP type, MT1-MMP, is increased in abundance and activity with I/R and is likely attributed, at least in part, to changes in intracellular trafficking.
Studying Cancer Families to Identify Kidney Cancer Genes
Authors: Berton Zbar, Richard Klausner, W. Marston Linehan
Journal: Annual Review of Medicine (2003)

We studied families with multiple members affected with renal cancer to delineate clinically distinct forms of inherited renal cancer, and to identify and characterize the genes responsible for these disorders. Today, cancer geneticists recognize seven clinically distinct, inherited forms of epithelial renal cancer; genes responsible for five inherited predispositions have been found. Positional cloning efforts for one kidney cancer gene are nearing completion. These discoveries will provide diagnostic tests for these diseases, a foundation for studies of the relationship between genotype and phenotype, and a basis for studies of the pathophysiology of the diverse types of epithelial renal cancer.
Effect of atropine on proximal gastric motor and sensory function in normal subjects
Authors: I Lidums
Journal: Gut (2000)

Distension of the proximal stomach is a major stimulus for triggering transient lower oesophageal sphincter (LOS) relaxations. We have shown recently that atropine inhibits triggering of transient LOS relaxations in both normal subjects and patients with gastro-oesophageal reflux disease. Atropine could potentially act centrally by inhibiting the central integrating mechanism in the brain stem, or act peripherally by altering the response of the stomach to distension. The aim of this study was to investigate the effect of atropine on fasting gastric compliance and postprandial gastric tone using an electronic barostat.Fasting and postprandial proximal gastric motor and sensory functions were assessed in 10 normal healthy volunteers. Oesophageal manometry and pH were simultaneously measured. On separate days, atropine (15 microg/kg bolus, 4 microg/kg/h intravenous infusion) or saline was given and maintained for the duration of the recording period.In the fasting period, atropine significantly reduced minimum distending pressure (5.5 (0.4) v 4.4 (0.4) mm Hg; p<0.005) and increased proximal gastric compliance (81.3 (5.3) v 102. 1 (8.7) ml/ mm Hg; p<0.05). In response to a meal, maximal gastric relaxation was similar on both study days. However, during atropine infusion, there was no recovery of proximal gastric tone in the two hour postprandial observation period. Postprandial fullness scores were higher during atropine infusion and correlated with changes in intrabag volume. Atropine significantly reduced the rate of postprandial transient LOS relaxations: first hour, 7.0 (5.3-10.0) v 3.0 (1.0-4.0) (p<0.02); second hour, 5.0 (3.3-5.8) per hour v 1.0 (0-3.0) per hour (p<0.05).In humans, fasting and postprandial proximal gastric motor function is under cholinergic control. Atropine induced inhibition of transient LOS relaxations is unlikely to be caused by its effect on the proximal stomach, but rather by a central action on the integrating mechanisms in the brain stem.
Resting transmembrane potential difference of skeletal muscle in normal subjects and severely ill patients
Authors: J. N. Cunningham, N. W. Carter, F. C. Rector, D. W. Seldin
Journal: Journal of Clinical Investigation (1971)

The resting membrane potential difference (Em) of skeletal muscle was measured in 26 normal human subjects, 7 patients with mild illness, and 21 patients with severe, debilitating medical disorders. A closed transcutaneous approach to the muscle was made by needle puncture and the Em was measured utilizing standard Ling electrodes. Measurements revealed an Em of -88 +/-3.8 mv in healthy subjects and -89 +/-2.1 mv in patients hospitalized for minor medical problems. The mean Em in 21 in-hospital patients, judged to be severely ill clinically from a variety of causes, was -66.3 +/-9.0 mv. Open deltoid muscle biopsies were performed in 7 of the healthy subjects and in 13 of the severely ill group. Estimation of the intra-extracellular water partition was made by calculating the chloride space from the previously measured Em. Analysis of the muscle samples revealed no significant difference in the intra-extracellular potassium ratios of the two groups biopsied. Intracellular Na(+) concentrations were uniformly increased in the muscle samples of the severely ill subjects and averaged 42.3% higher than those of the normal subjects. The mechanisms which might account for the elevation of intracellular Na(+) and a depression of Em independent of changes in intra-extracellular K(+) ratios are discussed and it is suggested that this defect may be a generalized cellular abnormality which is a common quality of serious illnesses.
Effect of Adrenergic Antagonists on the Peripheral Constrictor Action of Kinekard, A Cardioactive Plasma Fraction
Authors: WINIFRED G. NAYLER, MAURICE ROSENBAUM, IAN E. MCLNNES, DAVID RACE, THOMAS E. LOWE
Journal: Circulation Research (1966)

The possibility that endogenous epinephrine, norepinephrine or angioten-sin is involved in the response of the peripheral circulation to kinekard, a plasma pressor fraction of relatively low molecular weight, was investigated in anesthetized dogs on heart-lung bypass and isolated perfused gracilis muscle preparations. The prior administration of bretylium tosylate, guanethidine or the β-adrenergic antagonist, propranolol, failed to modify the pressor action of kinekard. This pressor action was blocked by the prior addition of the α-adrenergic antagonist, phenoxybenzamine. These results have been interpreted to mean that kinekard acts on the α-receptor sites in the peripheral circulation to cause constriction and that this response does not involve or depend on the release of stored catecholamines.
A phase I safety, pharmacological and biological study of the farnesyl protein transferase inhibitor, tipifarnib and capecitabine in advanced solid tumors
Authors: L. Gore, S.N. Holden, R.B. Cohen, M. Morrow, A.S. Pierson, C.L. O'Bryant, M. Persky, D. Gustafson, C. Mikule, S. Zhang, P.A. Palmer, S.G. Eckhardt
Journal: Annals of Oncology (2006)
Sustained effect of grass pollen subcutaneous immunotherapy on suppression of allergen‐specific basophil response; a real‐life, nonrandomized controlled study
Authors: M. Zidarn, M. Košnik, M. Šilar, N. Bajrović, P. Korošec
Journal: Allergy (2015)

An important advantage of allergen immunotherapy as compared to pharmacotherapy for allergic rhinitis is the long-term effect that persists after completing immunotherapy. The mechanism of the sustained effect of allergen immunotherapy is not completely understood.We conducted a 7-year study of monitoring allergen-specific basophil response and serological markers in 20 subjects with moderate-to-severe grass pollen-allergic rhinitis just before beginning and after up-dosing of subcutaneous grass pollen immunotherapy, before the first pollen season, and 1-2 years after completion of 3-5 years of treatment. Comparable untreated rhinitis subjects were followed at the same time points. Clinical outcomes included assessment of symptoms, use of rescue medication, and quality of life. The basophil response was also monitored after removal of IgG antibodies.Basophil response assessed as area under the curve (AUC) halved during initiation of SCIT and was 55% lower 1-2 years after completing SCIT. In the untreated group, the basophil response remained comparable. Although immunotherapy-induced grass pollen-specific IgG4 levels decreased to near pre-immunotherapy levels after completing SCIT, the removal of IgG antibodies resulted in an increase in basophil response almost to the pre-immunotherapy levels. In untreated subjects, removal of IgG did not have any effect on basophil response.Grass pollen immunotherapy induces sustained suppression of the allergen-specific basophil response that persists after completion of treatment and could account for long-term clinical tolerance. It also seems to be associated with persistent blocking activity of IgG antibodies.
Tuberculous pleural effusions: increased culture yield with bedside inoculation of pleural fluid and poor diagnostic value of adenosine deaminase.
Authors: G Maartens, E D Bateman
Journal: Thorax (1991)

A prospective study of 111 adult patients with a pleural effusion was carried out in an area with a high prevalence of tuberculosis to compare the yield of bedside with laboratory inoculation of pleural fluid, and the yield and speed of a radiometric mycobacterial culture system (BACTEC) with that of conventional culture. The use of adenosine deaminase activity in pleural fluid as a diagnostic test for tuberculosis was also evaluated. In the 62 cases of tuberculosis confirmed histologically or by culture, or both, the BACTEC system had the same culture yield as conventional mycobacterial culture (positive in 14 cases-23%), but was significantly faster (18 versus 33 days). Bedside inoculation had a culture yield significantly higher than laboratory inoculation in the 24 patients tested (11 versus four). The remaining three diagnostic categories were malignant (28), miscellaneous (10), and undiagnosed (11). Median adenosine deaminase activity was significantly higher in tuberculous effusions than in any of the other categories, but there was considerable overlap between the groups. It is concluded that the BACTEC system is significantly faster than conventional mycobacterial culture and that bedside inoculation of pleural fluid substantially increases culture yield. Adenosine deaminase does not provide as valuable a diagnostic test of pleural tuberculosis as has been suggested.
The Evolutionary History of Termites as Inferred from 66 Mitochondrial Genomes
Authors: Thomas Bourguignon, Nathan Lo, Stephen L. Cameron, Jan Šobotník, Yoshinobu Hayashi, Shuji Shigenobu, Dai Watanabe, Yves Roisin, Toru Miura, Theodore A. Evans
Journal: Molecular Biology and Evolution (2014)

Termites have colonized many habitats and are among the most abundant animals in tropical ecosystems, which they modify considerably through their actions. The timing of their rise in abundance and of the dispersal events that gave rise to modern termite lineages is not well understood. To shed light on termite origins and diversification, we sequenced the mitochondrial genome of 48 termite species and combined them with 18 previously sequenced termite mitochondrial genomes for phylogenetic and molecular clock analyses using multiple fossil calibrations. The 66 genomes represent most major clades of termites. Unlike previous phylogenetic studies based on fewer molecular data, our phylogenetic tree is fully resolved for the lower termites. The phylogenetic positions of Macrotermitinae and Apicotermitinae are also resolved as the basal groups in the higher termites, but in the crown termitid groups, including Termitinae + Syntermitinae + Nasutitermitinae + Cubitermitinae, the position of some nodes remains uncertain. Our molecular clock tree indicates that the lineages leading to termites and Cryptocercus roaches diverged 170 Ma (153–196 Ma 95% confidence interval [CI]), that modern Termitidae arose 54 Ma (46–66 Ma 95% CI), and that the crown termitid group arose 40 Ma (35–49 Ma 95% CI). This indicates that the distribution of basal termite clades was influenced by the final stages of the breakup of Pangaea. Our inference of ancestral geographic ranges shows that the Termitidae, which includes more than 75% of extant termite species, most likely originated in Africa or Asia, and acquired their pantropical distribution after a series of dispersal and subsequent diversification events.
Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis
Authors: Gihad E. Nesrallah, Robert M. Lindsay, Meaghan S. Cuerden, Amit X. Garg, Friedrich Port, Peter C. Austin, Louise M. Moist, Andreas Pierratos, Christopher T. Chan, Deborah Zimmerman, Robert S. Lockridge, Cécile Couchoud, Charles Chazot, Norma Ofsthun, Adeera Levin, Michael Copland, Mark Courtney, Andrew Steele, Philip A. McFarlane, Denis F. Geary, Robert P. Pauly, Paul Komenda, Rita S. Suri
Journal: Journal of the American Society of Nephrology (2012)

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.
Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice.
Authors: H Cantor, L McVay-Boudreau, J Hugenberger, K Naidorf, F W Shen, R K Gershon
Journal: The Journal of Experimental Medicine (1978)

We have shown that (a) purified T-helper cells induce cells of another T-cell set-, expressing the Ly123+Qa1+ surface phenotype, to exert potent suppressive activity, (b) this T-T interaction plays an important role in regulating in vivo immune responses, and (c) this interaction represents an important barrier to protocols intended to augment the immune status of individuals by adoptive (or active) immunotherapy. Our results also indicate that the Ly123+ T-cell set mediating feedback suppression in vivo is sensitive to both low doses of cyclophosphamide and removal of the thymus in adult life. The importance of this T-T interaction to normal, physiologic regulation of the immune system is emphasized by the finding that the major T-cell deficit of NZB mice (an inbred strain of mice that spontaneously develops an autoimmune disorder) is the absence or malfunction of an Ly123+ T-cell set responsible for feedback inhibition.
Detection of immunoglobulins G and A to Aspergillus fumigatus by immunoblot analysis for monitoring Aspergillus-induced lung diseases
Authors: MT van Rens, R Vernooy-Jeras, M Merton-de Ridder, H van Velzen-Blad, JM van den Bosch
Journal: European Respiratory Journal (1998)

The aim of the study was to investigate whether patients with Aspergillus-induced lung disease can be monitored by immunoblot analysis to detect antibodies to Aspergillus fumigatus (Af). Immunoblotting was performed by incubating 57 longitudinally collected sera from 13 patients on nitrocellulose sheets, blotted with Af antigen, separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Bound antibodies were demonstrated by peroxidase-labelled antihuman immunoglobulins (Ig)G and IgA antiserum and diaminobenzidine plus H2O2 as substrate. The immunoblot patterns were related to the patients' clinical status and time. Each patient had a characteristic immunoblot pattern that varied with time. There was a relationship between disease activity or clinical response and changes in immunoblot antibody patterns: a rise in anti-Af IgG and IgA antibodies was seen in sera collected during active disease, compared with before active disease, and a significant decline in anti-Af IgG and IgA was demonstrated in sera collected during recovery, compared with during active disease. Only in the acute stage of allergic bronchopulmonary aspergillosis were IgA antibodies against Af antigens of &lt;20,000 Da demonstrated. Immunoblot analysis can be used to monitor the disease activity and the responses to treatment of patients with Aspergillus-induced lung diseases. Changes in specific immunoglobulin A may be more informative than specific immunoglobulin G.
Comparative Genome Analysis and Gene Finding in Candida Species Using CGOB
Authors: Sarah L. Maguire, Seán S. ÓhÉigeartaigh, Kevin P. Byrne, Markus S. Schröder, Peadar O’Gaora, Kenneth H. Wolfe, Geraldine Butler
Journal: Molecular Biology and Evolution (2013)

The Candida Gene Order Browser (CGOB) was developed as a tool to visualize and analyze synteny relationships in multiple Candida species, and to provide an accurate, manually curated set of orthologous Candida genes for evolutionary analyses. Here, we describe major improvements to CGOB. The underlying structure of the database has been changed significantly. Genomic features are now based directly on genome annotations rather than on protein sequences, which allows non-protein features such as centromere locations in Candida albicans and tRNA genes in all species to be included. The data set has been expanded to 13 species, including genomes of pathogens (C. albicans, C. parapsilosis, C. tropicalis, and C. orthopsilosis), and those of xylose-degrading species with important biotechnological applications (C. tenuis, Scheffersomyces stipitis, and Spathaspora passalidarum). Updated annotations of C. parapsilosis, C. dubliniensis, and Debaryomyces hansenii have been incorporated. We discovered more than 1,500 previously unannotated genes among the 13 genomes, ranging in size from 29 to 3,850 amino acids. Poorly conserved and rapidly evolving genes were also identified. Re-analysis of the mating type loci of the xylose degraders suggests that C. tenuis is heterothallic, whereas both Spa. passalidarum and S. stipitis are homothallic. As well as hosting the browser, the CGOB website (http://cgob.ucd.ie) gives direct access to all the underlying genome annotations, sequences, and curated orthology data.