tbuckley/cabot-search huggingface dataset:
Dissecting Molecular Evolution in the Highly Diverse Plant Clade Caryophyllales Using Transcriptome Sequencing
Authors: Ya Yang, Michael J. Moore, Samuel F. Brockington, Douglas E. Soltis, Gane Ka-Shu Wong, Eric J. Carpenter, Yong Zhang, Li Chen, Zhixiang Yan, Yinlong Xie, Rowan F. Sage, Sarah Covshoff, Julian M. Hibberd, Matthew N. Nelson, Stephen A. Smith
Journal: Molecular Biology and Evolution (2015)

Many phylogenomic studies based on transcriptomes have been limited to "single-copy" genes due to methodological challenges in homology and orthology inferences. Only a relatively small number of studies have explored analyses beyond reconstructing species relationships. We sampled 69 transcriptomes in the hyperdiverse plant clade Caryophyllales and 27 outgroups from annotated genomes across eudicots. Using a combined similarity- and phylogenetic tree-based approach, we recovered 10,960 homolog groups, where each was represented by at least eight ingroup taxa. By decomposing these homolog trees, and taking gene duplications into account, we obtained 17,273 ortholog groups, where each was represented by at least ten ingroup taxa. We reconstructed the species phylogeny using a 1,122-gene data set with a gene occupancy of 92.1%. From the homolog trees, we found that both synonymous and nonsynonymous substitution rates in herbaceous lineages are up to three times as fast as in their woody relatives. This is the first time such a pattern has been shown across thousands of nuclear genes with dense taxon sampling. We also pinpointed regions of the Caryophyllales tree that were characterized by relatively high frequencies of gene duplication, including three previously unrecognized whole-genome duplications. By further combining information from homolog tree topology and synonymous distance between paralog pairs, phylogenetic locations for 13 putative genome duplication events were identified. Genes that experienced the greatest gene family expansion were concentrated among those involved in signal transduction and oxidoreduction, including a cytochrome P450 gene that encodes a key enzyme in the betalain synthesis pathway. Our approach demonstrates a new approach for functional phylogenomic analysis in nonmodel species that is based on homolog groups in addition to inferred ortholog groups.
A monkey model for Epstein Barr virus-associated lymphomagenesis in human acquired immunodeficiency syndrome.
Authors: H Feichtinger, S L Li, E Kaaya, P Putkonen, K Grünewald, K Weyrer, D Böttiger, I Ernberg, A Linde, G Biberfeld
Journal: The Journal of Experimental Medicine (1992)

High-grade malignant nonHodgkin's lymphomas--five lymphoblastic, three pleomorphic, and two immunoblastic--developed in 10/25 cynomolgus monkeys (Macaca fascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cells transformation. Southern blot demonstration of immunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLV-associated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.
Genetic Screening Reveals an Essential Role of p27kip1 in Restriction of Breast Cancer Progression
Authors: Yuhui Yuan, Li Qin, Dan Liu, Ray-Chang Wu, Paola Mussi, Suoling Zhou, Zhou Songyang, Jianming Xu
Journal: Cancer Research (2007)

Abstract The genetic changes and mechanisms underlying the progression of estrogen-dependent breast cancers to estrogen-independent, antiestrogen-resistant, and metastatic breast cancers are unclear despite being a major problem in endocrine therapy. To identify genes responsible for this progression, we carried out a genetic screening by an enhanced retroviral mutagen (ERM)–mediated random mutagenesis in the estrogen-dependent T47D breast cancer cells. We found that T47D cells contain only one p27kip1 (p27) allele coding for the p27 cyclin-dependent kinase (CDK) inhibitor. An ERM insertion into the p27 locus of T47D cells disrupted the p27 gene and created estrogen-independent and antiestrogen-resistant breast cancer cells that still maintained functional estrogen receptors. Disruption of p27 in T47D cells resulted in several changes, and most of these changes could be rescued by p27 restoration. First, CDK2 activity was increased in the absence of estrogen or in the presence of estrogen antagonists tamoxifen or ICI 182780; second, amplified in breast cancer 1 (AIB1), a cancer overexpressed transcriptional coactivator, was hyperphosphorylated, which made AIB1 a better coactivator for E2F1; and third, growth factor receptor binding protein 2–associated binder 2 (Gab2) and Akt activity were increased following E2F1 overactivation, leading to a significant enhancement of cell migration and invasion. Furthermore, the p27-deficient cells, but not T47D control cells, developed lung metastasis in an ovarian hormone–independent manner when they were i.v. injected into nude mice. In sum, loss of p27 activated AIB1, E2F1, Gab2, and Akt; increased cell migration and invasion; caused antiestrogen insensitivity; and promoted metastasis of breast cancer cells. These findings suggest that p27 plays an essential role in restriction of breast cancer progression. [Cancer Res 2007;67(17):8032–42]
Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis.
Authors: V A Lennon, M E Seybold, J M Lindstrom, C Cochrane, R Ulevitch
Journal: The Journal of Experimental Medicine (1978)

An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membranes of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immmunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo.
Development of a novel ELISA system for detection of anti-BP180 IgG and characterization of autoantibody profile in bullous pemphigoid patients
Authors: F. Mariotti, F. Grosso, M. Terracina, M. Ruffelli, P. Cordiali-Fei, F. Sera, G. Zambruno, A. Mastrogiacomo, G. Di Zenzo
Journal: British Journal of Dermatology (2004)

The NC16A immunodominant region of the bullous pemphigoid (BP) antigen BP180 has been used to develop several enzyme-linked immunosorbent assays (ELISAs) as diagnostic tools for BP autoantibody detection.Because BP180 autoantibody reactivity is not restricted to NC16A, we have investigated the possibility of developing an ELISA based on selected epitopes additional to this immunodominant region.Initially 78 BP sera were tested using an NC16A ELISA and IgG reactivity was detected in 64 BP sera (82%). The 14 NC16A-negative BP sera were then analysed by immunological screening against seven BP180-specific epitopes. Recombinant phages displaying BP180 epitopes were grown as plaques, blotted onto a nitrocellulose filter and incubated with BP sera.Three and five NC16A-negative BP sera reacted with epitopes AA 1080-1107 and AA 1331-1404 of the BP180 ectodomain, respectively. Thus, a novel ELISA with GST-1080 and GST-1331 (GST-1080/1331) was developed: 32 of 78 BP sera (41%) proved positive by this assay. The combined use of ELISAs with GST-NC16A and GST-1080/1331 detected IgG reactivity in 72 of 78 BP sera, increasing the sensitivity from 82% to 92%. In addition, autoreactivity against the three extracellular epitopes appeared to be related to the presence of both skin and mucosal involvement as assessed by Fisher's exact probability test.Our findings further characterize the autoimmune response in BP by identifying a subgroup of NC16A-negative patients who react with different BP180 extracellular epitopes. The developed ELISA system appears more sensitive than the ELISA based on NC16A alone and also informative about the epitope profile of BP patients.
Risk Factors for Early, Persistent, and Late-onset Wheezing in Young Children
Authors: FRANCA RUSCONI, CLAUDIA GALASSI, GIUSEPPE M. CORBO, FRANCESCO FORASTIERE, ANNIBALE BIGGERI, GIOVANNINO CICCONE, ELISABETTA RENZONI
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Wheezing in childhood is not a single disorder and different wheezing-associated respiratory illnesses have been recently described. We investigated the association between wheezing conditions and familial, pre-, peri-, and postnatal risk factors. We studied 16,333 children, 6 to 7 yr old, enrolled in a population-based study. Standardized questionnaires were filled in by parents. A total of 1,221 children had transient early wheezing, 671 had persistent wheezing, 918 had late-onset wheezing, and 13,523 never had wheezing or asthma (control group). Maternal asthma or chronic obstructive airway disease were significantly (p < 0.0001) more associated with persistent wheezing than with transient early and late-onset wheezing. The same pattern was observed for exposure to maternal smoke during pregnancy. Having a mother > 35 yr old was protective against transient early wheezing (odds ratio [OR]: 0.68, 95% confidence intervals [95% CI]: 0.53 to 0.86). Breast feeding ⩾ 6 mo was slightly protective against transient early wheezing (OR: 0.82, 95% CI: 0.68 to 0.97), whereas it was a moderate risk factor for late-onset wheezing (OR: 1.22, 95% CI: 0.99 to 1.50). On the contrary, having siblings and attending a day care center were both risk factors for transient early wheezing (OR: 1.41 [95% CI: 1.21 to 1.64] and 1.70 [95% CI: 1.48 to 1.96], respectively) and protective factors against wheezing of late onset (OR: 0.83 [95% CI: 0.70 to 0.97] and 0.72 [95% CI: 0.59 to 0.88]). There was a stronger (p < 0.0001) positive association between personal history of eczema or allergic rhinitis and persistent and late-onset wheezing than transient early wheezing. Our findings suggest a different contribution of risk factors to wheezing conditions in childhood. Rusconi F, Galassi C, Corbo GM, Forastiere F, Biggeri A, Ciccone G, Renzoni E, and the SIDRIA Collaborative Group. Risk factors for early, persistent, and late-onset wheezing in young children.
TREATMENT OF HEAD-AND-NECK CANCER
Authors: G.M Mead, F.R Macbeth, J.A Green, C.J Williams, J.M.A Whitehouse, P Clifford, A.D O'Connor, R.L Carter, V.M Dalley, A.J Darby, G Deutsch, D.J Durden-Smith, W.G Edwards, H Grant, N.G Mcguire
Journal: The Lancet (1982)
Sweat collection from athletes.
Authors: P A Pilardeau, P Harichaux, M T Chalumeau, B Vasseur, J Vaysse, M Garnier
Journal: British Journal of Sports Medicine (1985)

The difficulty in taking sweat during heavy physical exercise has drawn the authors into testing a technique of sampling generally used in paediatrics. The fact that the results, which have been dealt with statistically, should coincide with the physiological facts already published allows us to consider a use of the technique in order to investigate the physiological mechanisms in action during sweating under different metabolic conditions.
Plasma gastrin and acid secretion in man following stimulation by food, meat extract, and insulin
Authors: J. H. Wyllie, P. B. Boulos, M. R. Lewin, B. H. Stagg, C. G. Clark
Journal: Gut (1972)

A radioimmunoassay for gastrin was set up and its sensitivity and specificity were studied. The assay was then used to investigate the plasma gastrin responses in man to a normal meal and to stimulation by insulin hypoglycaemia or by instilling meat extract into the stomach. The results showed that insulin and meat extract produced very similar plasma gastrin responses which were certainly not less than those produced by feeding. However, the acid secretory response to insulin was greater than that to meat extract. This indicated that the tests acted in different ways and both may be useful in the assessment of gastric secretion.
Cardiometabolic Implications of Postpartum Weight Changes in the First Year After Delivery
Authors: Simone Kew, Chang Ye, Anthony J. Hanley, Philip W. Connelly, Mathew Sermer, Bernard Zinman, Ravi Retnakaran
Journal: Diabetes Care (2014)

OBJECTIVE The cumulative effect of postpartum weight retention from each pregnancy in a woman’s life may contribute to her ultimate risk of diabetes and vascular disease. However, there is little direct evidence supporting this hypothesis. In this context, we sought to evaluate the cardiometabolic implications of patterns of postpartum weight change and the time course thereof in the first year after pregnancy. RESEARCH DESIGN AND METHODS Three hundred five women underwent cardiometabolic characterization at recruitment in pregnancy and at 3 and 12 months postpartum. Based on their respective weight changes between prepregnancy and 3 months postpartum (loss or gain) and between 3 and 12 months postpartum (loss or gain), participants were stratified into four groups: loss/loss, gain/loss, loss/gain, and gain/gain. RESULTS Most women (81.0%) had higher weight at 3 months postpartum compared with prepregnancy. Between 3 and 12 months, most women (74.4%) lost weight. At 3 months, there were modest differences between the four groups in mean adjusted LDL cholesterol (P = 0.01) and apolipoprotein-B (apoB; P = 0.02) but no significant differences in adjusted blood pressure, fasting and 2-h glucose, HDL, triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and C-reactive protein. By 12 months postpartum, however, clear gradients emerged, with mean adjusted diastolic blood pressure (P = 0.02), HOMA-IR (P = 0.0003), LDL (P = 0.001), and apoB (P &amp;lt; 0.0001) all progressively increasing from the loss/loss group to gain/loss to loss/gain to gain/gain. Similarly, at 12 months, mean adjusted adiponectin showed a stepwise decrease from loss/loss to gain/loss to loss/gain to gain/gain (P = 0.003). CONCLUSIONS An adverse cardiometabolic profile emerges as early as 1 year postpartum in women who do not lose weight between 3 and 12 months after delivery.
Elevated Fear Conditioning to Socially Relevant Unconditioned Stimuli in Social Anxiety Disorder
Authors: Shmuel Lissek, Jessica Levenson, Arter L. Biggs, Linda L. Johnson, Rezvan Ameli, Daniel S. Pine, Christian Grillon
Journal: American Journal of Psychiatry (2007)

Objective: Though conditioned fear has long been acknowledged as an important etiologic mechanism in social anxiety disorder, past psychophysiological experiments have found no differences in general conditionability among social anxiety patients using generally aversive but socially nonspecific unconditioned stimuli (e.g., unpleasant odors and painful pressure). The authors applied a novel fear conditioning paradigm consisting of socially relevant unconditioned stimuli of critical facial expressions and verbal feedback. This study represents the first effort to assess the conditioning correlates of social anxiety disorder within an ecologically enhanced paradigm. Method: Subjects with social anxiety disorder and age- and gender-matched healthy comparison subjects underwent differential classical conditioning. Conditioned stimuli included images of three neutral facial expressions, each of which was paired with one of three audiovisual unconditioned stimuli: negative insults with critical faces (US neg ), positive compliments with happy faces (US pos ), or neutral comments with neutral faces (US neu ). The conditioned response was measured as the fear-potentiation of the startle-blink reflex elicited during presentation of the conditioned stimuli. Results: Only social anxiety subjects demonstrated fear conditioning in response to facial expressions, as the startle-blink reflex was potentiated by the CS neg versus both CS neu and CS pos among those with the disorder, while healthy comparison subjects displayed no evidence of conditioned startle-potentiation. Such group differences in conditioning were independent of levels of anxiety to the unconditioned stimulus, implicating associative processes rather than increased unconditioned stimulus reactivity as the active mechanism underlying enhanced conditioned startle-potentiation among social anxiety subjects. Conclusions: Results support a conditioning contribution to social anxiety disorder and underscore the importance of disorder-relevant unconditioned stimuli when studying the conditioning correlates of pathologic anxiety.
The Relationship between Genotype and Exercise Tolerance in Children with Cystic Fibrosis
Authors: HIRAN C. SELVADURAI, KAREN O. McKAY, CAMERON J. BLIMKIE, PETER J. COOPER, CRAIG M. MELLIS, PETER P. VAN ASPEREN
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The relationship between fitness and genotype in children with cystic fibrosis (CF) and at least one copy of the Δ F508 mutation was examined. Genotype was classified according to the second CF mutation. Fitness was measured by peak aerobic capacity (using a modified Bruce protocol during treadmill exercise) and anaerobic power (using the Wingate test on a cycle ergometer). The class of cystic fibrosis transmembrane regulator proteins (CFTR) mutation was statistically related with aerobic capacity, peak anaerobic power, body mass index, lung function (forced expiratory volume in one second), and disease severity as measured by the Shwachman score. Patients with mutations causing defective CFTR production (Class I) or processing (Class II) had a significantly lower peak aerobic capacity (28.6 ± 4.2 ml/kg/min and 31.7 ± 5.4 ml/kg/min, respectively) than those with a mutation conferring defective regulation of CFTR (Class III) (43.9 ± 6.4 ml/kg/min). The peak anaerobic power in subjects with mutations inducing decreased CFTR conduction (Class IV) or CFTR mRNA (Class V), were significantly higher (11.4 ± 1.7 and 11.6 ± 1.5 watts/kg, respectively) than children with Class I (9.7 ± 1.4 watts/kg), Class II (9.8 ± 1.4 watts/kg), or Class III (10.5 ± 1.8 watts/kg) mutations. There were no statistically significant differences in the lung function of patients with the different mutations. These results indicate a relationship between CF genotype and some measures of fitness, the mechanisms of which remain to be determined.
T cell-replacing factor for glucocorticosteroid-induced immunoglobulin production. A unique steroid-dependent cytokine.
Authors: F M Orson, J Grayson, S Pike, V De Seau, R M Blaese
Journal: The Journal of Experimental Medicine (1983)

Glucocorticosteroids (GCS) added to otherwise unstimulated cultures of human peripheral blood mononuclear cells (PBMC) induce the synthesis and secretion of all classes of immunoglobulin. The magnitude of this response is similar to that seen with other polyclonal B cell activators such as pokeweed mitogen (PWM), and like that of PWM, the steroid effect is dependent on both T cells and monocytes. To determine the cellular target for GCS in these cultures, separated populations of T cells and non-T cells were preincubated with steroids and then recombined. No immunoglobulin was produced in any of these preincubation experiments. As a different approach to this question, supernatants were collected from various cell populations following stimulation with PWM, concanavalin A (Con A), phytohemagglutinin (PHA), alloantigens, or GCS. These supernatants were tested for their effects on GCS-induced Ig production by B cells. Supernatants from 3-d cultures of unstimulated, as well as GCS-treated, PBMC contained a T cell-replacing factor that permitted T-depleted PBMC to produce Ig upon steroid stimulation. This supernatant factor (TRF-S) could be produced in the absence of steroid stimulation, but both the factor and GCS were necessary for the induction of Ig synthesis. Production of the TRF-S required the presence of both T cells and adherent cells in culture and was found in the highest concentrations at 3-4 d of culture. Supernatants from cultures stimulated with PWM, PHA, Con A, and alloantigens did not contain detectable TRF-S activity, and TRF-S was unable to replace helper T cells for PWM-induced Ig production. TRF-S required the presence of adherent cells in the T cell-depleted responder population for its action. Further, it was effective in inducing Ig production along with GCS in the presence of a sufficient concentration of cyclosporin A to block all T cell helper activity for primary responses of PBMC to PWM or GCS. TRF-S was inactivated by trypsin treatment, heating to 56 degrees C, freezing, lyophilization, and storage at 4 degrees C for greater than 3 wk. Its molecular weight is probably 10,000 daltons or more, since TRF-S activity is not rapidly dialyzable. These experiments indicate that GCS-induced Ig production by human B cells does not require the presence of intact T cells in the cultures and therefore the steroids are not exerting their influence directly on T suppressor or T helper cells. Furthermore, they demonstrate a previously unrecognized cytokine that induces the differentiation of human B cells to Ig production in the presence of GCS.
Outdoor air pollution is associated with disease severity in 1-antitrypsin deficiency
Authors: A. M. Wood, R. M. Harrison, S. Semple, J. G. Ayres, R. A. Stockley
Journal: European Respiratory Journal (2009)

The aim of this study was to determine whether long-term air pollution exposure is associated with clinical phenotype in α 1 -antitrypsin deficiency. In total, 304 PiZZ subjects underwent full lung function testing and quantitative high-resolution computed tomography to identify the presence and severity of the disease. Mean annual air pollutant data for 2006 was matched to the location of patients' houses and used in regression models to identify phenotypic associations with pollution, controlling for covariates. Relative trends in pollution levels were assessed to validate use of a single year's data to indicate long-term exposure. Pollutant levels correlated significantly with one another, with higher levels of primary particles, SO 2 and NO 2 being associated with lower ozone levels. Regression models showed that estimated higher exposure to ozone was associated with worse gas transfer and more severe emphysema. Regression parameters suggested that significance from other pollutants was due to collinearity with ozone. The 2006 pollutant levels showed linear relationships with cumulative years, thus validating the model. Higher exposures to ozone may be associated with worse respiratory status in α 1 -antitrypsin deficiency, identifying a group susceptible to ambient air pollution.