tbuckley/cabot-search huggingface dataset:
CodonPhyML: Fast Maximum Likelihood Phylogeny Estimation under Codon Substitution Models
Authors: Manuel Gil, Marcelo Serrano Zanetti, Stefan Zoller, Maria Anisimova
Journal: Molecular Biology and Evolution (2013)

Markov models of codon substitution naturally incorporate the structure of the genetic code and the selection intensity at the protein level, providing a more realistic representation of protein-coding sequences compared with nucleotide or amino acid models. Thus, for protein-coding genes, phylogenetic inference is expected to be more accurate under codon models. So far, phylogeny reconstruction under codon models has been elusive due to computational difficulties of dealing with high dimension matrices. Here, we present a fast maximum likelihood (ML) package for phylogenetic inference, CodonPhyML offering hundreds of different codon models, the largest variety to date, for phylogeny inference by ML. CodonPhyML is tested on simulated and real data and is shown to offer excellent speed and convergence properties. In addition, CodonPhyML includes most recent fast methods for estimating phylogenetic branch supports and provides an integral framework for models selection, including amino acid and DNA models.
Humoral and cellular immunity in children with active and quiescent atopic dermatitis
Authors: F. CHIARELLI, GIOVANNA CANFORA, A. VERROTTI, P. AMERIO, G. MORGESE
Journal: British Journal of Dermatology (1987)

Serum immunoglobulins (IgG, IgM, IgA and IgE), C3, and C4, T lymphocyte subsets, neutrophil chemotaxis and natural killer cell-mediated cytotoxic activity were measured in 34 children with atopic dermatitis and 31 healthy controls. Twenty-four patients were re-evaluated when their dermatitis was quiescent. Serum levels of IgG, IgM and IgE were significantly higher in the patients with atopic dermatitis than in the controls, while levels of serum IgA did not differ significantly between the two groups. C3 levels were lower in the patients than in the controls and correlated inversely with clinical disease severity. C4 levels were not significantly altered. Numbers of suppressor/cytotoxic T lymphocytes and polymorphonuclear leukocyte chemotaxis were significantly reduced in the atopic patients. There was a significant inverse correlation between the natural killer cell-mediated cytotoxic activity and the severity and extent of the dermatitis. These results support the hypothesis that atopic dermatitis is connected with a defect in cellular immunity.
Hypoxia Inhibits Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis by Blocking Bax Translocation
Authors: Moonil Kim, Sang-Youel Park, Hyun-Sook Pai, Tae-Hyoung Kim, Timothy R. Billiar, Dai-Wu Seol
Journal: Cancer Research (2004)

Abstract The hypoxic environment in solid tumors results from oxygen consumption by rapid proliferation of tumor cells. Hypoxia has been shown to facilitate the survival of tumor cells and to be a cause of malignant transformation. Hypoxia also is well known to attenuate the therapeutic activity of various therapies in cancer management. These observations indicate that hypoxia plays a critical role in tumor biology. However, little is known about the effects of hypoxia on apoptosis, especially on apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent apoptosis inducer that has been shown to specifically limit tumor growth without damaging normal cells and tissues in vivo. To address the effects of hypoxia on TRAIL-induced apoptosis, HCT116 human colon carcinoma cells were exposed to hypoxic or normoxic conditions and treated with soluble TRAIL protein. Hypoxia dramatically inhibited TRAIL-induced apoptosis in HCT116 cells, which are highly susceptible to TRAIL in normoxia. Hypoxia increased antiapoptotic Bcl-2 family member proteins and inhibitors of apoptosis proteins. Interestingly, these hypoxia-increased antiapoptotic molecules were decreased by TRAIL treatment to the levels lower than those of the untreated conditions, suggesting that hypoxia inhibits TRAIL-induced apoptosis via other mechanisms rather than up-regulation of these antiapoptotic molecules. Additional characterization revealed that hypoxia significantly inhibits TRAIL-induced translocation of Bax from the cytosol to the mitochondria in HCT116 and A549 cells, with the concomitant inhibition of cytochrome c release from the mitochondria. Bax-deficient HCT116 cells were completely resistant to TRAIL regardless of oxygen content, demonstrating a pivotal role of Bax in TRAIL-induced apoptotic signaling. Thus, our data indicate that hypoxia inhibits TRAIL-induced apoptosis by blocking Bax translocation to the mitochondria, thereby converting cells to a Bax-deficient state.
THE USE OF SURGERY IN PULMONARY TUBERCULOSIS
Authors: H. M. Davies
Journal: BMJ (1930)

687.~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~EIA JO _AJ and lie felt bouind to stand still for a few minutes, after whichl he was able to carry on again.The pain hiad never, occurred at nighit, hut was definitely produced more easily after food.The attacks hiad gradually got snore frequent, though niot more severe, and the exercise of quiet walking was sufficient to br-ing one oni.Latterly hie hiad had two or three attacks a day.Onl physica-l examinati-on thbe-hieart was inot enlarged.An x-ray outline was taken, an(l this sliowed a hieart of niormial shiape, butt the aortic shadow was wider than normal.The hieart souinds were clear, thioughi the fir-St sounid was rathier highl-pitchied; the,
Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans
Authors: Tetsuo Iida, Noriko Hayashi, Takako Yamada, Yuko Yoshikawa, Shoko Miyazato, Yuka Kishimoto, Kazuhiro Okuma, Masaaki Tokuda, Ken Izumori
Journal: Metabolism (2009)
Allo-Immune Membranous Nephropathy and Recombinant Aryl Sulfatase Replacement Therapy
Authors: Hanna Debiec, Vassili Valayannopoulos, Olivia Boyer, Laure-Hélène Nöel, Patrice Callard, Hélène Sarda, Pascale de Lonlay, Patrick Niaudet, Pierre Ronco
Journal: Journal of the American Society of Nephrology (2013)

Nephrotic syndrome was reported in a highly-sensitized patient receiving enzyme replacement therapy (ERT) for Pompe disease, but the prevalence of ERT-induced renal complications and mechanisms to facilitate readministration of ERT in these patients remain unexplored. This work identifies a new antigen responsible for secondary membranous nephropathy (MN) in a patient with mucopolysaccharidosis type VI caused by aryl sulfatase B (ASB) deficiency. ERT (recombinant human ASB [rhASB]; 1 mg/kg per week) started at the age of 4 years led to a high anti-rhASB titer and dramatically improved clinical manifestations. However, 16 months later, the patient suddenly developed nephrotic syndrome resistant to steroid therapy 1 week after orthopedic surgery. Examination of the kidney biopsy specimen revealed glomerular deposition of IgG (mostly IgG4, C3, and C5b-9) in a granular pattern typical of MN. Double immunofluorescence staining showed that subepithelial granular deposits contained rhASB colocalized with IgG. Ig eluted from the patient's biopsy specimen reacted specifically with rhASB. On discontinuation of ERT, proteinuria progressively decreased, but the patient's clinical condition markedly deteriorated. Induction of tolerance to rhASB was initiated by coadministration of low-dose corticosteroids, rituximab, intravenous Igs, and oral methotrexate. ERT was resumed 8 weeks after starting immunosuppressive therapy without inducing a rebound of antibody titer or an increase in proteinuria. We conclude that the allo-immune response to the recombinant rhASB caused the nephropathy. Considering the critical requirement for ERT in patients with such enzyme deficiencies, immune tolerance induction should be advocated in the patients with allo-immune MN.
Progressive Familial Hypertrophic Neuritis
Authors: E. L. Cooper
Journal: BMJ (1936)

<h3><b>Background</b></h3> People with spinal cord injury (SCI) may benefit from resistive inspiratory muscle training (RIMT). Current evidence is weak, and little is known about the effect on functional outcomes and long-term effects. <h3><b>Objective</b></h3> The purpose of this study was to assess immediate and long-term effects of RIMT in people with SCI. <h3><b>Design</b></h3> This was a single-blinded randomized controlled trial. <h3><b>Setting</b></h3> The study was conducted at 4 specialized SCI units in the Netherlands. <h3><b>Patients</b></h3> The study participants were 40 people with SCI (15 with motor complete tetraplegia, 16 with incomplete tetraplegia, 8 with motor complete paraplegia, and 1 with incomplete paraplegia) who had impaired pulmonary function and were admitted for initial inpatient rehabilitation. <h3><b>Intervention</b></h3> Study participants were randomized to an RIMT group or a control group. All participants received usual rehabilitation care. In addition, participants in the intervention group performed RIMT with a threshold trainer. <h3><b>Measurements</b></h3> Measurements were performed at baseline, after 8 weeks of intervention, 8 weeks later, and 1 year after discharge from inpatient rehabilitation. Primary outcome measures were: respiratory muscle function, lung volumes and flows, and perceived respiratory function. Secondary outcome measures concerned patient functioning, which included health-related quality of life, limitations in daily life due to respiratory problems, and respiratory complications. <h3><b>Results</b></h3> During the intervention period, maximum inspiratory pressure (MIP) improved more in the RIMT group than in the control group (11.7 cm H<sub>2</sub>O, 95% confidence interval=4.3 to 19.0). At follow-up, this effect was no longer significant. No effect on other primary or secondary outcome measures was found except for an immediate effect on mental health. <h3><b>Limitations</b></h3> The sample size was insufficient to study effects on respiratory complications. <h3><b>Conclusions</b></h3> Resistive inspiratory muscle training has a positive short-term effect on inspiratory muscle function in people with SCI who have impaired pulmonary function during inpatient rehabilitation.
Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis
Authors: Srividya Seshadri, Sesh Kamal Sunkara
Journal: Human Reproduction Update (2013)

Embryo implantation is a complex process involving maternal hormonal changes, immune responses and maturational events in the embryo. A pregnancy could fail when these events are not synchronized. It is speculated that in women, an elevation of natural killer (NK) cells may have an effect on reproductive performance, and NK cell levels in blood are currently being used as a diagnostic test to guide the initiation of therapies in patients with infertility. We conducted a systematic review to evaluate the (i) levels of NK cells in blood and endometrium in infertile versus fertile women, (ii) association between NK cells and IVF outcome, (iii) levels of NK cells in blood and endometrium in women with recurrent miscarriage (RM) versus controls. The following electronic databases were searched: Medline, EMBASE, Cochrane Library, Web of Science and National Research Register. A total of 22 studies were included. Meta-analysis of studies that evaluated peripheral and uterine NK (uNK) cell percentages in infertile versus fertile women showed no significant difference between the two groups [standardized mean difference (SMD) −0.33; 95% confidence intervals (CI) −1.06, 0.4; P = 0.37; SMD −1.82; 95% CI −4.80, 1.17; P = 0.23 respectively]. Pooling of studies that reported peripheral NK cells as numbers showed significantly higher NK cell numbers in infertile women compared with fertile controls (SMD 3.16; 95% CI 1.07, 5.24; P = 0.003). Meta-analysis of studies that evaluated the role of NK cells in IVF outcome showed no significant difference in live birth rates in women with elevated NK cells or NK cell activity compared with women without elevated peripheral NK cells or NK cell activity (NK activity assessed using a cytotoxicity assay) (relative risk 0.57; 95% CI 0.06, 5.22; P = 0.62). Meta-analysis of studies that evaluated peripheral NK cell percentages in women with RM versus controls showed significantly higher NK cell percentages in women with RM (SMD 1.36; 95% CI 0.04, 2.69; P = 0.04). Meta-analysis of studies that evaluated peripheral NK cell numbers showed significantly higher NK cell numbers in women with RM compared with controls (SMD 0.81; 95% CI 0.47, 1.16; P < 0.00001). Meta-analysis of studies that evaluated uNK cells showed no significant difference in women with RM compared with controls (SMD 0.40; 95% CI −1.24, 2.04; P = 0.63). Further research is needed before NK cell assessment can be recommended as a diagnostic tool in the context of female infertility or RM. There is no clear explanation as to why the results differ when data for NK cells are expressed as numbers or a percentage. On the basis of current evidence, NK cell analysis and immune therapy should be offered only in the context of clinical research.
P198 New Approaches To The Culture Of Mycobacterium Abscessus Complex From Patients With Cystic Fibrosis
Authors: J. Foweraker, S. Jalili, V. Athithan, D. Grogono, M. Curran, R. Floto
Journal: Thorax (2014)

<h3>Introduction</h3> M.abscessus complex (Mab) are Rapid Growing Mycobacteria (RGM) that can cause severe infection. Prevalence is increasing and a recent study using whole genome sequencing showed cross infection between Cystic Fibrosis patients. Frequent surveillance for Mab infection may allow earlier diagnosis and prevent spread. Automated broth (e.g. MGIT), is a sensitive rapid method for mycobacterial culture. Decontamination is needed to kill other bacteria and yeasts before culturing CF sputa in MGIT, but decontamination may reduce Mab numbers. Other possibilities include chlorhexidine decontamination which yields more Mab but is incompatible with MGIT. Some mycobacteria grow directly from sputum on <i>Burkholderia cepacia</i> selective agar (Bcc) after extended incubation, without prior decontamination. The aim of this study was to improve Mab culture from CF sputum. <h3>Methods</h3> We compared MGIT culture of CF sputa with extended incubation of Bcc used in the routine laboratory. We compared growth of 30 known Mab on 3 formulations of Bcc and 2 Middlebrooke selective agars. We took 12 sputa from 9 CF patients with Mab infection and compared MGIT with culture on selective agars or chlorhexidine decontamination followed by culture onto non selective agar. Mycobacteria were identified by the National Mycobacterium Reference Laboratory and an in house PCR. <h3>Results</h3> Eighteen of 515 CF sputa grew RGM (9 on Bcc agar and MGIT, 3 MGIT alone, 4 Bcc alone and 2 on Bcc with no MGIT culture). Contamination with other bacteria and fungi made it extremely difficult to see RGM on the routine Bcc. Thirty sequenced M.abscessus abscessus, M.bolletii and M. massilliense all grew on the 3 commercial Bcc and 2 Middlebrooke agars. One Bcc and one Middlebrooke agar successfully cultured RGM from all 12 sputa with fewest contaminants. Chlorhexidine decontamination and blood agar was effective but labour-intensive. Only 8 of 12 MGIT cultures grew RGM. There was no difference in time to positive culture between agar and MGIT. <h3>Conclusion</h3> Culture onto selective agar may be more sensitive than MGIT. It is quantitative and provides pure culture for identification, typing and susceptibility testing. This may be a sensitive cost-effective way to screen sputa from patients at risk.
Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors.
Authors: M A Caligiuri, A Zmuidzinas, T J Manley, H Levine, K A Smith, J Ritz
Journal: The Journal of Experimental Medicine (1990)

In this study, we have used radiolabeled IL-2 binding assays, Northern blot analysis, immunofluorescent flow cytometry and cell sorting, as well as proliferation and cytotoxicity assays to perform an extensive phenotypic and functional characterization of the IL-2 receptor in normal resting human peripheral blood lymphocytes. Our results indicate that almost all T cells (greater than 98%) express neither the high affinity IL-2 receptor nor the functional intermediate affinity p75 chain of the IL-2 receptor without prior activation. In contrast, most NK cells constitutively express the isolated intermediate affinity p75 IL-2 receptor. In addition, a subpopulation of NK cells, distinguished by high density expression of the NKH1 antigen, constitutively express the high affinity IL-2 receptor, in addition to an excess of the isolated intermediate affinity p75 IL-2 receptor. These NKH1bright+ cells exhibit a brisk proliferative response to IL-2, similar to that seen with antigen-activated T cells, yet do so in the absence of any known antigenic stimuli. No other resting peripheral blood lymphocyte population, including CD4+, CD8+, and CD20 cells, exhibits this property. The intermediate affinity p75 IL-2 receptor, as it exists in its isolated form on resting NK cells, does not transduce a growth signal equivalent to that seen in NK cells expressing the high affinity IL-2 receptor, despite doses of IL-2 that are known to fully saturate the isolated p75 chain. This strongly suggests that additional structural or functional components are involved in generating the proliferative response following the binding of IL-2 to the high affinity heterodimeric form of the IL-2 receptor. The constitutive expression of this functional high affinity IL-2 receptor on a small population of resting NK cells provides further evidence in support of a role for these cells in the host's early defense against viral infection or malignant transformation, before the more delayed but specific T cell response.
P2X Receptors and Nociception
Authors: Boris A. Chizh, Peter Illes
Journal: Pharmacological Reviews (2001)

The potential importance for nociception of P2X receptors, the ionotropic receptors activated by ATP, is underscored by the variety of pain states in which this endogenous ligand can be released. Several important findings have been made recently indicating that P2X receptors can be involved in pain mechanisms both centrally and in the periphery. The roles of ATP at these two sites and the P2X receptor subtypes involved appear to be different. In the periphery, ATP can be released as a result of tissue injury, visceral distension, or sympathetic activation and can excite nociceptive primary afferents by acting at homomeric P2X(3) or heteromeric P2X(2/3) receptors. Centrally, ATP released from central afferent terminals or second order neurons can modulate neurotransmitter release or postsynaptically activate neurons involved in central nociceptive transmission, with P2X(2), P2X(4), P2X(6), and some other receptors being potentially involved. Evidence from in vivo studies suggests that peripheral ATPergic mechanisms are most important under conditions of acute tissue injury and inflammation whereas the relevance of central mechanisms appears to be more limited. Furthermore, the release of ATP and P2X receptor-mediated afferent activation appear to have been implicated in visceral and neuropathic pain; the importance of the ATPergic component in these states needs to be investigated further. Thus, peripheral P2X receptors, and homomeric P2X(3) and/or heteromeric P2X(2/3) receptors in particular, constitute attractive targets for analgesic drugs. The development of selective antagonists of these receptors, suitable for a systemic in vivo use although apparently difficult, may prove a useful strategy to generate analgesics with a novel mechanism of action.
Stimulation of gastrin release by bombesin and canine gastrin-releasing peptides. Studies with isolated canine G cells in primary culture.
Authors: K Sugano, J Park, A H Soll, T Yamada
Journal: Journal of Clinical Investigation (1987)

Bombesin, a polypeptide derived from frog skin, has been shown to stimulate gastrin release from the gastric antrum in vivo and in vitro. To elucidate the mechanisms of this effect, we developed a method to culture isolated and enriched G cells from canine stomach. After digestion of antral mucosa with collagenase and EDTA, dispersed cells were fractionated by counterflow elutriation then cultured on a collagen support. Bombesin and three molecular forms of canine gastrin-releasing peptides all stimulated gastrin release from G cells in a dose-dependent manner. The effect of bombesin was suppressed by somatostatin and potentiated by dibutyryl cyclic AMP (10(-3) M) but not by carbachol (10(-6) M). Extracellular calcium depletion attenuated the stimulation of gastrin release by bombesin but not by forskolin. These findings suggest that the bombesin family peptides directly activate G cells through calcium-dependent mechanisms to cause gastrin release.
Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors.
Authors: I Goldschneider, K L Komschlies, D L Greiner
Journal: The Journal of Experimental Medicine (1986)

We describe a quantitative intrathymic (i.t.) adoptive transfer system for detecting thymocyte precursor cells in rats and mice. In this system, the generation of donor-origin thymocytes is analyzed on the FACS after the injection of test cells directly into the thymus of sublethally irradiated, histocompatible, RT-7 (rat) or Ly-1 (mouse) alloantigen-disparate recipients. Like the standard i.v. adoptive transfer assays for prothymocytes, the i.t. transfer assay is time, dose, and irradiation dependent. However, unlike the i.v. assays, the i.t. assay is highly sensitive, independent of cell migration, and specific for T-lineage precursor cells. Thus, the i.t. system requires between 25- and 50-fold fewer precursor cells than do the i.v. systems to generate a given number of donor-origin thymocytes; it detects nonmigratory as well as migratory subsets of precursor cells; it detects prethymic and intrathymic precursor cells with equal facility; and it produces a discrete, self-limited wave of donor-origin thymocytes and peripheral T cells. Moreover, neither hemopoietic nor lymphopoietic stem cell chimerism occurs at extrathymic sites. Comparison of the kinetics of thymocytopoiesis in the i.t. and i.v. transfer systems suggest that the seeding efficiency of prothymocytes in the i.v. assay approximates 0.04; the lag phase of the time-response curve is not due to a delay in the entry of prothymocytes into the thymus; and the relative amount of thymocyte precursor activity in various lymphohemopoietic tissues is highest in bone marrow, lowest (or absent) in lymph node, and intermediate in spleen, blood, and thymus. Moreover, the occurrence of saturation kinetics in the dose-response curve of the i.t. system supports the hypothesis that a finite number of microenvironmental niches for prothymocytes may exist in the thymus. These initial observations will require confirmation and extension in future studies. However, based on the present findings and related observations, we anticipate that the i.t. adoptive transfer system will contribute importantly to the definitive analysis of both normal and abnormal thymocytopoiesis.