tbuckley/cabot-search huggingface dataset:
Majority-rule reduced consensus trees and their use in bootstrapping
Authors: M. Wilkinson
Journal: Molecular Biology and Evolution (1996)

Bootstrap analyses are usually summarized with majority-rule component consensus trees. This consensus method is based on replicated components and, like all component consensus methods, it is insensitive to other kinds of agreement between trees. Recently developed reduced consensus methods can be used to summarize much additional agreement on hypothesised phylogenetic relationships among multiple trees. The new methods are "strict" in the sense that they require agreement among all the trees being compared for any relationships to be represented in a consensus tree. Majority-rule reduced consensus methods are described and their use in bootstrap analyses is illustrated with a hypothetical and a real example. The new methods provide summaries of the bootstrap proportions of all n-taxon statements/partitions and facilitate the identification of hypotheses of relationships that are supported by high bootstrap proportions, in spite of a lack of support for particular components or clades. In practice majority-rule reduced consensus profiles may contain many trees. The size of the profile can be reduced by constraints on minimal bootstrap proportions and/or cardinality of the included trees. Majority-rule reduced consensus trees can also be selected a posteriori from the profile. Surrogates to the majority-rule reduced consensus methods using partition tables or tree pruning options provided by widely used phylogenetic inference software are also described. The methods are designed to produce more informative summaries of bootstrap analyses and thereby foster more informed assessment of the strengths and weaknesses of complex phylogenetic hypotheses.
The Effects of Platelet-Derived Growth Factor Antagonism in Experimental Glomerulonephritis Are Independent of the Transforming Growth Factor–β System
Authors: Tammo Ostendorf, Uta Kunter, Claudia van Roeyen, Steven Dooley, Nebojsa Janjic, Judy Ruckman, Frank Eitner, Jürgen Floege
Journal: Journal of the American Society of Nephrology (2002)

Platelet-derived growth factor B-chain (PDGF-B)- and transforming growth factor beta (TGF-beta)-mediated accumulation of extracellular matrix proteins contributes to many progressive renal diseases. In vivo, specific antagonism of either PDGF-B or TGF-beta in experimental mesangioproliferative glomerulonephritis resulted in an almost complete inhibition of matrix protein accumulation, which suggests an interaction between signaling pathways of these two growth factors. Because nothing is known on the nature of this possible interaction, PDGF-B was antagonized in the rat anti-Thy 1.1 model of glomerulonephritis by use of specific aptamers and its effects on the TGF-beta system were investigated. Antagonism of PDGF-B led to a significant reduction of glomerular matrix accumulation compared with scrambled aptamer-treated nephritic controls. PDGF-B antagonism had no effect on the overexpression of glomerular TGF-beta mRNA, TGF-beta protein, or the expression of TGF-beta receptor type I and II mRNA. By immunohistology, it was possible to detect overexpression of the cytoplasmic TGF-beta signaling molecules Smad2 (agonistic) and Smad7 (antagonistic) in glomeruli of nephritic control rats which peaked on day 7 after disease induction, i.e., the peak of mesangial cell proliferation in this model. However, immunohistology and Western blot analysis again revealed no difference in the glomerular expression of both Smad proteins between PDGF-B antagonized and nonantagonized nephritic animals. In addition, no difference in the glomerular expression of phosphorylated Smad2 (P-Smad2) was detected between the differently treated nephritic groups. These observations suggest that the effects of PDGF-B antagonism are independent of TGF-beta in mesangioproliferative glomerulonephritides.
The effectiveness of BCG vaccination in preventing<i>Mycobacterium tuberculosis</i>infection and disease in Greenland
Authors: S W Michelsen, B Soborg, A Koch, L Carstensen, S T Hoff, E M Agger, T Lillebaek, H C F Sorensen, J Wohlfahrt, M Melbye
Journal: Thorax (2014)

<h3>Background</h3> The BCG vaccine9s ability to prevent <i>Mycobacterium tuberculosis</i> infection (MTI) remains highly debated. In Greenland, BCG vaccination was introduced in 1955, but was temporarily discontinued (1991–1996) due to nationwide policy changes. The study aimed to use the transient stop in BCG vaccination to evaluate the effect of vaccination on MTI prevalence and TB incidence. <h3>Methods</h3> MTI study: A cross-sectional study (2012), comprising East Greenlanders born during 1982–2006, evaluated the effect of BCG vaccination on MTI prevalence; a positive interferon γ release assay defined an MTI case. Associations were estimated using logistic regression. TB study: a cohort study covering the same birth cohorts with follow-up until 2012 evaluated the vaccine9s effect on TB incidence. A personal identifier allowed for follow-up in the TB notification system. Associations were estimated using Cox regression. <h3>Results</h3> MTI study: Included 953 participants; 81% were BCG-vaccinated; 29% had MTI, 23% among vaccinated and 57% among non-vaccinated. BCG vaccination reduced the odds of MTI, OR 0.52 (95% CI 0.32 to 0.85), p=0.01. Vaccine effectiveness against MTI was 20%. TB study: Included 1697 participants followed for 21 148 person-years. 6% were notified with TB, 4% among vaccinated and 11% among non-vaccinated. BCG vaccination reduced the risk of TB, HR 0.50 (95% CI 0.26 to 0.95), p=0.03, yielding a vaccine effectiveness of 50%. <h3>Conclusions</h3> BCG vaccination was effective in reducing both MTI and TB disease among children and young adults in a TB high-endemic setting in Greenland.
TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration
Authors: Shinichiro Yamamoto, Shunichi Shimizu, Shigeki Kiyonaka, Nobuaki Takahashi, Teruaki Wajima, Yuji Hara, Takaharu Negoro, Toshihito Hiroi, Yuji Kiuchi, Takaharu Okada, Shuji Kaneko, Ingo Lange, Andrea Fleig, Reinhold Penner, Miyuki Nishi, Hiroshi Takeshima, Yasuo Mori
Journal: Nature Medicine (2008)
A Major Clade of Prokaryotes with Ancient Adaptations to Life on Land
Authors: F. U. Battistuzzi, S. B. Hedges
Journal: Molecular Biology and Evolution (2008)

Evolutionary trees of prokaryotes usually define the known classes and phyla but less often agree on the relationships among those groups. This has been attributed to the effects of horizontal gene transfer, biases in sequence change, and large evolutionary distances. Furthermore, higher level clades of prokaryote phyla rarely are supported by information from ecology and cell biology. Nonetheless, common patterns are beginning to emerge as larger numbers of species are analyzed with sophisticated methods. Here, we show how combined evidence from phylogenetic, cytological, and environmental data support the existence of an evolutionary group that appears to have had a common ancestor on land early in Earth's history and includes two-thirds of known prokaryote species. Members of this terrestrial clade (Terrabacteria), which includes Cyanobacteria, the gram-positive phyla (Actinobacteria and Firmicutes), and two phyla with cell walls that differ structurally from typical gram-positive and gram-negative phyla (Chloroflexi and Deinococcus–Thermus), possess important adaptations such as resistance to environmental hazards (e.g., desiccation, ultraviolet radiation, and high salinity) and oxygenic photosynthesis. Moreover, the unique properties of the cell wall in gram-positive taxa, which likely evolved in response to terrestrial conditions, have contributed toward pathogenicity in many species. These results now leave open the possibility that terrestrial adaptations may have played a larger role in prokaryote evolution than currently understood.
Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 (<i>Tlr4</i>)
Authors: Salman T. Qureshi, Line Larivière, Gary Leveque, Sophie Clermont, Karen J. Moore, Philippe Gros, Danielle Malo
Journal: The Journal of Experimental Medicine (1999)

Bacterial lipopolysaccharide (LPS) provokes a vigorous, generalized proinflammatory state in the infected host. Genetic regulation of this response has been localized to the Lps locus on mouse chromosome 4, through study of the C3H/HeJ and C57BL/10ScCr inbred strains. Both C3H/HeJ and C57BL/10ScCr mice are homozygous for a mutant Lps allele (Lpsd/d) that confers hyporesponsiveness to LPS challenge, and therefore exhibit natural tolerance to its lethal effects. Genetic and physical mapping of 1,345 backcross progeny segregating this mutant phenotype confined Lps to a 0.9-cM interval spanning 1.7 Mb. Three transcription units were identified within the candidate interval, including Toll-like receptor 4 (Tlr4), part of a protein family with members that have been implicated in LPS-induced cell signaling. C3H/HeJ mice have a point mutation within the coding region of the Tlr4 gene, resulting in a nonconservative substitution of a highly conserved proline by histidine at codon 712, whereas C57BL/ 10ScCr mice exhibit a deletion of Tlr4. Identification of distinct mutations involving the same gene at the Lps locus in two different hyporesponsive inbred mouse strains strongly supports the hypothesis that altered Tlr4 function is responsible for endotoxin tolerance.
Adverse Prognostic Significance of <i>KIT</i> Mutations in Adult Acute Myeloid Leukemia With inv(16) and t(8;21): A Cancer and Leukemia Group B Study
Authors: Peter Paschka, Guido Marcucci, Amy S. Ruppert, Krzysztof Mrózek, Hankui Chen, Rick A. Kittles, Tamara Vukosavljevic, Danilo Perrotti, James W. Vardiman, Andrew J. Carroll, Jonathan E. Kolitz, Richard A. Larson, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2006)

To analyze the prognostic impact of mutated KIT (mutKIT) in core-binding factor acute myeloid leukemia (AML) with inv(16)(p13q22) and t(8;21)(q22;q22).Sixty-one adults with inv(16) and 49 adults with t(8;21), assigned to postremission therapy with repetitive cycles of higher dose cytarabine were analyzed for mutKIT in exon 17 (mutKIT17) and 8 (mutKIT8) by denaturing high-performance liquid chromatography and direct sequencing at diagnosis. The median follow-up was 5.3 years.Among patients with inv(16), 29.5% had mutKIT (16% with mutKIT17 and 13% with sole mutKIT8). Among patients with t(8;21), 22% had mutKIT (18% with mutKIT17 and 4% with sole mutKIT8). Complete remission rates of patients with mutKIT and wild-type KIT (wtKIT) were similar in both cytogenetic groups. In inv(16), the cumulative incidence of relapse (CIR) was higher for patients with mutKIT (P = .05; 5-year CIR, 56% v 29%) and those with mutKIT17 (P = .002; 5-year CIR, 80% v 29%) compared with wtKIT patients. Once data were adjusted for sex, mutKIT predicted worse overall survival (OS). In t(8;21), mutKIT predicted higher CIR (P = .017; 5-year CIR, 70% v 36%), but did not influence OS.We report for the first time that mutKIT, and particularly mutKIT17, confer higher relapse risk, and both mutKIT17 and mutKIT8 appear to adversely affect OS in AML with inv(16). We also confirm the adverse impact of mutKIT on relapse risk in t(8;21) AML. We suggest that patients with core-binding factor AML should be screened for mutKIT at diagnosis for both prognostic and therapeutic purposes, given that activated KIT potentially can be targeted with novel tyrosine kinase inhibitors.
Different susceptibilities to the formation of cholesterol gallstones in mice
Authors: Manfred Alexander, Oscar W. Portman
Journal: Hepatology (1987)

In the search for an animal model of genetic determinants of cholesterol cholelithiasis, we found strain, gender and individual differences in mice. Male black (C57BL6J) mice had a 50% incidence of cholesterol gallstones after they consumed lithogenic food similar to that used by Tepperman et al. for 2 weeks, whereas similarly treated male agouti (CBA/J) mice and females of both strains were free of gallstones. The male and female mice of both strains were fertile at 8 weeks of age, and the male black mice were first susceptible to induction of gallstones at 24 weeks of age. Male agouti mice of the same age did not form gallstones until they had consumed the lithogenic food for 8 weeks. The gallbladder biles of both strains were supersaturated with cholesterol during the lithogenic regimen. The male agouti mice had much higher fractional turnover rates of [24- 14 C]cholic acid than did the male black mice. In spite of their small total cholate pools, the agouti mice had higher rates of new cholate synthesis than did the black mice. The rate of disappearance of [1,2- 3 H]cholesterol from the blood was higher in the male agouti than in the black mice. The gallbladders of the agouti mice contained less bile and weighed less empty than gallbladders of the black mice. They also did not increase in volume in response to the lithogenic diet as much as gallbladders of the black mice. The difference in gallstone induction times between male and female black mice was as great as the difference between the two strains. In spite of their resistance to gallstone formation, the black females had gallbladder bile that was usually supersaturated with cholesterol; however, in one experiment their increase in biliary cholesterol concentration was delayed compared to that of males. The concentrations of esterified cholesterol in the liver were higher in the females than in the males, and the plasma cholesterol concentrations were lower. The pattern of metabolism of labeled cholate and cholesterol in the black females was intermediate between that of black male and agouti male mice. The empty gallbladders of the black females were heavier and increased more in volume during the lithogenic regimen than those of the black males. The black males that formed gallstones had bile which was more supersaturated with cholesterol after 2 weeks on the lithogenic regimen than the black males which were free of stones. They also had lower rates of new cholate synthesis and lower concentrations of esterified cholesterol in the liver than the animals which were free of stones. After 4 and 8 weeks of the experiment, the concentrations of esterified cholesterol in the livers of agouti mice with gallstones were also less than in the livers of those without stones. Thus, resistance to cholesterol gallstone formation in mice may be related to increased activities of the liver in converting cholesterol to bile acids and to esterified cholesterol.
Clinical and functional characteristics of patients two years after being affected by the soybean asthma epidemic in Barcelona.
Authors: J Sabria, J M Anto, J Sunyer, J Roca, F Morell, R Rodriguez-Roisin, M J Rodrigo, R Codina
Journal: Thorax (1994)

BACKGROUND--Patients affected during the asthma outbreaks caused by soybean dust inhalation in Barcelona presented with sudden onset of severe asthma followed by the rapid relief of symptoms after treatment. Two years after the epidemics ended, a case-control study was conducted in which the clinical, functional, and immunological characteristics of these asthma patients (a randomised sample of asthmatic patients admitted as emergency cases on epidemic days, n = 213) were compared with those of a control group (a random sample of asthmatic patients admitted as emergency cases for attacks of asthma on non-epidemic days, n = 170). METHODS--The study included the administration of the ATS-DLD78 standardised respiratory questionnaire, the measurement of atopy, and performance of spirometric tests and a methacholine inhalation test. RESULTS--Patients with epidemic asthma reported fewer symptoms of asthma, had attended emergency departments less frequently during the previous year for acute attacks of asthma, were taking fewer inhaled corticosteroids at the time of the study, and attended medical follow up less frequently than did the patients with non-epidemic asthma. However, the cases and controls showed no differences in ventilatory capacity or reactivity to the methacholine bronchoprovocation test. CONCLUSIONS--Two years after the end of the soybean epidemics, people affected by epidemic asthma had a favourable prognosis. This finding contrasts with a higher risk of life threatening asthma and death during the epidemics. This paradox could be the result of a complex interaction between host and conditions of exposure.
661 DIAGNOSTIC PERFORMANCE OF NON-INVASIVE SCORES FOR THE DIAGNOSIS OF LIVER FIBROSIS IN CHRONIC HEPATITIS B
Authors: V. Leroy, N. Sturm, C. Trocme, M.N. Hilleret, P. Faure, J.C. Renversez, F. Morel, J.P. Zarski
Journal: Journal of Hepatology (2008)
White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children
Authors: M Korppi, T Heiskanen-Kosma, M Leinonen
Journal: European Respiratory Journal (1997)

We evaluated the applicability of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and absolute neutrophil count (ANC), in the screening of pneumococcal (PNC) pneumonia in children. In 1981-1982, 161 children were treated for radiologically verified community-acquired pneumonia in the hospital during a period of 12 months. The Streptococcus pneumoniae aetiology of infection was studied by antigen, antibody and immune complex assays in acute and convalescent sera. In acute blood samples, CRP was measured by the immunonephelometric method, ESR by the Westergren method, WBC using an automatic cell counter, and thereafter the ANC was calculated after microscopic examination of peripheral smears. CRP and ESR were significantly higher in patients with alveolar (n=53) than in those with interstitial (n=108) pneumonia. CRP, ESR and ANC were significantly higher in PNC (n=29) than in viral (n=23) pneumonia. The values in mixed PNC and viral infections (n=17) were approximately midway between PNC and viral cases. All cases with serologic evidence of S. pneumoniae aetiology were combined (n=46) for calculation of diagnostic parameters. When a cut-off limit of 60 mg x L(-1) was used, CRP had a sensitivity of 26% and a specificity of 83% in the screening of PNC pneumonia. We conclude that C-reactive protein and erythrocyte sedimentation rate have a limited capacity to differentiate between pneumococcal and nonpneumococcal pneumonia. C-reactive protein is recommended as the first-line method of screening, and the value of 60 mg x L(-1) as the cut-off limit.
Atypical Protein Kinase Cι Expression and Aurothiomalate Sensitivity in Human Lung Cancer Cells
Authors: Roderick P. Regala, E. Aubrey Thompson, Alan P. Fields
Journal: Cancer Research (2008)

Abstract The antirheumatoid agent aurothiomalate (ATM) is a potent inhibitor of oncogenic PKCι. ATM inhibits non–small lung cancer (NSCLC) growth by binding PKCι and blocking activation of a PKCι-Par6-Rac1-Pak-Mek 1,2-Erk 1,2 signaling pathway. Here, we assessed the growth inhibitory activity of ATM in a panel of human cell lines representing major lung cancer subtypes. ATM inhibited anchorage-independent growth in all lines tested with IC50s ranging from ∼300 nmol/L to &amp;gt;100 μmol/L. ATM sensitivity correlates positively with expression of PKCι and Par6, but not with the PKCι binding protein p62, or the proposed targets of ATM in rheumatoid arthritis (RA), thioredoxin reductase 1 or 2. PKCι expression profiling revealed that a significant subset of primary NSCLC tumors express PKCι at or above the level associated with ATM sensitivity. ATM sensitivity is not associated with general sensitivity to the cytotoxic agents cis-platin, placitaxel, and gemcitabine. ATM inhibits tumorigenicity of both sensitive and insensitive lung cell tumors in vivo at plasma drug concentrations achieved in RA patients undergoing ATM therapy. ATM inhibits Mek/Erk signaling and decreases proliferative index without effecting tumor apoptosis or vascularization in vivo. We conclude that ATM exhibits potent antitumor activity against major lung cancer subtypes, particularly tumor cells that express high levels of the ATM target PKCι and Par6. Our results indicate that PKCι expression profiling will be useful in identifying lung cancer patients most likely to respond to ATM therapy in an ongoing clinical trial. [Cancer Res 2008;68(14):5888–95]
Accounting for Uncertainty in the Tree Topology Has Little Effect on the Decision-Theoretic Approach to Model Selection in Phylogeny Estimation
Authors: Zaid Abdo, Vladimir N. Minin, Paul Joyce, Jack Sullivan
Journal: Molecular Biology and Evolution (2004)

Currently available methods for model selection used in phylogenetic analysis are based on an initial fixed-tree topology. Once a model is picked based on this topology, a rigorous search of the tree space is run under that model to find the maximum-likelihood estimate of the tree (topology and branch lengths) and the maximum-likelihood estimates of the model parameters. In this paper, we propose two extensions to the decision-theoretic (DT) approach that relax the fixed-topology restriction. We also relax the fixed-topology restriction for the Bayesian information criterion (BIC) and the Akaike information criterion (AIC) methods. We compare the performance of the different methods (the relaxed, restricted, and the likelihood-ratio test [LRT]) using simulated data. This comparison is done by evaluating the relative complexity of the models resulting from each method and by comparing the performance of the chosen models in estimating the true tree. We also compare the methods relative to one another by measuring the closeness of the estimated trees corresponding to the different chosen models under these methods. We show that varying the topology does not have a major impact on model choice. We also show that the outcome of the two proposed extensions is identical and is comparable to that of the BIC, Extended-BIC, and DT. Hence, using the simpler methods in choosing a model for analyzing the data is more computationally feasible, with results comparable to the more computationally intensive methods. Another outcome of this study is that earlier conclusions about the DT approach are reinforced. That is, LRT, Extended-AIC, and AIC result in more complicated models that do not contribute to the performance of the phylogenetic inference, yet cause a significant increase in the time required for data analysis.
Long-term complete remission with belinostat in a patient with chemotherapy refractory peripheral t-cell lymphoma
Authors: Peter Reimer, Shanta Chawla
Journal: Journal of Hematology & Oncology (2013)

Peripheral T/NK-cell lymphomas (PTCL) are rare malignancies with a poor prognosis. Due to the lack of randomised studies, standard therapy has not been established. First-line treatment with anthracycline-based polychemotherapy followed by consolidation with high-dose therapy and autologous stem cell transplant in responding patients has demonstrated good feasibility with low toxicity in prospective studies and is widely used in eligible patients. In relapsed and refractory patients, who are not candidates for transplant approaches, therapeutic options are limited and are usually palliative. Several new agents are currently under investigation to improve the outcome of PTCL in the first line and salvage settings. Belinostat, a histone deacetylase (HDAC) inhibitor, has demonstrated broad antineoplastic activity in preclinical studies, and promising results in advanced relapsed/refractory lymphomas. Here, we report the case of a 73 year old patient with heavily pre-treated refractory PTCL in complete remission with belinostat for 39 months.