tbuckley/cabot-search huggingface dataset:
Comparison of dot chromosome sequences from D. melanogaster and D. virilisreveals an enrichment of DNA transposon sequences in heterochromatic domains
Authors: Elizabeth E Slawson, Christopher D Shaffer, Colin D Malone, Wilson Leung, Elmer Kellmann, Rachel B Shevchek, Carolyn A Craig, Seth M Bloom, James Bogenpohl, James Dee, Emiko TA Morimoto, Jenny Myoung, Andrew S Nett, Fatih Ozsolak, Mindy E Tittiger, Andrea Zeug, Mary-Lou Pardue, Jeremy Buhler, Elaine R Mardis, Sarah CR Elgin
Journal: Genome biology (2006)

Abstract Background Chromosome four of Drosophila melanogaster , known as the dot chromosome, is largely heterochromatic, as shown by immunofluorescent staining with antibodies to heterochromatin protein 1 (HP1) and histone H3K9me. In contrast, the absence of HP1 and H3K9me from the dot chromosome in D. virilis suggests that this region is euchromatic. D. virilis diverged from D. melanogaster 40 to 60 million years ago. Results Here we describe finished sequencing and analysis of 11 fosmids hybridizing to the dot chromosome of D. virilis (372,650 base-pairs) and seven fosmids from major euchromatic chromosome arms (273,110 base-pairs). Most genes from the dot chromosome of D. melanogaster remain on the dot chromosome in D. virilis , but many inversions have occurred. The dot chromosomes of both species are similar to the major chromosome arms in gene density and coding density, but the dot chromosome genes of both species have larger introns. The D. virilis dot chromosome fosmids have a high repeat density (22.8%), similar to homologous regions of D. melanogaster (26.5%). There are, however, major differences in the representation of repetitive elements. Remnants of DNA transposons make up only 6.3% of the D. virilis dot chromosome fosmids, but 18.4% of the homologous regions from D. melanogaster ; DINE-1 and 1360 elements are particularly enriched in D. melanogaster . Euchromatic domains on the major chromosomes in both species have very few DNA transposons (less than 0.4 %). Conclusion Combining these results with recent findings about RNAi, we suggest that specific repetitive elements, as well as density, play a role in determining higher-order chromatin packaging.
Tamoxifen Use and Osteoporotic Fracture Risk: A Population-Based Analysis
Authors: Andrew L. Cooke, Colleen Metge, Lisa Lix, Heather J. Prior, William D. Leslie
Journal: Journal of Clinical Oncology (2008)

Purpose Although tamoxifen has been shown to increase bone mineral density in clinical trials, it is less clear whether this significantly affects fracture rates. Even fewer data are available on skeletal outcomes when tamoxifen is used outside of the context of a clinical trial. A population-based case-control study was undertaken to determine whether tamoxifen use is associated with osteoporotic fractures in routine clinical practice. Patients and Methods Population-based administrative data for the Province of Manitoba, Canada, were examined for tamoxifen use and nontraumatic fracture codes in women 50 years of age or older. Women with osteoporotic fractures (vertebral, wrist or hip; n = 11,096) from 1996 to 2004 were each compared with three controls without fracture, matched for age, ethnicity, and comorbidity (n = 33,209). Tamoxifen use was classified as never, past use, or current use. Results Lower osteoporotic fracture rates were associated with current tamoxifen use (univariate odds ratio [OR] = 0.68; 95% CI, 0.55 to 0.84). After controlling for demographic and medical diagnoses known to affect fracture risk, current use was associated with a significantly reduced overall osteoporotic fracture risk (adjusted OR = 0.68; 95% CI, 0.55 to 0.88) and of hip fractures (adjusted OR = 0.47; 95% CI, 0.28 to 0.77). Neither recent nor remote past tamoxifen use was associated with reduced osteoporotic fracture risk. Breast cancer was not independently associated with osteoporotic fractures (adjusted OR = 0.95; 95% CI, 0.81 to 1.12). Conclusion In a population-based case-control study, current tamoxifen use was associated with a substantial reduction in osteoporotic fractures.
SOCIAL MOBILITY AND MENTAL ILLNESS
Authors: A. B. HOLLINGSHEAD, F. C. REDLICH
Journal: American Journal of Psychiatry (1955)

1. The hypothesis that social mobility is related to psychoneurosis and schizophrenia was tested as part of a large study on social class and psychiatric disorders in the metropolitan New Haven community. 2. Methods in studying the social mobility of 25 psychoneurotics and 25 schizophrenics divided between social classes III and V and a number of control subjects are described. 3. These psychoneurotics and schizophrenics are more mobile than the control subjects. 4. There is a discrepancy between achieved and aspired mobility in the psychiatric patients. 5. The implications of the above findings for phenomenology, etiology, and treatment of psychoneurosis and schizophrenia are discussed.
Immunoregulatory T cell circuits in man. Alloantigen-primed inducer T cells activate alloantigen-specific suppressor T cells in the absence of the initial antigenic stimulus.
Authors: N K Damle, E G Engleman
Journal: The Journal of Experimental Medicine (1983)

Although alloantigen-specific suppressor T cells are generated in MLR, the cellular signals that lead to activation of suppressor T cells as opposed to cytotoxic T cells are unknown. The current study was undertaken to characterize interactions among T cell subsets involved in the generation of suppressor T cells in MLR. Human peripheral blood Leu-2+ (suppressor/cytotoxic) and Leu-3+ (helper/inducer) T cell subsets were activated with allogeneic non-T cells and then examined for their inductive effects on fresh autologous T cells. Fresh Leu-2+ cells proliferated in response to alloantigen-primed Leu-3+ cells and subsequently suppressed the response of fresh autologous Leu-3+ cells to the original, but not third party, allogeneic stimulator non-T cells. Moreover, only Leu-2+ cells that lacked the 9.3 marker, an antigen present on the majority of T cells including precursors of cytotoxic T cells, differentiated into suppressor cells. The alloantigen-specific suppressive effect of Leu-2+,9.3-cells was not mediated by cytolysis of allogeneic stimulator cells, nor could it be explained by alteration of MLR kinetics. Suppression was observed only when activated Leu-2+ cells were added to fresh MLRs within 24 h of initiation of cultures, suggesting that these cells block an early phase of the activation of Leu-3+ cells in MLR. These results indicate that alloantigen-primed inducer T cells can activate alloantigen-specific suppressor T cells in the absence of allogeneic stimulator cells.
Telephone administered cognitive behaviour therapy for treatment of obsessive compulsive disorder: randomised controlled non-inferiority trial
Authors: Karina Lovell, Debbie Cox, Gillian Haddock, Christopher Jones, David Raines, Rachel Garvey, Chris Roberts, Sarah Hadley
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To compare the effectiveness of cognitive behaviour therapy delivered by telephone with the same therapy given face to face in the treatment of obsessive compulsive disorder. <b>Design</b> Randomised controlled non-inferiority trial. <b>Setting</b> Two psychology outpatient departments in the United Kingdom. <b>Participants</b> 72 patients with obsessive compulsive disorder. <b>Intervention</b> 10 weekly sessions of exposure therapy and response prevention delivered by telephone or face to face. <b>Main outcome measures</b> Yale Brown obsessive compulsive disorder scale, Beck depression inventory, and client satisfaction questionnaire. <b>Results</b> Difference in the Yale Brown obsessive compulsive disorder checklist score between the two treatments at six months was −0.55 (95% confidence interval −4.26 to 3.15). Patient satisfaction was high for both forms of treatment. <b>Conclusion</b> The clinical outcome of cognitive behaviour therapy delivered by telephone was equivalent to treatment delivered face to face and similar levels of satisfaction were reported. <b>Trial registration</b> Current Controlled Trials ISRCTN500103984[controlled-trials.com].
Reducing the toll of road traffic accidents
Authors: R. C Denney
Journal: Journal of the Royal Society of Medicine (2003)

Rodger Charlton and Gary Smith (October 2003, JRSM1) refer to the sizeable number of deaths in motorcyclists. Although constituting only 4% of total road traffic accidents they contribute 14% of the deaths. 80% of motorcycle deaths are from head injury. I have patented and produced a prototype of a new design for head protection which has been shown by the Transport Research Laboratory to provide between 47–59% more protection against rotational forces than conventional helmets. This is a development of my observation that the scalp in the human head provides most of the protection against rotational forces, a major factor in head injury: the Phillips Helmet has a membrane which simulates the scalp in being able to slide over the surface of the shell as the scalp does over the skull. That existing helmet manufacturers are reluctant to take on this invention is maybe not surprising. More disturbing is the lack of response from the Department of Transport, to which I have written twice.
Peptide Aggregation in Neurodegenerative Disease
Authors: Regina M. Murphy
Journal: Annual Review of Biomedical Engineering (2002)

In the not-so-distant past, insoluble aggregated protein was considered as uninteresting and bothersome as yesterday's trash. More recently, protein aggregates have enjoyed considerable scientific interest, as it has become clear that these aggregates play key roles in many diseases. In this review, we focus attention on three polypeptides: beta-amyloid, prion, and huntingtin, which are linked to three feared neurodegenerative diseases: Alzheimer's, "mad cow," and Huntington's disease, respectively. These proteins lack any significant primary sequence homology, yet their aggregates possess very similar features, specifically, high beta-sheet content, fibrillar morphology, relative insolubility, and protease resistance. Because the aggregates are noncrystalline, secrets of their structure at nanometer resolution are only slowly yielding to X-ray diffraction, solid-state NMR, and other techniques. Besides structure, the aggregates may possess similar pathways of assembly. Two alternative assembly pathways have been proposed: the nucleation-elongation and the template-assisted mode. These two modes may be complementary, not mutually exclusive. Strategies for interfering with aggregation, which may provide novel therapeutic approaches, are under development. The structural similarities between protein aggregates of dissimilar origin suggest that therapeutic strategies successful against one disease may have broad utility in others.
Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells
Authors: J. Dannull
Journal: Journal of Clinical Investigation (2005)

In this study, we investigated whether elimination of CD4+/CD25+ Tregs using the recombinant IL-2 diphtheria toxin conjugate DAB(389)IL-2 (also known as denileukin diftitox and ONTAK) is capable of enhancing the immunostimulatory efficacy of tumor RNA-transfected DC vaccines. We show that DAB(389)IL-2 is capable of selectively eliminating CD25-expressing Tregs from the PBMCs of cancer patients without inducing toxicity on other cellular subsets with intermediate or low expression of CD25. DAB(389)IL-2-mediated Treg depletion resulted in enhanced stimulation of proliferative and cytotoxic T cell responses in vitro but only when DAB(389)IL-2 was omitted during T cell priming. DAB(389)IL-2 significantly reduced the number of Tregs present in the peripheral blood of metastatic renal cell carcinoma (RCC) patients and abrogated Treg-mediated immunosuppressive activity in vivo. Moreover, DAB(389)IL-2-mediated elimination of Tregs followed by vaccination with RNA-transfected DCs significantly improved the stimulation of tumor-specific T cell responses in RCC patients when compared with vaccination alone. Our findings may have implications in the design of immune-based strategies that may incorporate the Treg depletion strategy to achieve potent antitumor immunity with therapeutic impact.
Identification of Candidate Alkylator-Induced Cancer Susceptibility Genes by Whole Genome Scanning in Mice
Authors: Timothy S. Fenske, Christine McMahon, Deepa Edwin, Joseph C. Jarvis, James M. Cheverud, Matthew Minn, Vikram Mathews, Molly A. Bogue, Michael A. Province, Howard L. McLeod, Timothy A. Graubert
Journal: Cancer Research (2006)

Abstract Secondary malignancies are a serious adverse consequence of alkylator chemotherapy. The risk of developing an alkylator-associated malignancy is influenced by genetic background, although the relevant genetic factors are poorly understood. To screen for novel susceptibility factors, we established a mouse model of alkylator-induced malignancy. We exposed mice from 20 inbred strains to the prototypical alkylating agent, N-nitroso-N-ethylurea (ENU). ENU was a potent carcinogen in many of the strains tested, inducing 140 tumors in 240 ENU-treated mice (66% incidence of at least one tumor in evaluable mice), compared with a background incidence of 8% spontaneous tumors in 240 strain-, age-, and sex-matched control mice (relative risk, 8.4; P &amp;lt; 0.0001). A wide variety of tumor histologies were noted, including epithelial carcinomas, soft tissue sarcomas, and hematopoietic tumors. Cancer susceptibility was a heritable trait for the most common tumor types, lung adenocarcinoma (H2 = 0.25), T cell lymphoma (H2 = 0.19), and myeloid malignancies (H2 = 0.10). Quantitative trait locus mapping identified regions on chromosomes 3, 6, 9, and 15 containing candidate genes associated with lung adenoma, lung carcinoma, and lymphoma susceptibility. This novel mouse model recapitulates many features of human alkylator-associated cancer and supports the hypothesis that susceptibility to this syndrome is influenced by inherited polymorphisms that could be used to make informed clinical treatment decisions. (Cancer Res 2006; 66(10): 5029-38)
Short term improvement in exercise capacity and symptoms following exercise training in interstitial lung disease
Authors: A E Holland, C J Hill, M Conron, P Munro, C F McDonald
Journal: Thorax (2008)

Background: Interstitial lung disease (ILD) is characterised by exertional dyspnoea, exercise limitation and reduced quality of life. The role of exercise training in this diverse patient group is unclear. The aims of this study were to establish the safety of exercise training in ILD; its effects on exercise capacity, dyspnoea and quality of life; and whether patients with idiopathic pulmonary fibrosis (IPF) had similar responses to those with other types of ILD. Methods: 57 subjects with ILD (34 IPF) were randomised to receive 8 weeks of supervised exercise training or weekly telephone support. The 6 min walk distance (6MWD), incremental exercise test, modified Medical Research Council (MRC) dyspnoea score and Chronic Respiratory Disease Questionnaire (CRDQ) were performed at baseline, following intervention and at 6 months. Results: 80% of subjects completed the exercise programme and no adverse events were recorded. The 6MWD increased following training (mean difference to control 35 m, 95% CI 6 to 64 m). A significant reduction in MRC score was observed (0.7 points, 95% CI 0.1 to 1.3) along with improvements in dyspnoea (p = 0.04) and fatigue (p&lt;0.01) on the CRDQ. There was no change in peak oxygen uptake; however, exercise training reduced heart rate at maximum isoworkload (p = 0.01). There were no significant differences in response between those with and without IPF. After 6 months there were no differences between the training and control group for any outcome variable. Conclusions: Exercise training improves exercise capacity and symptoms in patients with ILD, but these benefits are not sustained 6 months following intervention. Trial registration number: NCT00168285
Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow
Authors: Jaeyop Lee, Gaëlle Breton, Thiago Yukio Kikuchi Oliveira, Yu Jerry Zhou, Arafat Aljoufi, Sarah Puhr, Mark J. Cameron, Rafick-Pierre Sékaly, Michel C. Nussenzweig, Kang Liu
Journal: The Journal of Experimental Medicine (2015)

In mice, two restricted dendritic cell (DC) progenitors, macrophage/dendritic progenitors (MDPs) and common dendritic progenitors (CDPs), demonstrate increasing commitment to the DC lineage, as they sequentially lose granulocyte and monocyte potential, respectively. Identifying these progenitors has enabled us to understand the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34+ hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, and NK and B cells. Using this culture system, we defined the pathway for human DC development and revealed the sequential origin of human DCs from increasingly restricted progenitors: a human granulocyte-monocyte-DC progenitor (hGMDP) that develops into a human monocyte-dendritic progenitor (hMDP), which in turn develops into monocytes, and a human CDP (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte-macrophage progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues.
Glimepiride, a Novel Sulfonylurea, Does Not Abolish Myocardial Protection Afforded by Either Ischemic Preconditioning or Diazoxide
Authors: Mihaela M. Mocanu, Helen L. Maddock, Gary F. Baxter, Christina L. Lawrence, Nicholas B. Standen, Derek M. Yellon
Journal: Circulation (2001)

Background —The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial K ATP channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic K ATP channels less than does Glib. We examined the effects of Glim on IP and on the protection afforded by diazoxide (Diaz), an opener of mitochondrial K ATP channels. Methods and Results —Rat hearts were Langendorff-perfused, subjected to 35 minutes of regional ischemia and 120 minutes of reperfusion, and assigned to 1 of the following treatment groups: (1) control; (2) IP of 2× 5 minutes each of global ischemia before lethal ischemia; or pretreatment with (3) 30 μmol/L Diaz, (4) 10 μmol/L Glim, (5) 10 μmol/L Glib, (6) IP+Glim, (7) IP+Glib, (8) Diaz+Glim, or (9) Diaz+Glib. IP limited infarct size (18.5±1% vs 43.7±3% in control, P &lt;0.01) as did Diaz (22.2±4.7%, P &lt;0.01). The protective actions of IP or Diaz were not abolished by Glim (18.5±3% in IP+Glim, 22.3±3% in Diaz+Glim; P &lt;0.01 vs control). However, Glib abolished the infarct-limiting effects of IP and Diaz. Patch-clamp studies in isolated rat ventricular myocytes confirmed that both Glim and Glib (each at 1 μmol/L) blocked sarcolemmal K ATP currents. However, in isolated cardiac mitochondria, Glim (10 μmol/L) failed to block the effects of K ATP opening by GTP, in contrast to the blockade caused by Glib. Conclusions —Although it blocks sarcolemmal currents in rat cardiac myocytes, Glim does not block the beneficial effects of mitochondrial K ATP channel opening in the isolated rat heart. These data may have significant implications for the treatment of type 2 diabetes in patients with ongoing ischemic heart disease.
The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus
Authors: Erich M Schwarz, Pasi K Korhonen, Bronwyn E Campbell, Neil D Young, Aaron R Jex, Abdul Jabbar, Ross S Hall, Alinda Mondal, Adina C Howe, Jason Pell, Andreas Hofmann, Peter R Boag, Xing-Quan Zhu, T Gregory, Alex Loukas, Brian A Williams, Igor Antoshechkin, C Brown, Paul W Sternberg, Robin B Gasser
Journal: Genome biology (2013)

The barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites. The draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules. The draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders.
SKIN CAUTERISATION MARKS ON PATIENTS IN SAUDI ARABIA
Authors: Abdulsamea Mohammad, Bent Nielsen, Farouch Hawash, Fransisco Fortunate, Ibrahim Addulhamin, Khaled Abdu, Louis Pedersen, Poul Halberg, SabahM. Fayed, Taghrid Hassan, Ibrahim Kassim
Journal: The Lancet (1983)