tbuckley/cabot-search huggingface dataset:
Analysis of Nuclear Receptor Pseudogenes in Vertebrates: How the Silent Tell Their Stories
Authors: Z. D. Zhang, P. Cayting, G. Weinstock, M. Gerstein
Journal: Molecular Biology and Evolution (2007)

Transcription factor pseudogenes have not been systematically studied before. Nuclear receptors (NRs) constitute one of the largest groups of transcription factors in animals (e.g., 48 NRs in human). The availability of whole-genome sequences enables a global inventory of the NR pseudogenes in a number of vertebrate model organisms. Here we identify the NR pseudogenes in 8 vertebrate organisms and make our results available online at http://www.pseudogene.org/nr. The assignments reveal that NR pseudogenes as a group have characteristics related to generation and distribution contrary to expectations derived from previous large-scale pseudogene studies. In particular, 1) despite its large size, the NR gene family has only a very small number of pseudogenes in each of the vertebrate genomes examined; 2) despite the low transcription levels of NR genes, except for one, all other NR pseudogenes identified in this study are retropseudogenes; and 3) no duplicated NR pseudogenes are found, contrary to the fact that the NR gene family was expanded through several waves of gene duplication events. Our analyses further reveal a number of interesting aspects of NR pseudogenes. Specifically, through careful sequence analysis, we identify remnant introns in 2 mouse retropseudogenes, ψRev-erbβ and ψLRH1. Generated from partially processed pre-mRNAs, they appear to be rare examples of highly unusual "semiprocessed" pseudogenes. Second, by comparing the genomic sequences, we uncover a pseudogene that is unique to the human lineage relative to chimpanzee. Generated by a recent duplication of a segment in the human genome, this pseudogene is a "duplicated–processed" pseudogene, belonging to a new pseudogene species. Finally, FXRβ was nonfunctionalized in the human lineage and thus appears to be an example of a rare unitary pseudogene. By comparing orthologous sequences, we dated the FXR–FXRβ duplication and the nonfunctionalization of FXRβ in primates.
Psoriasis and chronic obstructive pulmonary disease: a case-control study
Authors: J. Dreiher, D. Weitzman, J. Shapiro, B. Davidovici, A.D. Cohen
Journal: British Journal of Dermatology (2008)

Previous reports have demonstrated an association between psoriasis and the metabolic syndrome. Chronic obstructive pulmonary disease (COPD) has also been associated with the metabolic syndrome.To assess the association between psoriasis and COPD in a population-based case-control study.A case-control study was performed utilizing the database of Clalit Health Services, a large healthcare provider organization in Israel. Patients over the age of 20 years who were diagnosed with psoriasis ('cases') were compared with a sample of age- and gender-matched enrollees without psoriasis ('controls') regarding the prevalence of COPD. Group matching was performed. Data on health-related lifestyles and other comorbidities were collected. Chi(2) tests, t-tests and logistic regression models were used to compare between study groups.The study included 12,502 psoriasis cases and 24,287 controls. The prevalence of COPD was significantly higher in patients with psoriasis [5.7% vs. 3.6%, P < 0.001, odds ratio (OR) 1.63, 95% confidence interval (CI) 1.47-1.81]. A multivariate logistic regression model demonstrated that psoriasis was significantly associated with COPD, after controlling for confounders, including age, sex, socioeconomic status, smoking and obesity (adjusted OR 1.27, 95% CI 1.13-1.42, P < 0.001).In this large, population-based case-control study, psoriasis was found to be associated with COPD. Dermatologists caring for patients with psoriasis should be aware of this association, consult an internist or pulmonologist, and advise the patients to stop smoking and reduce additional risk factors for COPD.
Sleep-disordered breathing in African-American elderly.
Authors: S Ancoli-Israel, M R Klauber, C Stepnowsky, E Estline, A Chinn, R Fell
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Although sleep-disordered breathing (SDB) has been shown to be very prevalent in the elderly, little has been done to examine differences between the elderly of different racial groups. It has been well documented that SDB often results in hypertension and that hypertension is more common in African-Americans than in Caucasians. Therefore, one might suspect that SDB might be more common in African-Americans. Caucasians (n = 346) and African-Americans (n = 54) older than 65 yr of age were studied. African-Americans reported less satisfaction with sleep (p = 0.017), more difficulty falling asleep (p < 0.001), more daytime sleepiness (p = 0.0014), and more frequent morning headaches (p = 0.0043). African-Americans napped 0.8 times more frequently per evening (p = 0.05) and 11 min longer per nap (p = 0.019) than did Caucasians, and they showed a trend toward more total sleep time (428 versus 408 min). Of greater interest was the fact that more African-Americans had severe SDB with a relative risk twofold as great (relative risk = 2.13) as that for Caucasians, which was confirmed in a logistic regression analysis where race was associated with the presence of SDB (RDI > or = 30) independently of age, sex, and body mass index. The mean RDI for those African-Americans with severe SDB was significantly higher than that for Caucasians (72.1 versus 43.3; p = 0.014).
OCCLUSION OF THE OS FOLLOWING SURGICAL TREATMENT OF UTERINE AND VAGINAL PROLAPSE
Authors: J. N. Stark
Journal: BMJ (1924)

It must always be remembered, however, that manipulationis of any kind can introduce virulent organisms into the uterus.It is impossible to sterilize absolutely a vagina, however thoroughly it may be attempted, and many virulent organisms can and do exist and multiply there with no -harmful results.But if those same organisms gain access to the inside of the uterus they may do untold damage.Two of my cases were of that most fatal kind, the acute aplastic type of streptococcal infection.Both had been infected with gonorrhoea, and one had subacute gonorrhoea at the time of delivery.She was also hypermature, had a flat pelvis, and required craniotomy into the bargain.
A novel mode of chromosomal evolution peculiar to filamentous Ascomycete fungi
Authors: James K Hane, Thierry Rouxel, Barbara J Howlett, Gert HJ Kema, Stephen B Goodwin, Richard P Oliver
Journal: Genome biology (2011)

Gene loss, inversions, translocations, and other chromosomal rearrangements vary among species, resulting in different rates of structural genome evolution. Major chromosomal rearrangements are rare in most eukaryotes, giving large regions with the same genes in the same order and orientation across species. These regions of macrosynteny have been very useful for locating homologous genes in different species and to guide the assembly of genome sequences. Previous analyses in the fungi have indicated that macrosynteny is rare; instead, comparisons across species show no synteny or only microsyntenic regions encompassing usually five or fewer genes. To test the hypothesis that chromosomal evolution is different in the fungi compared to other eukaryotes, synteny was compared between species of the major fungal taxa.These analyses identified a novel form of evolution in which genes are conserved within homologous chromosomes, but with randomized orders and orientations. This mode of evolution is designated mesosynteny, to differentiate it from micro- and macrosynteny seen in other organisms. Mesosynteny is an alternative evolutionary pathway very different from macrosyntenic conservation. Surprisingly, mesosynteny was not found in all fungal groups. Instead, mesosynteny appears to be restricted to filamentous Ascomycetes and was most striking between species in the Dothideomycetes.The existence of mesosynteny between relatively distantly related Ascomycetes could be explained by a high frequency of chromosomal inversions, but translocations must be extremely rare. The mechanism for this phenomenon is not known, but presumably involves generation of frequent inversions during meiosis.
Lack of Influence of Hypophysectomy on Estrogen-Induced DNA Synthesis in Leydig Cells of BALB/c Mice2
Authors: Robert A. Huseby, Leo T. Samuels
Journal: JNCI Journal of the National Cancer Institute (1977)

In mice of strains susceptible to Leydig cell tumor induction, treatment with estrogens induced a "spurt" of DNA synthesis within the first few days. This synthetic activity generally subsided, until areas of Leydig cell hyperplasia developed several months later. Autoradiographic and quantitative biochemical studies indicated that in BALB/c mice this initial DNA synthetic activity occurred in the absence of the hypophysis and apparently was the result of effects of estrogen directly on Leydig cells. Although hypophysectomy inhibited sperm maturation, [3H]thymidine incorporation into spermatogonia was reduced only slightly 2 weeks after surgery, as was the induced DNA spurt in the interstitial tissues.
Genomic Analyses of Three Malaria Vectors Reveals Extensive Shared Polymorphism but Contrasting Population Histories
Authors: Samantha M. O’Loughlin, Stephen Magesa, Charles Mbogo, Franklin Mosha, Janet Midega, Susan Lomas, Austin Burt
Journal: Molecular Biology and Evolution (2014)

Anopheles gambiae s.l. are important malaria vectors, but little is known about their genomic variation in the wild. Here, we present inter- and intraspecies analysis of genome-wide RADseq data, in three Anopheles gambiae s.l. species collected from East Africa. The mosquitoes fall into three genotypic clusters representing described species (A. gambiae, A. arabiensis, and A. merus) with no evidence of cryptic breeding units. Anopheles merus is the most divergent of the three species, supporting a recent new phylogeny based on chromosomal inversions. Even though the species clusters are well separated, there is extensive shared polymorphism, particularly between A. gambiae and A. arabiensis. Divergence between A. gambiae and A. arabiensis does not vary across the autosomes but is higher in X-linked inversions than elsewhere on X or on the autosomes, consistent with the suggestion that this inversion (or a gene within it) is important in reproductive isolation between the species. The 2La/2L+a inversion shows no more evidence of introgression between A. gambiae and A. arabiensis than the rest of the autosomes. Population differentiation within A. gambiae and A. arabiensis is weak over approximately 190–270 km, implying no strong barriers to dispersal. Analysis of Tajima's D and the allele frequency spectrum is consistent with modest population increases in A. arabiensis and A. merus, but a more complex demographic history of expansion followed by contraction in A. gambiae. Although they are less than 200 km apart, the two A. gambiae populations show evidence of different demographic histories.
Pleural procedures and thoracic ultrasound: British Thoracic Society pleural disease guideline 2010
Authors: T. Havelock, R. Teoh, D. Laws, F. Gleeson
Journal: Thorax (2010)

In hospital practice, pleural aspiration (thoracocentesis) and chest drain insertion may be required in many different clinical settings for a variety of indications. Doctors in most specialities will be exposed to patients requiring pleural drainage and need to be aware of safe techniques. There have been many reports of the dangers of large-bore chest drains and it had been anticipated that, with the previous guidelines, better training and the advent of small-bore Seldinger technique chest drains, there would have been an improvement. Unfortunately the descriptions of serious complications continue, and in 2008 the National Patient Safety Agency (NPSA) issued a report making recommendations for safer practice.1 These updated guidelines take into consideration the recommendations from this report and describe the technique of pleural aspiration and Seldinger chest drain insertion and ultrasound guidance. Much of this guideline consists of descriptions of how to do these procedures but, where possible, advice is given when evidence is available.

Before undertaking an invasive pleural procedure, all operators should be appropriately trained and have been initially supervised by an experienced trainer. Many of the complications described in the NPSA report were the result of inadequate training or supervision. A recent survey of UK NHS Trusts showed that the majority did not have a formal training policy for chest drain insertion in 2008.2

Studies of clinical practice have shown that there is a wide variation in the knowledge and skills of doctors inserting chest drains. In a published study3 where doctors were asked to indicate where they would insert a chest drain, 45% indicated they would insert the drain outside of the safety triangle, …
Implications for the Neural Basis of Social Cognition for the Study of Schizophrenia
Authors: Amy E. Pinkham, David L. Penn, Diana O. Perkins, Jeffrey Lieberman
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The study of social cognition in schizophrenia has received growing attention in recent years. At the same time, a large body of work has explored the neural basis of social cognition in both nonclinical and clinical groups, other than those with schizophrenia. The gap between these two literatures is considerable and may slow progress in creating a comprehensive social cognitive model of schizophrenia. This article attempts to bridge this gap by discussing how the neural basis of social cognition may inform future clinical research in schizophrenia. METHOD: PsycINFO and MEDLINE were systematically searched for articles pertaining to the neural basis of social cognition and social cognition in schizophrenia. Relevant studies were obtained and synthesized into a comprehensive review and integrative formulation. RESULTS: Striking parallels between these two areas of research were found. CONCLUSIONS: These parallels might help to better elucidate the underlying mechanisms for social cognitive and social behavioral impairments in schizophrenia as well as provide potential targets for treatment and drug development.
Intraflagellar Transport and Cilia-Dependent Renal Disease
Authors: Gregory J. Pazour
Journal: Journal of the American Society of Nephrology (2004)

Epithelial cells that line mammalian kidney nephrons have solitary nonmotile primary cilium projecting from their surface into the lumens of the ducts and tubules. Mutations that block the assembly of these cilia cause cystic kidney disease. The products of human autosomal dominant and recessive polycystic kidney disease genes and products of the nephronophthisis disease genes are at least partially localized to primary cilia. This suggests that the cilium serves as an organizing center for the early steps of the signal transduction pathway that is responsible for monitoring the integrity of the kidney nephron and controlling cell proliferation and differentiation.
ERM proteins mediate the effects of Na+/H+ exchanger (NHE1) activation in cardiac myocytes
Authors: A. Darmellah, C. Rucker-Martin, D. Feuvray
Journal: Cardiovascular Research (2008)

Ezrin, radixin, and moesin (ERM) proteins have been implicated in regulating signalling molecules. The aim of the present study was to investigate the activity and subcellular distribution of ERM proteins in cardiac myocytes from both Wistar and diabetic Goto-Kakizaki (GK) rats, and the role of these proteins in mediating the downstream effects of the cardiac sarcolemmal Na+/H+ exchanger (NHE1) activation in response to cell acidification.Immunofluorescence microscopy revealed that activated ERM proteins were localized predominantly at the intercalated disc regions in left ventricular (LV) myocytes of both Wistar and GK rats under basal conditions. After acid loading, profound changes in activated ERM distribution were observed in both groups of myocytes, with immunolabelling detected in regions corresponding to the transverse tubules. This correlated with a marked increase in phospho-ERM levels in both groups, which was higher in GK myocytes and blocked by NHE1 inhibitor treatment. Levels of phospho-Akt paralleled those of phospho-ERM under the various experimental conditions used; in particular, the marked acid-induced increase in both phospho-ERM and phospho-Akt in GK myocytes was abolished by an NHE1 inhibitor treatment. Moreover, the pattern of glycogen synthase kinase-3beta (GSK-3beta) phosphorylation in these myocytes was strikingly similar to that observed for Akt activity under the conditions used.Activated ERM proteins mediate the effects of acid-induced NHE1 activation in LV myocytes. Akt is a downstream effector in the cascade activated by NHE1-ERM interaction. In addition, GSK-3beta phosphorylation is required for downstream effects of NHE1/ERM-Akt signalling.
Cytarabine Dose of 36 g/m<sup>2</sup> Compared With 12 g/m<sup>2</sup> Within First Consolidation in Acute Myeloid Leukemia: Results of Patients Enrolled Onto the Prospective Randomized AML96 Study
Authors: Markus Schaich, Christoph Röllig, Silke Soucek, Michael Kramer, Christian Thiede, Brigitte Mohr, Uta Oelschlaegel, Norbert Schmitz, Reingard Stuhlmann, Hannes Wandt, Kerstin Schäfer-Eckart, Walter Aulitzky, Martin Kaufmann, Heinrich Bodenstein, Joachim Tischler, Anthony Ho, Alwin Krämer, Martin Bornhäuser, Johannes Schetelig, Gerhard Ehninger
Journal: Journal of Clinical Oncology (2011)

To assess the optimal cumulative dose of cytarabine for treatment of young adults with acute myeloid leukemia (AML) within a prospective multicenter treatment trial.Between 1996 and 2003, 933 patients (median age, 47 years; range 15 to 60 years) with untreated AML were randomly assigned at diagnosis to receive cytarabine within the first consolidation therapy at either a intermediate-dose of 12 g/m² (I-MAC) or a high-dose of 36 g/m² (H-MAC) combined with mitoxantrone. Autologous hematopoietic stem-cell transplantation or intermediate-dose cytarabine (10 g/m²) were offered as second consolidation. Patients with a matched donor could receive an allogeneic transplantation in a risk-adapted manner.After double induction therapy including intermediate-dose cytarabine (10 g/m²), mitoxantrone, etoposide, and amsacrine, complete remission was achieved in 66% of patients. In the primary efficacy analysis population, a consolidation with either I-MAC or H-MAC did not result in significant differences in the 5-year overall (30% v 33%; P = .77) or disease-free survival (37% v 38%; P = .86) according to the intention-to-treat analysis. Besides a prolongation of neutropenia and higher transfusion demands in the H-MAC arm, rates of serious adverse events were comparable in the two groups.In young adults with AML receiving intermediate-dose cytarabine induction, intensification of the cytarabine dose beyond 12 g/m² within first consolidation did not improve treatment outcome.
Adventitial Cells Do Not Contribute to Neointimal Mass After Balloon Angioplasty of the Rat Common Carotid Artery
Authors: Hector De Leon, Jeremy D. Ollerenshaw, Kathy K. Griendling, Josiah N. Wilcox
Journal: Circulation (2001)

Previous studies suggest that the migration of adventitial cells into the neointima after balloon angioplasty might have an important role in vascular lesion formation. The current experiments were designed to study the migration of adventitial cells in response to mechanical injury of the rat carotid artery.Adventitial cells were stained in situ with PKH26, a fluorescent dye, after balloon angioplasty of the rat common carotid artery. Animals were killed at different time points, and tissue sections were examined under light and fluorescence microscopy. PKH26-labeled cells were detected exclusively in the adventitia. No labeled cells were present in the media or the neointima at any time point examined. A highly cellular neoadventitial layer composed of myofibroblasts exhibited an extensive proliferative response 3 days after injury over the entire adventitial circumference.Despite the prominent role that adventitial myofibroblasts seem to have in the postangioplasty remodeling process, they do not migrate to the medial or intimal layers in the rat carotid artery angioplasty model.
The Role of Fat-Storing Cells in Disse Space Fibrogenesis in Alcoholic Liver Disease
Authors: Yukihito Minato, Yasushi Hasumura, Jugoro Takeuchi
Journal: Hepatology (1983)

Liver biopsy samples from 40 chronic alcoholic patients, including 9 with minimal changes of the liver, 6 with mild hepatic fibrosis, 14 with moderate fibrosis, and 11 with severe fibrosis (cirrhosis) were studied by electron microscopy to assess fibrogenesis in the Disse space and the role of fat-storing cells in this process. In the Disse space of normal liver, collagen fibers are few, and while lipid droplets containing fat-storing cells exist, their rough endoplasmic reticulum (RER) is inconspicuous. In the course of progressive hepatic fibrosis, collagen in the Disse space increased. This was significantly associated with gradual development of RER in fat-storing cells, confirmed by morphometric analysis. It is likely, therefore, that the development of RER in the fat-storing cells is a morphological correlative of their activated fibrogenesis and transformation into fibroblasts. To further clarify this, the rate of collagen synthesis was measured by the method of in vitro incorporation of [ 3 H]proline into collagen in 17 liver biopsy samples from alcoholic patients and compared with the degree of morphological changes of RER in fat-storing cells. In liver samples with well-developed RER in fat-storing cells, a significantly higher rate of collagen synthesis was observed. These results suggest that in alcoholic liver injury, fat-storing cells may play an important role in Disse space fibrogenesis.
The scandal of poor epidemiological research: ***
Authors: Erik von Elm, Matthias Egger
Journal: BMJ (2004)

has to be reconsidered.Thirdly, we must find ways of preventing further similar episodes (box).Single phase III drug trials are simply not big enough to detect relatively uncommon but important adverse events, which may affect large numbers of people in routine clinical use. 6The potential public health impact of previously undetected drug related adverse events is likely to be made worse if widely marketed new drugs are prescribed haphazardly and rapidly to large numbers of people.Within five months of the launch of rofecoxib, more than 42 000 patients had been prescribed the drug in England, 11 even though newly marketed drugs carry a black triangle warning, indicating an incomplete safety profile.Unfortunately, postmarketing surveillance is not a panacea to determine safety, as methodological flaws may produce inaccurate results.We therefore recommend that drug companies are legally required to make all data on serious adverse events from clinical studies available to the public immediately after completion of the research.This will allow independent, timely, and updated systematic reviews of serious adverse events.In addition, we advocate the phased introduction of new interventions through randomised trials, which are independent from the pharmaceutical industry and are large enough to study rare outcomes, together with systematic, more robust, and comprehensive approaches to pharma-covigilance. 12Although these measures will not be popular with pharmaceutical companies, they will limit the numbers of patients exposed unsystematically to unknown hazards and provide robust and unbiased evidence on adverse events before a drug is licensed fully.