tbuckley/cabot-search huggingface dataset:
Functional Diversification of the Twin-Arginine Translocation Pathway Mediates the Emergence of Novel Ecological Adaptations
Authors: X. Jiang, M. A. Fares
Journal: Molecular Biology and Evolution (2011)

Microorganisms occupy a myriad of ecological niches that show an astonishing diversity. The molecular mechanisms underlying microbes’ ecological diversity remain a fundamental conundrum in evolutionary biology. Evidence points to that the secretion of a particular set of proteins mediates microbes’ interaction with the environment. Several systems are involved in this secretion, including the Sec secretion system and the Tat pathway. Shifts in the functions of proteins from the secretion systems may condition the set of secreted proteins and can, therefore, mediate adaptations to new ecological niches. In this manuscript, we have investigated processes of functional divergence (FD)—a term used here to refer to the emergence of novel functions by the modification of ancestral ones—of Tat pathway proteins using a large set of microbes with different lifestyles. The application of a novel approach to identify FD allowed us to distinguish molecular changes in the three Tat proteins among different groups of archaea and bacteria. We found these changes as well as the composition of secreted proteins to be correlated with differences in microbe’s lifestyles. We identified major signatures of FD in halophilic and thermophilic archaea as well as in pathogenic bacteria. The location of amino acids affected by FD in functionally important domains of Tat proteins made it possible to find the link between the molecular changes in Tat, the set of secreted proteins and the environmental features of the microbes. We present evidence that links specific molecular changes in secretion mediating proteins of microbes to their ecological adaptations.
You don't say: Figurative language and thought
Authors: Gregory A. Bryant, Raymond W. Gibbs
Journal: Behavioral and Brain Sciences (2002)

Carruthers has proposed a novel and quite interesting hypothesis for the role of language in conceptual integration, but his treatment does not acknowledge work in cognitive science on metaphor and analogy that reveals how diverse knowledge structures are integrated. We claim that this body of research provides clear evidence that cross-domain conceptual connections cannot be driven by syntactic processes alone.
Gastric retention and wireless capsule endoscopy in adults: a modified technique for direct duodenal deployment
Authors: A. Qasim, B. Ryan, N. Breslin, C. O'Morain
Journal: Gut (2010)

We read with interest the recent multicentre European study by Fritscher-Ravens et al on the feasibility of wireless capsule endoscopy (WCE) in a paediatric population.1 In this study a large proportion of the study population needed direct deployment of WCE using various devices. However, the authors encountered significant complications with the use of a polyp retrieval net. Complications included traumatic oesophageal intubation and the cumbersome nature of release of the capsule in the duodenum.

While swallowing is not a major issue in adults, gastric retention of the capsule remains a noticeable complication in ∼5% of individuals.2 Various techniques including body position, motility medications, …
Recurrence of leiomyomata after myomectomy
Authors: A. Fauconnier
Journal: Human Reproduction Update (2000)

Abdominal myomectomy (by laparotomy or by laparoscopy) enables all the myomata to be excised while maintaining reproductive function. The actual risk of recurrence after abdominal myomectomy is difficult to assess because of methodological problems. Studies using life-table analysis find a cumulative risk of clinically significant recurrence of ∼10% at 5 years for myomectomy by laparotomy. This risk probably underestimates the true prevalence of myomata as assessed by systematic ultrasound investigation. After laparoscopic myomectomy there appears to be a greater risk of recurrence. In one third of cases, recurrence becomes the reason for a hysterectomy. The risk of recurrence increases when there is more than one myoma. The use of gonadotrophin-releasing hormone agonists preoperatively could increase the risk of recurrence. Persistence or recurrence of the myoma thus reduces the chances of conception or taking a pregnancy full term after the myomectomy. It is essential to obtain the most complete exeresis possible in order to reduce the risk of recurrence to a minimum. However, it is inevitable that small, undetectable nuclei will remain within the myometrium whatever approach is used (laparoscopy or laparotomy). It would be an advantage to know what the growth factors are and how to identify groups at high risk of recurrence so that the treatment strategies could be better adapted and appropriate prophylactic methods developed.
The B-Oligomer of Pertussis Toxin Deactivates Cc Chemokine Receptor 5 and Blocks Entry of M-Tropic HIV-1 Strains
Authors: Massimo Alfano, Helena Schmidtmayerova, Carol-Ann Amella, Tatiana Pushkarsky, Michael Bukrinsky
Journal: The Journal of Experimental Medicine (1999)

Infection of target cells by HIV-1 requires initial binding interactions between the viral envelope glycoprotein gp120, the cell surface protein CD4, and one of the members of the seven-transmembrane G protein–coupled chemokine receptor family. Most primary isolates (R5 strains) use chemokine receptor CCR5, but some primary syncytium-inducing, as well as T cell line–adapted, strains (X4 strains) use the CXCR4 receptor. Signaling from both CCR5 and CXCR4 is mediated by pertussis toxin (PTX)-sensitive Gi proteins and is not required for HIV-1 entry. Here, we show that the PTX holotoxin as well as its binding subunit, B-oligomer, which lacks Gi-inhibitory activity, blocked entry of R5 but not X4 strains into primary T lymphocytes. Interestingly, B-oligomer inhibited virus production by peripheral blood mononuclear cell cultures infected with either R5 or X4 strains, indicating that it can affect HIV-1 replication at both entry and post-entry levels. T cells treated with B-oligomer did not initiate signal transduction in response to macrophage inflammatory protein (MIP)-1β or RANTES (regulated upon activation, normal T cell expressed and secreted); however, cell surface expression of CCR5 and binding of MIP-1β or HIV-1 to such cells were not impaired. The inhibitory effect of B-oligomer on signaling from CCR5 and on entry of R5 HIV-1 strains was reversed by protein kinase C (PKC) inhibitors, indicating that B-oligomer activity is mediated by signaling events that involve PKC. B-oligomer also blocked cocapping of CCR5 and CD4 induced by R5 HIV-1 in primary T cells, but did not affect cocapping of CXCR4 and CD4 after inoculation of the cultures with X4 HIV-1. These results suggest that the B-oligomer of PTX cross-deactivates CCR5 to impair its function as a coreceptor for HIV-1.
Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans
Authors: Cristina González-Aguilera, Kohta Ikegami, Cristina Ayuso, Alberto de Luis, María Íñiguez, Juan Cabello, Jason D Lieb, Peter Askjaer
Journal: Genome biology (2014)

Laminopathies are diseases characterized by defects in nuclear envelope structure. A well-known example is Emery-Dreifuss muscular dystrophy, which is caused by mutations in the human lamin A/C and emerin genes. While most nuclear envelope proteins are ubiquitously expressed, laminopathies often affect only a subset of tissues. The molecular mechanisms underlying these tissue-specific manifestations remain elusive. We hypothesize that different functional subclasses of genes might be differentially affected by defects in specific nuclear envelope components.Here we determine genome-wide DNA association profiles of two nuclear envelope components, lamin/LMN-1 and emerin/EMR-1 in adult Caenorhabditis elegans. Although both proteins bind to transcriptionally inactive regions of the genome, EMR-1 is enriched at genes involved in muscle and neuronal function. Deletion of either EMR-1 or LEM-2, another integral envelope protein, causes local changes in nuclear architecture as evidenced by altered association between DNA and LMN-1. Transcriptome analyses reveal that EMR-1 and LEM-2 are associated with gene repression, particularly of genes implicated in muscle and nervous system function. We demonstrate that emr-1, but not lem-2, mutants are sensitive to the cholinesterase inhibitor aldicarb, indicating altered activity at neuromuscular junctions.We identify a class of elements that bind EMR-1 but do not associate with LMN-1, and these are enriched for muscle and neuronal genes. Our data support a redundant function of EMR-1 and LEM-2 in chromatin anchoring to the nuclear envelope and gene repression. We demonstrate a specific role of EMR-1 in neuromuscular junction activity that may contribute to Emery-Dreifuss muscular dystrophy in humans.
Sleep-Disordered Breathing, Hypertension, and Obesity in Retired National Football League Players
Authors: Felipe N. Albuquerque, Fatima H. Sert Kuniyoshi, Andrew D. Calvin, Justo Sierra-Johnson, Abel Romero-Corral, Francisco Lopez-Jimenez, Charles F. George, David M. Rapoport, Robert A. Vogel, Bijoy Khandheria, Martin E. Goldman, Arthur Roberts, Virend K. Somers
Journal: Journal of the American College of Cardiology (2010)
Promoting equality for ethnic minority NHS staff—what works?
Authors: Naomi Priest, Aneez Esmail, Roger Kline, Mala Rao, Yvonne Coghill, David R Williams
Journal: BMJ (2015)

NHS organisations are now being judged on indicators of ethnic diversity. Naomi Priest and colleagues look at the international evidence on how they should tackle discrimination For decades research has shown that discrimination, harassment, and exclusion are pervasive experiences for staff from black and minority ethnic (BME) backgrounds in the National Health Service.1 2 3 4 5 6 In recognition of limited progress in achieving the goals of the now decade old NHS Race Equality Action Plan,7 the NHS has agreed a mandatory workforce race equality standard. The standard requires NHS organisations to collect baseline information from April 2015 on nine indicators of workforce equality for ethnic minority staff, including representation on boards, and to publish annual updates on these metrics (box). Organisations that fail to make progress on these metrics will be in breach of the NHS standard contract, and this will affect whether regulators judge them to be "well led."8 9 We review the international evidence on the effectiveness of diversity initiatives to assess how best to achieve the standard's intended outcomes. #### Indicators for the workforce race equality standard ##### Workforce metrics ###### For each of these four workforce indicators, the standard compares the metrics for white and BME staff ##### National NHS staff survey findings ###### For each of these five staff survey indicators, the standard compares the metrics for each survey question response for white and BME staff
Dosage compensation on the active X chromosome minimizes transcriptional noise of X-linked genes in mammals
Authors: Shanye Yin, Ping Wang, Wenjun Deng, Hancheng Zheng, Landian Hu, Laurence D Hurst, Xiangyin Kong
Journal: Genome biology (2009)

Theory predicts that haploid-expressed genes should have noisier expression than comparable diploid-expressed ones with the same expression level. However, in mammals there are several classes of gene that are monoallelically expressed, including X-linked genes, imprinted genes and some other autosomal genes. Does it follow that the evolution of X chromosomes in eukaryotes comes at the cost of increased transcriptional noise in the heterogametic sex? Moreover, is escaping X-inactivation in mammalian females associated with an increase in transcriptional variation? To address these questions, we analyze gene expression variation between replicate samples of diverse mammalian cell lines in steady-state using microarray data. We observe that transcriptional variation of X-linked genes is no different to that of autosomal genes both before and after control for transcript abundance. By contrast, autosomal genes subject to allelic exclusion do have unusually high noise levels even allowing for their low transcript abundance. The prior theory we suggest was insufficient, at least as regards X-chromosomes, as it failed to appreciate the regulatory complexity of gene expression, not least the effects of genomic neighborhood. These results suggest that high noise is not a necessary consequence of haploid expression and emphasize the primacy of expression level as a determinant of noise. The latter has consequences for understanding the etiology of haplo-insufficiency and the evolution of gene expression levels. Given the coupling between expression level and noise on the X-chromosome, we suggest that part of the selective advantage of dosage compensation is noise abatement of X-linked genes.
Abdominal Sarcoma Infiltrating the Abdominal Wall
Authors: J. W. Cousins
Journal: BMJ (1894)

I I ~~~~~~~~~~~__ ___MEDICALL JOURN&L life," in decided contrast to the rate of growtlh as recorded by M%essrs.Lincoln an1ild Bennett.At present, withlout inore evidence, IImy case elin lcardly be roinouneed one-of osteitis defoI-rian1s, a Intid yet tthe enlarging ead occurs in that disease, anld is not found associated with arthiritis deformifans; .ilso 11(iW growtlh is ofte-n founid withl osteitis deforian1ns, as in several of Sir; Janmes Ilaget's case.In MNlr.Lunn 's case there was a sarcomna in the pelvis.The eii- tire skeleton is in the St. Thiomas's MIuseum, and is beauti- fully figured in St. Thointm'8s Report., 1883, and de^scribed( by I'rofessor Stewart.As rarefying osteitis is the chlief feature of the disease in osteitis deforinans, this would afford also the best explanation of the symmetrically enlarging cranial vault in my patieint.
Metabolic Syndrome and Asymptomatic Peripheral Artery Disease in Subjects Over 60 Years of Age
Authors: C. Lahoz
Journal: Diabetes Care (2006)

The ankle-brachial index (ABI) is a noninvasive, low-cost, and useful test for detecting asymptomatic peripheral artery disease (PAD). An ABI  60 years of age without a history of cardiovascular disease or diabetes. Also, we assessed whether the association persisted after adjustment for classical risk factors.

The participants of the study were subjects of both genders aged 60–79 years who accessed the Fuencarral Health Centre (Madrid) and voluntarily agreed to have an ABI measurement. Of the 1,361 subjects in whom the ABI was measured, 360 were excluded from the present study because of a diagnosis of cardiovascular disease or diabetes. The final number of participants was 1,001. Blood was …
Physiology and Pathophysiology of Renal Aquaporinsa
Authors: SØREN NIELSEN, TAE-HWAN KWON, BIRGITTE MØNSTER CHRISTENSEN, DOMINIQUE PROMENEUR, JØRGEN FRØKIÆR, DAVID MARPLES
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. AQP2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated trafficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Importantly, multiple studies have now identified a critical role of AQP2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP4 are basolateral water channels located in the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.
Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial
Authors: Patrice Piola, Carolyn Nabasumba, Eleanor Turyakira, Mehul Dhorda, Niklas Lindegardh, Dan Nyehangane, Georges Snounou, Elizabeth A Ashley, Rose McGready, Francois Nosten, Philippe J Guerin
Journal: The Lancet Infectious Diseases (2010)
Effect of Prolonged Periods of Anoxia on Atrioventricular Conduction and Cardiac Muscle
Authors: CAPT. JAY D. COFFMAN, F. BRUCE LEWIS, DONALD E. GREGG
Journal: Circulation Research (1960)

The return of A-V conduction according to the electrocardiogram, the ability to maintain the blood pressure, the cardiac muscle ATP, the coronary venous pH, lactic acid, and potassium were studied to delineate the effects on the heart of prolonged periods of anoxia in dogs maintained on an extracorporeal circulation. Myocardial anoxia for 100 minutes was the limit for return of A-V conduction in all dogs in these experiments. Only 2 of 5 hearts anoxic for 120 minutes, and 1 of 3 hearts anoxic for 150 minutes regained A-V conduction. One heart subjected to anoxia for 165 minutes did not show A-V conduction on reperfusion of the coronary arteries. The dogs whose hearts were subjected to periods of anoxia longer than 100 minutes could not maintain the blood pressure on removal from the extracorporeal circulation. This was due to the development of an unusual firmness of the left ventricular muscle, usually appearing after 90 minutes of anoxia and progressing to involve the entire heart. This firmness was not reversible on reperfusion of the heart. Since A-V conduction and speed of conduction returned in some of these firm hearts, it was concluded that there was earlier permanent damage to the myocardial muscle than to the conduction system during anoxia. Cardiac muscle ATP values were not definitely changed after 30 minutes of anoxia, but were decreased and regenerated on reperfusion of the heart after 60 minutes of anoxia. The low levels of ATP did not return toward normal on reperfusion of the heart after 90 and 120 minutes of myocardial anoxia. Additional experiments on anoxic hearts of nonperfused dogs also demonstrated the marked decrease in ATP levels. In both types of studies, the earliest onsets of firmness showed some correlation with low ATP levels. The high lactic acid levels and low pH values of the coronary venous blood found after long periods of anoxia may be related to the failure of ATP regeneration and to the onset of firmness in these hearts. Potassium arrest of hearts subjected to anoxia showed no difference in the return of A-V conduction, in the ability to maintain blood pressure on removal from the extracorporeal circulation, in the onset or degree of myocardial firmness, nor in the levels of cardiac muscle ATP, coronary venous pH, and lactic acid, from the anoxic, nonarrested hearts. The variability of the effect of anoxia on A-V conduction and myocardial muscle of different hearts by the parameters measured in this study is stressed.
Occupational exposure to organic dust increases lung cancer risk in the general population
Authors: Susan Peters, Hans Kromhout, Ann C Olsson, Heinz-Erich Wichmann, Irene Brüske, Dario Consonni, Maria Teresa Landi, Neil Caporaso, Jack Siemiatycki, Lorenzo Richiardi, Dario Mirabelli, Lorenzo Simonato, Per Gustavsson, Nils Plato, Karl-Heinz Jöckel, Wolfgang Ahrens, Hermann Pohlabeln, Paolo Boffetta, Paul Brennan, David Zaridze, Adrian Cassidy, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Peter Rudnai, Eleonora Fabianova, Francesco Forastiere, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Isabelle Stücker, Rodica Stanescu Dumitru, Simone Benhamou, Bas Bueno-de-Mesquita, Benjamin Kendzia, Beate Pesch, Kurt Straif, Thomas Brüning, Roel Vermeulen
Journal: Thorax (2011)

Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk, while exposure to microbial components (eg, endotoxin) has been associated with a decreased risk. To date there has not been a comprehensive evaluation of the possible association between occupational organic dust exposure (and its specific constituents) and lung cancer risk in the general population.The SYNERGY project has pooled information on lifetime working and smoking from 13 300 lung cancer cases and 16 273 controls from 11 case-control studies conducted in Europe and Canada. A newly developed general population job-exposure matrix (assigning no, low or high exposure to organic dust, endotoxin, and contact with animals or fresh animal products) was applied to determine level of exposure. ORs for lung cancer were estimated by logistic regression, adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk.Occupational organic dust exposure was associated with increased lung cancer risk. The second to the fourth quartile of cumulative exposure showed significant risk estimates ranging from 1.12 to 1.24 in a dose-dependent manner (p<0.001). This association remained in the highest quartile after restricting analyses to subjects without chronic obstructive pulmonary disease or asthma. No association was observed between lung cancer and exposure to endotoxin or contact with animals or animal products.Occupational exposure to organic dust was associated with increased lung cancer risk in this large pooled case-control study.
Users' Guides to the Medical Literature
Authors: C. David Naylor
Journal: JAMA (1996)

<h3>CLINICAL SCENARIO</h3> You are a general internist attending a medical advisory committee meeting as the newly appointed chief of staff in a large community hospital affiliated with a major health maintenance organization. A junior administrator presents data showing that the hospital's utilization of percutaneous transluminal coronary angioplasty (PTCA) is high relative to similar-sized centers with similar numbers of interventional cardiologists. He insinuates that unnecessary PTCAs are being done. The cardiologists present are infuriated, and the meeting degenerates into a shouting match. After the hospital chief executive officer brings the meeting back to order, you and the chief of cardiology agree to research the matter independently and report back in 1 week. <h3>THE SEARCH</h3> Raw utilization data are insufficient to assess whether cardiologists at your hospital are using PTCA inappropriately. You need to review their practice in light of criteria for deciding whether each application of PTCA was likely, given a