tbuckley/cabot-search huggingface dataset:
The integrative framework for the behavioural sciences has already been discovered, and it is the adaptationist approach
Authors: Michael E. Price, William M. Brown, Oliver S. Curry
Journal: Behavioral and Brain Sciences (2007)

The adaptationist framework is necessary and sufficient for unifying the social and natural sciences. Gintis's “beliefs, preferences, and constraints” (BPC) model compares unfavorably to this framework because it lacks criteria for determining special design, incorrectly assumes that standard evolutionary theory predicts individual rationality maximisation, does not adequately recognize the impact of psychological mechanisms on culture, and is mute on the behavioural implications of intragenomic conflict.
RNAi-mediated silencing of MLL-AF9 reveals leukemia-associated downstream targets and processes
Authors: Katrin K Fleischmann, Philipp Pagel, Irene Schmid, Adelbert A Roscher
Journal: Molecular Cancer (2014)

The translocation t(9;11)(p22;q23) leading to the leukemogenic fusion gene MLL-AF9 is a frequent translocation in infant acute myeloid leukemia (AML). This study aimed to identify genes and molecular processes downstream of MLL-AF9 (alias MLL-MLLT3) which could assist to develop new targeted therapies for such leukemia with unfavorable prognosis. In the AML cell line THP1 which harbors this t(9;11) translocation, endogenous MLL-AF9 was silenced via siRNA while ensuring specificity of the knockdown and its efficiency on functional protein level. The differential gene expression profile was validated for leukemia-association by gene set enrichment analysis of published gene sets from patient studies and MLL-AF9 overexpression studies and revealed 425 differentially expressed genes. Gene ontology analysis was consistent with a more differentiated state of MLL-AF9 depleted cells, with involvement of a wide range of downstream transcriptional regulators and with defined functional processes such as ribosomal biogenesis, chaperone binding, calcium homeostasis and estrogen response. We prioritized 41 gene products as candidate targets including several novel and potentially druggable effectors of MLL-AF9 (AHR, ATP2B2, DRD5, HIPK2, PARP8, ROR2 and TAS1R3). Applying the antagonist SCH39166 against the dopamine receptor DRD5 resulted in reduced leukemic cell characteristics of THP1 cells. Besides potential new therapeutic targets, the described transcription profile shaped by MLL-AF9 provides an information source into the molecular processes altered in MLL aberrant leukemia.
Complementary Role of CD4+ T Cells and Secondary Lymphoid Tissues for Cross-presentation of Tumor Antigen to CD8+ T Cells
Authors: Ping Yu, Michael T. Spiotto, Youjin Lee, Hans Schreiber, Yang-Xin Fu
Journal: The Journal of Experimental Medicine (2003)

MHC class I–restricted tumor antigens can be presented to CD8+ T cells by two distinct pathways: via direct and indirect presentation. The relative contribution of these two pathways toward the initial activation of tumor antigen–specific CD8+ T cells and their subsequent tumor rejection is still vigorously debated. Using a tumor model able to dissect the relative contributions of direct and indirect presentation, we show unequivocally the inefficiency of direct presentation and the essential requirement of indirect presentation for the priming of naive tumor antigen–specific T cells leading to tumor rejection. Moreover, we characterize the essential environment under which indirect presentation occurs, and find efficient cross-priming of tumor-specific CD8+ T cells in the complete absence of secondary lymphoid tissues. The independence of this process from local lymph nodes is compromised, however, in the absence of CD4+ T cell help. Therefore, our paper demonstrates that effective immune protection against tumors requires the cross-priming of CD8+ T cells under conditions that require either CD4+ T cell help, or draining lymph nodes.
Prevalence and risk factors for pneumonia in a cohort with clinical suspicion of influenza A (H1N1)
Authors: Mireia Serra, Silvia Capilla, Gema Navarro, Eduard Monsó, Carles Grimau, Miguel Gallego
Journal: European Respiratory Journal (2012)

Due to the potentially life-threatening of H1N1 infection, mainly influenza pneumonia (IP), distinguishing IP from non-influenza pneumonia (NIP) is crucial to adequate the appropriate treatment.   Aim:   1.- To determine the prevalence of IP and NIP in a cohort with suspected pandemic H1N1.  2.- To evaluate the presence of risk factors for pneumonia in both groups.   Methods:  Retrospective observational study undertaken in patients with clinically suspected influenza admitted to emergency room, from August to December of 2009. Nasopharyngeal swabs were obtained from patients and RT-PCR was performed. Episodes in patients under age 18, nosocomial acquisition and infections in health-care workers were excluded. Demographic variables, comorbidities, final diagnosis and administered treatment were recorded.   Results:  326 episodes were evaluated (59.8% women). In 141 cases (43.2%) pandemic H1N1 was confirmed. IP was diagnosed in 33/326 (10.1%) and NIP in 86/326 (26.4%). 84.8% of IP episodes required hospital admission (27.3% in ICU). On the other hand, 79.1 % of NIP needed hospitalization (17.4% in ICU). 24% of IP were classified as PSI class IV/V vs. 44.2% of NIP (p=0. 045). Mortality in both groups was 9.1% vs. 10.5% respectively. Regarding to risk factors, statistical significant differences were found in age (47.5 ± 15.9 vs. 58.7 ±19.5, p=0.002), asthma (18.2 % vs. 5.8%, p=0.037) and COPD (9.1% vs. 30.2%, p=0.016). Obesity and pregnancy did not show significant differences.   Conclusions:   1. - The overall prevalence of pneumonia was 36.5% (10.1% for H1N1).  2. - Older age and COPD were risk factors associated with non-influenza pneumonia while asthma was associated with influenza pneumonia.
Chronic Absorptive Arthritis or Opera-Glass Hand: Report of Eight Cases
Authors: W. M. Solomon, R. M. Stecher
Journal: Annals of the Rheumatic Diseases (1950)

Opera-glass hand, la main en lorgnette, has been described as a very rare con- dition.The term has been used only occasionally, but the disease to which it refers is neither so rare nor of such recent origin as is usually assumed.The present paper calls attention to reports of the same disorder under a variety of names, and describes eight additional cases from the authors' experience.Cases from the Literature.-Marie and Leri (1913) described a 66-year-old woman with curious deformities of the hands.She had had severe generalized rheumatoid arthritis (rhumatisme deformant generalise) for 28 years.Photographs of the hands showed that the fingers and wrists were shortened and contracted and the skin wrinkled, redundant, and thrown into transverse folds, giving the impression that the phalanges were retracted one into the other like an opera glass (les phalanges etaient rentrees en lorgnette les unes dans les autres).Dissection revealed that the phalanges had lost their normal shape, the regular cylinders had become irregular truncated cones, the articular ends had completely disappeared.These changes had been seen in a radiograph which showed similar absorption of bone at the distal ends of the radii, ulni, carpals, and metacarpals, and marked radiolucence of all the bones.Microscopic examination showed massive degeneration of bones, cartilage, and muscles sparing only the blood vessels, nerves, and tendons.The authors mentioned another patient with a similar deformity limited to one finger.The term " doigts en lorgnette " was used by Brumpt (1906) to describe a deformity seen in a Sudanese Negro.The history was unreliable because of the ignorance and superstition of the patient and his associates.A line drawing of the hands showed most of the fingers to be markedly shortened, the skin soft and redun- dant, and the bones obviously shortened and distorted.The author stated that the fingers could be drawn out like a lorgnette and made to assume their normal length.The right ring finger and the left thumb and little fingers were normal.The hands were useless and the muscles were weak but not paralysed.Weigeldt (1929) described a 64-year-old woman with " mains en lorgnette" whose arthritis began at 46.The photograph showed hands similar to those described by Marie and LUri.The published radiograph showed extensive bone destruction.A case published by Nelson (1938) showed similar areas of bone destruction and absorption.A parathyroid adenoma was discovered at autopsy,
Quantitative Assessment of the SR Ca <sup>2+</sup> Leak-Load Relationship
Authors: Thomas R. Shannon, Kenneth S. Ginsburg, Donald M. Bers
Journal: Circulation Research (2002)

Increased diastolic SR Ca2+ leak (J(leak)) could depress contractility in heart failure, but there are conflicting reports regarding the J(leak) magnitude even in normal, intact myocytes. We have developed a novel approach to measure SR Ca2+ leak in intact, isolated ventricular myocytes. After stimulation, myocytes were exposed to 0 Na+, 0 Ca2+ solution +/-1 mmol/L tetracaine (to block resting leak). Total cell [Ca2+] does not change under these conditions with Na+-Ca2+ exchange inhibited. Resting [Ca2+]i declined 25% after tetracaine addition (126+/-6 versus 94+/-6 nmol/L; P<0.05). At the same time, SR [Ca2+] ([Ca2+](SRT)) increased 20% (93+/-8 versus 108+/-6 micromol/L). From this Ca2+ shift, we calculate J(leak) to be 12 micromol/L per second or 30% of the SR diastolic efflux. The remaining 70% is SR pump unidirectional reverse flux (backflux). The sum of these Ca2+ effluxes is counterbalanced by unidirectional forward Ca2+ pump flux. J(leak) also increased nonlinearly with [Ca2+](SRT) with a steeper increase at higher load. We conclude that J(leak) is 4 to 15 micromol/L cytosol per second at physiological [Ca2+](SRT). The data suggest that the leak is steeply [Ca2+](SRT)-dependent, perhaps because of increased [Ca2+]i sensitivity of the ryanodine receptor at higher [Ca2+](SRT). Key factors that determine [Ca2+](SRT) in intact ventricular myocytes include (1) the thermodynamically limited Ca2+ gradient that the SR can develop (which depends on forward flux and backflux through the SR Ca2+ ATPase) and (2) diastolic SR Ca2+ leak (ryanodine receptor mediated).
Zonal and regional differences identified from precision mapping of vitamin a-storing lipid droplets of the hepatic stellate cells in pig liver: A novel concept of addressing the intralobular area of heterogeneity
Authors: Zhenzhen Zou, Wichai Ekataksin, Kenjiro Wake
Journal: Hepatology (1998)

Knowledge of hepatic heterogeneity has been strikingly increased, while an accurate means for addressing intralobular positions is still lacking. We examined pig liver preparations of the gold impregnation method for vitamin A-storing lipid droplets in hepatic stellate cells. Droplet morphometry was performed under oil immersion, and the calculated volumes plotted on computerized maps. The heterogeneous results were assessed with five concentric zones and five radial regions; the latter were determined based on midseptum visualized by portal injection. Zonation and regionation thus subdivided lobules into 5-zone/5-region (5Z/5R) compartmentalization. Distribution of values exhibited a distinct zonal gradient, heightened at peripheral zones 1 and 2, decreased over intermediate zone 3 toward centrilobular zones 4 and 5; peak was always found at zone 2. Within a single zone, variations were obvious, forming a regional gradient. Values were significantly higher at periportal than midseptal regions. Digitized mapping showed that low values filled up centrilobular zones, whereas high values concentrated in periportal regions. Along the periphery, inlet venules were quantified, revealing an occurrence rate of 60% at periportal, and 5% at midseptal regions, closely compatible with the regional gradient of vitamin A-storing capacity. The interweaving between zonal and regional gradients results in a vitamin A-low territory, a compound area composed of centrilobular zones plus extensions into midseptal regions. Because the results could account for physiological and pathological events, we regard the 5Z/5R compartmentalization a model worth routine adoption for a precise description of any morphofunctionally demonstrable heterogeneity of the liver lobules.
Improved variant discovery through local re-alignment of short-read next-generation sequencing data using SRMA
Authors: Nils Homer, Stanley F Nelson
Journal: Genome biology (2010)

A primary component of next-generation sequencing analysis is to align short reads to a reference genome, with each read aligned independently. However, reads that observe the same non-reference DNA sequence are highly correlated and can be used to better model the true variation in the target genome. A novel short-read micro re-aligner, SRMA, that leverages this correlation to better resolve a consensus of the underlying DNA sequence of the targeted genome is described here.
Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma
Authors: A I Sarela
Journal: Gut (2000)

<h3>BACKGROUND/AIMS</h3> Inhibition of programmed cell death (apoptosis) is associated with increased tumour aggressiveness, and expression of<i>Survivin</i>, an antiapoptosis gene, in colorectal carcinomas may provide important prognostic information. <h3>PATIENTS/METHODS</h3> Expression of <i>Survivin</i> messenger RNA was evaluated by reverse transcription-polymerase chain reaction in 144 colorectal carcinomas and 86 adjacent histologically normal mucosa samples from patients for whom long term follow up data were available. <h3>RESULTS</h3> <i>Survivin</i>transcripts were detected in a significantly greater proportion of carcinomas (63.5%) than normal mucosa samples (29.1%; p&lt;0.001). The prevalence of <i>Survivin</i> expression was independent of advancing pathological stage. Death due to recurrent cancer following curative resection was predicted independently by tumour expression of <i>Survivin</i> (hazard ratio (HR) 2.60; 95% confidence interval (95% CI) 1.17–5.75) and lymph node metastases (HR 2.38; 95% CI 1.21–4.70). On stage wise analysis, the predictive value of <i>Survivin</i> expression was limited to patients with stage II colorectal carcinomas; those with <i>Survivin</i> negative tumours had a five year survival rate of 94.4% compared with 44.8% for patients with<i>Survivin</i> positive tumours (p=0.004, log rank test). <h3>CONCLUSION</h3> In patients with stage II colorectal carcinomas,<i>Survivin</i> expression provides prognostic information that may have important therapeutic implications.
Permeability of rat atrial endocardium, epicardium, and myocardium to large molecules. Stretch-dependent effects.
Authors: E Page, J Upshaw-Earley, G Goings
Journal: Circulation Research (1992)

Atrial distension, which stimulates atrial natriuretic peptide secretion by atrial myocytes, also stretches nonmuscle cells. In a noncontracting in vitro preparation of combined right and left atria we demonstrated by electron microscopy that, at 37 degrees C, transition from zero pressure to a physiological distending pressure of 5.1 mm Hg rapidly rendered atrial endocardial endothelium permeable to the macromolecular probes horseradish peroxidase (HRP; M(r), approximately 40,000) and wheat germ agglutinin-HRP (M(r), approximately 70,000); each probe was introduced at the atrial cavitary endocardial surface. Stretch-dependent permeabilization was also demonstrable in spontaneously contracting atria, was reversed by removing the distending pressure, and was unaffected by varying external Ca2+ concentration from 0.2 to 1.4 mM or by experimental perturbations that markedly decrease ANP secretory rates. Although transendocardial HRP and wheat germ agglutinin-HRP passage required stretch, native ferritin (M(r), = 500,000) could traverse unstretched endocardium. Probes were detected in noncoated endocardial vesicles and intercellular junctions between endocardial cells, but the relative contributions of vesicular transcytosis and paracellular diffusion could not be determined. Although HRP entered plasmalemmal caveolae of myocytes in stretched atria, myocytes did not internalize HRP by fluid-phase endocytosis. Distending pressure also caused apparent flow reversal in thebesian blood vessels, with retrograde transfer of HRP across the endocardium into the myocardium. HRP and ferritin presented at the external surface of the epicardium (visceral pericardium) were endocytosed by mesothelial cells, entered junctions between mesothelial cells, and readily crossed the epicardium of both stretched and unstretched preparations.
Infant Gut Microbial Composition Alters IgE Response to Tetanus Toxoid Immunization
Authors: Dennis R. Ownby, Alexandra R. Sitarik, Kei Fujimura, Suzanne Havstad, Haejin Kim, Kevin Bobbitt, Kimberley J. Woodcroft, Edward M. Zoratti, Nicholas W. Lukacs, Homer A. Boushey, Albert M. Levin, Susan V. Lynch, Christine Cole Johnson
Journal: Journal of Allergy and Clinical Immunology (2015)
832 HEPATIC NUCLEAR FACTOR-1a (HNF-1a) LOSS OF DNA BINDING ACTIVITY IS ESSENTIAL FOR HCV CORE-MEDIATED MODULATION OF LIPID METABOLISM REGULATORY FACTOR ANGIOPOIETIN-LIKE 3 (ANGPTL3) EXPRESSION
Authors: P. Foka, E. Karamichali, P.P. Doumba, G Dalagiorgou, E. Serti, E. Kochlios, J. Koskinas, U. Georgopoulou, P. Mavromara
Journal: Journal of Hepatology (2012)
CLINICAL STUDIES WITH RECOMBINANT-DNA-DERIVED METHIONYL HUMAN GROWTH HORMONE IN GROWTH HORMONE DEFICIENT CHILDREN
Authors: S. L. Kaplan, G. P. August, S. L. Blethen, D. R. Brown, R. L. Hintz, A. Johansen, L. P. Plotnick, L. E. Underwood, J. J. Bell, R. M. Blizzard, T. P. Foley, N. J. Hopwood, R. T. Kirkland, R. G. Rosenfeld, J. J. Van Wyk
Journal: The Lancet (1986)
Human Study of Biatrial Electrical Coupling
Authors: Robert Lemery, Luc Soucie, Bruno Martin, Anthony S.L. Tang, Martin Green, Jeff Healey
Journal: Circulation (2004)

The relative contribution of the atrial septum and interatrial connections to biatrial activation is a fundamental concept of human cardiac electrophysiology that has yet to be fully characterized. The purpose of the present study was to determine how both atria are coupled electrically.Twenty patients (16 men; mean age 54+/-11years) with a history of symptomatic atrial fibrillation (AF) underwent simultaneous biatrial noncontact mapping before catheter ablation of AF. The multiple electrode array catheters were positioned, respectively, in the left atrium (LA; transseptally) and the right atrium (RA). In all but 2 patients, isopotential maps revealed that endocardial septal activations of the RA and LA were separate, independent, and asynchronous of each other. Interatrial conduction was related to the site of initial atrial depolarization, revealing conduction over Bachmann's bundle in all patients during sinus rhythm, high RA pacing, and pacing from the LA appendage. Pacing from the coronary sinus was associated with conduction over the interatrial connection at the level of the coronary sinus in all patients, and conduction over Bachmann's bundle also occurred in 5 (26%) of 19 patients. Interatrial conduction over the fossa ovalis occurred in only 2 (2%) of the 116 segments analyzed.Electrical coupling of the RA and LA in humans is predominantly provided by muscular connections at the level of Bachmann's bundle and the coronary sinus. The true septum (the fossa ovalis and its limbus) of the RA and LA is asynchronous and discordant, usually without contralateral conduction during sinus rhythm or atrial pacing.
Comparative sequence analysis reveals an intricate network among REST, CREB and miRNA in mediating neuronal gene expression.
Authors: Jie Wu, Xiaohui Xie
Journal: Genome biology (2006)

Abstract Background Two distinct classes of regulators have been implicated in regulating neuronal gene expression and mediating neuronal identity: transcription factors such as REST/NRSF (RE1 silencing transcription factor) and CREB (cAMP response element-binding protein), and microRNAs (miRNAs). How these two classes of regulators act together to mediate neuronal gene expression is unclear. Results Using comparative sequence analysis, here we report the identification of 895 sites (NRSE) as the putative targets of REST . A set of the identified NRSE sites is present in the vicinity of the miRNA genes that are specifically expressed in brain-related tissues, suggesting the transcriptional regulation of these miRNAs by REST . We have further identified target genes of these miRNAs, and discovered that REST and its cofactor complex are targets of multiple brain-related miRNAs including miR-124a, miR-9 and miR-132. Given the role of both REST and miRNA as repressors, these findings point to a double-negative feedback loop between REST and the miRNAs in stabilizing and maintaining neuronal gene expression. Additionally, we find that the brain-related miRNA genes are highly enriched with evolutionarily conserved cAMP response elements (CRE) in their regulatory regions, implicating the role of CREB in the positive regulation of these miRNAs. Conclusion The expression of neuronal genes and neuronal identity are controlled by multiple factors, including transcriptional regulation through REST and post-transcriptional modification by several brain-related miRNAs. We demonstrate that these different levels of regulation are coordinated through extensive feedbacks, and propose a network among REST , CREB proteins and the brain-related miRNAs as a robust program for mediating neuronal gene expression.
Evaluation of different methods used to assess disease activity in rheumatoid arthritis: analyses of abatacept clinical trial data
Authors: M Dougados, N Schmidely, M Le Bars, C Lafosse, M Schiff, J S Smolen, D Aletaha, P van Riel, G Wells
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the Abatacept in Inadequate Responders to Methotrexate (AIM) trial. Methods: 424 active (abatacept ∼10 mg/kg) and 214 placebo-treated patients with rheumatoid arthritis (RA) were evaluated. Methods of reporting included: (1) response (American College of Rheumatology (ACR) criteria) versus state (disease activity score in 28 joints (DAS28) criteria); (2) stringency (ACR20 vs 50 vs 70; moderate disease activity state (MDAS; DAS28 &lt;5.1) vs low disease activity state (LDAS; DAS28 ⩽3.2) vs DAS28-defined remission (DAS28 &lt;2.6)); (3) time to onset (time to first ACR50/LDAS) and (4) sustainability of ACR50/LDAS for consecutive visits. Methods were assessed according to: (1) discriminatory capacity (number of patients needed to study (NNS)); (2) structural progression (Genant-modified Sharp score) and (3) patient satisfaction with treatment. Positive likelihood ratios (LR) evaluated the ability of the above methods to reflect structural damage and patient satisfaction. Results: MDAS and ACR20 had the highest discriminatory capacity (NNS 49 and 69). Sustained LDAS best reflected no radiographic progression (positive LR ⩾2). More stringent criteria (at least ACR50/LDAS), faster onset (⩽3 months) and sustainability (&gt;3 visits) of ACR50/LDAS best reflected patient satisfaction (positive LR &gt;10). Conclusions: The optimal method for reporting a measure of disease activity may differ depending on the outcome of interest. Time to onset and sustainability can be important factors when evaluating treatment response and disease status in patients with RA.
Differential Effects of Antihypertensive Treatment on Left Ventricular Diastolic Function
Authors: Robyn J. Tapp, Andrew Sharp, Alice V. Stanton, Eoin O'Brien, Nishi Chaturvedi, Neil R. Poulter, Peter S. Sever, Simon A. McG. Thom, Alun D. Hughes, Jamil Mayet
Journal: Journal of the American College of Cardiology (2010)