tbuckley/cabot-search huggingface dataset:
B cell activator PAX5 promotes lymphomagenesis through stimulation of B cell receptor signaling
Authors: Diana Cozma, Duonan Yu, Suchita Hodawadekar, Anna Azvolinsky, Shannon Grande, John W. Tobias, Michele H. Metzgar, Jennifer Paterson, Jan Erikson, Teresa Marafioti, John G. Monroe, Michael L. Atchison, Andrei Thomas-Tikhonenko
Journal: Journal of Clinical Investigation (2007)

The presumed involvement of paired box gene 5 (PAX5) in B-lymphomagenesis is based largely on the discovery of Pax5-specific translocations and somatic hypermutations in non-Hodgkin lymphomas. Yet mechanistically, the contribution of Pax5 to neoplastic growth remains undeciphered. Here we used 2 Myc-induced mouse B lymphoma cell lines, Myc5-M5 and Myc5-M12, which spontaneously silence Pax5. Reconstitution of these cells with Pax5-tamoxifen receptor fusion protein (Pax5ER(TAM)) increased neoplastic growth in a hormone-dependent manner. Conversely, expression of dominant-negative Pax5 in murine lymphomas and Pax5 knockdown in human lymphomas negatively affected cell expansion. Expression profiling revealed that Pax5 was required to maintain mRNA levels of several crucial components of B cell receptor (BCR) signaling, including CD79a, a protein with the immunoreceptor tyrosine-based activation motif (ITAM). In contrast, expression of 2 known ITAM antagonists, CD22 and PIR-B, was suppressed. The key role of BCR/ITAM signaling in Pax5-dependent lymphomagenesis was corroborated in Syk, an ITAM-associated tyrosine kinase. Moreover, we observed consistent expression of phosphorylated BLNK, an activated BCR adaptor protein, in human B cell lymphomas. Thus, stimulation of neoplastic growth by Pax5 occurs through BCR and is sensitive to genetic and pharmacological inhibitors of this pathway.
Relaxed Selection on the CBF/DREB1 Regulatory Genes and Reduced Freezing Tolerance in the Southern Range of Arabidopsis thaliana
Authors: Y. Zhen, M. C. Ungerer
Journal: Molecular Biology and Evolution (2008)

Elucidating the molecular basis of adaptive phenotypic variation represents a central aim in evolutionary biology. Traits exhibiting patterns of clinal variation represent excellent models for studies of molecular adaptation, especially when variation in phenotype can be linked to organismal fitness in different environments. Natural accessions of the model plant species Arabidopsis thaliana exhibit clinal variation in freezing tolerance that follows a gradient of temperature variability across the species' native range (Zhen Y, Ungerer MC. 2008. Clinal variation in freezing tolerance among natural accessions of A. thaliana. New Phytol. 177:419-427). Here, we report that this pattern of variation is attributable, at least in part, to relaxed purifying selection on members of a small family of transcriptional activators (the CBF/DREB1s) in the species' southern range. These regulatory genes play a critical role in the ability of A. thaliana plants to undergo cold acclimation and thereby achieve maximum freezing tolerance. Relative to accessions from northern regions, accessions of A. thaliana from the southern part of their geographic range exhibit levels of nonsynonymous nucleotide polymorphism that are approximately 2.8-fold higher across this small gene subfamily. Relaxed selection on the CBF/DREB1s in southern accessions also has resulted in multiple mutations in regulatory regions resulting in abrogated expression of particular subfamily members in particular accessions. These coding-region and regulatory mutations compromise the ability of these genes to act as efficient transcriptional activators during the cold acclimation process, as determined by reductions in rates of induction and maximum levels of expression in the downstream genes they regulate. This study highlights the potential role of regulatory genes in underlying adaptive phenotypic variation in nature.
Adiponectin and Leptin Concentrations May Aid in Discriminating Disease Forms in Children and Adolescents With Type 1 and Type 2 Diabetes
Authors: Alba Morales, Clive Wasserfall, Todd Brusko, Carolyn Carter, Desmond Schatz, Janet Silverstein, Tamir Ellis, Mark Atkinson
Journal: Diabetes Care (2004)

OBJECTIVE—The incidence of pediatric type 2 diabetes has recently seen an alarming increase. To improve our understanding of pediatric type 2 diabetes and identify markers that discriminate these subjects from those with type 1 diabetes, we performed a multivariant analysis associating serum adiponectin and leptin levels with anthropometrical parameters and disease state. RESEARCH DESIGN AND METHODS—Samples from children and adolescents with type 1 diabetes (n = 41) and type 2 diabetes (n = 17) and from nondiabetic individuals of similar age from the general population (n = 43) were investigated. An analysis included the parameters of matching for BMI and Tanner stage. Receiver-operator characteristic (ROC) curves were established to assess these analytes’ association with disease. RESULTS—Contrary to studies of adult type 1 diabetes, adiponectin levels in our pediatric type 1 diabetic subjects (10.2 μg/ml [95% CI 8.6–11.7]) did not differ from those of healthy control subjects (10.6 μg/ml [9.2–12.0]; P = NS). Children with type 2 diabetes (5.5 μg/ml [4.8–6.2]) had significantly lower adiponectin levels than both of those groups. Conversely, type 2 diabetic subjects showed marked elevations in serum leptin concentrations (24.3 ng/ml [17.1–31.5]) compared with healthy control subjects (2.7 ng/ml [1.3–4.1]; P &amp;lt; 0.001) and type 1 diabetic subjects (5.1 ng/ml [3.5–6.7]; P &amp;lt; 0.001). Importantly, each of the properties ascribed to pediatric type 2 diabetes was present when the comparison was restricted to healthy children or type 1 diabetic patients whose BMI was &amp;gt;85th percentile or who had Tanner stage 4 and 5. The evaluation of adiponectin-to-leptin ratios revealed a striking difference between children with type 1 diabetes (6.3 [3.8–8.8]) and type 2 diabetes (0.3 [0.2–0.5]; P &amp;lt; 0.001). CONCLUSIONS—In pediatric diabetes, where diagnosis of disease is often difficult, these studies suggest that the adiponectin-to-leptin ratio may provide additional help in the discrimination between type 1 and type 2 diabetes.
Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice
Authors: Niall C. Tebbutt, Andrew S. Giraud, Melissa Inglese, Brendan Jenkins, Paul Waring, Fiona J. Clay, Sina Malki, Barbara M. Alderman, Dianne Grail, Frédéric Hollande, Joan K. Heath, Matthias Ernst
Journal: Nature Medicine (2002)
Self-experimentation: Friend or foe?
Authors: Seth Roberts
Journal: Behavioral and Brain Sciences (2004)

The topics discussed in this response are in four broad areas: (1) Idea generation, including the failure to discuss and teach idea generation and how to nurture new ideas (sect. R2), sources of ideas worth testing with self-experimentation (sect. R3), and unusual features of the situation that may have increased the discovery rate (sect. R4); (2) Miscellaneous methodological issues, such as the value of mental experiments (sect. R5) and the limitations of double-blind experiments (sect. R6); (3) Subject-matter issues, including the relationship of this work to other evolutionary psychology studies and a new way to test evolutionary explanations (sect. R7), as well as questions about the mood results (sect. R8) and the weight results (sect. R9); and (4) Self-experimentation, including its difficulty (sect. R10) and future (sect. R11).
Reducing non-specific binding and uptake of nanoparticles and improving cell targeting with an antifouling PEO-b-PγMPS copolymer coating
Authors: Hongwei Chen, Liya Wang, Julie Yeh, Xinying Wu, Zehong Cao, Yongqiang A. Wang, Minming Zhang, Lily Yang, Hui Mao
Journal: Biomaterials (2010)
ANGIOTENSIN AND RENIN IN RAT AND DOG BRAIN
Authors: Catalina Fischer-Ferraro, Victor E. Nahmod, Daniel J. Goldstein, Samuel Finkielman
Journal: The Journal of Experimental Medicine (1971)

An enzyme with the characteristics of classical renin was isolated from brain extracts of nephrectomized dogs. This enzyme is thermolabile, nondialyzable, and forms a vasoconstrictive material when incubated with renin plasma substrate at pH 7. A short lasting pressor activity was also found in brain extracts of dogs and rats. This activity was due to a substance identified by chemical and pharmacological tests as angiotensin. Countercurrent distribution of brain extracts of rats showed that 38% of the pressor activity corresponded to angiotensin II and the remainder to angiotensin I. A remarkable correlation was found between angiotensin and norepinphrine concentrations in different portions of the encephalon of the dog.
Death on the road to international development
Authors: Ian Roberts
Journal: BMJ (2005)

W e don't know much about her. All we know is that in 2003 a small Tanzanian girl died after having been run over by a truck, a truck belonging to a company managed by CDC (formerly the Commonwealth Development Corporation, and now wholly owned by the Department for International Development of the UK government). According to CDC records the girl did not die at the scene, but “following poor care she died in the hospital 3dayslater.”

CDC's mission is to create wealth in emerging markets, particularly poorer countries, by investing in “sustainable” private sector businesses. In 2003 CDC made a pretax profit of £45m ($85m; €65m), some £15.6m of which was made from its investment in Africa.

Last year I gave a lunchtime seminar on road safety to CDC managers. Before the seminar I was given a summary of the fatal “accidents” attributable to CDC managed businesses in 2003. The Tanzanian girl was not the only child to have died on the road to international development in 2003. The same year a two year old …
Muscle Physiology and Contraction Theories
Authors: John V. Taggart, RICHARD J. PODOLSKY
Journal: Circulation (1961)

The structural basis of current contraction theories is the double array of thick and thin myofilaments revealed by the electron microscope. The physiologic properties that characterize the contractile process are natural consequences of this structure if (a) during shortening the 2 sets of filaments move relative to each other and (b) the flux of chemical energy through the contractile mechanism is limited by interaction between complementary sites distributed along the 2 sets of filaments. Contraction models fitted to these ideas differ largely in the mechanism by which force is generated. In the sliding model , force is developed by mechanical interaction between the thick and thin filaments, and filament length remains constant during contraction. In the folding model , force is developed in the thin filament, which shortens during contraction. Both models quantitatively account for the force-velocity relation and the Fenn effect. They also accommodate the quick-release phenomenon and predict, at least qualitatively, the isotonic velocity transients that can be seen after quick release from tetanic tension.
The Different Effects on the Serum Lipids and Fecal Steroids of High Carbohydrate Diets Given Orally or Intravenously
Authors: Lawrence DenBesten, Roberto H. Reyna, William E. Connor, Lewis D. Stegink
Journal: Journal of Clinical Investigation (1973)

The hypothesis that diets high in carbohydrate produce hyperlipidemia in man was tested in new experiments which provided all calories either by the intravenous route or orally. After a base-line general diet, eight healthy men were fed fat-free diets consisting of 80% of the calories from glucose and 20% from an amino acid hydrolysate. The calories were adequate to maintain body weight. The solutions (1 cal/ml) were infused by constant drip over a 24 h period through either a superior vena cava catheter or a nasogastric tube. Each feeding was for 12 days in sequence but assigned in random order. The high CHO diet given orally, as expected, increased the mean base-line serum triglyceride level from 176+/-29 (SE) to 274+/-47. The identical diet given intravenously (i.v.) failed to produce hypertriglyceridemia; triglyceride levels were not significantly changed, 154+/-37, nor were blood glucose levels. Serum insulin levels were higher during the intravenous feeding. In contrast, both i.v. and oral feedings greatly lowered mean serum cholesterol concentration from the base-line value of 220+/-13 mg/100 ml to 135+/-11 and 151+/-13, respectively. However, the serum cholesterol level was significantly lower (P < 0.01) with the intravenous feeding than with the oral feeding. In addition, the fecal excretion of both neutral sterols and bile acids diminished greatly during the period of intravenous feeding. The fecal mass was likewise decreased. The bacterial conversion of cholesterol to conprostanol did not occur with either intravenous or oral feeding, but with both regimens secondary bile acids predominated, as usual, in the bile acid fraction of the stool. These results emphasize the key role of the intestinal mucosa in the etiology of carbohydrate-induced hypertriglyceridemia and as a direct or indirect contributor to plasma triglyceride and cholesterol levels in the absence of dietary lipids. When the gut mucosa was bypassed, carbohydrate-induced hypertriglyceridemia did not occur and both serum triglyceride and serum cholesterol levels decreased greatly at a time when the excretion of steroids in the stool was also reduced.
845 LIVER, RENAL, AND CIRCULATORY DYSFUNCTION IN HEPATORENAL SYNDROME WITH AND WITHOUT BACTERIAL INFECTION. A PROSPECTIVE STUDY
Authors: M. Guevara, M. Martín Llahi, M. Marinelli, C. Fagundes, G. Pereira, E. Solá, M. Pavesi, J. Fernández, V. Arroyo, P. Ginès
Journal: Journal of Hepatology (2010)
Scientists and the folk have the same concepts
Authors: Neil Levy
Journal: Behavioral and Brain Sciences (2010)

Abstract If Knobe is right that ordinary judgments are normatively suffused, how do scientists free themselves from these influences? I suggest that because science is distributed and externalized, its claims can be manipulated in ways that allow normative influences to be hived off. This allows scientists to deploy concepts which are not normatively suffused. I suggest that there are good reasons to identify these normatively neutral concepts with the folk concepts.
Partner notification for the control of sexually transmitted infections
Authors: S. Hawkes
Journal: BMJ (2003)

several other promising candidate genes, including neuregulin-1 and dysbindin. 12Interestingly, neuregulin-1 and dysbindin proteins are known to have important roles in neurodevelopment and synaptic functions, like DISC-1.In addition to deficits in neural development, several aspects of the pathogenesis of schizophrenia have been studied, including dysfunctions of glutamatergic and dopaminergic neurotransmission.Possible environmental factors superimposed on genetic vulnerability include virus infection as well as gestational and birth complications.By studying genetically engineered mice with susceptibility factors such as DISC-1 in combination with environmental stresses, it may be possible to provide a more definitive, integrated model for the pathogenesis of schizophrenia in the future.
Experimental immune treatment of hepatitis C virus (HCV) infection:Passive anti-HCV (HCIg) transfer in chronically infected chimpanzees
Authors: K. Krawczynski, A. Fattom, D. Culver, S. Kamili, J. Spelbring, L. Basham, C. Sapan, R. Naso, M. Purdy, D. Carson
Journal: Journal of Hepatology (2000)
Reduction of variceal pressure by propranolol: Comparison of the effects on portal pressure and azygos blood flow in patients with cirrhosis
Authors: Faust Feu, Josep María Bordas, Angelo Luca, Joan Carles García-Pagán, Angels Escorsell, Jaume Bosch, Joan Rodes
Journal: Hepatology (1993)

This study investigated the correlation between changes in hepatic hemodynamics and esophageal variceal pressure–measured with a noninvasive, pressure-sensitive endoscopic gauge–in 37 portal-hypertensive cirrhotic patients receiving propranolol (0.15 mg/kg, intravenously; n = 21) or placebo (n = 16) under strict double-blind conditions. Placebo administration had no effect on hepatic venous pressure gradient, azygos blood flow or variceal pressure. Propranolol caused a significant reduction in hepatic venous pressure gradient (from 19.6 ± 1 to 17.3 ± 1 mm Hg, p < 0.001), azygos blood flow (from 0.61 ± 0.06 to 0.39 ± 0.03 L/min, p < 0.001) and variceal pressure (from 13.1 ± 0.9 to 10.2 ± 0.9 mm Hg, p < 0.001). In eight patients (propranolol nonresponders) hepatic venous pressure gradient was not modified or decreased by less than 10% after propranolol (mean change, −4.1 ± 1.6%). However, we found no significant differences between propranolol responders and nonresponders with regard to the decrease in variceal pressure (3.3 ± 0.7 vs. 2.3 ± 1.4 mm Hg) and azygos blood flow (0.23 ± 0.07 vs. 0.21 ± 0.07 L/min). As expected, in most propranolol responders (11 of 13), reduction in hepatic venous pressure gradient was accompanied by a similar response in variceal pressure (>10% decrease). However, among propranolol nonresponders, in terms of reduction in hepatic venous pressure gradient, four out of eight patients had decreases greater than 10% in variceal pressure. The results of this study confirm that reduction in hepatic venous pressure gradient by propranolol is associated with a significant decrease in variceal pressure and azygos blood flow. These favorable effects are also observed in some patients in whom hepatic venous pressure gradient fails to decrease by more than 10% of the baseline value, suggesting that propranolol administration has beneficial effects in some of these patients. (HEPATOLOGY 1993;18:1082-1089).
Viral Hepatitis Abroad
Authors: Robert D. Woodson
Journal: JAMA (1972)

Hepatitis incidence was studied retrospectively in a group of 1,314 Catholic missionaries living in various developing countries. Overall incidence of icteric illnesses was 1.7 cases per 100 person-years exposure. There were large differences in hepatitis incidence in the various countries, with rates varying from a low of 0.2 cases per 100 person-years in Japan to a high of 4.0 cases per 100 person-years in some countries of Central and South America. Risk was sustained at fairly high levels for at least ten years. It is suggested that the high risk warrants prophylaxis with immune serum globulin.
The influence of patients' hopes of receiving a prescription on doctors' perceptions and the decision to prescribe: a questionnaire survey
Authors: N. Britten, O. Ukoumunne
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To measure patients9 expectations of receiving prescriptions and general practitioners9 perceptions of these expectations and to determine the factors most closely associated with the decision to prescribe. <b>Design:</b> Questionnaires were completed by patients waiting to see their general practitioners, and by their doctors immediately after the consultations. <b>Setting:</b> Four non-fundholding group practices in southeast London. <b>Subjects:</b> 544 unselected patients consulting 15 general practitioners. <b>Main outcome measures:</b> Doctors9 perceptions of patients9 expectations; doctors9 decisions to prescribe. <b>Results:</b> 67% (354/526) of patients hoped for a prescription; doctors perceived that 56% (305/542) of patients wanted prescriptions; and doctors wrote prescriptions in 59% (321/543) of consultations. Despite the close agreement between patients9 hopes and doctors9 perceptions, 25% (89/353) of patients hoped for a prescription but did not receive one. In 22% (68/313) of consultations in which prescriptions were written, they were not strictly indicated on purely medical grounds, and in only 66% (202/306) of consultations in which prescriptions were written were they both indicated and hoped for. Doctors9 perceptions of patients9 expectations were the strongest predictor of the decision to prescribe, but the final regression model also included patients9 hopes and ethnic group, and the doctor9s feeling of being pressurised. <b>Conclusions:</b> In an area of low prescribing and high expectations the decision to prescribe was closely related to actual and perceived expectations, but the latter was the more significant influence. <h3>Key messages</h3> Evidence that patients9 expectations influence general practitioners9 prescribing is equivocal; in this study patients9 hopes of receiving a prescription exceeded both doctors9 perceptions and the level of prescribing Over a quarter of patients who hoped for a prescription did not receive one In a fifth of consultations in which a prescription was written, the prescription was not strictly indicated on purely medical grounds Doctors9 perceptions were the strongest determinant of the decision to prescribe Doctors who felt pressurised were less likely to write a prescription if they perceived that the patient wanted one, and if they did write a prescription, it was less likely to be indicated than when the doctor did not feel pressurised
Pit Latrines and Their Impacts on Groundwater Quality: A Systematic Review
Authors: Jay P. Graham, Matthew L. Polizzotto
Journal: Environmental Health Perspectives (2013)

Pit latrines are one of the most common human excreta disposal systems in low-income countries, and their use is on the rise as countries aim to meet the sanitation-related target of the Millennium Development Goals. There is concern, however, that discharges of chemical and microbial contaminants from pit latrines to groundwater may negatively affect human health.Our goals were to a) calculate global pit latrine coverage, b) systematically review empirical studies of the impacts of pit latrines on groundwater quality, c) evaluate latrine siting standards, and d) identify knowledge gaps regarding the potential for and consequences of groundwater contamination by latrines.We used existing survey and population data to calculate global pit latrine coverage. We reviewed the scientific literature on the occurrence of contaminants originating from pit latrines and considered the factors affecting transport of these contaminants. Data were extracted from peer-reviewed articles, books, and reports identified using Web of ScienceSM, PubMed, Google, and document reference lists.We estimated that approximately 1.77 billion people use pit latrines as their primary means of sanitation. Studies of pit latrines and groundwater are limited and have generally focused on only a few indicator contaminants. Although groundwater contamination is frequently observed downstream of latrines, contaminant transport distances, recommendations based on empirical studies, and siting guidelines are variable and not well aligned with one another.In order to improve environmental and human health, future research should examine a larger set of contextual variables, improve measurement approaches, and develop better criteria for siting pit latrines.