tbuckley/cabot-search huggingface dataset:
CONTRAST: a discriminative, phylogeny-free approach to multiple informant de novo gene prediction
Authors: Samuel S Gross, Chuong B Do, Marina Sirota, Serafim Batzoglou
Journal: Genome biology (2007)

Abstract We describe CONTRAST, a gene predictor which directly incorporates information from multiple alignments rather than employing phylogenetic models. This is accomplished through the use of discriminative machine learning techniques, including a novel training algorithm. We use a two-stage approach, in which a set of binary classifiers designed to recognize coding region boundaries is combined with a global model of gene structure. CONTRAST predicts exact coding region structures for 65% more human genes than the previous state-of-the-art method, misses 46% fewer exons and displays comparable gains in specificity.
Effect of reducing caffeine intake on birth weight and length of gestation: randomised controlled trial
Authors: Bodil Hammer Bech, Carsten Obel, Tine Brink Henriksen, Jørn Olsen
Journal: BMJ (2007)

<b>Objective</b> To estimate the effect of reducing caffeine intake during pregnancy on birth weight and length of gestation. <b>Design</b> Randomised double blind controlled trial. <b>Setting</b> Denmark. <b>Participants</b> 1207 pregnant women drinking at least three cups of coffee a day, recruited before 20 weeks9 gestation. <b>Interventions</b> Caffeinated instant coffee (568 women) or decaffeinated instant coffee (629 women). <b>Main outcome measures</b> Birth weight and length of gestation. <b>Results</b> Data on birth weight were obtained for 1150 liveborn singletons and on length of gestation for 1153 liveborn singletons. No significant differences were found for mean birth weight or mean length of gestation between women in the decaffeinated coffee group (whose mean caffeine intake was 182 mg lower than that of the other group) and women in the caffeinated coffee group. After adjustment for length of gestation, parity, prepregnancy body mass index, and smoking at entry to the study the mean birth weight of babies born to women in the decaffeinated group was 16 g (95% confidence interval −40 to 73) higher than those born to women in the caffeinated group. The adjusted difference (decaffeinated group−caffeinated group) of length of gestation was −1.31 days (−2.87 to 0.25). <b>Conclusion</b> A moderate reduction in caffeine intake in the second half of pregnancy has no effect on birth weight or length of gestation. <b>Trial registration</b> Clinical Trials NCT00131690.
A novel urokinase receptor-targeted inhibitor for plasmin and matrix metalloproteinases suppresses vein graft disease
Authors: Daniel Eefting, Leonard Seghers, Jos M. Grimbergen, Margreet R. de Vries, Hetty C. de Boer, Jan-Willem H.P. Lardenoye, J. Wouter Jukema, J. Hajo van Bockel, Paul H.A. Quax
Journal: Cardiovascular Research (2010)

Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems simultaneously. MMP and plasmin activity were inhibited at the cell surface by this hybrid protein, consisting of the receptor-binding amino-terminal fragment (ATF) of urokinase-type PA, linked to both the tissue inhibitor of metalloproteinases (TIMP-1) and bovine pancreas trypsin inhibitor (BPTI), a potent protease inhibitor. The effect of overexpression of this protein on vein graft disease was studied. A non-viral expression vector encoding the hybrid protein TIMP-1.ATF.BPTI was constructed and validated. Next, cultured segments of human veins were transfected with this vector. Expressing TIMP-1.ATF.BPTI in vein segments resulted in a mean 36 ± 14% reduction in neointima formation after 4 weeks. In vivo inhibition of vein graft disease by TIMP-1.ATF.BPTI is demonstrated in venous interpositions placed into carotid arteries of hypercholesterolaemic APOE*3Leiden mice. After 4 weeks, vein graft thickening was significantly inhibited in mice treated with the domains TIMP-1, ATF, or BPTI (36–49% reduction). In the TIMP-1.ATF.BPTI-treated mice, vein graft thickening was reduced by 67±4%, which was also significantly stronger when compared with the individual components. These data provide evidence that cell surface-bound inhibition of the PA and MMP system by the hybrid protein TIMP-1.ATF.BPTI, overexpressed in distant tissues after electroporation-mediated non-viral gene transfer, is a powerful approach to prevent vein graft disease.
Diagnosis of autism: Use of autistic spectrum shows undisciplined thinking
Authors: P V F. Cosgrove
Journal: BMJ (2004)

Editor—The use by Baird et al in their clinical review of the diagnosis “autism” and “autistic spectrum disorders” confuses me.1 The authors list five outcomes in box 8 that indicate the success of therapeutic and teaching interventions and may help us to comprehend what is the cardinal feature of autism: normal use of verbal language, some use of verbal language for a range of purposes, some functional use of language, ability to use an alternative system of communication, the child's idiosyncratic communication is better understood.

In each of these five successful outcomes for autism is one constant thread—the abnormal use of language for communication. I suggest that autism is none other than this—as opposed to the delayed development of speech. If that is so, then we do not need a spectrum any more than we need an asthmatic spectrum or a diabetic spectrum.

The diagnosing clinician must decide either that the child has autism or he or she does not have autism. If there is uncertainty, then this can be expressed reasonably. Responsible clinicians can justifiably give some idea of the severity of the autism by saying that it is severe or it is moderate or it is mild.

I believe that the use of autistic spectrum (as opposed to a straightforward diagnosis of autism) is undisciplined thinking. Either children have abnormal use of language for communication or they do not. Don't leave them on the autistic spectrum when you cannot come to a clear and definite diagnosis of autism.
GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO
Authors: G. J. Thorbecke
Journal: The Journal of Experimental Medicine (1960)

Gamma globulin formation in vitro by various tissues was studied using the incorporation of C(14)-L-lysine into a protein precipitable by a specific anti rabbit gamma globulin serum prepared in a sheep. It was demonstrated that the rate of gamma globulin formation in similar numbers of spleen cells is much higher if taken from an immunized rabbit at the height of antibody formation than that in normal spleen cells. Besides spleen, other tissues shown to form gamma globulin in normal adult rabbits were: peripheral lymph nodes, bone marrow, lung, mesenteric lymph nodes, appendix, and thymus. In tissues from newborn rabbits gamma globulin formation could not be demonstrated. Rabbits 1 week old already showed a beginning of significant gamma globulin formation in appendix tissue, followed approximately 3 weeks later by gamma globulin synthesis in spleen and thymus. Histological observations on these tissues were described and correlated with findings on gamma globulin formation. In the discussion an attempt has been made to relate these observations on newborn and immature rabbits to those available in the literature on antibody formation in newborn animals.
Intracardiac, intravascular, two-dimensional, high-frequency ultrasound imaging of pulmonary artery and its branches in humans and animals.
Authors: N G Pandian, A Weintraub, A Kreis, S L Schwartz, M A Konstam, D N Salem
Journal: Circulation (1990)

Intravascular ultrasound imaging is a promising new method for assessing vascular morphology. We evaluated the capability of intravascular ultrasound to quantify pulmonary artery (PA) morphology in vitro and explored the feasibility of in vivo PA imaging in animals and humans. In the in vitro study of 15 PA segments, we used a 20-MHz prototype ultrasound catheter. Intravascular ultrasound (y) provided crisp images of PA segments and demonstrated excellent correlations with anatomic measurements (x) in the estimation of luminal area (y = 0.89x + 2.95, r = 0.99, p less than 0.001), luminal diameter (n = 30, y = 0.79x + 0.96, r = 0.92, p less than 0.001), and vessel wall thickness (n = 60, y = 0.65x + 0.33, r = 0.85, p less than 0.001). We subsequently introduced the probe into the PA of 10 dogs and were able to obtain real-time, two-dimensional images of the main PA, its major branches, and farther smaller branches as far as the wedge level. To evaluate the in vivo feasibility of PA imaging in conscious humans, we used a commercially available, 20-MHz intravascular ultrasound (IVUS) catheter in 22 subjects through a femoral or jugular venous sheath at the end of standard diagnostic cardiac catheterization. In 20 subjects, we acquired dynamic, high-resolution, cross-sectional images of the proximal and distal PA. Changes in shape and decreasing luminal area could be clearly recognized as the IVUS catheter reached branching points and as it passed more distally. There were no complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal secretory and absorptive function in Trichinella spiralis mouse model of postinfective gut dysfunction: role of bile acids
Authors: N Kalia, J Hardcastle, C Keating, P Pelegrin, D Grundy, L Grasa, K D Bardhan
Journal: Gut (2007)

<h3>Objective:</h3> Observations showing that bile acid malabsorption is frequent in irritable bowel syndrome (IBS) suggest that alterations in bile acid-induced secretion and absorption could contribute to IBS-associated diarrhoea. The secretory response to bile acids, fluid transport and bile absorption was examined in intestinal tissues from a <i>Trichinella spiralis</i> mouse model of postinfectious gut dysfunction <i>in vitro</i>. Changes in the protein expression of apical sodium-dependent bile acid transporter (ASBT) were also measured. <h3>Design:</h3> <i>T. spiralis</i>-infected mice were killed at 18 and 25 days postinfection. Jejunal, ileal, proximal and distal colon segments were exposed to taurodeoxycholic acid (TDCA) or cholic acid. Short circuit current (SCC) increases were determined. Tritiated taurocholic acid (3H-TCA) absorption was determined in everted jejunal and ileal sacs. ASBT protein expression was determined by Western blot analysis and immunohistochemistry. <h3>Results:</h3> Basal SCC increased in ileum and distal colon at 18 and 25 days postinfection, respectively. Ileal SCC responses to TDCA and cholic acid were enhanced at 18 days postinfection. Distal colon SCC response to TDCA was raised at 18 days postinfection but was significantly reduced by 25 days. Ileal 3H-TCA uptake was significantly reduced at 18 and 25 days postinfection. Surprisingly, increased ASBT expression was observed in infected animals. <h3>Conclusions:</h3> In a <i>T. spiralis</i> model of postinfectious gut dysfunction, decreased bile absorption and enhanced secretion in response to bile acids was observed. Decreased absorption was not, however, caused by decreased ASBT as increased expression was observed. If similar events occur postinfection, the combined effects of these disturbances may contribute to some symptoms observed in postinfectious IBS patients.
Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery
Authors: David Vaudry, Anthony Falluel-Morel, Steve Bourgault, Magali Basille, Delphine Burel, Olivier Wurtz, Alain Fournier, Billy K. C. Chow, Hitoshi Hashimoto, Ludovic Galas, Hubert Vaudry
Journal: Pharmacological Reviews (2009)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid C-terminally α-amidated peptide that was first isolated 20 years ago from an ovine hypothalamic extract on the basis of its ability to stimulate cAMP formation in anterior pituitary cells (Miyata et al., 1989. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-secretin-growth hormone-releasing hormone-glucagon superfamily. The sequence of PACAP has been remarkably well conserved during evolution from protochordates to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide, the activity of which remains unknown. Two types of PACAP binding sites have been characterized: type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP, whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes: the PACAP-specific PAC1-R, which is coupled to several transduction systems, and the PACAP/VIP-indifferent VPAC1-R and VPAC2-R, which are primarily coupled to adenylyl cyclase. PAC1-Rs are particularly abundant in the brain, the pituitary and the adrenal gland, whereas VPAC receptors are expressed mainly in lung, liver, and testis. The development of transgenic animal models and specific PACAP receptor ligands has strongly contributed to deciphering the various actions of PACAP. Consistent with the wide distribution of PACAP and its receptors, the peptide has now been shown to exert a large array of pharmacological effects and biological functions. The present report reviews the current knowledge concerning the pleiotropic actions of PACAP and discusses its possible use for future therapeutic applications.
<b> <i>Calcineurin A</i> </b> β Gene Targeting Predisposes the Myocardium to Acute Ischemia-Induced Apoptosis and Dysfunction
Authors: Orlando F. Bueno, Daniel J. Lips, Robert A. Kaiser, Benjamin J. Wilkins, Yan-Shan Dai, Betty J. Glascock, Raisa Klevitsky, Timothy E. Hewett, Thomas R. Kimball, Bruce J. Aronow, Pieter A. Doevendans, Jeffery D. Molkentin
Journal: Circulation Research (2003)

Cardiovascular disease is the leading cause of mortality and morbidity within the industrialized nations of the world, with coronary heart disease (CHD) accounting for as much as 66% of these deaths. Acute myocardial infarction is a typical sequelae associated with long-standing coronary heart disease resulting in large scale loss of ventricular myocardium through both apoptotic and necrotic cell death. In this study, we investigated the role that the calcium calmodulin-activated protein phosphatase calcineurin (PP2B) plays in modulating cardiac apoptosis after acute ischemia-reperfusion injury to the heart. Calcineurin A β gene–targeted mice showed a greater loss of viable myocardium, enhanced DNA laddering and TUNEL, and a greater loss in functional performance compared with strain-matched wild-type control mice after ischemia-reperfusion injury. RNA expression profiling was performed to uncover potential mechanisms associated with this loss of cardioprotection. Interestingly, calcineurin A β −/− hearts were characterized by a generalized downregulation in gene expression representing approximately 6% of all genes surveyed. Consistent with this observation, nuclear factor of activated T cells (NFAT)-luciferase reporter transgenic mice showed reduced expression in calcineurin A β −/− hearts at baseline and after ischemia-reperfusion injury. Finally, expression of an activated NFAT mutant protected cardiac myocytes from apoptotic stimuli, whereas directed inhibition of NFAT augmented cell death. These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart.
Dose-related Effects of Ragweed Allergy Immunotherapy Tablet on Nasal and Ocular Symptoms of Allergic Rhinoconjunctivitis During the Peak Ragweed Pollen Seasons in Europe and North America
Authors: J. Maloney, H. Nolte, K. Nekam, P. Creticos, G. Berman, A. Kaur, J. Hebert
Journal: Journal of Allergy and Clinical Immunology (2012)
A Rho Kinase/Myocardin-Related Transcription Factor-A–Dependent Mechanism Underlies the Sphingosylphosphorylcholine-Induced Differentiation of Mesenchymal Stem Cells Into Contractile Smooth Muscle Cells
Authors: Eun Su Jeon, Won Sun Park, Mi Jeong Lee, Young Mi Kim, Jin Han, Jae Ho Kim
Journal: Circulation Research (2008)

Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue–derived mesenchymal stem cells (hADSCs) to smooth muscle cells (SMCs). In the present study, we characterized contractile and ion channel properties of SMCs differentiated from hADSCs (hADSC-SMCs) as a result of SPC treatment, and we investigated the molecular mechanisms involved in the SPC-induced differentiation. Using in vitro collagen gel lattice contraction and whole cell patch clamp, we showed that the hADSC-SMCs expressed functional L-type voltage-gated Ca 2+ channels and contractile activities in response to KCl, carbachol, and the L-type Ca 2+ channel opener Bay K8644, whereas the L-type Ca 2+ channel blocker nifedipine abrogated the contractility of hADSC-SMCs. Furthermore, hADSC-SMCs expressed functional big conductance Ca 2+ -activated K + (BK Ca ) channels, and the BK Ca channel blocker iberiotoxin potentiated the Bay K8644-stimulated contractility of the hADSC-SMCs, indicating that these cells exhibited SMC-like contractile characteristics. SPC activated RhoA in hADSCs and pretreatment with the Rho kinase inhibitor Y27632 or by overexpression of dominant-negative mutants of RhoA or Rho kinase completely abrogated the SPC-induced differentiation of hADSCs into SMCs. SPC also increased the expression levels of myocardin-related transcription factor (MRTF)-A, a transcription factor involved in smooth muscle differentiation, in hADSCs. Small interference RNA–mediated depletion of endogenous MRTF-A abolished the SPC-induced differentiation of hADSCs into SMCs. Furthermore, SPC promoted nuclear translocation of MRTF-A, and pharmacological inhibition of Rho kinase blocked this effect. These results suggest that SPC induced differentiation of hADSCs into contractile SMCs through a mechanism involving RhoA/Rho kinase–dependent nuclear translocation of MRTF-A.
Curtailing Endothelial TGF-β Signaling Is Sufficient to Reduce Endothelial-Mesenchymal Transition and Fibrosis in CKD
Authors: Sandhya Xavier, Radovan Vasko, Kei Matsumoto, Joseph A. Zullo, Robert Chen, Julien Maizel, Praveen N. Chander, Michael S. Goligorsky
Journal: Journal of the American Society of Nephrology (2014)

Excessive TGF-β signaling in epithelial cells, pericytes, or fibroblasts has been implicated in CKD. This list has recently been joined by endothelial cells (ECs) undergoing mesenchymal transition. Although several studies focused on the effects of ablating epithelial or fibroblast TGF-β signaling on development of fibrosis, there is a lack of information on ablating TGF-β signaling in the endothelium because this ablation causes embryonic lethality. We generated endothelium-specific heterozygous TGF-β receptor knockout (TβRII(endo+/-)) mice to explore whether curtailed TGF-β signaling significantly modifies nephrosclerosis. These mice developed normally, but showed enhanced angiogenic potential compared with TβRII(endo+/+) mice under basal conditions. After induction of folic acid nephropathy or unilateral ureteral obstruction, TβRII(endo+/-) mice exhibited less tubulointerstitial fibrosis, enhanced preservation of renal microvasculature, improvement in renal blood flow, and less tissue hypoxia than TβRII(endo+/+) counterparts. In addition, partial deletion of TβRII in the endothelium reduced endothelial-to-mesenchymal transition (EndoMT). TGF-β-induced canonical Smad2 signaling was reduced in TβRII(+/-) ECs; however, activin receptor-like kinase 1 (ALK1)-mediated Smad1/5 phosphorylation in TβRII(+/-) ECs remained unaffected. Furthermore, the S-endoglin/L-endoglin mRNA expression ratio was significantly lower in TβRII(+/-) ECs compared with TβRII(+/+) ECs. These observations support the hypothesis that EndoMT contributes to renal fibrosis and curtailing endothelial TGF-β signals favors Smad1/5 proangiogenic programs and dictates increased angiogenic responses. Our data implicate endothelial TGF-β signaling and EndoMT in regulating angiogenic and fibrotic responses to injury.
Renal Carcinoma After Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Carmen L. Wilson, Kirsten K. Ness, Joseph P. Neglia, Sue Hammond, Margarett Shnorhavorian, Wendy L. Leisenring, Marilyn Stovall, Leslie L. Robison, Gregory T. Armstrong
Journal: JNCI Journal of the National Cancer Institute (2013)

Adult survivors of childhood cancer are known to be at increased risk of subsequent malignancy, but only limited data exist describing the incidence and risk factors for secondary renal carcinoma. Among 14 358 5-year survivors diagnosed between 1970 and 1986, we estimated standardized incidence ratios (SIRs) for subsequent renal carcinoma and identified associations with primary cancer therapy using Poisson regression. Twenty-six survivors were diagnosed with renal carcinoma (median = 22.6 years from diagnosis; range = 6.3-35.7 years), reflecting a statistically significant excess (SIR = 8.0, 95% confidence interval [CI] = 5.2 to 11.7) compared with the general population. Highest risk was observed among neuroblastoma survivors (SIR = 85.8, 95% CI = 38.4 to 175.2) and, in multivariable analyses, with renal-directed radiotherapy of 5 Gy or greater (relative risk [RR] = 3.8, 95% CI = 1.6 to 9.3) and platinum-based chemotherapy (RR = 3.5, 95% CI = 1.0 to 11.2). To our knowledge, this is the first report of an association between cisplatin and subsequent renal carcinoma among survivors of childhood cancer.
Legal, Financial, and Public Health Consequences of HIV Contamination of Blood and Blood Products in the 1980s and 1990s
Authors: Peter D. Weinberg, Jennie Hounshell, Laurence A. Sherman, John Godwin, Shirin Ali, Cecilia Tomori, Charles L. Bennett
Journal: Annals of Internal Medicine (2002)

Ensuring the safety of the blood supply connects politics and science. The business and service sectors share responsibility for the collection and processing of blood donations, and government agencies perform regulatory and surveillance roles. The onset of the AIDS epidemic has challenged the interface among these systems, leading to widespread fears about compromised safety of the blood supply. Because of public concern about blood-supply decisions made in the 1980s, developed countries in the 1990s established reimbursement programs for persons with transfusion-acquired viral infections from blood or blood products, adopted diagnostic tests and procedures that improved the safety of the blood supply, and held criminal judicial investigations of government officials and industry leaders accused of delaying implementation of potential blood-safety measures. In contrast, developing countries continue to struggle with blood-supply safety issues. This paper summarizes the current status of these safety concerns in developed countries, where viral transmission from contaminated blood or blood products is extremely rare, and in developing countries, where up to 10% of HIV infections result from transfusion of blood or blood products.