tbuckley/cabot-search huggingface dataset:
Natural Selection on Synonymous and Nonsynonymous Mutations Shapes Patterns of Polymorphism in Populus tremula
Authors: P. K. Ingvarsson
Journal: Molecular Biology and Evolution (2009)

One important goal of population genetics is to understand the relative importance of different evolutionary processes for shaping variation in natural populations. Here, I use multilocus data to show that natural selection on both synonymous and nonsynonymous mutations plays an important role in shaping levels of synonymous polymorphism in European aspen (Populus tremula). Previous studies have documented a preferential fixation of synonymous mutations encoding preferred codons in P. tremula. The results presented here show that this has resulted in an increase in codon bias in P. tremula, consistent with stronger selection acting on synonymous codon usage. In addition, positive selection on nonsynonymous mutations appears to be common in P. tremula, with approximately 30% of all mutations having been fixed by positive selection. In addition, the recurrent fixation of beneficial mutations also reduces standing levels of polymorphism as evidenced by a significantly negative relationship between the rate of protein evolution synonymous site diversity and silent site diversity. Finally, I use approximate Bayesian methods to estimate the strength of selection acting on beneficial substitutions. These calculations show that recurrent hitchhiking reduces polymorphism by, on average, 30%. The product of strength of selection acting on beneficial mutations and the rate by which these occur across the genome (2Neλs) equals 1.54×10 − 7, which is in line with estimates from Drosophila where recurrent hitchhiking has also been shown to have significant effects on standing levels of polymorphism.
Cutaneous Manifestations of the Benign Inflammatory Reticuloses
Authors: Clarence S. Livingood
Journal: JAMA (1961)

This book is an excellent summary of the benign cutaneous reticuloses. Dr. Orlando Canizares wrote the chapters "Lymphogranuloma Venereum" and "Cat Scratch Disease," and Dr. Daniel S. Kushner contributed the chapter "Histoplasmosis." Both the student and the practicing physician will find the discussion stimulating and comprehensive. Dr. Bluefarb summarizes the available information in a correlated and authoritative manner, and he has included a long list of carefully selected references. Indeed, throughout the book the references are complete, and the illustrations are excellent. For many years Dr. Bluefarb has been interested in diseases of the reticuloendothelial system. He has been a tireless and dedicated worker in carrying out the tremendous task of summarizing his vast accumulation of knowledge. His series of books on this subject now includes:<i>The Cutaneous Manifestations of the Benign Inflammatory Reticuloses, The Cutaneous Manifestations of the Reticulo-Endothelial Granulomas, Leukemia Cutis, The Cutaneous Manifestations of the Malignant Lymphomas,</i>
Severe haemolysis associated with hepatitis A and normal glucose-6-phosphate dehydrogenase status.
Authors: D J Lyons, J M Gilvarry, J F Fielding
Journal: Gut (1990)

We report massive acute haemolysis associated with hepatitis A in a 36 year old Irish woman. Although mild anaemia is not uncommon during viral hepatitis, haemolysis of the severity observed in this patient has previously been reported only in patients with glucose-6-phosphate dehydrogenase deficiency.
Early assessment of cancer outcomes in New York City firefighters after the 9/11 attacks: an observational cohort study
Authors: Rachel Zeig-Owens, Mayris P Webber, Charles B Hall, Theresa Schwartz, Nadia Jaber, Jessica Weakley, Thomas E Rohan, Hillel W Cohen, Olga Derman, Thomas K Aldrich, Kerry Kelly, David J Prezant
Journal: The Lancet (2011)
The Therapeutic and Preventive Effect of RRR-α-Vitamin E Succinate on Prostate Cancer via Induction of Insulin-Like Growth Factor Binding Protein-3
Authors: Yi Yin, Jing Ni, Ming Chen, Matthew A. DiMaggio, Yinglu Guo, Shuyuan Yeh
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Insulin-like growth factor binding protein-3 (IGFBP-3) is a well-known antiproliferative and proapoptotic molecule in prostate cancer, suggesting that targeting IGFBP-3 might produce clinical benefits. In prostate cancer cells, RRR-α-vitamin E succinate (VES) inhibits cell proliferation and induces apoptosis, yet the mechanisms remain to be elucidated. We hypothesize that the protective effects of VES in prostate cancer are mediated by IGFBP-3 up-regulation. Using prostate cancer models, the involvement of IGFBP-3 in the anticancer effect of VES was investigated. Experimental Design: IGFBP-3 mRNA and protein were determined by real-time PCR and Western blotting in prostate cancer cells, xenografted tumors of nude mice, and prostate tumors of transgenic adenocarcinoma mouse prostate (TRAMP) mice. The serum levels of IGFBP-3 were assessed by ELISA. The importance of IGFBP-3 in VES-mediated antitumor effects was confirmed by small interfering RNA knockdown strategy. Results: We found that VES induced IGFBP-3 mRNA and protein levels in human prostate cancer cell lines. Knockdown of IGFBP-3 by small interfering RNA attenuated VES-induced IGFBP-3 expression and VES-mediated antiproliferative and proapoptotic functions. Furthermore, administration of VES resulted in a significant therapeutic effect on LNCaP and PC3 xenografts and a preventive effect on tumorigenic progression in the TRAMP model without overt toxicity. Notably, the therapeutic and preventive efficacy of VES correlated with increased accumulation of IGFBP-3 in mouse serum as well as in the xenograft tumors and TRAMP prostate samples. Consequently, reduced proliferation and induced apoptosis were witnessed. Conclusions: VES mediates its therapeutic and preventive effects against prostate cancer at least partially through up-regulating IGFBP-3, which inhibits cell proliferation and promotes cell apoptosis.
Drugs for Allosteric Sites on Receptors
Authors: Cody J. Wenthur, Patrick R. Gentry, Thomas P. Mathews, Craig W. Lindsley
Journal: The Annual Review of Pharmacology and Toxicology (2011)

The presence of druggable, topographically distinct allosteric sites on a wide range of receptor families has offered new paradigms for small molecules to modulate receptor function. Moreover, ligands that target allosteric sites offer significant advantages over the corresponding orthosteric ligands in terms of selectivity, including subtype selectivity within receptor families, and can also impart improved physicochemical properties. However, allosteric ligands are not a panacea. Many chemical issues (e.g., flat structure-activity relationships) and pharmacological issues (e.g., ligand-biased signaling) that are allosteric centric have emerged. Notably, the fact that allosteric sites are less evolutionarily conserved leads to improved selectivity; however, this can also lead to species differences that can hinder safety assessment. Many allosteric ligands possess molecular switches, wherein a small structural change (chemical or metabolic) can modulate the mode of pharmacology or receptor subtype selectivity. As the field has matured, as described here, key principles and strategies have emerged for the design of ligands/drugs for allosteric sites.
Mechanisms for Regulation of Fluid Shear Stress Response in Circulating Leukocytes
Authors: Shunichi Fukuda, Takanori Yasu, Dan N. Predescu, Geert W. Schmid-Schönbein
Journal: Circulation Research (2000)

Abstract —We have shown that leukocytes retract their pseudopods and detach from substrates after exposure to physiological fluid shear stresses (≈1.5 dyn/cm 2 ). In inflammation, however, pseudopod projection during spreading and firm adhesion on endothelium is observed even in microvessels with normal blood flow and fluid shear stresses. Thus, we examined mechanisms that may serve to regulate the shear stress response of circulating leukocytes. In the presence of inflammatory mediators (platelet-activating factor [PAF] f-met-leu-phe), a subgroup of cells ceases to respond to shear stress. cGMP analogs and nitric oxide (NO) donors enhance the shear stress response and reverse the inhibitory effect of inflammatory mediators on the shear stress response, whereas depletion of cGMP leads to cessation of the shear stress response even in unstimulated leukocytes. The ability of cGMP to enhance the shear stress response is not associated with CD18 expression, because cGMP has no effect on CD18 expression in response to shear stress. The shear stress response of leukocytes in endothelial nitric oxide synthase (−/−) mice, in which NO level in blood is decreased, is attenuated compared with that in wild-type mice. In rat mesentery venules stimulated by PAF under normal blood flow, a cGMP analog diminishes pseudopod projection of leukocytes, whereas inhibition of NO leads to enhanced pseudopod projection and spreading. The evidence suggests that inflammatory mediators suppress the shear stress response of leukocytes leading to spreading even under normal physiological shear stress, whereas cGMP may serve to maintain shear stress response even in inflammation. The full text of this article is available at http://www.circresaha.org.
Exempting patients from a smoke-free hospital policy on compassionate grounds
Authors: P. Fitzpatrick, I. Gilroy, K. Doherty, G. Conlon, L. Daly, C. Kelleher
Journal: BMJ (2014)

The situations that Mearns describes were discussed at the beginning of the planning process for implementing a tobacco-free campus policy in St Vincent’s University Hospital, Dublin.1 2 It was recognised that in some circumstances special arrangements would be needed to allow patients to smoke on the hospital site. To deal with such …
Behavioral Versus Genetic Correlates of Lipoproteins and Adiposity in Identical Twins Discordant for Exercise
Authors: Paul T. Williams, Patricia J. Blanche, Ronald M. Krauss
Journal: Circulation (2005)

Lipoprotein and weight differences between vigorously active and sedentary monozygotic (MZ) twins were used to (1) estimate the effects of training while controlling for genotype and (2) estimate genetic concordance (ie, similarity) in the presence of divergent lifestyles.Thirty-five pairs of MZ twins (25 male, 10 female) were recruited nationally who were discordant for vigorous exercise (running distances differed by > or =40 km in male and > or =32 km in female twins). The active twins ran an average (mean+/-SD) of 63.0+/-20.4 km/wk, whereas the mostly sedentary twins averaged 7.0+/-13.5 km/wk. The active twins had significantly lower body mass index (difference+/-SE, -2.12+/-0.57 kg/m2, P=0.0007) and significantly higher HDL cholesterol (0.14+/-0.04 mmol/L, P=0.004), HDL2 (2.71+/-1.04 U, P=0.01), and apolipoprotein (apo) A-I (0.10+/-0.03 g/L, P=0.004). Despite the difference in lifestyle, when adjusted for sex, the correlations between the discordant MZ twin pairs were significant (P<0.01) for HDL cholesterol (r=0.69), apoA-I (r=0.58), and HDL2 (r=0.67). There was no significant MZ twin correlation for body mass index (r=0.17). None of the active twins having an overweight twin were themselves overweight.Behavior (vigorous exercise) may reduce genetic influences on body mass index. In contrast, genetics (or shared environment) substantially influences HDL cholesterol and HDL subclasses, even in the presence of extreme behavioral differences. There may be greater individual control over moderate degrees of obesity, whereas low HDL cholesterol may be largely predetermined and less effectively treated by vigorous exercise.
The Pathologic Basis of the Strontium Bone Scan
Authors: N. David Charkes
Journal: JAMA (1968)

Bone biopsy specimens were obtained from 30 cancer patients who had been scanned following injection of strontium chloride Sr 85 or strontium nitrate Sr 85; autopsies were done in 4 additional patients. In 15 cases the<sup>85</sup>Sr concentration of the specimens was determined. Deposits of<sup>85</sup>Sr in actively proliferating new bone formed in reaction to tumor invasion. If strontium chloride Sr 85 or strontium nitrate Sr 85 is injected when the reactive process is completed, the scan is normal although the roentgenogram may be dense. Lesions which are radiolucent but scan-normal show no evidence of reactive bone formation. The scan depicts the activity of the reactive process, whereas the roentgenogram shows the net changes which have occurred, both destructive (radiolucencies) and reparative (radiodensities). Tumor cells were found in bone at the site of the abnormal scan in 22 of the 28 patients (79%).
Abnormal degradation of von Willebrand factor main subunit in pulmonary hypertension
Authors: AA Lopes, NY Maeda
Journal: European Respiratory Journal (1995)

We wished to investigate whether the abnormalities in multimeric structure and biological function of von Willebrand factor (vWF) observed in pulmonary hypertensive patients could be related to increased proteolytic degradation. We therefore analysed plasma vWF subunit composition in 24 pulmonary hypertensive patients, aged 1.2-45 yrs. After immunoisolation, vWF was subjected to 5.5% sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western immunoblotting, vWF intact subunit (225 kDa) and four proteolytic fragments (189, 176, 150 and 140 kDa) were visualized by peroxidase staining and analysed in a laser densitometer. In pulmonary hypertensive patients, the relative density of the intact subunit was decreased, and this was associated with an increase in the 176 kDa proteolytic fragment. The mean densities of the other fragments were not significantly changed, but in some patients the 150 and 140 kDa polypeptides were markedly increased. Abnormalities in multimeric structure of vWF (loss of high molecular weight multimers and increase in low molecular weight forms in comparison with controls), were associated with a significant decrease in biological activity (62-92% activity, 95% confidence interval (CI) for the mean). Total proteolytic fragment density correlated positively with multimeric abnormalities (rs = 0.45), and negatively with biological activity of vWF (rs = -0.49). Thus, in pulmonary hypertension, multimeric abnormalities and decreased biological activity are related to proteolytic degradation of vWF main subunit, possibly reflecting extensive endothelial dysfunction.
Causes of Cervical Cancer in the Philippines: a Case-Control Study
Authors: Cora Ngelange, Nubia Muñoz, F. Xavier Bosch, Mario R. Festin, Judith Deacon, Marcel V. Jacobs, Mercedes Santamaria, Chris J. L. M. Meijer, Jan M. M. Walboomers
Journal: JNCI Journal of the National Cancer Institute (1998)

Among the numerous human papillomavirus (HPV) types, only types 16 and 18 have been formally classified as human carcinogens. To evaluate the associations of 33 HPV types and other risk factors with squamous cell carcinoma and adenocarcinoma of the cervix, we performed a hospital-based, case-control study in the Philippines.The study included 356 case subjects who had histologically confirmed cervical cancer (323 incident cases of squamous cell carcinoma and 33 incident cases of adenocarcinoma/adenosquamous carcinoma) and 381 control subjects. Information on risk factors was obtained by personal interview. HPV DNA was detected in exfoliated cervical cells and biopsy specimens by use of a polymerase chain reaction assay.HPV DNA was detected in 93.8% of case subjects with squamous cell carcinoma and in 90.9% of case subjects with adenocarcinoma/adenosquamous carcinoma compared with 9.2% of control subjects, giving age-adjusted odds ratios of 156 (95% confidence interval [CI] = 87-280) for squamous cell carcinoma and 111 (95% CI = 31-392) for adenocarcinoma/adenosquamous carcinoma. Fifteen different HPV types were detected in squamous cell carcinoma, and six different HPV types were detected in adenocarcinoma/adenosquamous carcinoma. Among HPV types other than types 16 and 18, the associations of HPV with risk of squamous cell carcinoma were strongest for HPV45. In addition to HPV, high parity, low socioeconomic status, and smoking were also associated with both types of cervical cancer.As has been shown for squamous cell carcinoma, HPV is the central cause of adenocarcinoma/adenosquamous carcinoma of the uterine cervix. The observed associations of less prevalent HPV types with cervical cancer have important implications for cervical cancer prevention strategies.
The Clinical Importance of Nephron Mass
Authors: Valerie A. Luyckx, Barry M. Brenner
Journal: Journal of the American Society of Nephrology (2010)

Abundant evidence supports the association between low birth weight (LBW) and renal dysfunction in humans. Anatomic measurements of infants, children, and adults show significant inverse correlation between LBW and nephron number. Nephron numbers are also lower in individuals with hypertension compared with normotension among white and Australian Aboriginal populations. The relationship between nephron number and hypertension among black individuals is still unclear, although the high incidence of LBW predicts low nephron number in this population as well. LBW, a surrogate for low nephron number, also associates with increasing BP from childhood to adulthood and increasing risk for chronic kidney disease in later life. Because nephron numbers can be counted only postmortem, surrogate markers such as birth weight, prematurity, adult height, reduced renal size, and glomerulomegaly are potentially useful for risk stratification, for example, during living-donor assessment. Because early postnatal growth also affects subsequent risk for higher BP or reduced renal function, postnatal nutrition, a potentially modifiable factor, in addition to intrauterine effects, has significant influence on long-term cardiovascular and renal health.
Temporary Affection of Speech (Aphasia): 'Aphasic' Writing
Authors: J. H. Jackson
Journal: BMJ (1874)

The difficulties of uinderstanding the propagation of new growths through the blood are not greater than in the cases of pyremia, syphilis, or inoculated variola, nior in the cases of the diffusion of lead, mercury, or silver through the system.Malignant disease means a form of malady which infects the whole system from a local source.The characterof the disease clearly depends in great measure on local influences.Some new formations cannot propo- gate themselves, and others can; this depends on their structure.Why is the body liable to a number of local affections which vary in this way?Here lies a difficulty; but, because it cannot be answered, it does not
Long-Term Conservation of Six Duplicated Structural Genes in Cephalopod Mitochondrial Genomes
Authors: Shin-ichi Yokobori, Naoya Fukuda, Mitsue Nakamura, Tomoko Aoyama, Tairo Oshima
Journal: Molecular Biology and Evolution (2004)

The complete nucleotide sequences of the mitochondrial (mt) genomes of three cephalopods, Octopus vulgaris (Octopodiformes, Octopoda, Incirrata), Todarodes pacificus (Decapodiformes, Oegopsida, Ommastrephidae), and Watasenia scintillans (Decapodiformes, Oegopsida, Enoploteuthidae), were determined. These three mt genomes encode the standard set of metazoan mt genes. However, W. scintillans and T. pacificus mt genomes share duplications of the longest noncoding region, three cytochrome oxidase subunit genes and two ATP synthase subunit genes, and the tRNA(Asp) gene. Southern hybridization analysis of the W. scintillans mt genome shows that this single genome carries both duplicated regions. The near-identical sequence of the duplicates suggests that there are certain concerted evolutionary mechanisms, at least in cephalopod mitochondria. Molecular phylogenetic analyses of mt protein genes are suggestive, although not statistically significantly so, of a monophyletic relationship between W. scintillans and T. pacificus.
Prolactin in inferior petrosal sinuses
Authors: G. Lombardi, B. Merola, A. Colao, G. La Tessa, R. Spaziante, L. Annunziato, R. Paradisi, S. Venturoli, E. Porcu, C. Flamigni, G. Frank, E. Galassi
Journal: The Lancet (1990)
Evidence Mounts That Other Infections May Trigger AIDS Virus Replication
Authors: None Chris
Journal: JAMA (1987)

CAN T-CELL-MEDIATED responses to other bacterial, viral, or protozoal infections trigger multiplication of a heretofore dormant human immunodeficiency virus (HIV) infection? A just-announced finding—identification of a protein unique to activated T cells that greatly enhances the in vitro expression of HIV (<i>Nature</i>1987;326:711-713)— lends credence to this concept. At least one scientist believes that the data suggest a new approach to intervention, although—as in other antiviral research —many, perhaps insurmountable, hurdles remain. At the very least, the report supports the merits of having persons who are HIV-positive reduce their exposure, insofar as possible, to other infections. Gary Nabel, MD, PhD, a molecular biologist at the Whitehead Institute for Biomedical Research in Cambridge, Mass, reports that the study involved two steps. First, based on previous studies that showed that HIV established itself better in activated rather than resting T cells, they tried to identify a factor unique to such cells. Nabel
Innateness, autonomy, universality? Neurobiological approaches to language
Authors: Ralph-Axel Müller
Journal: Behavioral and Brain Sciences (1996)

Abstract The concepts of the innateness, universality, species-specificity, and autonomy of the human language capacity have had an extreme impact on the psycholinguistic debate for over thirty years. These concepts are evaluated from several neurobiological perspectives, with an emphasis on the emergence of language and its decay due to brain lesion and progressive brain disease. Evidence of perceptuomotor homologies and preadaptations for human language in nonhuman primates suggests a gradual emergence of language during hominid evolution. Regarding ontogeny, the innate component of language capacity is likely to be polygenic and shared with other developmental domains. Dissociations between verbal and nonverbal development are probably rooted in the perceptuomotor specializations of neural substrates rather than the autonomy of a grammar module. Aphasiologicaldata often assumed to suggest modular linguistic subsystems can be accounted for in terms of a neurofunctional model incorporating perceptuomotor-based regional specializationsand distributivity of representations. Thus, dissociations between grammatical functors and content words are due to different conditions of acquisition and resulting differences in neural representation. Human brains are characterized by multifactorial interindividual variability, and strict universality of functional organization is biologically unrealistic. A theoretical alternative is proposed according to which (1) linguistic specialization of brain areas is due to epigenetic and probabilistic maturational events, not to genetic ”hard-wiring,” and (2) linguistic knowledge is neurally represented in distributed cell assemblies whose topography reflects the perceptuomotor modalities involved in the acquisition and use of a given item of knowledge.