tbuckley/cabot-search huggingface dataset:
Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle
Authors: Stephen D E Park, David A. Magee, Paul A. McGettigan, Matthew D. Teasdale, Ceiridwen J. Edwards, Amanda J. Lohan, Alison Murphy, Martin Braud, Mark T. Donoghue, Yuan Liu, Andrew T. Chamberlain, Kévin Rue-Albrecht, Steven Schroeder, Charles Spillane, Shuaishuai Tai, Daniel G. Bradley, Tad S. Sonstegard, Brendan J. Loftus, David E. MacHugh
Journal: Genome biology (2015)

Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought.
Growth and Activation of Natural Killer Cells<i>Ex Vivo</i>from Children with Neuroblastoma for Adoptive Cell Therapy
Authors: Yin Liu, Hong-Wei Wu, Michael A. Sheard, Richard Sposto, Srinivas S. Somanchi, Laurence J.N. Cooper, Dean A. Lee, Robert C. Seeger
Journal: Clinical Cancer Research (2013)

Adoptive transfer of natural killer (NK) cells combined with tumor-specific monoclonal antibodies (mAb) has therapeutic potential for malignancies. We determined if large numbers of activated NK (aNK) cells can be grown ex vivo from peripheral blood mononuclear cells (PBMC) of children with high-risk neuroblastoma using artificial antigen-presenting cells (aAPC).Irradiated K562-derived Clone 9.mbIL21 aAPC were cocultured with PBMC, and propagated NK cells were characterized with flow cytometry, cytotoxicity assays, Luminex multicytokine assays, and a nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of disseminated neuroblastoma.Coculturing patient PBMC with aAPC for 14 days induced 2,363- ± 443-fold expansion of CD56(+)CD3(-)CD14(-) NK cells with 83% ± 3% purity (n = 10). Results were similar to PBMC from normal donors (n = 5). Expression of DNAM-1, NKG2D, FcγRIII/CD16, and CD56 increased 6- ± 3-, 10- ± 2-, 21- ± 20-, and 18- ± 3-fold, respectively, on day 14 compared with day 0, showing activation of NK cells. In vitro, aNK cells were highly cytotoxic against neuroblastoma cell lines and killing was enhanced with GD2-specific mAb ch14.18. When mediating cytotoxicity with ch14.18, release of TNF-α, granulocyte macrophage colony-stimulating factor, IFN-γ, sCD40L, CCL2/MCP-1, CXCL9/MIG, and CXCL11/I-TAC by aNK cells increased 4-, 5-, 6-, 15-, 265-, 917-, and 363-fold (151-9,121 pg/mL), respectively, compared with aNK cells alone. Survival of NOD/SCID mice bearing disseminated neuroblastoma improved when treated with thawed and immediately intravenously infused cryopreserved aNK cells compared with untreated mice and was further improved when ch14.18 was added.Propagation of large numbers of aNK cells that maintain potent antineuroblastoma activities when cryopreserved supports clinical testing of adoptive cell therapy with ch14.18.
Macrophage IL-10 Blocks CD8+ T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells
Authors: Brian Ruffell, Debbie Chang-Strachan, Vivien Chan, Alexander Rosenbusch, Christine M.T. Ho, Nancy Pryer, Dylan Daniel, E. Shelley Hwang, Hope S. Rugo, Lisa M. Coussens
Journal: Cancer Cell (2014)
Increased Insulin Requirements During Exercise at Very High Altitude in Type 1 Diabetes
Authors: Pieter de Mol, Suzanna T. de Vries, Eelco J.P. de Koning, Rijk O.B. Gans, Cees J. Tack, Henk J.G. Bilo
Journal: Diabetes Care (2011)

Safe, very high altitude trekking in subjects with type 1 diabetes requires understanding of glucose regulation at high altitude. We investigated insulin requirements, energy expenditure, and glucose levels at very high altitude in relation to acute mountain sickness (AMS) symptoms in individuals with type 1 diabetes.Eight individuals with complication-free type 1 diabetes took part in a 14-day expedition to Mount Meru (4,562 m) and Mount Kilimanjaro (5,895 m) in Tanzania. Daily insulin doses, glucose levels, energy expenditure, and AMS symptoms were determined. Also, energy expenditure and AMS symptoms were compared with a healthy control group.We found a positive relation between AMS symptoms and insulin requirements (r = 0.78; P = 0.041) and AMS symptoms and glucose levels (r = 0.86; P = 0.014) for Mount Kilimanjaro. Compared with sea level, insulin doses tended to decrease by 14.2% (19.7) (median [interquartile range]) (P = 0.41), whereas glucose levels remained stable up to 5,000 m altitude. However, at altitudes >5,000 m, insulin dose was unchanged (36.8 ± 17 vs. 37.6 ± 19.1 international units [mean ± SD] P = 0.75), but glucose levels (7.5 ± 0.6 vs. 9.5 ± 0.8 mmol/L [mean ± SD] P = 0.067) and AMS scores (1.3 ± 1.6 vs. 4.4 ± 4 points [mean ± SD] P = 0.091) tended to increase. Energy expenditure and AMS symptoms were comparable in both groups (P = 0.84).Our data indicate that in complication-free individuals with type 1 diabetes, insulin requirements tend to increase during altitudes above 5,000 m despite high energy expenditure. This change may be explained, at least partly, by AMS.
MicroRNAs -the Next Generation Therapeutic Targets in Human Diseases
Authors: Sakthivel Srinivasan, Subramanian Tamil Selvan, Govindaraju Archunan, Balazs Gulyas, Parasuraman Padmanabhan
Journal: Theranostics (2013)

MicroRNAs (miRNAs), an abundant class of ~22-nucleotide non-coding RNAs, regulate the expression of genes at post transcriptional level.MiRNAs are important regulators of eukaryotic gene expression and therefore implicated in a wide range of biological processes.The miR-NA-related genetic alterations are possibly more implicated human diseases than currently appreciated.Genetic variants in miRNA target sites, called miRNA genes are identified to be associated with human diseases.This review discusses about the role of micro-RNA genes in various human diseases such as neurodegenerative disorders, cardio-vascular diseases, and metabolic disorders, and how they can be targeted as a new therapeutic tool in future with reference to drug discoveries/ development.
Rotavirus capsid surface protein VP4-coated Fe3O4 nanoparticles as a theranostic platform for cellular imaging and drug delivery
Authors: Weihong Chen, Yuhua Cao, Min Liu, Qinghuan Zhao, Jie Huang, Hailu Zhang, Zongwu Deng, Jianwu Dai, David F. Williams, Zhijun Zhang
Journal: Biomaterials (2012)
The Impact of Prevention on Reducing the Burden of Cardiovascular Disease
Authors: Richard Kahn, Rose Marie Robertson, Robert Smith, David Eddy
Journal: Circulation (2008)

Cardiovascular disease (CVD) is prevalent and expensive. While many interventions are recommended to prevent CVD, the potential effects of a comprehensive set of prevention activities on CVD morbidity, mortality, and costs have never been evaluated. We therefore determined the effects of 11 nationally recommended prevention activities on CVD-related morbidity, mortality, and costs in the United States.We used person-specific data from a representative sample of the US population (National Health and Nutrition Education Survey IV) to determine the number and characteristics of adults aged 20-80 years in the United States today who are candidates for different prevention activities related to CVD. We used the Archimedes model to create a simulated population that matched the real US population, person by person. We then used the model to simulate a series of clinical trials that examined the effects over the next 30 years of applying each prevention activity one by one, or altogether, to those who are candidates for the various activities and compared the health outcomes, quality of life, and direct medical costs to current levels of prevention and care. We did this under two sets of assumptions about performance and compliance: 100% success for each activity and lower levels of success considered aggressive but still feasible.Approximately 78% of adults aged 20-80 years alive today in the United States are candidates for at least one prevention activity. If everyone received the activities for which they are eligible, myocardial infarctions and strokes would be reduced by 63% and 31%, respectively. If more feasible levels of performance are assumed, myocardial infarctions and strokes would be reduced 36% and 20%, respectively. Implementation of all prevention activities would add approximately 221 million life-years and 244 million quality-adjusted life-years to the US adult population over the coming 30 years, or an average of 1.3 years of life expectancy for all adults. Of the specific prevention activities, the greatest benefits to the US population come from providing aspirin to high-risk individuals, controlling pre-diabetes, weight reduction in obese individuals, lowering blood pressure in people with diabetes, and lowering LDL cholesterol in people with existing coronary artery disease (CAD). As currently delivered and at current prices, most prevention activities are expensive when considering direct medical costs; smoking cessation is the only prevention strategy that is cost-saving over 30 years.Aggressive application of nationally recommended prevention activities could prevent a high proportion of the CAD events and strokes that are otherwise expected to occur in adults in the United States today. However, as they are currently delivered, most of the prevention activities will substantially increase costs. If preventive strategies are to achieve their full potential, ways must be found to reduce the costs and deliver prevention activities more efficiently.
Psychological Distress and Disease Course for Women With Breast Cancer: One Answer, Many Questions
Authors: D. Spiegel
Journal: JNCI Journal of the National Cancer Institute (1996)

In this issue of the Journal, Tross et al. (7) report on an exceptionally fine study of the relationship between psychological distress and both disease-free and overall survival in women with stage II breast cancer. Their report is noteworthy not only for the rigor of its methods but especially for the open-minded and balanced way in which it is written. The authors found no relationship between psychological distress, as measured by the Symptom Check List-90-Revised (SCL-90-R), and recurrence of disease in or survival of patients with breast cancer. Their study was conducted on a large subsample of patients in the Cancer and Leukemia Group B (CALGB) national clinical trial of adjuvant therapy for stage II breast cancer. Two hundred eighty women, 31% of the total sample, were entered in the study. Even a casual examination of the survival curves for these women shows little support for the idea that distress, as measured by the SCL-90-R, is associated with longer or shorter disease-free or overall survival time. In their report, Tross et al. note the limitations of their study. Although their study was prospective in design, the psychosocial component was apparently retrospective, a useful add-on to an intervention trial. Another important issue is sample bias. The authors were able to assess fewer than a third of the total sample, although it was a sizable number of women. Some of the reasons for this subsample selection, i.e., patient refusal and attrition, might have restricted the range of distress found, thereby reducing the ability of the study to detect a relationship between variance in distress and survival. Indeed, Tross et al. noted that the sample of patients was relatively nondepressed. Being depressed might be a reason for refusal to fill out additional questionnaires. Other reasons, such as a tendency to be uncooperative, have been reported to be associated with longer survival (2). Thus, patients who participated in the study might be self-selected for lacking the depression that might predict poorer outcome or the feistiness that other authors (7,3) have found to predict better outcome.
Familial Hypertrophic Cardiomyopathy-Linked Mutant Troponin T Causes Stress-Induced Ventricular Tachycardia and Ca <sup>2+</sup> -Dependent Action Potential Remodeling
Authors: Björn C. Knollmann, Paulus Kirchhof, Syevda G. Sirenko, Hubertus Degen, Anne E. Greene, Tilmann Schober, Jessica C. Mackow, Larissa Fabritz, James D. Potter, Martin Morad
Journal: Circulation Research (2003)

The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy or fibrosis. Enhanced cardiac function has been associated with myofilament Ca2+ sensitization, suggesting altered cellular Ca2+ handling. In the present study, we compare cellular Ca2+ transients and electrophysiological parameters of 64 I79N-Tg and 106 control mice in isolated myocytes, isolated perfused hearts, and whole animals. Ventricular action potentials (APs) measured in isolated I79N-Tg hearts and myocytes were significantly shortened only at 70% repolarization. No significant differences were found either in L-type Ca2+ or transient outward K+ currents, but inward rectifier K+ current (IK1) was significantly decreased. More critically, Ca2+ transients of field-stimulated ventricular I79N-Tg myocytes were reduced and had slow decay kinetics, consistent with increased Ca2+ sensitivity of I79N mutant fibers. AP differences were abolished when myocytes were dialyzed with Ca2+ buffers or after the Na+-Ca2+ exchanger was blocked by Li+. At higher pacing rates or in presence of isoproterenol, diastolic Ca2+ became significantly elevated in I79N-Tg compared with control myocytes. Ventricular ectopy could be induced by isoproterenol-challenge in isolated I79N-Tg hearts and anesthetized I79N-Tg mice. Freely moving I79N-Tg mice had a higher incidence of nonsustained ventricular tachycardia (VT) during mental stress (warm air jets). We conclude that the TnT-I79N mutation causes stress-induced VT even in absence of hypertrophy and/or fibrosis, arising possibly from the combination of AP remodeling related to altered Ca2+ transients and suppression of IK1.
Non-invasive characterization of structure and morphology of silk fibroin biomaterials using non-linear microscopy
Authors: William L. Rice, Shamaraz Firdous, Sharad Gupta, Martin Hunter, Cheryl W.P. Foo, Yongzhong Wang, Hyeon Joo Kim, David L. Kaplan, Irene Georgakoudi
Journal: Biomaterials (2008)
Tuberculosis and noncommunicable diseases: neglected links and missed opportunities
Authors: J. Creswell, M. Raviglione, S. Ottmani, G.B. Migliori, M. Uplekar, L. Blanc, G. Sotgiu, K. Lönnroth
Journal: European Respiratory Journal (2010)

Globally, the incidence of tuberculosis (TB) is declining very slowly, and the noncommunicable disease (NCD) burden for many countries is steadily increasing. Several NCDs, such as diabetes mellitus, alcohol use disorders and smoking-related conditions, are responsible for a significant proportion of TB cases globally, and in the European region, represent a larger attributable fraction for TB disease than HIV. Concrete steps are needed to address NCDs and their risk factors. We reviewed published studies involving TB and NCDs, and present a review and discussion of how they are linked, the implications for case detection and management, and how prevention efforts may be strengthened by integration of services. These NCDs put patients at increased risk for developing TB and at risk for poor treatment outcomes. However, they also present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for both TB and NCDs. Hastening the global decline in TB incidence may be assisted by strengthening these types of activities.
Lack of UCP2 reduces fas-mediated liver injury inob/ob mice and reveals importance of cell-specific UCP2 expression
Authors: Péter Fülöp, Zoltán Derdák, Anthony Sheets, Edmond Sabo, Eric P. Berthiaume, Murray B. Resnick, Jack R. Wands, György Paragh, György Baffy
Journal: Hepatology (2006)

Fatty liver is vulnerable to conditions that challenge hepatocellular energy homeostasis. Lipid-laden hepatocytes highly express uncoupling protein-2 (UCP2), a mitochondrial carrier that competes with adenosine triphosphate (ATP) synthesis by mediating proton leak. However, evidence for a link between UCP2 expression and susceptibility of liver to acute injury is lacking. We asked whether absence of UCP2 protects ob/ob mice from Fas-mediated acute liver damage. UCP2-deficient ob/ob mice (ob/ob:ucp2-/-) and UCP2-competent littermates (ob/ob:ucp2+/+) received a single dose of agonistic anti-Fas antibody (Jo2). Low-dose Jo2 (0.15 mg/kg intraperitoneally) caused less serum alanine aminotransferase (ALT) elevation and lower apoptosis rates in ob/ob:ucp2-/- mice. High-dose Jo2 (0.40 mg/kg intraperitoneally) proved uniformly fatal; however, ob/ob:ucp2-/- mice survived longer with less depletion of liver ATP stores, indicating that fatty hepatocytes may benefit from lack of UCP2 during Jo2 challenge. Although UCP2 reportedly controls mitochondrial oxidant production, its absence had no apparent effect on fatty liver tissue malondialdehyde levels augmented by Jo2. This finding prompted us to determine UCP2 expression in Kupffer cells, a major source of intrahepatic oxidative stress. UCP2 expression was found diminished in Kupffer cells of untreated ob/ob:ucp2+/+ mice, conceivably contributing to increased oxidative stress in fatty liver and limiting the impact of UCP2 ablation. In conclusion, whereas UCP2 abundance in fatty hepatocytes exacerbates Fas-mediated injury by compromising ATP stores, downregulation of UCP2 in Kupffer cells may account for persistent oxidative stress in fatty liver. Our data support a cell-specific approach when considering the therapeutic effects of mitochondrial uncoupling in fatty liver disease.
New Strategies in Ovarian Cancer: Uptake and Experience of Women at High Risk of Ovarian Cancer Who Are Considering Risk-Reducing Salpingo-Oophorectomy
Authors: Suzanne M. Miller, Pagona Roussi, Mary B. Daly, John Scarpato
Journal: Clinical Cancer Research (2010)

Here, we review factors associated with uptake of risk-reducing salpingo-oophorectomy by women at increased hereditary risk for ovarian cancer, as well as quality of life issues following surgery. Forty-one research studies identified through PubMed and PsychInfo met inclusion criteria. Older age, having had children, a family history of ovarian cancer, a personal history of breast cancer, prophylactic mastectomy, and BRCA1/2 mutation carrier status increase the likelihood of undergoing surgery. Psychosocial variables predictive of surgery uptake include greater perceived risk of ovarian cancer and cancer-related anxiety. Most women report satisfaction with their decision to undergo surgery and both lower perceived ovarian cancer risk and less cancer-related anxiety as benefits. Hormonal deprivation is the main disadvantage reported, particularly by premenopausal women who are not on hormonal replacement therapy (HRT). The evidence is mixed about satisfaction with the level of information provided prior to surgery, although generally, women report receiving insufficient information about the pros and cons of HRT. These findings indicate that when designing decision aids, demographic, medical history, and psychosocial variables need to be addressed in order to facilitate quality decision making.
Some impressions of India and the Sports Medicine Course
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1980)

appeared to be satisfactory.There were difficulties reported with two lectures in respect of language -this emphasises the point that the lecturers for courses of this type must be really experienced and fluent in the vernacular of the course.It is interesting that Professor Lubs presented more difficulty to the Indians than to the students from other countries (previously in Thailand Professor Lubs had presented no difficulty in respect of understanding).It therefore appears that the problem may in fact be less one of fluency than of accent.The apparent difficulty was not reflected in the scoring in the examination papers, so that although students may have had problems with the lecturers there were no apparent difficulties with understanding of the actual material.
Brain-Derived Neurotrophic Factor and Neurotrophin-4/5 Are Expressed in Breast Cancer and Can Be Targeted to Inhibit Tumor Cell Survival
Authors: Elsa Vanhecke, Eric Adriaenssens, Stéphanie Verbeke, Samuel Meignan, Emmanuelle Germain, Nathalie Berteaux, Victor Nurcombe, Xuefen Le Bourhis, Hubert Hondermarck
Journal: Clinical Cancer Research (2011)

Given that nerve growth factor has previously been shown to be involved in breast cancer progression, we have tested here the hypothesis that the other neurotrophins (NT) are expressed and have an influence in breast tumor growth.The expression of brain-derived neurotrophic factor (BDNF), NT-3 and NT-4/5, as well as the neurotrophin receptor p75(NTR), TrkB, and TrkC, was studied by RT-PCR, Western blotting, and immunohistochemistry in cell lines and tumor biopsies. The biological impacts of neurotrophins, and associated mechanisms, were analyzed in cell cultures and xenografted mice.BDNF and NT-4/5 were expressed and secreted by breast cancer cells, and the use of blocking antibodies suggested an autocrine loop mediating cell resistance to apoptosis. The corresponding tyrosine kinase receptor TrkB was only rarely observed at full length, whereas the expression of TrkB-T1, lacking the kinase domain, as well as p75(NTR), were detected in all tested breast cancer cell lines and tumor biopsies. In contrast, NT-3 and TrkC were not detected. SiRNA against p75(NTR) and TrkB-T1 abolished the antiapoptotic effect of BDNF and NT-4/5, whereas the pharmacological inhibitors K252a and PD98059 had no effect, suggesting the involvement of p75(NTR) and TrkB-T1, but not kinase activities from Trks and MAPK. In xenografted mice, anti-BDNF, anti-NT-4/5, anti-p75(NTR), or anti-TrkB-T1 treatments resulted in tumor growth inhibition, characterized by an increase in cell apoptosis, but with no change in proliferation.BDNF and NT-4/5 contribute to breast cancer cell survival and can serve as prospective targets in attempts to inhibit tumor growth.