tbuckley/cabot-search huggingface dataset:
The dog and rat olfactory receptor repertoires.
Authors: Pascale Quignon, Mathieu Giraud, Maud Rimbault, Patricia Lavigne, Sandrine Tacher, Emmanuelle Morin, Elodie Retout, Anne-Sophie Valin, Kerstin Lindblad-Toh, Jacques Nicolas, Francis Galibert
Journal: Genome biology (2005)

Abstract Background Dogs and rats have a highly developed capability to detect and identify odorant molecules, even at minute concentrations. Previous analyses have shown that the olfactory receptors (ORs) that specifically bind odorant molecules are encoded by the largest gene family sequenced in mammals so far. Results We identified five amino acid patterns characteristic of ORs in the recently sequenced boxer dog and brown Norway rat genomes. Using these patterns, we retrieved 1,094 dog genes and 1,493 rat genes from these shotgun sequences. The retrieved sequences constitute the olfactory receptor repertoires of these two animals. Subsets of 20.3% (for the dog) and 19.5% (for the rat) of these genes were annotated as pseudogenes as they had one or several mutations interrupting their open reading frames. We performed phylogenetic studies and organized these two repertoires into classes, families and subfamilies. Conclusion We have established a complete or almost complete list of OR genes in the dog and the rat and have compared the sequences of these genes within and between the two species. Our results provide insight into the evolutionary development of these genes and the local amplifications that have led to the specific amplification of many subfamilies. We have also compared the human and rat ORs with the human and mouse OR repertoires.
Evolutionary Diversity and Potential Recombinogenic Role of Integration Targets of Non-LTR Retrotransposons
Authors: Andrew J. Gentles, Oleksiy Kohany, Jerzy Jurka
Journal: Molecular Biology and Evolution (2005)

Short interspersed elements (SINEs) make up a significant fraction of total DNA in mammalian genomes, providing a rich substrate for chromosomal rearrangements by SINE-SINE recombinations. Proliferation of mammalian SINEs is mediated primarily by long interspersed element 1 (L1) non–long terminal repeat retrotransposons that preferentially integrate at DNA sequence targets with an average length of ∼15 bp and containing conserved endonucleolytic nicking signals at both ends. We report that sequence variations in the first of the two nicking signals, represented by a 5′-TT-AAAA consensus sequence, affect the position of the second signal thus leading to target site duplications (TSDs) of different lengths. The length distribution of TSDs appears to be affected also by L1-encoded enzyme variants because targets with the same 5′ nicking site can be of different average lengths in different mammalian species. Taking this into account, we reanalyzed the second nicking site and found that it is larger and includes more conserved sites than previously appreciated, with a consensus of 5′-ANTNTN-AA. We also studied potential involvement of the nicking sites in stimulating recombinations between SINEs. We determined that SINEs retaining TSDs with perfect 5′-TT-AAAA nicking sites appear to be lost relatively rapidly from the human and rat genomes and less rapidly from dog. We speculate that the introduction of DNA breaks induced by recurring endonucleolytic attacks at these sites, combined with the ubiquitousness of SINEs, may significantly promote recombination between repetitive elements, leading to the observed losses. At the same time, new L1 subfamilies may be selected for “incompatibility” with preexisting targets. This provides a possible driving force for the continual emergence of new L1 subfamilies which, in turn, may affect selection of L1-dependent SINE subfamilies.
Europe’s refugee crisis: an urgent call for moral leadership
Authors: Kamran Abbasi, Kiran Patel, Fiona Godlee
Journal: BMJ (2015)

Offering asylum is a minimum standard of civilised society

Europe’s refugee crisis is the greatest test of humanity faced by the world’s rich countries this century. It isn’t a new crisis. Nor was it difficult for politicians to anticipate. Refugees have fled to Europe since at least the premature optimism of the Arab Spring in 2011. Today, optimism is replaced by desperation, a promise of freedom overshadowed by death. Western nations rushed to support the democratic principles of the Arab Spring yet are reluctant to address the root causes and the consequences, which include civil war and state brutality, most notably in Syria. Oil rich Arab States have played their part by allowing political oppression and conflict to flourish in their region. A funding crisis in UN organisations is affecting the humanitarian effort in the Middle East, driving refugees to Europe in greater numbers.1 Ignoring injustice and inequity in poorer countries and in areas of conflict has not prevented the consequences reaching the shores and borders of the rich world.

Over 300 000 refugees and migrants have …
Trials on Preoperative Chemotherapy in Resectable Colorectal Liver Metastases Need Prospective Evaluation of Predictive Factors of Response
Authors: Guglielmo Nasti, Alessandro Ottaiano, Vincenzo Rosario Iaffaioli, Massimiliano Berretta, Paolo Delrio
Journal: Journal of Clinical Oncology (2008)

believe that the absence of staining in oncocytoma and chromophobe RCC (reiterated in their Table) may prove useful for pathologists reviewing needle biopsy specimens of renal masses.
Late recurrence of Wegener's granulomatosis presenting as solitary upper lobe pulmonary mass
Authors: TS van der Werf, CA Stegeman, KJ Meuzelaar, W Timens
Journal: European Respiratory Journal (1994)

Recurrent Wegener's granulomatosis (WG) was diagnosed in a 40 year old man presenting with a solitary mass in the right lung apex and with possible lymph node enlargement in the anterior mediastinum, resembling malignancy. Eight years previously, a first episode of WG involving the upper airways and kidneys, but not the lungs, had been successfully treated with prednisolone and cyclophosphamide, which could be stopped after 2 yrs. The antineutrophil cytoplasmic antibody titres (anti-protease 3), which had been very high during the first disease episode, failed to predict the recurrence.
A Mouse Model of Human Breast Cancer Metastasis to Human Bone
Authors: Charlotte Kuperwasser, Scott Dessain, Benjamin E. Bierbaum, Dan Garnet, Kara Sperandio, Gregory P. Gauvin, Stephen P. Naber, Robert A. Weinberg, Michael Rosenblatt
Journal: Cancer Research (2005)

Abstract Currently, an in vivo model of human breast cancer metastasizing from the orthotopic site to bone does not exist, making it difficult to study the many steps of skeletal metastasis. Moreover, models used to identify the mechanisms by which breast cancer metastasizes to bone are limited to intracardiac injection, which seeds the cancer cells directly into the circulation, thus bypassing the early steps in the metastatic process. Such models do not reflect the full process of metastasis occurring in patients. We have developed an animal model of breast cancer metastasis in which the breast cancer cells and the bone target of osteotropic metastasis are both of human origin. The engrafted human bone is functional, based on finding human IgG in the mouse bloodstream, human B cells in the mouse spleen, and normal bone histology. Furthermore, orthotopic injection of a specific human breast cancer cell line, SUM1315 (derived from a metastatic nodule in a patient), later resulted in both bone and lung metastases. In the case of bone, metastasis was to the human implant and not the mouse skeleton, indicating a species-specific osteotropism. This model replicates the events observed in patients with breast cancer skeletal metastases and serves as a useful and relevant model for studying the disease.
Augmented Expression of Cardiotrophin-1 in Failing Human Hearts Is Accompanied by Diminished Glycoprotein 130 Receptor Protein Abundance
Authors: Oliver Zolk, Leong L. Ng, Russell J. O’Brien, Michael Weyand, Thomas Eschenhagen
Journal: Circulation (2002)

Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily, is a potent inducer of cardiomyocyte hypertrophy that prolongs myocyte survival. Although cardiac CT-1 gene expression is known to be upregulated in some animal models of congestive heart failure, the activation state of the CT-1 system in patients with congestive heart failure is unknown.This study was designed to determine left ventricular expression of CT-1 and its glycoprotein 130 (gp130)/leukemia inhibitory factor receptor complex in human end-stage heart failure due to ischemic and dilated cardiomyopathy. In addition, we investigated the activation state of signal transducer and activator of transcription 3 (STAT3), the downstream effector of gp130 signaling. In the failing left ventricular myocardium, expression levels of CT-1 mRNA and protein were significantly increased by 142% and 68%, respectively, compared with non-failing donor hearts. Immunohistochemistry confirmed the increased expression of CT-1 in cardiac myocytes. Although gp130 gene expression was increased by 91% (P<0.001), gp130 protein abundance was significantly diminished by 34% in the failing myocardium. In contrast, leukemia inhibitory factor receptor and suppressor of cytokine signaling-3 protein concentrations were not changed. In addition, the ratio of activated tyrosine phosphorylated STAT3 to total STAT3 was not significantly altered in failing hearts compared with non-failing controls.Our data suggest that gp130 receptor downregulation balances enhanced CT-1 expression in human heart failure and thereby inhibits excessive activation of the gp130 signaling pathway.
Associations of Insulin Resistance With Cardiovascular Risk Factors and Inflammatory Cytokines in Normal-Weight Hispanic Women
Authors: Chantal A. Vella, Ximena Burgos, Carla J. Ellis, Raul Y. Zubia, Diana Ontiveros, Hector Reyes, Claudia Lozano
Journal: Diabetes Care (2012)

OBJECTIVE To investigate the associations of markers of insulin resistance with cardiovascular disease risk factors and inflammation in young, normal-weight, Hispanic women. RESEARCH DESIGN AND METHODS Seventy-one normal-weight (BMI &amp;lt;25 kg/m2) Hispanic women (age, 20–39 years) participated in a fasting blood draw for glucose, insulin, lipids, and inflammatory markers; a glucose tolerance test; anthropometric and blood pressure measurements; body composition by dual-energy x-ray absorptiometry; and measurements of cardiorespiratory fitness via Vo2max and daily physical activity by accelerometer. RESULTS Six percent of participants had impaired fasting glucose, 14% had impaired glucose tolerance, and 48% had at least one cardiovascular disease risk factor. Homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin were positively correlated with glucose, triglycerides, systolic blood pressure, and diastolic blood pressure, and were negatively correlated with adiponectin (P &amp;lt; 0.05). The 2-h insulin was positively correlated with diastolic blood pressure, triglycerides, and high-sensitivity C-reactive protein. HOMA-IR and fasting insulin remained significantly and positively related to glucose, triglycerides, and blood pressure after adjustment for body composition. The relationships between markers of insulin resistance and adiponectin and high-sensitivity C-reactive protein were attenuated after adjustment for body composition. CONCLUSIONS Surrogate markers of insulin resistance were associated with cardiovascular disease risk factors and inflammation in young, normal-weight, Hispanic women. Our findings suggest that HOMA-IR, fasting, and 2-h insulin may be important clinical markers for identifying young, normal-weight, Hispanic women who may be at risk for development of type 2 diabetes and cardiovascular disease. Our findings show the importance of early screening for prevention of type 2 diabetes and cardiovascular disease in this population.
Would regional government have been good for your health?
Authors: David J Hunter, John Wilkinson, Edward Coyle
Journal: BMJ (2005)

England may have missed an opportunity to improve public health 

T he resounding “no” vote for a regional assembly in the North East of England has firmly put the lid on the prospect of elected regional government for the foreseeable future. There is considerable debate in the North East as to the reasons for the rejection of the proposal, which may have come down to a distaste for having more politicians, a suspected higher council tax, intraregional rivalries, too few powers, or perhaps a mix of these. In the white paper announcing the regional referendums, assemblies would not have any direct responsibility for health care,1 although many would have liked to have seen such an outcome in the spirit of the government's devolution policy and commitment to localism.2 But the assemblies would have had a specific remit for public health.

The white paper announcing the regional referendums pointed out the high impact that housing, transport, and economic development have on public health and promoted the joining up of these policies to reduce health inequalities. Nevertheless, it remained a cautious document, produced against a background of little interest in the issue of elected regional assemblies.3

A public health presence already exists at regional level—a process that began with the NHS …
A practical method for removing catheter distortions from indicator-dilution curves
Authors: K. H. NORWICH, C. PINTO, J. E. MORCH, S. ZELIN
Journal: Cardiovascular Research (1974)

Journal Article A practical method for removing catheter distortions from indicator-dilution curves Get access KENNETH H. NORWICH, KENNETH H. NORWICH 1 1Department of Physiology and Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar CHRISTOPHER PINTO, CHRISTOPHER PINTO Search for other works by this author on: Oxford Academic PubMed Google Scholar JOHN E. MORCH, JOHN E. MORCH Search for other works by this author on: Oxford Academic PubMed Google Scholar SAMUEL ZELIN SAMUEL ZELIN Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 3, May 1974, Pages 430–438, https://doi.org/10.1093/cvr/8.3.430 Published: 01 May 1974
Labour promises new fund to provide 8000 more GPs
Authors: A. O'Dowd
Journal: BMJ (2014)

A new annual “NHS Time to Care Fund” will be created if the Labour party wins the next general election, which will allow for 8000 more GPs to be recruited, Labour’s leader, Ed Miliband, has announced.

The £2.5bn (€3.2bn; $4.1bn) fund, which will come from introducing a new levy on tobacco companies, a £1.1bn clampdown on tax avoidance, and a “mansion tax” on houses worth more than £2m, will also fund 20 000 more nurses, 3000 more midwives, and 5000 more care workers, all by 2020. Giving his address to the party’s annual conference in Manchester on 23 September, Miliband promised that he would introduce the fund if Labour won next year’s general election. …
Factors influencing longitudinal change in knee cartilage volume measured from magnetic resonance imaging in healthy men
Authors: Fahad Hanna, Peter Robert Ebeling, Y Wang, Richard M O'Sullivan, Susan Davis, Anita E Wluka, Flavia Maria Cicuttini
Journal: Annals of the Rheumatic Diseases (2005)

To determine whether the amount of joint cartilage in healthy, middle aged men is stable or changes over time, and what factors may influence this.In a cohort study, 28 healthy men (70% of the original cohort; mean (SD) age, 51.9 (12.8) years) had baseline knee magnetic resonance imaging (MRI) of their dominant knee and repeat MRI of the same knee approximately 2.0 years later. Knee cartilage volume was measured at baseline and follow up. Risk factors assessed at baseline, including sex hormones and metabolic bone markers, were tested for their association with change in knee cartilage volume over time.Mean (SD) reduction in tibial cartilage volume per year was 162 (93) microl. This represented a 2.8% reduction in total tibial articular cartilage per year (95% confidence interval, 0.2% to 5.5%). Tibial cartilage loss was associated with serum free testosterone level, independently of age, body mass index, baseline tibial cartilage volume tibial plateau area, and total bone mineral content. Overall, testosterone accounted for 14.5% (partial r2) of the variation in change in tibial cartilage volume. There was a trend towards a positive association between tibial cartilage loss and urinary N-telopeptide cross-links of type I collagen (Ntx) (p = 0.057).Further studies will be required to determine whether hormonal manipulation or treatment with antiresorptive drugs will reduce the risk of knee osteoarthritis in men in later life.
Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans
Authors: D M K Keefe
Journal: Gut (2000)

<h3>BACKGROUND AND AIMS</h3> The mechanism of gastrointestinal damage (mucositis) induced by cancer chemotherapy remains uncertain. The aims of this study were to define the time course and mechanism of small intestinal damage following chemotherapy in humans. <h3>METHODS</h3> Patients receiving chemotherapy underwent upper gastrointestinal endoscopy (a maximum of two per patient) with duodenal biopsy prior to chemotherapy and again at 1, 3, 5, and 16 days after chemotherapy. Tissue was taken for morphometry, disaccharidase assays, electron microscopy, and for assessment of apoptosis using the Tdt mediated dUTP-biotin nick end labelling (TUNEL) method. Villus area, crypt length, and mitotic index were measured by a microdissection technique. <h3>RESULTS</h3> Apoptosis increased sevenfold in intestinal crypts at one day, and villus area, crypt length, mitotic count per crypt, and enterocyte height decreased at three days after chemotherapy. Disaccharidase activities remained unchanged. Electron microscopy showed increased open tight junctions of enterocytes at day 3, consistent with more immature cells. All indices improved by 16 days. <h3>CONCLUSION</h3> Small intestinal mucositis is associated with apoptosis in crypts that precedes hypoplastic villous atrophy and loss of enterocyte height.
Getting stents to go with the flow
Authors: R. Wayne Alexander
Journal: Journal of Clinical Investigation (2004)

Implantation of expandable stents into stenotic arteries after percutaneous coronary intervention to relieve arterial narrowing has become a standard therapeutic tool. The improvement in vascular interventional technology, and especially stent technology, has, arguably, outstripped understanding of the biologic consequences of opening an obstructed artery. In the case of bifurcation stenoses, new evidence suggests that opening a stenotic subsidiary branch may create unfavorable hemodynamics in the stented main branch that can lead to in-stent restenosis.
Dyslipidaemia in type II diabetic mice does not aggravate contractile impairment but increases ventricular stiffness
Authors: An Van den Bergh, Annelies Vanderper, Peter Vangheluwe, Fanny Desjardins, Ines Nevelsteen, Wim Verreth, Frank Wuytack, Paul Holvoet, Willem Flameng, Jean-Luc Balligand, Paul Herijgers
Journal: Cardiovascular Research (2007)

Type II diabetes, often associated with abdominal obesity, frequently leads to heart failure. Clinical and epidemiological evidence suggests that supplemental dyslipidaemia and hypertension, as clustered in the metabolic syndrome, aggravate the cardiovascular outcome. The differential impact of type II diabetes and the metabolic syndrome on left ventricular function, however, remains incompletely defined. We studied left ventricular function in vivo using pressure–volume analysis in obese diabetic mice with leptin deficiency (ob/ob) and obese diabetic dyslipidemic mice with combined leptin and low-density lipoprotein-receptor deficiency (DKO). ob/ob and DKO mice developed a diabetic cardiomyopathy, characterized by impaired contractility and relaxation, from the age of 24 weeks onwards. This was—at least partially—explained by increased apoptosis and disturbed Ca2+ reuptake in the sarcoplasmic reticulum (SR) in both mouse models. DKO, but not ob/ob, developed increased end-diastolic ventricular stiffness, paralleled by increased left ventricular myocardial fibrosis. Cardiac output was preserved in ob/ob mice by favourable loading conditions, whereas it decreased in DKO mice. Type II diabetes in mice leads to impaired contractility and relaxation due to disturbed Ca2+ reuptake in the SR, but only when dyslipidaemia and hypertension are superimposed does vascular–ventricular stiffening increase and left ventricular myocardial fibrosis develop.
Brief perfusion with diluted whole blood after global myocardial ischaemia increases reperfusion injury
Authors: P. F McDonagh, J. M Reynolds
Journal: Cardiovascular Research (1994)

Objectives: In vivo studies indicate that blood components, especially leucocytes, contribute to reperfusion injury after myocardial ischaemia. This study was designed to: (1) develop a small animal heart model of ischaemia-reperfusion that demonstrates the contribution of blood to reperfusion injury; (2) determine when the presence of blood in the heart – that is, during ischaemia or during early reperfusion – caused greater dysfunction; and (3) attempt to limit the blood contribution to reperfusion injury by leucocyte depletion. Methods: Adult rat hearts were perfused in situ with a Krebs-albumin red cell solution (K2RBC), then isolated. Cardiac pump function was assessed with an intraventricular balloon as left ventricular developed pressure and contractility (dP/dt). Group I served as a non-ischaemic control group. Group II was subjected to global, no flow ischaemia for 30 min followed by 45 min reperfusion. In group III, diluted whole blood replaced the K2RBC for five min immediately before ischaemia. In group IV, diluted whole blood was perfused during the first five min reperfusion. In group V, the hearts were reperfused with leucocyte poor diluted whole blood. Results: Pre-ischaemic pump function values were similar to other blood perfused, isolated heart models. Group I showed no increase in coronary resistance or decrease in pump function with time or in response to diluted whole blood. After 35 min reperfusion, the recovery (% control) of dP/dt in group II was 56(12), in group III it was 39(15) and in group IV it was only 19(6) (p < 0.05). Large increases in coronary vascular resistance, oedema, and contracture during reperfusion were also seen in group IV. When leucocytes were depleted from the diluted whole blood (group V), the recoveries were similar to reperfusion without diluted whole blood (group II). Conclusions: Thirty min of global, normothermic ischaemia caused significant cardiac dysfunction early during reperfusion. Perfusion with unstimulated blood for a limited period further impaired the recovery of function and enhanced myocardial oedema. Dysfunction was particularly evident when diluted whole blood was perfused during the first minutes of reperfusion. The leucocyte depletion studies suggest that leucocytes are necessary, but may not be sufficient, to demonstrate the blood contribution to reperfusion injury. Cardiovascular Research 1994;28:1157-1165