tbuckley/cabot-search huggingface dataset:
Sequence-Repeat Polymorphisms Exhibit the Signature of Recombination in Lodgepole Pine Chloroplast DNA
Authors: H. Dawn Marshall, Craig Newton, Kermit Ritland
Journal: Molecular Biology and Evolution (2001)

The chloroplast genome is widely used in plant systematic studies (Olmstead and Palmer 1994), in part because it is slowly evolving and is assumed to be nonrecombining (Clegg 1993). Microsatellite markers have also been identified within this genome (Powell et al. 1995; Provan et al. 1996; Vendramin et al. 1996; Newton et al. 1999), and these markers are sufficiently variable for phylogeographic studies within a species (Schaal et al. 1998; Newton et al. 1999; Marshall, Newton, and Ritland 2001). Lack of recombination reduces homoplasy, which in turn increases the precision of phylogenetic inference in such studies. However, recently there has emerged some evidence of recombination in another organelle, the mitochondrion. Lunt and Hyman (1997) found end products of mitochondrial genome recombination in the nematode Meloidogyne javanica. Saville, Kohli, and Anderson (1998) reported a discrepancy in the expected genotypic structure of mitochondrial DNA (mtDNA) sequences in the fungus Armillaria gallica relative to expectations under purely clonal transmission, consistent with observations of mitochondrial heteroplasmy. Using both sequence and restriction fragment length polymorphism data from humans, Awadalla, Eyre-Walker, and Maynard Smith (1999) found linkage disequilibria to decrease with increasing physical distance, consistent with mtDNA recombination. Phylogenetic trees constructed using similar data contained a larger number of homoplasies than expected on the basis of simulated data, which may indicate recombination (Eyre-Walker, Smith, and Maynard Smith 1999). Biologically, mtDNA recombination in humans is feasible, since mitochondria contain the necessary enzymes (Thyagarajan, Padua, and Campbell 1996), and a few paternal mitochondria are contributed to the egg during fertilization. The human mtDNA recombination issue is, however, still the subject of much debate (see EyreWalker 2000; Ingman et al. 2000). Here, we look for signatures of recombination in the chloroplast of lodgepole pine (Pinus contorta). Lodgepole pine is common in the forests of western North America, with a climactically and edaphically diverse natural range covering over 2.6 3 107 ha. A windpollinated outcrosser and aggressive pioneer, it is thought to have colonized its present range in a north-
Central integrative role of oestrogen in the regulation of placental steroidogenic maturation and the development of the fetal pituitary-adrenocortical axis in the baboon
Authors: G J Pepe, E D Albrecht
Journal: Human Reproduction Update (1998)

The purpose of this review is to summarize the experimental data establishing the baboon as a non-human primate model for the study of the endocrinology of human pregnancy, and to outline the results of in-vivo experiments in the baboon which show that oestrogen plays a central integrative role in the regulation of placental steroidogenic maturation as well as the function and maturation of the fetal adrenal gland. Thus, oestrogen regulates the receptor-mediated uptake of low density lipoprotein-cholesterol and the P450 cholesterol side-chain cleavage system within syncytiotrophoblasts to promote the production of progesterone. Oestrogen concomitantly acts on the fetal adrenal gland to modulate the production of androgen precursors which ensures maintenance of physiologic levels of oestrogen during the course of gestation. In addition, oestrogen regulates the 11beta-hydroxysteroid dehydrogenase enzymes controlling placental cortisol-cortisone metabolism and their secretion into the fetal circulation and thus indirectly regulates the fetal hypothalamic-pituitary-adrenocortical axis. Collectively, these oestrogen-regulated processes ensure the maintenance of pregnancy and the maturation of the fetus including the development in utero of adrenocortical self-sufficiency essential for neonatal survival.
Recent segmental and gene duplications in the mouse genome
Authors: Joseph Cheung, Michael D Wilson, Junjun Zhang, Razi Khaja, Jeffrey R MacDonald, Henry HQ Heng, Ben F Koop, Stephen W Scherer
Journal: Genome biology (2003)

The high quality of the mouse genome draft sequence and its associated annotations are an invaluable biological resource. Identifying recent duplications in the mouse genome, especially in regions containing genes, may highlight important events in recent murine evolution. In addition, detecting recent sequence duplications can reveal potentially problematic regions of the genome assembly. We use BLAST-based computational heuristics to identify large (>/= 5 kb) and recent (>/= 90% sequence identity) segmental duplications in the mouse genome sequence. Here we present a database of recently duplicated regions of the mouse genome found in the mouse genome sequencing consortium (MGSC) February 2002 and February 2003 assemblies.We determined that 33.6 Mb of 2,695 Mb (1.2%) of sequence from the February 2003 mouse genome sequence assembly is involved in recent segmental duplications, which is less than that observed in the human genome (around 3.5-5%). From this dataset, 8.9 Mb (26%) of the duplication content consisted of 'unmapped' chromosome sequence. Moreover, we suspect that an additional 18.5 Mb of sequence is involved in duplication artifacts arising from sequence misassignment errors in this genome assembly. By searching for genes that are located within these regions, we identified 675 genes that mapped to duplicated regions of the mouse genome. Sixteen of these genes appear to have been duplicated independently in the human genome. From our dataset we further characterized a 42 kb recent segmental duplication of Mater, a maternal-effect gene essential for embryogenesis in mice.Our results provide an initial analysis of the recently duplicated sequence and gene content of the mouse genome. Many of these duplicated loci, as well as regions identified to be involved in potential sequence misassignment errors, will require further mapping and sequencing to achieve accuracy. A Genome Browser database was set up to display the identified duplication content presented in this work. This data will also be relevant to the growing number of investigators who use the draft genome sequence for experimental design and analysis.
Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle
Authors: Hakon Hakonarson, Neil Maskeri, Carrie Carter, Michael M. Grunstein
Journal: Journal of Clinical Investigation (1999)

CD4+ T helper (TH)1- and TH2-type cytokines reportedly play an important role in the pathobiology of asthma. Recent evidence suggests that proasthmatic changes in airway smooth muscle (ASM) responsiveness may be induced by the autocrine release of certain proinflammatory cytokines by the ASM itself. We examined whether TH1- and TH2-type cytokines are expressed by atopic asthmatic sensitized ASM and serve to autologously regulate the proasthmatic phenotype in the sensitized ASM. Expression of these cytokines and their receptors was examined in isolated rabbit and human ASM tissues and cultured cells passively sensitized with sera from atopic asthmatic patients or control subjects. Relative to controls, atopic sensitized ASM cells exhibited an early increased mRNA expression of the TH2-type cytokines, interleukin-5 (IL-5) and granulocyte–macrophage colony-stimulating factor (GM-CSF), and their receptors. This was later followed by enhanced mRNA expression of the TH1-type cytokines, IL-2, IL-12, and interferon-γ (IFN-γ), as well as their respective receptors. In experiments on isolated ASM tissue segments (a) exogenous administration of IL-2 and IFN-γ to atopic asthmatic serum–sensitized ASM ablated both their enhanced constrictor responsiveness to acetylcholine (ACh) and their attenuated relaxation responsiveness to β-adrenoceptor stimulation with isoproterenol, and (b) administration of IL-5 and GM-CSF to naive ASM induced significant increases in their contractility to ACh and impaired their relaxant responsiveness to isoproterenol. Collectively, these observations provide new evidence demonstrating that human ASM endogenously expresses both TH1- and TH2-type cytokines and their receptors, that these molecules are sequentially upregulated in the atopic asthmatic sensitized state, and that they act to downregulate and upregulate proasthmatic perturbations in ASM responsiveness, respectively.
A Single Nucleotide Change in the Mouse Genome Accelerates Breast Cancer Progression
Authors: Nina Seitzer, Thomas Mayr, Sylvia Streit, Axel Ullrich
Journal: Cancer Research (2010)

In the growth factor receptor gene FGFR4 the presence of the common single nucleotide polymorphism Arg388 has been associated with progression of various types of cancer including breast cancer. However, a causative relationship is not readily assigned due to genetic heterogeneity in different patient cohorts. To address this issue, we compared the effects of this allele on malignant progression in the WAP-TGFalpha transgenic mouse model of breast cancer. A knock-in strain was generated to introduce an analogous Arg385 allele into the murine FGFR4 gene. Mouse embryonic fibroblasts derived from this strain displayed accelerated cell transformation, with transformed cells exhibiting greater motility and invasive behavior. In the in vivo context of TGFalpha-induced mammary carcinogenesis, tumor development and progression was significantly advanced in tumor mass, size, and onset of pulmonary metastases. Our findings definitively identify the FGFR4 Arg388 allele as a functional prognostic marker for breast cancer progression.
Military Aeromedical Evacuation and Psychiatric Patients During the Viet Nam War
Authors: FRANK W. HAYES
Journal: American Journal of Psychiatry (1969)

A statistical study of all patients in the aeromedical system who entered Travis Air Force Base during a six-month period reveals the percentage of psychiatric patients (by individual military service) and also the percentage of patients with psychoses, neuroses, and character disorders. Studies during World War II and the Korean War are utilized to assess the effectiveness of present-day preventive psychiatric practices in the military. The author also discusses the effect of the Vietnamese war on psychiatric patients at David Grant USAF Hospital.
A Novel ORAI1 Mutation Resulting In T+B+NK+ SCID With Normal Lymphocyte Proliferation
Authors: Janet S. Chou, Christina S.K. Yee, Wayne Bainter, Luigi D. Notarangelo, Suleiman M.S.E. Al-Hammadi, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2014)

RATIONALE: ORAI1 encodes a calcium channel subunit essential for lymphocyte activation.Severely impaired lymphocyte proliferation is a hallmark of human mutations in ORAI1, resulting in T + B + NK + SCID with opportunistic infections and hypotonia.We report two patients with a novel frameshift mutation in ORAI1 that permits normal lymphocyte proliferation, but causes impaired NK and CD8 + T cell cytotoxicity, CMV viremia, and hypotonia.METHODS: Immunophenotyping was performed on Patient 2 prior to transplant; Patient 1 had been previously transplanted.Whole genome and Sanger sequencing was performed on patients' fibroblast lines, their parents, and a healthy sibling.ORAI1 expression was studied with immunoblotting.Store-operated calcium entry in fibroblast lines was assessed with intracellular fluorescent calcium ion indicators.RESULTS: Our patient had normal T, B, and NK cell numbers.Lymphocyte proliferation to mitogens was normal and present to antigens.IgG and IgM were normal, IgA was elevated, and he had positive pneumococcal titers.NK cell cytotoxicity was absent and CD8 + T cell cytotoxicity was minimal.Whole genome sequencing revealed a frameshift nonsense mutation in ORAI1 (p.H164PfsX1) that abolished expression of the protein's last two C-terminal domains.Fibroblasts from both patients demonstrated significantly decreased, but not absent, store-operated calcium flux.This may due to residual ORAI1 expression or compensation by ORAI2/3.Ongoing studies will determine if retroviral reconstitution of ORAI1-deficient fibroblasts with ORAI H164PfsX1 permits residual ORAI1 expression and calcium flux.CONCLUSIONS: This is the first human ORAI1 mutation that permits normal lymphocyte proliferation to mitogens, thus expanding the clinical phenotype associated with this disease.
Prophylactic Use of Human Leukocyte Interferon After Allogeneic Marrow Transplantation
Authors: J D Meyers, N Flournoy, J E Sanders, R W McGuffin, B A Newton, L D Fisher, L G Lum, F R Appelbaum, K Doney, K M Sullivan
Journal: Annals of Internal Medicine (1987)

To determine the efficacy of prophylactic interferon for prevention of cytomegalovirus infection and relapse of leukemia after allogeneic marrow transplantation.Randomized trial with intermittent interferon administration to day 80 after transplantation.Marrow transplantation units of a cancer research center.Consecutive patients with acute lymphocytic leukemia in remission at the time of transplantation. Thirty-nine patients received interferon, and 40 were control patients.Partially purified human leukocyte interferon given every 3 days beginning after marrow engraftment and continuing to day 80 after transplantation. After initial safety testing, the starting and minimum dose was 6 X 10(4) units/kg of body weight, with dose escalations determined by the circulating neutrophil count. Transplant conditioning and post-transplantation prophylaxis of graft-versus-host disease with methotrexate followed standard procedures.No difference was observed in the probability or severity of cytomegalovirus infection or in the probability or severity of graft-versus-host disease. Relapse of leukemia occurred in 9 interferon recipients and 21 control patients, with a minimum follow-up of 4 years among surviving patients. The probability of relapse among all interferon recipients was 0.36 (95% confidence interval [Cl], 0.56 to 0.17) and among all control patients was 0.74 (95% Cl, 0.91 to 0.58) (p = 0.04 by log-rank test). Among patients who received transplants in first or second remission, the probability of relapse among interferon recipients was 0.19 (95% Cl, 0.37 to 0.02) compared with 0.71 (95% Cl, 0.97 to 0.51) among control patients (p = 0.008 by log-rank test). Survival rates did not differ between interferon recipients and control patients. Transient decreases in leukocyte count and anorexia and nausea occurred among interferon recipients. Six interferon recipients, all of whom had received chemoradiotherapy of the central nervous system before transplantation, developed leukoencephalopathy after transplantation.These data suggest that interferon given after transplantation reduces the risk for subsequent relapse of leukemia. The effect of longer administration and of administration in patients with other underlying diseases will require additional trials. No effect was observed on cytomegalovirus infection, either because interferon was not initiated until a median of 18 days after transplantation or because of a lesser effect among marrow allograft recipients.
Long-Term Safety and Tolerability of Tadalafil in the Treatment of Erectile Dysfunction
Authors: F Montorsi, B Verheyden, E Meuleman, K.-P Jünemann, I Moncada, L Valiquette, A Casabé, C Pacheco, J Denne, J Knight, S Segal, V.S Watkins
Journal: European Urology (2003)
Magnitude and Time Course of Microvascular Obstruction and Tissue Injury After Acute Myocardial Infarction
Authors: Carlos E. Rochitte, João A. C. Lima, David A. Bluemke, Scott B. Reeder, Elliot R. McVeigh, Toshiya Furuta, Lewis C. Becker, Jacques A. Melin
Journal: Circulation (1998)

Microvascular obstruction within an area of myocardial infarction indicates worse functional recovery and a higher risk of postinfarction complications. After prolonged coronary occlusion, contrast-enhanced MRI identifies myocardial infarction as a hyperenhanced region containing a hypoenhanced core. Because the time course of microvascular obstruction after infarction/reperfusion is unknown, we examined whether microvascular obstruction reaches its full extent shortly after reperfusion or shows significant progression over the following 2 days.Seven dogs underwent 90-minute balloon occlusion of the left anterior descending coronary artery (LAD) followed by reflow. Gadolinium-DTPA-enhanced MRI performed at 2, 6, and 48 hours after reperfusion was compared with radioactive microsphere blood flow (MBF) measurements and myocardial staining to define microvascular obstruction (thioflavin S) and infarct size (triphenyltetrazolium chloride, TTC). The MRI hypoenhanced region increased 3-fold during 48 hours after reperfusion (3.2+/-1.8%, 6.7+/-4.4%, and 9.9+/-3.2% of left ventricular mass at 2, 6, and 48 hours, respectively, P<0.03) and correlated well with microvascular obstruction (MBF <50% of remote region, r=0.99 and thioflavin S, r=0.93). MRI hyperenhancement also increased (21.7+/-4.0%, 24.3+/-4.6%, and 28.8+/-5.1% at 2, 6, and 48 hours, P<0.006) and correlated well with infarct size by TTC (r=0.92). The microvascular obstruction/infarct size ratio increased from 13.0+/-4.8% to 22.6+/-8.9% and to 30.4+/-4.2% over 48 hours (P=0.024).The extent of microvascular obstruction and the infarct size increase significantly over the first 48 hours after myocardial infarction. These results are consistent with progressive microvascular and myocardial injury well beyond coronary occlusion and reflow.
Response to Comment on: Calleja et al. Insulin Resistance Is Associated With a Poor Response to Intravenous Thrombolysis in Acute Ischemic Stroke. Diabetes Care 2011;34:2413–2417
Authors: Ana I. Calleja, Juan F. Arenillas
Journal: Diabetes Care (2012)

We have read with interest the letter by Natarajan et al. (1) about our original article published in Diabetes Care (2). Our aim was to evaluate the prognostic effect of insulin resistance on the response to acute stroke thrombolysis. Insulin resistance was quantified with the homeostasis model assessment of insulin resistance (HOMA-IR) using fasting blood samples drawn 24–48 h after admission. We tried to design the study in a way that would minimize the potential confounding effect of hyperglycemia. First, on the basis of the results of the Glycemia in Acute Stroke study demonstrating that glycemia >155 mg/dL is an independent predictor of …
Moderate-and-vigorous physical activity from adolescence to adulthood and subclinical atherosclerosis in adulthood: prospective observations from the European Youth Heart Study
Authors: Mathias Ried-Larsen, Anders Grøntved, Peter Lund Kristensen, Karsten Froberg, Lars Bo Andersen
Journal: British Journal of Sports Medicine (2013)

To investigate the independent associations between mean exposure to or the change in moderate-and-vigorous physical activity (PA) from adolescence to adulthood and subclinical atherosclerosis in adulthood.This was a prospective cohort study among Danish boys and girls (N=277) followed for up to 12 years (age 15.7 (0.4) at baseline) enrolled in the European Youth Heart Study. PA intensity was objectively measured at baseline and follow-up, and ultrasonography was performed on the Carotid arteries at follow-up. Data on carotid intima-media thickness (cIMT), Carotid Compliance and Young's Elastic Modules were used as outcome measures.In the multivariable analyses (adjusted for personal-lifestyle and demographic factors) the mean exposure to moderate-and-vigorous PA from adolescence to adulthood was negatively associated with Young's Elastic Modules (β=-0.001×10(3) kPa (95% CI -0.0015 to -0.0002), p=0.02) and positively associated with Carotid Compliance (β=0.004 mm(2) kPa(-1) (95% CI 0.002 to 0.008), p=0.003) and cIMT (β=0.0003 mm (95% CI 0.00001 to 0.0007), p=0.013). Increases in moderate-and-vigorous PA from adolescence to adulthood were negatively associated with Young's Elastic Modules in adulthood (β=-0.00007×10(3) kPa (95% CI -0.0012 to -0.0001), p=0.01). Furthermore, participants with the largest decline in moderate-and-vigorous PA from adolescence to adulthood displayed significantly less compliant arteries compared with the remaining sample (p<0.05).High mean exposure to moderate-and-vigorous PA levels and increases herein were independently associated with lower levels of carotid arterial stiffness in adulthood.
Levalbuterol increases IL-4 and IL-5 and decreases IFN-gamma release from respiratory syncytial virus (RSV)-stimulated peripheral blood mononuclear cells (PBMCs)
Authors: J.A. Wendt, M. Peeples, J. Faro, R. Gandy, L. Phillips, J.N. Moy
Journal: Journal of Allergy and Clinical Immunology (2005)
Who owns and operates healthcare providers and does it matter?
Authors: Nigel Edwards, Richard Lewis
Journal: Journal of the Royal Society of Medicine (2008)

In explaining his economic reforms and the introduction of private ownership, Deng Xiao Ping famously said ‘It doesn't matter whether the cat is black or white as long as it catches mice’. Is there any reason to assume that this does not apply to the provision of healthcare?

Although the government's policy to bring in independent sector providers in hospital, community and primary care sectors is in line with policy in many other countries, it has led to some heated debate1 and adverse reactions from those who see this as the first stage in breaking up the NHS.2 This paper reviews the history of the debate and the evidence that is available about whether ownership matters.
The estrogen receptor-α agonist 16α-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats
Authors: T PELZER, V JAZBUTYTE, K HU, S SEGERER, M NAHRENDORF, P NORDBECK, A BONZ, J MUCK, K FRITZEMEIER, C HEGELEHARTUNG
Journal: Cardiovascular Research (2005)

Cardiac mass increases with age and with declining estradiol serum levels in postmenopausal women. Although the non-selective estrogen receptor-alpha and -beta agonist 17beta-estradiol attenuates cardiac hypertrophy in animal models and in observational studies, it remains unknown whether activation of a specific estrogen receptor subtype (ERalpha or ERbeta) might give similar or divergent results. Therefore, we analyzed myocardial hypertrophy as well as cardiac function and gene expression in ovariectomized, spontaneously hypertensive rats (SHR) treated with the subtype-selective ERalpha agonist 16alpha-LE2 or 17beta-estradiol.Long-term administration of 16alpha-LE2 or 17beta-estradiol did not affect elevated blood pressure, but both agonists efficiently attenuated cardiac hypertrophy and increased cardiac output, left ventricular stroke volume, papillary muscle strip contractility, and cardiac alpha-myosin heavy chain expression. The observed effects of E2 and 16alpha-LE2 were abrogated by the ER antagonist ZM-182780. Improved left ventricular function upon 16alpha-LE2 treatment was also observed in cardiac MRI studies. In contrast to estradiol and 16alpha-LE2, tamoxifen inhibited cardiac hypertrophy but failed to increase alpha-myosin heavy chain expression and cardiac output.These results support the hypothesis that activation of ERalpha favorably affects cardiac hypertrophy, myocardial contractility, and gene expression in ovariectomized SHR. Further studies are required to determine whether activation ERbeta mediates redundant or divergent effects.