tbuckley/cabot-search huggingface dataset:
Molecular phylogeny of the springhare, Pedetes capensis, based on mitochondrial DNA sequences
Authors: C. A. Matthee, T. J. Robinson
Journal: Molecular Biology and Evolution (1997)

The phylogenetic position of the Pedetidae, represented by a single species Pedetes capensis, is controversial, reflecting in part the retention of both Hystricomorphous and Sciurognathous characteristics in this rodent. In an attempt to clarify the species evolutionary relationships, mtDNA gene sequences from 10 rodent species (representing seven families) were analyzed using phenetic, parsimony, and maximum-likelihood methods of phylogenetic inference; the rabbit, Oryctolagus cuniculus (Order Lagomorpha), and cow, Bos taurus (Order Artiodactyla), were used as outgroups. Investigation of 714 base pairs of the protein-coding cytochrome b gene indicate strong base bias at the third codon position with significant rate heterogeneity evident between the three structural domains of this gene. Similar analyses conducted on 816 base pairs of the 12S rRNA gene revealed a transversion bias in the loop sections of all taxa. The cytochrome b gene sequences proved useful in resolving associations between closely related species but failed to produce consistent tree topologies at the family level. In contrast, phylogenetic analysis of the 12S rRNA gene resulted in strong support for the clustering of Pedetidae/Heteromyidae/Geomyidae and Muridae in one clade to the exclusion of the Hystricidae/Thryonomyidae and Sciuridae, a finding which is concordant with studies of rodent fetal membranes as well as reproductive and other anatomical features.
PMO-083 Are we meeting the nutritional needs of our acutely unwell surgical inpatients?
Authors: S Sarkar, A Sandison
Journal: Gut (2012)

<h3>Introduction</h3> Patients, admitted to a surgical ward who have undergone a prolonged pre-admission illness are likely to have some element of malnutrition. This may be compounded by surgical procedures (and subsequent fasting) after admission and these patients can go into severe malnutrition quickly, often before the treating team realises it. The presence of malnutrition in a surgical patient has a direct bearing on the overall outcome during hospitalisation. A nutritionally deprived patient is unable to mount an adequate response against infection and the surgical outcome is hence likely to be sub-optimal. Complications such as intestinal anastomosis leakage, wound dehiscence and overwhelming sepsis are more common in patients with malnutrition. The British Society of Gastroenterology has recognised that such patients are common in UK hospitals and on average their length of stay is almost doubled. This had led to the development of comprehensive guidelines regarding enteral feeding in adult hospitalised patients. The aim of the present study was to compare current practice in a district general hospital to the BSG guidelines. <h3>Methods</h3> A cross-sectional observational study of inpatients on general surgical wards over a 24-h period was performed. Medical and nursing notes were reviewed and data recorded regarding nutritional assessment and management. <h3>Results</h3> 72 patients were assessed over a 24-h period. Patients were divided into three groups, A elective surgery, B emergency surgery and C acute non-operative admission. Nutritional assessments were carried out on all patients, however BMI was not recorded in any. Pre admission nutritional intake was recorded in 61 (85%) patients. Data from these 61 patients were analysed to determine period of starvation. The median number of days between starvation and commencement of nutritional support was three (range 0–7), 6 (0–11) and 5 (0–12) respectively. <h3>Conclusion</h3> This study has shown that many of the patients on a general surgical ward have a significant period of starvation prior to and during their admission. While a nutritional assessment was performed in all patients, BMI and thus assessment of malnourishment as advocated by the BSG guidelines was not recorded in any patient. The nutritional needs of elective surgical patients appears to be well met in our hospital (median time to feeding 3 days) when compared to the BSG guidelines (3–5 days). Emergency admissions, however, were not as well managed with many waiting up to 1 week before nutritional support was instigated. Adequate assessment of nutritional status is important in all surgical patients, this is equally important for both patients undergoing surgery and those who do not require any surgical intervention. <h3>Competing interests</h3> None declared.
Increase of adipose tissue lipoprotein lipase activity with weight loss.
Authors: R S Schwartz, J D Brunzell
Journal: Journal of Clinical Investigation (1981)

Obese subjects have elevated adipose tissue lipoprotein lipase activity per fat cell when compared with lean control subjects. This enzyme, which is rate limiting for the uptake and storage of lipoprotein triglyceride in adipose tissue, has been shown to be further elevated in a group of previously obese subjects who had been weight stable at a reduced weight for 4-28 mo. In the present prospective study of eight obese subjects, adipose tissue lipoprotein lipase activity was demonstrated to increase after weight stabilization at a reduced weight (0.33 mU/10(6) cells). In three subjects who lost weight and subsequently regained their lost weight, the enzyme activity increased after weight loss and then returned toward the original basal level with weight gain. One subject who maintained his weight loss for 10 mo. continued to have an elevated level of enzyme activity. Because adipose tissue lipoprotein lipase activity does not "normalize" after weight loss, we hypothesize that this enzyme may play a counterregulatory role in resisting deviation from a "set point" for fat mass or fat cell size and thereby predispose to reattainment of the original obese state.
Once-daily tobramycin in the treatment of adult patients with cystic fibrosis
Authors: A. Whitehead, S.P. Conway, C. Etherington, N.A. Caldwell, N. Setchfield, S. Bogle
Journal: European Respiratory Journal (2002)

The aim of this study was to test the equivalence of once- and thrice-daily dosing with tobramycin by comparing efficacy and safety in adult patients with cystic fibrosis. Sixty adult patients with an acute respiratory exacerbation were randomized to receive either 10 mg·kg<sup>−1</sup> tobramycin once-daily or 3.3 mg·kg<sup>−1</sup> tobramycin thrice-daily. Primary efficacy and safety endpoints were defined as changes in respiratory function and changes in renal function and hearing. Both groups showed a significant increase in respiratory function without a clinically significant change in renal function. For changes in forced vital capacity % predicted and serum potassium and magnesium levels, equivalence was demonstrated. For the variables forced expiratory volume in one second and forced mid-expiratory flow % pred and serum creatinine levels, there was insufficient power to demonstrate equivalence. One patient in each group showed bilateral impairment in pure tone audiogram after treatment. This study demonstrated significant clinical improvement with both once- and thrice-daily tobramycin dosing. Equivalence between the two regimens was shown for some, but not all primary endpoints. Once-daily dosing should be used with careful monitoring of safety and efficacy until large multicentre studies confirm these encouraging results.
Phosphodiesterase-5 Inhibitor, Tadalafil, Protects Against Myocardial Ischemia/Reperfusion Through Protein-Kinase G–Dependent Generation of Hydrogen Sulfide
Authors: Fadi N. Salloum, Vinh Q. Chau, Nicholas N. Hoke, Antonio Abbate, Amit Varma, Ramzi A. Ockaili, Stefano Toldo, Rakesh C. Kukreja
Journal: Circulation (2009)

Tadalafil is a novel long-acting inhibitor of phosphodiesterase-5. Because cGMP-dependent protein kinase (PKG) signaling plays a key role in cardioprotection, we hypothesized that PKG activation with tadalafil would limit myocardial ischemia/reperfusion (I/R) injury and dysfunction. Additionally, we contemplated that cardioprotection with tadalafil is mediated by hydrogen sulfide (H(2)S) signaling in a PKG-dependent fashion.After baseline transthoracic echocardiography (TTE), adult ICR mice were injected i.p. with vehicle (10% DMSO) or tadalafil (1 mg/kg) with or without KT5823 (KT, PKG blocker, 1 mg/kg) or dl-propargylglycine (PAG, Cystathionine-gamma-lyase [CSE, H(2)S-producing enzyme] blocker; 50 mg/kg) 1 hour before coronary artery ligation for 30 minutes and reperfusion for 24 hours, whereas C57BL wild-type and CSE-knockout mice were treated with either vehicle or tadalafil. After reperfusion, TTE was performed and hearts were collected for infarct size (IS) measurement using TTC staining. Survival was increased with tadalafil (95%) compared with control (65%, P<0.05). Infarct size was reduced with tadalafil (13.2+/-1.7%) compared to vehicle (40.6+/-2.5%; P<0.05). KT and PAG abolished tadalafil-induced protection (IS: 39.2+/-1% and 51.2+/-2.4%, respectively) similar to genetic deletion of CSE (47.2+/-5.1%). Moreover, tadalafil preserved fractional shortening (FS: 31+/-1.5%) compared to control (FS: 22+/-4.8%, P<0.05). Baseline FS was 44+/-1.7%. KT and PAG abrogated the preservation of LV function with tadalafil by decline in FS to 17+/-1% and 23+/-3%, respectively. Compared to vehicle, myocardial H(2)S production was significantly increased with tadalafil and was abolished with KT.PKG activation with tadalafil limits myocardial infarction and preserves LV function through H(2)S signaling.
Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood donor population
Authors: M.-F. Yuen, C.-K. Lee, D. K.-H. Wong, J. Fung, I. Hung, A. Hsu, D. Y.-K. But, T.-K. Cheung, P. Chan, J. C.-H. Yuen, F. K.-C. Fung, W.-K. Seto, C.-K. Lin, C.-L. Lai
Journal: Gut (2010)

The aim of the present study was to determine the population prevalence of occult hepatitis B (OHB) infection and its clinical profile in a highly endemic area of chronic hepatitis B virus disease.OHB was first identified by individual sample testing for hepatitis B surface antigen (HBsAg) followed by nucleic acid testing (NAT) and vice versa for 3044 (cohort 1, stored sera from donation within 1 year) and 9990 (cohort 2, prospective study) blood donors, respectively. OHB was confirmed meticulously by ≥2 out of 3 tests with detectable hepatitis B virus (HBV) DNA using a sensitive standardised assay. Detailed serology and viral load in the serum and liver were studied.The prevalence of OHB was 0.13% (4/3044) and 0.11% (11/9967) for cohort 1 and 2, respectively. In cohort 2, 10 out of 11 OHB samples were positive for anti-HBc (hepatitis B core antigen) antibody (all were immunoglobulin G). Seven had detectable anti-HBs. The serum HBV DNA levels were extremely low (highest 14.1 IU/ml). Of the six donors who underwent liver biopsies, all had normal liver biochemistry, extremely low liver HBV DNA (highest 6.21 copies/cell) and nearly normal liver histology. For those with viral sequence generation, none had the common HBsAg mutant G145R.The prevalence of OHB in a highly endemic area of chronic HBV was very low, thus implying a low impact on transfusion services. To implement universal screening, the high cost of NAT should be taken into account. OHB blood donors had very low HBV replication, and normal liver biochemistry and histology, conferring a favourable prognosis.
Manganese Superoxide Dismutase Regulates a Metabolic Switch during the Mammalian Cell Cycle
Authors: Ehab H. Sarsour, Amanda L. Kalen, Zhen Xiao, Timothy D. Veenstra, Leena Chaudhuri, Sujatha Venkataraman, Philip Reigan, Garry R. Buettner, Prabhat C. Goswami
Journal: Cancer Research (2012)

Proliferating cells consume more glucose to cope with the bioenergetics and biosynthetic demands of rapidly dividing cells as well as to counter a shift in cellular redox environment. This study investigates the hypothesis that manganese superoxide dismutase (MnSOD) regulates cellular redox flux and glucose consumption during the cell cycle. A direct correlation was observed between glucose consumption and percentage of S-phase cells in MnSOD wild-type fibroblasts, which was absent in MnSOD homozygous knockout fibroblasts. Results from electron paramagnetic resonance spectroscopy and flow cytometric assays showed a significant increase in cellular superoxide levels in S-phase cells, which was associated with an increase in glucose and oxygen consumption, and a decrease in MnSOD activity. Mass spectrometry results showed a complex pattern of MnSOD-methylation at both lysine (68, 89, 122, and 202) and arginine (197 and 216) residues. MnSOD protein carrying a K89A mutation had significantly lower activity compared with wild-type MnSOD. Computational-based simulations indicate that lysine and arginine methylation of MnSOD during quiescence would allow greater accessibility to the enzyme active site as well as increase the positive electrostatic potential around and within the active site. Methylation-dependent changes in the MnSOD conformation and subsequent changes in the electrostatic potential around the active site during quiescence versus proliferation could increase the accessibility of superoxide, a negatively charged substrate. These results support the hypothesis that MnSOD regulates a "metabolic switch" during progression from quiescent through the proliferative cycle. We propose MnSOD as a new molecular player contributing to the Warburg effect.
Detection of a new mutation in the beta-myosin heavy chain gene in an individual with hypertrophic cardiomyopathy.
Authors: A J Marian, Q T Yu, A Mares, R Hill, R Roberts, M B Perryman
Journal: Journal of Clinical Investigation (1992)

Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant disease affecting primarily the myocardium. The gene responsible for FHCM has been localized to chromosome 14 in some families and several mutations have been described in the beta-myosin heavy chain (beta MHC), a candidate gene for the disease. We recently identified a family with HCM in whom we did not detect any of the known mutations in the beta MHC gene (the alpha/beta MHC hybrid gene and the missense mutation in exons 13 and 9). However, we did observe a novel 9.5-kb BamHI restriction fragment length polymorphism detected by a beta MHC probe on Southern blots of DNA from the proband of this family. Similarly, a novel 3.8-kb TaqI polymorphism and a novel 4.3-kb HindIII polymorphism were detected on Southern blots of DNA from the same proband. Polymerase chain reaction (PCR) was used to amplify the segment of the beta MHC that was detected by pSC14 probe. PCR amplification of the distal 3'-end of the beta MHC gene yielded an additional product in the DNA template from the proband which was subsequently cloned and sequenced. The sequence analysis showed a 2.4-kb nucleotide deletion involving one allele of the beta MHC gene. The deletion includes part of the intron 39, exon 40 including the 3'-untranslated region and the polyadenylation signal, and part of the beta-alpha MHC intergenic region. This deletion was inherited in Mendelian fashion in an additional three members of this small family of which only the proband has developed clinically diagnosed HCM at a very late onset (age 59 yr), the other three family members are younger and have not developed the disease at the ages of 10, 32, and 33 yr.
Antibodies against Vascular Endothelial Growth Factor Improve Early Renal Dysfunction in Experimental Diabetes
Authors: AN S. DE VRIESE, RONALD G. TILTON, MARLIES ELGER, CLIFFORD C. STEPHAN, WILHELM KRIZ, NORBERT H. LAMEIRE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.
Interrogation of global mutagenesis data with a genome scale model of Neisseria meningitidis to assess gene fitness in vitro and in sera
Authors: Tom A Mendum, Jane Newcombe, Ahmad A Mannan, Andrzej M Kierzek, Johnjoe McFadden
Journal: Genome biology (2011)

Neisseria meningitidis is an important human commensal and pathogen that causes several thousand deaths each year, mostly in young children. How the pathogen replicates and causes disease in the host is largely unknown, particularly the role of metabolism in colonization and disease. Completed genome sequences are available for several strains but our understanding of how these data relate to phenotype remains limited. To investigate the metabolism of N. meningitidis we generated and then selected a representative Tn5 library on rich medium, a minimal defined medium and in human serum to identify genes essential for growth under these conditions. To relate these data to a systems-wide understanding of the pathogen's biology we constructed a genome-scale metabolic network: Nmb_iTM560. This model was able to distinguish essential and non-essential genes as predicted by the global mutagenesis. These essentiality data, the library and the Nmb_iTM560 model are powerful and widely applicable resources for the study of meningococcal metabolism and physiology. We demonstrate the utility of these resources by predicting and demonstrating metabolic requirements on minimal medium, such as a requirement for phosphoenolpyruvate carboxylase, and by describing the nutritional and biochemical status of N. meningitidis when grown in serum, including a requirement for both the synthesis and transport of amino acids. This study describes the application of a genome scale transposon library combined with an experimentally validated genome-scale metabolic network of N. meningitidis to identify essential genes and provide novel insight into the pathogen's metabolism both in vitro and during infection.
Transient Overexpression of TGF-β1 Induces Epithelial Mesenchymal Transition in the Rodent Peritoneum
Authors: Peter J. Margetts, Philippe Bonniaud, Limin Liu, Catherine M. Hoff, Clifford J. Holmes, Judith A. West-Mays, Margaret M. Kelly
Journal: Journal of the American Society of Nephrology (2004)

Epithelial mesenchymal transition (EMT), a process involved in many growth and repair functions, has been identified in the peritoneal tissues of patients who undergo peritoneal dialysis. The sequence of changes in gene regulation and cellular events associated with EMT after TGF-beta1-induced peritoneal fibrosis is reported. Sprague-Dawley rats received an intraperitoneal injection of an adenovirus vector that transfers active TGF-beta1 (AdTGF-beta1) or control adenovirus, AdDL. Animals were killed 0 to 21 days after infection. Peritoneal effluent and tissue were analyzed for markers of EMT. In the animals that were treated with AdTGF-beta1, an increase in expression of genes associated with EMT and fibrosis, such as type I collagen A2, alpha-smooth muscle actin, and the zinc finger regulatory protein Snail, was identified. Transition of mesothelial cells 4 to 7 d after infection, with appearance of epithelial cells in the submesothelial zone 7 to 14 d after exposure to AdTGF-beta1, was demonstrated. This phase was associated with disruption of the basement membrane and increased expression of matrix metalloproteinase 2. By 14 to 21 d after infection, there was evidence of restoration of normal submesothelial architecture. These findings suggest that EMT occurs in vivo after TGF-beta1 overexpression in the peritoneum. Cellular changes and gene regulation associated with EMT are evident throughout the fibrogenic process and are not limited to early time points. This further supports the central role of TGF-beta1 in peritoneal fibrosis and provides an important model to study the sequence of events involved in TGF-beta1-induced EMT.
Role of Serum Cortisol Levels in Children with Asthma
Authors: ANNEKE M. LANDSTRA, DIRKJE S. POSTMA, H. MARIKE BOEZEN, WIM M. C. VAN AALDEREN
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Decreased serum cortisol levels have been proposed to contribute to nocturnal airway obstruction. We investigated whether endogenous cortisol levels are lower, and also whether the 24-h cortisol variation is greater, in children with asthma than in control subjects and assessed the relationship between serum cortisol and nocturnal airflow limitation in children with asthma. Cortisol and FEV1 were measured every 4 h over 24 h; blood eosinophils, airway responsiveness to methacholine and adenosine 5 ′ -monophosphate (AMP) were measured at 0400 and 1600. Children with asthma had lower cortisol levels than did control subjects; at midnight the difference was significant. Subjects with nocturnal asthma (24-h FEV1 variation ⩾ 15%) had significantly lower cortisol levels than did control subjects at 0000, 0800, and 1200. A higher mean 24-h cortisol level in subjects with asthma was associated with a significantly higher FEV1 as a percentage of the predicted value (FEV1 %pred) at 0400, 0800, and 2000, yet not in control subjects. Higher 24-h cortisol variation was associated with lower FEV1 %pred at all time points in both control subjects and subjects with nonnocturnal asthma. There was no significant association between the level or variation of cortisol and PD20 methacholine (provocative dose of methacholine causing a 20% fall in FEV1), PD20 AMP, or eosinophils. Our data suggest that lower cortisol levels contribute to both overall lower levels of FEV1 especially at night. This may be due to a lack of suppression of airway inflammation.