tbuckley/cabot-search huggingface dataset:
Intragenomic Base Content Variation Is a Potential Source of Biases When Searching for Horizontally Transferred Genes
Authors: Stéphane Guindon, Guy Perrière
Journal: Molecular Biology and Evolution (2001)

Horizontal transfers in bacteria have been extensively studied, and most of the methods developed to identify transferred sequences are based on the assumption that exogenous genes have characteristics that differ from those shared by endogenous ones. Up to now, the most common way to look at the peculiar characteristics exhibited by ‘‘alien’’ sequences has been to analyze biases in synonymous codon usage (Medigue et al. 1991; Lawrence and Ochman 1997, 1998; Aravind et al. 1998; Karlin, Campbell, and Mrazek 1998; Karlin, Mrazek, and Campbell 1998; Nelson et al. 1999). The main underlying hypothesis of this approach is that synonymous codons presented by genes coming from distantly related species are different from those shared by endogenous sequences. In this paper, we show that the results obtained may be biased due to intragenomic base content variations that may occur in bacterial genomes. As the most complete studies on horizontal transfer have been realized on Escherichia coli (Lawrence and Ochman 1997, 1998; Karlin, Mrazek, and Campbell 1998), we decided to center our analysis on this species. Moreover, as a detailed list of putatively transferred genes was available (Lawrence and Ochman 1998), it was possible to use it as a reference. In the study published by Lawrence and Ochman (1998), two codon usage indices were used to identify transferred genes: the codon adaptation index (CAI) (Sharp and Li 1987) and a x2 of codon usage (Lawrence and Ochman 1997). The selection of sequences that showed atypical values for combinations of these two indices led them to identify 755 putatively horizontally transferred genes in E. coli (i.e., 17.6% of the total number of genes). From among these genes, we used in our study only those that were annotated in the complete genome. This corresponds to a total of 317 genes out of 4,254 E. coli genes of length .150 nt. These genes are referred to as HT* in this paper, while the others are referred to as non-HT*. All coding sequences were extracted from the EMGLib database (Perriere, Labedan, and Bessieres 2000). To discriminate HT* from non-HT* genes, we used three different codon usage indices: the CAI, bias in codons (BC); (Karlin, Campbell, and Mrazek 1998), and G1C contrast in codon third positions (G1C3c). This
Genotyping in primary ciliary dyskinesia: ready for prime time, or a fringe benefit?: Table 1
Authors: Claire Hogg, Andrew Bush
Journal: Thorax (2012)

Once upon a time, many diagnoses were easy—for example, if you had a high sweat chloride, you had cystic fibrosis (CF); if the sweat electrolytes were normal, you did not. Now, recent advances in molecular genetics and airway electrophysiology have pushed back and blurred the diagnosis of CF, such that what was once straightforward can in atypical cases become the source of endless debate. The same has become true in primary ciliary dyskinesia (PCD). The situation in PCD is even more complicated; diagnosis seldom relied on a single test, but has become confusing because of the large number of tests currently available, many of which are very sophisticated and only available in a small number of centres. So, what is a PCD diagnosis in the 21st century?

First, of course, is it necessary to make a specific diagnosis of PCD at all? There are several reasons why it is; the treatment of upper airway disease in PCD is counterintuitive1 and there are genetic implications both for PCD and other parts of the expanding ciliopathy spectrum for the families. Importantly, there are no big randomised controlled trials of treatment in PCD; most treatments are extrapolated from protocols used for CF, a disease with completely different pathophysiology (reduced airway surface liquid rather than primary ciliary dysmotility). So, if this deficiency is to be addressed, the accurate diagnosis of PCD is a prerequisite. The same is also true for studies in basic mechanisms, including finding novel PCD genes.

There is wide variation in availability of the different tests across Europe2; the range is summarised in table 1. There is no one …
Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers
Authors: P. Xepapadaki, N. G. Papadopoulos
Journal: European Respiratory Journal (2010)

Respiratory infections have been implicated in the origin and exacerbation of asthma in a variety of ways; however, systemisation of this knowledge in a way helpful for disease management remains suboptimal. Several conceptual issues need to be taken into account: the fact that the effects of an infection may vary according to genetic background, the current immune status of the host, and parallel environmental stimuli, in addition to the particular infectious agent itself. Moreover, childhood is a very special period because of the continuous processes taking place, such as neural, immune and respiratory maturation. Epidemiological studies have convincingly demonstrated that the majority of asthma exacerbations, in both adults and children, follow viral upper respiratory tract infections. Asthma exacerbations are still often unresponsive to current asthma treatment, and new therapeutic approaches are required. This review presents current knowledge on the associations between infection and exacerbation of established asthma with respect to definitions, epidemiology, mechanisms and treatment.
Changes in Insulin Secretion and Insulin Sensitivity in Relation to the Glycemic Outcomes in Subjects With Impaired Glucose Tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1)
Authors: Chamukuttan Snehalatha, Simon Mary, Sundaram Selvam, Cholaiyil Kizhakathil Sathish Kumar, Samith Babu Ananth Shetty, Arun Nanditha, Ambady Ramachandran
Journal: Diabetes Care (2009)

OBJECTIVE The Indian Diabetes Prevention Programme-1 (IDPP-1) showed that lifestyle modification (LSM) and metformin were effective for primary prevention of diabetes in subjects with impaired glucose tolerance (IGT). Among subjects followed up for 3 years (n = 502), risk reductions versus those for the control group were 28.5, 26.4, and 28.2% in LSM, metformin (MET), and LSM plus MET groups, respectively. In this analysis, the roles of changes in secretion and action of insulin in improving the outcome were studied. RESEARCH DESIGN AND METHODS For this analysis, 437 subjects (93 subjects with normoglycemia [NGT], 150 subjects with IGT, and 194 subjects with diabetes) were included. Measurements of anthropometry, plasma glucose, and plasma insulin at baseline and at follow-up were available for all of them. Indexes of insulin resistance (homeostasis model assessment of insulin resistance) and β-cell function (insulinogenic index [ΔI/G]: 30-min fasting insulin divided by 30-min glucose) were also analyzed in relation to the outcome. RESULTS Subjects with IGT showed a deterioration in β-cell function with time. Individuals with higher insulin resistance and/or low β-cell function at baseline had poor outcome on follow-up. In relation to no abnormalities, the highest incidence of diabetes occurred when both abnormalities coexisted (54.9 vs. 33.7%, χ2 = 7.53, P = 0.006). Individuals having abnormal insulin resistance (41.1%) or abnormal ΔI/G (51.2%, χ2 = 4.87, P = 0.027 vs. no abnormalities) had lower incidence. Normal β-cell function with improved insulin sensitivity facilitated reversal to NGT, whereas deterioration in both resulted in diabetes. The beneficial changes were better with intervention than in the control group. Intervention groups had higher rates of NGT and lower rates of diabetes. CONCLUSIONS In the IDPP-1 subjects, beneficial outcomes occurred because of improved insulin action and sensitivity caused by the intervention strategies.
Effect of Epidermal Growth Factor Receptor Inhibitor on Development of Estrogen Receptor-Negative Mammary Tumors
Authors: C. Lu, C. Speers, Y. Zhang, X. Xu, J. Hill, E. Steinbis, J. Celestino, Q. Shen, H. Kim, S. Hilsenbeck, S. K. Mohsin, A. Wakeling, C. K. Osborne, P. H. Brown
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Although antiestrogens have been effective in preventing estrogen receptor (ER)-positive breast cancer, chemopreventive agents are still needed to prevent ER-negative breast cancer. Tyrosine kinase inhibitors are promising agents for the treatment and prevention of human cancers. ZD1839 (gefitinib or Iressa) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that blocks signal transduction pathways in epithelial cells. We examined whether ZD1839 blocks signal transduction and prevents the development of ER-negative breast cancer. Methods: The ability of ZD1839 to block signal transduction in normal, immortalized, and malignant breast cells was assessed by western blotting with specific antibodies to detect phosphorylation of cytoplasmic signaling molecules. The effect of ZD1839 on growth of these breast cells was assessed with anchorage-dependent and anchorage-independent growth assays. Its effect on ER-negative mammary tumorigenesis was assessed in MMTV-erbB2 transgenic mice. All statistical tests were two-sided. Results: ZD1839 suppressed the phosphorylation of EGFR and mitogen-activated protein kinase in normal and malignant breast cells. ZD1839 treatment statistically significantly suppressed mammary tumorigenesis in MMTV-erbB2 transgenic mice; median time to tumor development was approximately 230 days in vehicle-treated mice and more than 310 days in mice treated with ZD1839 at 100 mg/kg (P<.001). ZD1839 reduced proliferation of normal breast cells by 20.3% (95% confidence interval [CI] = −13.7% to 44.2%) and of tumor cells by 42.0% (95% CI = 20.2% to 58.2%). ZD1839 also increased expression of the cell cycle regulator p27 in normal mammary tissue by 48.7% (95% CI = 27.0% to 74.2%) and in tumor tissue by 50.3% (95% CI = 35.8% to 66.7%). Conclusion: This study appears to provide the preclinical rationale for the development of these EGFR tyrosine kinase inhibitors for the prevention of human breast cancer.
2B4, the Natural Killer and T Cell Immunoglobulin Superfamily Surface Protein, Is a Ligand for CD48
Authors: Marion H. Brown, Kent Boles, P. Anton van der Merwe, Vinay Kumar, Porunelloor A. Mathew, A. Neil Barclay
Journal: The Journal of Experimental Medicine (1998)

2B4 is a cell surface glycoprotein related to CD2 and implicated in the regulation of natural killer and T lymphocyte function. A recombinant protein containing the extracellular region of mouse (m)2B4 attached to avidin-coated fluorescent beads bound to rodent cells, and binding was completely blocked by CD48 monoclonal antibodies (mAbs). Using surface plasmon resonance, we showed that purified soluble mCD48 bound m2B4 with a six- to ninefold higher affinity (Kd ≈ 16 μM at 37°C) than its other ligand, CD2. Human CD48 bound human 2B4 with a similar affinity (Kd ≈ 8 μM). The finding of an additional ligand for CD48 provides an explanation for distinct functional effects observed on perturbing CD2 and CD48 with mAbs or by genetic manipulation.
Strategic pluralism: Men and women start from a different point
Authors: John Archer, Mani Mehdikhani
Journal: Behavioral and Brain Sciences (2000)

Gangestad &amp; Simpson's (G&amp;S's) analysis of strategic pluralism is welcomed as a balance to the current emphasis on between-sex variation. It could have been clarified by acknowledging the extent to which males and females represent fundamentally different mating strategies, since this affects how we view within-sex strategic variation. The distinction between conditional and alternative strategies could also have been highlighted.
Reduction of Postprandial Hyperglycemia in Subjects With IDDM by Intravenous Infusion of AC137, a Human Amylin Analogue
Authors: Orville G Kolterman, Alan Gottlieb, Chris Moyses, Wayne Colburn
Journal: Diabetes Care (1995)

To demonstrate that intravenous administration of AC137 (25,28,29 tripro-human amylin), a human amylin analogue, modulates the rate of appearance of glucose derived from a standard oral meal in the peripheral circulation of patients with insulin-dependent diabetes mellitus (IDDM).After the observation that a 2-h infusion of AC137 at a rate of 150 micrograms/h, in conjunction with the subjects' usual morning insulin dose, decreased postprandial hyperglycemia in 6 subjects with IDDM, a double-blind placebo-controlled two-period crossover design in an additional 18 IDDM patients was undertaken to confirm and extend the observation. Based on reasoning that an effect to modulate the appearance of orally administered glucose would have no impact on the disposition of an intravenous glucose load, nine patients were challenged with an intravenous glucose loads (300 mg/kg), while another nine patients were challenged with a standardized Sustacal meal (350 kcal) during a 5-h infusion of AC137 (50 micrograms/h). On each occasion, the subjects received their usual morning doses of insulin subcutaneously. The impact of the AC137 infusion on the plasma glucose responses to these different challenges was assessed.Intravenous infusion of AC137 yielding steady state plasma concentrations of 225 +/- 15 pmol/l (mean +/- SE) reduced postprandial plasma glucose concentrations after the standardized Sustacal meal challenge. The mean area under the glucose curve, corrected for baseline, was reduced from -1,869 +/- 5,562 mg.dl-1.min during placebo infusion to -28,872 +/- 4,812 mg.dl-1.min during AC137 infusion, P = 0.0015. In contrast, an AC137 infusion producing steady-state concentrations of 234 +/- 16 pmol/l had no effect on the plasma glucose profile after administration of an intravenous glucose load.AC137 administration, in these patients with IDDM, reduced postprandial hyperglycemia apparently by affecting the delivery rate of glucose from the gastrointestinal tract. AC137 may prove to be a clinically useful addition to insulin regimens to facilitate the achievement of glycemic control.
Maximal response plateau to methacholine as a reliable index for reducing inhaled budesonide in moderate asthma
Authors: L Prieto, V Gutierrez, C Morales
Journal: European Respiratory Journal (1999)

Although some studies suggest that asthma deteriorates after reducing inhaled steroids, results of long-term studies indicate that this might not be true for all patients. The aim of this study was to determine the utility of the detection of a plateau on the concentration-response curves to inhaled methacholine as a marker for safely reducing the dose of inhaled budesonide in asthmatic patients who are well-controlled with a moderately high dose of this inhaled steroid. A total of 46 patients with moderate asthma, well-controlled for at least 6 months by treatment with 800 microg budesonide daily, were included in the study. Subjects were treated for a 2-week run-in period with their usual dose of budesonide. At the end of the run-in, all subjects were challenged with methacholine (0.095-200 mg x mL(-1)). Plateau responses, median effective concentration values, slopes and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) values were measured. For the subsequent 12 weeks, patients were treated in an open design with budesonide at a reduced dose (200 microg once daily), and were asked to record their peak expiratory flow (PEF) in the morning and in the evening. In addition, asthma symptoms and use of rescue terbutaline were recorded in diaries. Plateaus were present in 24 patients, whereas 22 subjects showed concentration-response curves without evidence of a plateau. Ten patients in the nonplateau group deteriorated after reducing inhaled budesonide, compared to one patient in the plateau group (p = 0.002). In the nonplateau group, FEV1 decreased from a baseline value of 3.28+/-0.19 L to 2.94+/-0.20 L at week 12 (p&lt;0.0001). Likewise, morning PEF decreased from 419+/-19 L x min(-1) at baseline to 394+/-19 L x min(-1) at week 12 (p = 0.02). By contrast, these variables remained unchanged in the plateau group. In conclusion, in asthmatic patients, well-controlled with a moderately high dose of budesonide, the detection of a plateau on the concentration-response curve to inhaled methacholine may be used as a marker for safely reducing the corticosteroid dose.
Healthy controls have as much bile reflux as gastric ulcer patients.
Authors: N E Schindlbeck, C Heinrich, F Stellaard, G Paumgartner, S A Muller-Lissner
Journal: Gut (1987)

Data on duodenogastric reflux of bile in gastric ulcer are conflicting. We therefore measured intragastric bile acid concentration and its composition from individual bile acids, duodenogastric bile acid reflux rate, gastric emptying rate, and secretion rates of volume and acid in 30 patients with gastric ulcer and in 66 healthy controls, both in the fasting state and after feeding a liquid meal. Patients had higher gastric bile acid concentrations (p less than 0.05) than controls in the fasting state, but the overlap between the groups was considerable. In fasting patients with corpus ulcer, gastric secretion rates were significantly decreased when compared with controls. There was no difference between patients and controls with respect to gastric emptying rate, bile acid reflux rate, intragastric amount of bile acids, and bile acid composition in the fasting state. Postprandially, all parameters tested were similar in patients and controls. Controls showed high reflux rates with similar frequency as did ulcer patients. We conclude that increased gastric bile acid concentrations in the fasting stomach of patients with gastric ulcer are the result of gastric hyposecretion and not of increased reflux. They probably are pathogenetically irrelevant.
A refined risk stratification scheme for clinical stage 1 NSGCT based on evaluation of both embryonal predominance and lymphovascular invasion
Authors: C.A. Lago-Hernandez, H. Feldman, E. O'Donnell, B.A. Mahal, V. Perez, S. Howard, M. Rosenthal, S.C. Cheng, P.L. Nguyen, C. Beard, A.V. D'Amico, C.J. Sweeney
Journal: Annals of Oncology (2015)
Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice
Authors: Azzeddine Dakhama, Young-Mok Lee, Hiroshi Ohnishi, Xia Jing, Annette Balhorn, Katsuyuki Takeda, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2008)
Hip arthroscopy: current concepts and review of literature
Authors: Vijay D Shetty, Richard N Villar
Journal: British Journal of Sports Medicine (2006)

Diagnosis and treatment of intra-articular hip problems in young patients present a challenge to hip surgeons. Previous studies have shown that non-invasive investigations such as radiography, computed tomography and magnetic resonance imaging provide limited help. Non-operative treatment is likely to result in persistent symptoms, and surgical options for intra-articular hip problems involve open arthrotomy of the hip joint, which carries potential risks associated with joint dislocation. Arthroscopy of the hip joint, therefore, seems to be an attractive option. It was once thought that introduction of a straight arthroscope into the ball-and-socket hip joint was almost impossible. Hip arthroscopy has seen several advances since then, and the speed at which it developed in recent years directly corresponded to the rate at which the conditions affecting the hip joint were identified. Athletes and other young individuals with hip injuries are increasingly being diagnosed with an ever evolving series of conditions. Many of these conditions were previously unrecognised and thus left untreated, resulting in premature ends to the patients’ competitive careers. Hip arthroscopy, as with any procedure, is not without risks. The procedure is not widely available as it requires specialist equipment and takes a long time to learn. Complications are few, occurring in &lt;5% of patients.
A cellular mechanism for impaired posthypoxic relaxation in isolated cardiac myocytes. Altered myofilament relaxation kinetics at reoxygenation.
Authors: H S Silverman, M Ninomiya, P S Blank, O Hano, H Miyata, H A Spurgeon, E G Lakatta, M D Stern
Journal: Circulation Research (1991)

Single, isolated rat ventricular myocytes were made hypoxic for 10 minutes and then reoxygenated. During hypoxia, there was a marked abbreviation of the mechanical twitch, without a decrease in its amplitude. Immediately after reoxygenation, both the time to peak shortening and the duration of relaxation were markedly prolonged, and they remained prolonged for 10-50 minutes. The alterations in contraction and relaxation were not associated with any change in the time course of either the transmembrane action potential or the cytosolic calcium transient, as recorded with the fluorescent probe indo 1. Intracellular pH, measured with a fluorescent probe (carboxyseminaphthorhodofluor), showed an acid shift during hypoxia and an alkaline rebound immediately after reoxygenation. The time courses of intracellular pH and contraction duration were not parallel during hypoxia or reoxygenation, and simulation of the alkaline pH shift by lowering PCO2 or superfusing NH4Cl (in the absence of exposure to hypoxia) did not quantitatively reproduce the prolongation of relaxation seen after reoxygenation. The prolongation of contraction after reoxygenation could be overridden by the beta-adrenergic agonist isoproterenol or the nonenzymatic phosphatase butanedione monoxime. We conclude that delayed relaxation after reoxygenation exists at the single cell level and is due to an alteration of the properties of the myofilaments. Intracellular pH is not the primary mediator of this alteration. We speculate that alteration of intracellular inorganic phosphate or covalent modification of the myofilaments might be involved.
CD80 in Immune Suppression by Mouse Ovarian Carcinoma–Associated Gr-1+CD11b+ Myeloid Cells
Authors: Rongcun Yang, Zhong Cai, Yuan Zhang, William H. Yutzy, Katherine F. Roby, Richard B.S. Roden
Journal: Cancer Research (2006)

Abstract An elevated number of Gr-1+CD11b+ myeloid cells has been described in mice bearing transplantable tumors, and has been associated with immune suppression. We examined the role of such myeloid suppressor cells in mice bearing the spontaneously transformed syngeneic mouse ovarian surface epithelial cell line, 1D8. We observed high levels of CD80 expression by Gr-1+CD11b+ cells from spleen, ascites, and tumor tissue of mice bearing 1D8 ovarian carcinoma, whereas CD40 and CD86 were absent. CD80 expression was not detected on Gr-1+CD11b+ cells from naïve mice. However, the expression of CD80 by Gr-1+CD11b+ cells from naïve mice was promoted by coculture with 1D8 cells. Because irradiated 1D8 cells, but not 1D8-conditioned medium, up-regulate CD80 expression by Gr-1+CD11b+ cells, this phenomenon likely requires direct interaction. Gr-1+CD11b+ cells derived from 1D8 tumor–bearing mice provided significant suppression of antigen-specific immune responses, but Gr-1+CD11b+ cells from naïve mice did not. Both short interfering RNA–mediated knockdown and genetic knockout of CD80 expression by Gr-1+CD11b+ cells of 1D8 tumor–bearing mice alleviated the suppression of antigen-specific immune responses. Suppression via CD80 on Gr-1+ CD11b+ myeloid cells was mediated by CD4+CD25+ T regulatory cells and required CD152. CD80 knockout or antibody blockade of either CD80 or CD152 retarded the growth of 1D8 tumor in mice, suggesting that expression of CD80 on Gr-1+CD11b+ myeloid cells triggered by 1D8 ovarian carcinoma suppresses antigen-specific immunity via CD152 signaling and CD4+CD25+ T regulatory cells. Thus, CD80-dependent responses to myeloid suppressor cells may contribute to tumor tolerance and the progression of ovarian carcinoma.(Cancer Res 2006; 66(13): 6807-15)