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41.
Tsipouri V Curtin JA Nolan PM Vizor L Parsons CA Clapham CM Latham ID Rooke LJ Martin JE Peters J Hunter AJ Rogers D Rastan S Brown SD Fisher EM Spurr NK Gray IC 《Comparative and Functional Genomics》2004,5(2):123-127
Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes. 相似文献
42.
43.
Kiterie M. E. Faller Debra J. Medway Dunja Aksentijevic Liam Sebag-Montefiore Jürgen E. Schneider Craig A. Lygate Stefan Neubauer 《PloS one》2013,8(6)
Background
Reduced levels of creatine and total adenine nucleotides (sum of ATP, ADP and AMP) are hallmarks of chronic heart failure and restoring these pools is predicted to be beneficial by maintaining the diseased heart in a more favourable energy state. Ribose supplementation is thought to support both salvage and re-synthesis of adenine nucleotides by bypassing the rate-limiting step. We therefore tested whether ribose would be beneficial in chronic heart failure in control mice and in mice with elevated myocardial creatine due to overexpression of the creatine transporter (CrT-OE).Methods and Results
Four groups were studied: sham; myocardial infarction (MI); MI+ribose; MI+CrT-OE+ribose. In a pilot study, ribose given in drinking water was bioavailable, resulting in a two-fold increase in myocardial ribose-5-phosphate levels. However, 8 weeks post-surgery, total adenine nucleotide (TAN) pool was decreased to a similar amount (8–14%) in all infarcted groups irrespective of the treatment received. All infarcted groups also presented with a similar and substantial degree of left ventricular (LV) dysfunction (3-fold reduction in ejection fraction) and LV hypertrophy (32–47% increased mass). Ejection fraction closely correlated with infarct size independently of treatment (r2 = 0.63, p<0.0001), but did not correlate with myocardial creatine or TAN levels.Conclusion
Elevating myocardial ribose and creatine levels failed to maintain TAN pool or improve post-infarction LV remodeling and function. This suggests that ribose is not rate-limiting for purine nucleotide biosynthesis in the chronically failing mouse heart and that alternative strategies to preserve TAN pool should be investigated. 相似文献44.
A combination of allozyme and mitochondrial DNA markers were used to determine the contribution of recent and ancient causes
of patterns of genetic variation within and among 46 populations of the endangered golden sun moth, Synemon plana. Allozyme analysis grouped the 46 populations into 5 major genetic clusters that corresponded closely with geographic location
following a classic isolation-by-distance model. Phylogenetic analysis of 14 mtDNA haplotypes revealed two reciprocally monophyletic
groups. One of these groups (containing 4 geographically distant populations) was clearly identified by allozyme analysis
and represents a distinct evolutionary unit. The remaining 4 allozyme groups were not distinguishable by mtDNA analysis. The
evidence suggests that the populations within these groups derived from a small founding population that underwent rapid demographic
expansion in ancient times. This was followed by more recent population bottlenecks resulting from habitat fragmentation associated
with the widespread introduction of agriculture into the region. The generally low levels of allozyme and nucleotide diversity
within these populations support this hypothesis.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
45.
CD200 expression on tumor cells suppresses antitumor immunity: new approaches to cancer immunotherapy 总被引:1,自引:0,他引:1
Kretz-Rommel A Qin F Dakappagari N Ravey EP McWhirter J Oltean D Frederickson S Maruyama T Wild MA Nolan MJ Wu D Springhorn J Bowdish KS 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(9):5595-5605
Although the immune system is capable of mounting a response against many cancers, that response is insufficient for tumor eradication in most patients due to factors in the tumor microenvironment that defeat tumor immunity. We previously identified the immune-suppressive molecule CD200 as up-regulated on primary B cell chronic lymphocytic leukemia (B-CLL) cells and demonstrated negative immune regulation by B-CLL and other tumor cells overexpressing CD200 in vitro. In this study we developed a novel animal model that incorporates human immune cells and human tumor cells to address the effects of CD200 overexpression on tumor cells in vivo and to assess the effect of targeting Abs in the presence of human immune cells. Although human mononuclear cells prevented tumor growth when tumor cells did not express CD200, tumor-expressed CD200 inhibited the ability of lymphocytes to eradicate tumor cells. Anti-CD200 Ab administration to mice bearing CD200-expressing tumors resulted in nearly complete tumor growth inhibition even in the context of established receptor-ligand interactions. Evaluation of an anti-CD200 Ab with abrogated effector function provided evidence that blocking of the receptor-ligand interaction was sufficient for control of CD200-mediated immune modulation and tumor growth inhibition in this model. Our data indicate that CD200 expression by tumor cells suppresses antitumor responses and suggest that anti-CD200 treatment might be therapeutically beneficial for treating CD200-expressing cancers. 相似文献
46.
Catherine P. Benziger Antonio Bernabé-Ortiz Robert H. Gilman William Checkley Liam Smeeth Germán Málaga J. Jaime Miranda CRONICAS Cohort Study group 《PloS one》2015,10(11)
Objective
We aimed to characterize metabolic status by body mass index (BMI) status.Methods
The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru’s capital, costal urban, highly urbanized), urban and rural Puno (both high-altitude), and Tumbes (costal semirural). Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30 kg/m2), and as metabolically healthy (0–1 metabolic abnormality) or metabolically unhealthy (≥2 abnormalities). Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance.Results
A total of 3088 (age 55.6±12.6 years, 51.3% females) had all measurements. Of these, 890 (28.8%), 1361 (44.1%) and 837 (27.1%) were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (p<0.001). Among normal weight individuals, 43.1% were metabolically unhealthy, and age ≥65 years, female, and highest socioeconomic groups were more likely to have this pattern. In contrast, only 16.4% of overweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile.Conclusions
Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose. 相似文献47.
48.
As part of our investigation of the mode of action of plant hormones in barley (Hordeum vulgare L.) aleurone layers, we have studied the expression of five identified and three unidentified mRNA species in the presence of exogenous gibberellic acid (GA3) and abscisic acid. Three of the mRNAs are GA3-inducible, three are suppressed by GA3, and two are constitutive. The extent of the GA3 effect differs considerably for both inducible and suppressible mRNAs. For example, a ten-fold higher concentration of GA3 (10-8 M) is required for full induction of the high-pl group -amylase mRNA than is required for the low-pI -amylase mRNA (10-9 M). Temporal regulation of mRNA abundance also varies between the two -amylase isoenzyme groups. The three GA3-suppressible mRNA species studied, alcohol dehydrogenase (ADH1), a probable amylase and protease inhibitor, and an unidentified barley mRNA species also varied in response to GA3. The ADH1 mRNA decreased drastically within 8 h of GA3 treatment, whereas the other two began to decrease in abundance only after 12–16 h of GA3 treatment. Abscisic-acid treatment counteracted the GA3 effects for both the inducible and suppressible mRNA species. Comparison of -amylase-mRNA levels and -amylase-synthesis rates showed a strong correlation between the two parameters, the only exception being a lack of -amylase synthesis in the presence of -amylase mRNA at low GA3 concentrations. Therefore, the expression of -amylase seems to be regulated primarily by its mRNA levels.Abbreviations ABA
abscisic acid
- ADH1
alcohol dehydrogenase 1
- cDNA
copy DNA
- GA3
gibberellic acid
- PAPI
probable amylase/protease inhibitor 相似文献
49.
Vidne M Ahmadian Y Shlens J Pillow JW Kulkarni J Litke AM Chichilnisky EJ Simoncelli E Paninski L 《Journal of computational neuroscience》2012,33(1):97-121
Synchronized spontaneous firing among retinal ganglion cells (RGCs), on timescales faster than visual responses, has been reported in many studies. Two candidate mechanisms of synchronized firing include direct coupling and shared noisy inputs. In neighboring parasol cells of primate retina, which exhibit rapid synchronized firing that has been studied extensively, recent experimental work indicates that direct electrical or synaptic coupling is weak, but shared synaptic input in the absence of modulated stimuli is strong. However, previous modeling efforts have not accounted for this aspect of firing in the parasol cell population. Here we develop a new model that incorporates the effects of common noise, and apply it to analyze the light responses and synchronized firing of a large, densely-sampled network of over 250 simultaneously recorded parasol cells. We use a generalized linear model in which the spike rate in each cell is determined by the linear combination of the spatio-temporally filtered visual input, the temporally filtered prior spikes of that cell, and unobserved sources representing common noise. The model accurately captures the statistical structure of the spike trains and the encoding of the visual stimulus, without the direct coupling assumption present in previous modeling work. Finally, we examined the problem of decoding the visual stimulus from the spike train given the estimated parameters. The common-noise model produces Bayesian decoding performance as accurate as that of a model with direct coupling, but with significantly more robustness to spike timing perturbations. 相似文献
50.
Eric I. Benchimol Liam Smeeth Astrid Guttmann Katie Harron David Moher Irene Petersen Henrik T. S?rensen Erik von Elm Sinéad M. Langan RECORD Working Committee 《PLoS medicine》2015,12(10)
Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting. 相似文献