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1.
Daily temperature measures are commonly used when examining the association between temperature and mortality. In fact, temperature measures are available 24 hours a day and more detailed records may provide a better prediction of mortality compared to daily statistics. In this article, monthly stratified analysis modeling for mortality is conducted for the total population as well as the stratified elderly and younger subgroups. We identified the most significant time during the day that is associated with daily mortality. Surprisingly, the estimates of relative risk and magnitude of associations derived from the hourly temperature measures are similar or even stronger compared to those modeled by the daily statistics. This phenomenon remains true for lagged hourly temperature measures and the changing patterns of associations from January through December are revealed. In summary, people are the most vulnerable to temperature variations in the early morning around 5 am and the night time around 8 pm. 相似文献
2.
Megana K. Prasad Kavita Bhalla Zhen Hua Pan Jeffrey R. O’Connell Alan B. Weder Aravinda Chakravarti Bin Tian Yen-Pei C. Chang 《PloS one》2013,8(10)
Although variants in many genes have previously been shown to be associated with blood pressure (BP) levels, the molecular mechanism underlying these associations are mostly unknown. We identified a multi-allelic T-rich sequence (TRS) in the 3’UTR of ATP1B1 that varies in length and sequence composition (T22-27 and T12GT 3GT6). The 3’UTR of ATP1B1 contains 2 functional polyadenylation signals and the TRS is downstream of the proximal polyadenylation site (A2). Therefore, we hypothesized that alleles of this TRS might influence ATP1B1 expression by regulating alternative polyadenylation. In vitro, the T12GT 3GT6 allele increases polyadenylation at the A2 polyadenylation site as compared to the T23 allele. Consistent with our hypothesis, the relative abundance of the A2-polyadenylated ATP1B1 mRNA was higher in human kidneys with at least one copy of the T12GT 3GT6 allele than in those lacking this allele. The T12GT 3GT6 allele is also associated with higher systolic BP (beta = 3.3 mmHg, p = 0.014) and diastolic BP (beta = 2.4 mmHg, p = 0.003) in a European-American population. Therefore, we have identified a novel multi-allelic TRS in the 3’UTR of ATP1B1 that is associated with higher BP and may mediate its effect by regulating the polyadenylation of the ATP1B1 mRNA. 相似文献
3.
Background
The development of pancreatic cancer is a process in which genes interact with environmental factors. We performed this study to determine the effects of the ABO blood group, obesity, diabetes mellitus, metabolic syndrome (MetS), smoking, alcohol consumption and hepatitis B viral (HBV) infection on patient survival.Methods
A total of 488 patients with pancreatic cancer were evaluated.Result
Patients who presented as chronic carriers of HBV infection were younger at disease onset (p = 0.001) and more predominantly male (p = 0.020) than those never exposed to HBV. Patients with MetS had later disease staging (p = 0.000) and a lower degree of pathological differentiation (p = 0.008) than those without MetS. In a univariate analysis, the ABO blood group, smoking and alcohol consumption were not associated with overall survival. HBsAg–positivity and elevated fasting plasma glucose were significantly associated with unfavorable survival though not in the multivariate analysis. The presence of MetS (HR: 1.541, 95% CI: 1.095–2.169, p = 0.013), age ≥65, an elevated CA19–9 baseline level, TNM staging, the type of surgery, the degree of differentiation and chemotherapy were independently associated with overall survival.Conclusion
We report, for the first time, that patients with chronic HBV infection may represent a special subtype of pancreatic cancer, who have a younger age of disease onset and male dominancy. Patients with MetS had later disease staging and a poorer histological grade. Patients with MetS demonstrated significantly poorer survival. 相似文献4.
There has been evidence of warming rate varying largely over space and between seasons. However, little has been done to evaluate the spatial and temporal variability of air temperature in the Tarim Basin, northwest China. In this study, we collected daily air temperature from 19 meteorological stations for the period of 1960–2012, and analyzed annual mean temperature (AMT), the annual minimum (Tmin) and maximum temperature (Tmax), and mean temperatures of all twelve months and four seasons and their anomalies. Trend analyses, standard deviation of the detrended anomaly (SDDA) and correlations were carried out to characterize the spatial and temporal variability of various mean air temperatures. Our data showed that increasing trend was much greater in the Tmin (0.55°C/10a) than in the AMT (0.25°C/10a) and Tmax (0.12°C/10a), and the fluctuation followed the same order. There were large spatial variations in the increasing trends of both AMT (from −0.09 to 0.43 °C/10a) and Tmin (from 0.15 to 1.12°C/10a). Correlation analyses indicated that AMT had a significantly linear relationship with Tmin and the mean temperatures of four seasons. There were also pronounced changes in the monthly air temperature from November to March at decadal time scale. The seasonality (i.e., summer and winter difference) of air temperature was stronger during the period of 1960–1979 than over the recent three decades. Our preliminary analyses indicated that local environmental conditions (such as elevation) might be partly responsible for the spatial variability, and large scale climate phenomena might have influences on the temporal variability of air temperature in the Tarim Basin. In particular, there was a significant correlation between index of El Niño-Southern Oscillation (ENSO) and air temperature of May (P = 0.004), and between the index of Pacific Decadal Oscillation (PDO) and air temperature of July (P = 0.026) over the interannual to decadal time scales. 相似文献
5.
Jacob M?rup Schlütter Ida Kirkegaard Olav Bj?rn Petersen Nanna Larsen Britta Christensen David M. Hougaard Steen K?lvraa Niels Uldbjerg 《PloS one》2014,9(9)
Objective
To identify factors influencing the number of fetal cells in maternal blood.Methods
A total of 57 pregnant women at a gestational age of weeks 11–14 were included. The number of fetal cells in maternal blood was assessed in 30 ml of blood using specific markers for both enrichment and subsequent identification.Results
Participants carrying male fetuses had a higher median number of fetal cells in maternal blood than those carrying female fetuses (5 vs. 3, p = 0.04). Certain cytokines (RANTES, IL-2 and IL-5) were significantly associated with the number of fetal cells in maternal blood.Conclusion
The number of fetal cells in maternal blood is associated with certain cytokines and fetal gender. 相似文献6.
Day — and night-forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) (PEP-C) were extracted from leaves of the CAM plant Kalanchoë daigremontiana. During storage after extraction, the day-form spontaneously lost its sensitivity towards the allosteric inhibitor l -malate. This effect was accelerated by inorganic phosphate, PEP, 3-PGA and G-6-P. l -Malate however stabilized the malate sensitivity of the day-form of PEP-C. Crude desalted extracts of the day-form and of the night-form of PEP-C were subjected to ultracentrifugation on a continuous sucrose gradient in the presence of malate and of marker enzymes. Both forms of PEP-C were found to have relative molecular masses of about 200,000. This suggests that both forms represent the dimers of the enzyme protein. The result also suggests that reversible dissociation and association of enzyme subunits is not the mechanism which brings about the interconversion of the two PEP-C forms during the diurnal CAM cycle in vivo. 相似文献
7.
Murri M García-Delgado R Alcázar-Ramírez J Fernández de Rota L Fernández-Ramos A Cardona F Tinahones FJ 《Biological trace element research》2011,143(3):1289-1301
Sleep apnea-hypopnea syndrome (SAHS) is characterized by recurrent episodes of hypoxia/reoxygenation, which seems to promote oxidative stress. SAHS patients experience increases in hypertension, obesity and insulin resistance (IR). The purpose was to evaluate in SAHS patients the effects of 1?month of treatment with continuous positive airway pressure (CPAP) on oxidative stress and the association between oxidative stress and insulin resistance and blood pressure (BP). Twenty-six SAHS patients requiring CPAP were enrolled. Measurements were recorded before and 1?month after treatment. Cellular oxidative stress parameters were notably decreased after CPAP. Intracellular glutathione and mitochondrial membrane potential increased significantly. Also, total antioxidant capacity and most of the plasma antioxidant activities increased significantly. Significant decreases were seen in BP. Negative correlations were observed between SAHS severity and markers of protection against oxidative stress. BP correlated with oxidative stress markers. In conclusion, we observed an obvious improvement in oxidative stress and found that it was accompanied by an evident decrease in BP with no modification in IR. Consequently, we believe that the decrease in oxidative stress after 1?month of CPAP treatment in these patients is not contributing much to IR genesis, though it could be related to the hypertension etiology. 相似文献
8.
Qianxia Li Huanlei Wu Bei Chen Guangyuan Hu Liu Huang Kai Qin Yu Chen Xianglin Yuan Zhongxing Liao 《PloS one》2012,7(12)
Purpose
Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis.Patients and Methods
We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis.Results
The median age of the 116 men and 45 women in the study was 58 years; 62 (39%) had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%). Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204–5.359, P = 0.014; and HR 1.885, 95% CI 1.086–3.273, P = 0.024), compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390–3.985, P = 0.001).Conclusions
We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis. 相似文献9.
Kurets V. K. Drosdov S. N. Popov E. G. Talanov A. V. Dembo E. D. 《Russian Journal of Plant Physiology》2003,50(1):72-78
The effect of soil temperature on the net photosynthetic rate was studied by the method of multifactor analysis at early growth stages of narrow-leaved lupine (Lupinus angustifolius L.), white cabbage (Brassica capitata Lisg.), spring wheat (Triticum aestivum L.), cucumber (Cucumis sativus L.), tomato (Lycopersicon esculentum Mill.), and cotton (Gossypium hirsutum L.) plant species and cultivars contrasting in their heat demand. The optimum level of the net photosynthetic rate was observed in a wide range of soil and air temperatures, from cold- to heat-hardening temperatures, irrespective of the sign of the temperature gradient, whereas the magnitude and sign of the temperature gradient favorable for the highest potential net photosynthetic rate were species- and cultivar-specific and were not related to the cold tolerance of a species or cultivar. 相似文献
10.
Rufina Leung Petroula Proitsi Andrew Simmons Katie Lunnon Andreas Güntert Deborah Kronenberg Megan Pritchard Magda Tsolaki Patrizia Mecocci Iwona Kloszewska Bruno Vellas Hilkka Soininen Lars-Olaf Wahlund Simon Lovestone 《PloS one》2013,8(6)
Markers of Alzheimer’s disease (AD) are being widely sought with a number of studies suggesting blood measures of inflammatory proteins as putative biomarkers. Here we report findings from a panel of 27 cytokines and related proteins in over 350 subjects with AD, subjects with Mild Cognitive Impairment (MCI) and elderly normal controls where we also have measures of longitudinal change in cognition and baseline neuroimaging measures of atrophy. In this study, we identify five inflammatory proteins associated with evidence of atrophy on MR imaging data particularly in whole brain, ventricular and entorhinal cortex measures. In addition, we observed six analytes that showed significant change (over a period of one year) in people with fast cognitive decline compared to those with intermediate and slow decline. One of these (IL-10) was also associated with brain atrophy in AD. In conclusion, IL-10 was associated with both clinical and imaging evidence of severity of disease and might therefore have potential to act as biomarker of disease progression. 相似文献
11.
Background
Eukaryotic chromosomes end with telomeres, which in most organisms are composed of tandem DNA repeats associated with telomeric proteins. These DNA repeats are synthesized by the enzyme telomerase, whose activity in most human tissues is tightly regulated, leading to gradual telomere shortening with cell divisions. Shortening beyond a critical length causes telomere uncapping, manifested by the activation of a DNA damage response (DDR) and consequently cell cycle arrest. Thus, telomere length limits the number of cell divisions and provides a tumor-suppressing mechanism. However, not only telomere shortening, but also damaged telomere structure, can cause telomere uncapping. Dyskeratosis Congenita (DC) and its severe form Hoyeraal-Hreidarsson Syndrome (HHS) are genetic disorders mainly characterized by telomerase deficiency, accelerated telomere shortening, impaired cell proliferation, bone marrow failure, and immunodeficiency.Methodology/Principal Findings
We studied the telomere phenotypes in a family affected with HHS, in which the genes implicated in other cases of DC and HHS have been excluded, and telomerase expression and activity appears to be normal. Telomeres in blood leukocytes derived from the patients were severely short, but in primary fibroblasts they were normal in length. Nevertheless, a significant fraction of telomeres in these fibroblasts activated DDR, an indication of their uncapped state. In addition, the telomeric 3′ overhangs are diminished in blood cells and fibroblasts derived from the patients, consistent with a defect in telomere structure common to both cell types.Conclusions/Significance
Altogether, these results suggest that the primary defect in these patients lies in the telomere structure, rather than length. We postulate that this defect hinders the access of telomerase to telomeres, thus causing accelerated telomere shortening in blood cells that rely on telomerase to replenish their telomeres. In addition, it activates the DDR and impairs cell proliferation, even in cells with normal telomere length such as fibroblasts. This work demonstrates a telomere length-independent pathway that contributes to a telomere dysfunction disease. 相似文献12.
Makoto Ikenaga Rafael Guevara Amanda L. Dean Cristina Pisani Joseph N. Boyer 《Microbial ecology》2010,59(2):284-295
Community structure of sediment bacteria in the Everglades freshwater marsh, fringing mangrove forest, and Florida Bay seagrass
meadows were described based on polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) patterns of 16S
rRNA gene fragments and by sequencing analysis of DGGE bands. The DGGE patterns were correlated with the environmental variables
by means of canonical correspondence analysis. There was no significant trend in the Shannon–Weiner index among the sediment
samples along the salinity gradient. However, cluster analysis based on DGGE patterns revealed that the bacterial community
structure differed according to sites. Not only were these salinity/vegetation regions distinct but the sediment bacteria
communities were consistently different along the gradient from freshwater marsh, mangrove forest, eastern-central Florida
Bay, and western Florida Bay. Actinobacteria- and Bacteroidetes/Chlorobi-like DNA sequences were amplified throughout all sampling sites. More Chloroflexi and members of candidate division WS3 were found in freshwater marsh and mangrove forest sites than in seagrass sites. The
appearance of candidate division OP8-like DNA sequences in mangrove sites distinguished these communities from those of freshwater
marsh. The seagrass sites were characterized by reduced presence of bands belonging to Chloroflexi with increased presence of those bands related to Cyanobacteria, γ-Proteobacteria, Spirochetes, and Planctomycetes. This included the sulfate-reducing bacteria, which are prevalent in marine environments. Clearly, bacterial communities
in the sediment were different along the gradient, which can be explained mainly by the differences in salinity and total
phosphorus. 相似文献
13.
Qingqin S. Li Antonio R. Parrado Mahesh N. Samtani Vaibhav A. Narayan Alzheimer’s Disease Neuroimaging Initiative 《PloS one》2015,10(8)
Proteolytic fragments of amyloid and post-translational modification of tau species in Cerebrospinal fluid (CSF) as well as cerebral amyloid deposition are important biomarkers for Alzheimer’s Disease. We conducted genome-wide association study to identify genetic factors influencing CSF biomarker level, cerebral amyloid deposition, and disease progression. The genome-wide association study was performed via a meta-analysis of two non-overlapping discovery sample sets to identify genetic variants other than APOE ε4 predictive of the CSF biomarker level (Aβ1–42, t-Tau, p-Tau181P, t-Tau:Aβ1–42 ratio, and p-Tau181P:Aβ1–42 ratio) in patients enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Loci passing a genome-wide significance threshold of P < 5 x 10−8 were followed-up for replication in an independent sample set. We also performed joint meta-analysis of both discovery sample sets together with the replication sample set. In the discovery phase, we identified variants in FRA10AC1 associated with CSF Aβ1–42 level passing the genome-wide significance threshold (directly genotyped SNV rs10509663 P
FE = 1.1 x 10−9, imputed SNV rs116953792 P
FE = 3.5 x 10−10), rs116953792 (P
one-sided = 0.04) achieved replication. This association became stronger in the joint meta-analysis (directly genotyped SNV rs10509663 P
FE = 1.7 x 10−9, imputed SNV rs116953792 P
FE = 7.6 x 10−11). Additionally, we identified locus 15q21 (imputed SNV rs1503351 P
FE = 4.0 x 10−8) associated with CSF Aβ1–42 level. No other variants passed the genome-wide significance threshold for other CSF biomarkers in either the discovery sample sets or joint analysis. Gene set enrichment analyses suggested that targeted genes mediated by miR-33, miR-146, and miR-193 were enriched in various GWAS analyses. This finding is particularly important because CSF biomarkers confer disease susceptibility and may be predictive of the likelihood of disease progression in Alzheimer’s Disease. 相似文献
14.
15.
Background
Early diagnosis is vital to HIV control. γδ T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described.Methods
Changes in γδ T cells, including subsets, function and activation, in treated and untreated acutely HIV-infected patients (n = 79) were compared by cytotoxicity assay and flow cytometry with healthy controls (n = 21) at month 0, 6, 12 and 18.Results
In acutely HIV-infected patients, Vδ1 cell proportion was elevated (P = 0.027) with Vδ2 population reduced (P = 0.002). Effector and central memory γδ T cell factions were decreased (P = 0.006 and P = 0.001, respectively), while proportion of terminal γδ T cells increased (P = 0.002). γδ T cell cytotoxicity was compromised over time. Fraction of IL-17-producing cells increased (P = 0.008), and IFN-γ-producing cells were unaffected (P = 0.115). Elevation of a microbial translocation marker, sCD14, was associated with γδ T cell activation (P = 0.001), which increased in a time-dependent manner, correlating with CD4/CD8 T cell activation set-points and CD4 counts. Antiretroviral therapy did not affect these changes.Conclusions
γδ T cell subpopulation and functions change significantly in acute HIV infection and over time. Early γδ T cell activation was associated with CD4/CD8 T cell activation set-points, which predict AIDS progression. Therefore, γδ T cell activation represents a potential surrogate marker of AIDS progression. 相似文献16.
Early diagnosis of Parkinson’s disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson’s Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted. 相似文献
17.
Xiaoming Yang Venkatesh L. Hegde Roshni Rao Jiajia Zhang Prakash S. Nagarkatti Mitzi Nagarkatti 《The Journal of biological chemistry》2014,289(27):18707-18718
Marijuana is one of the most abused drugs due to its psychotropic effects. Interestingly, it is also used for medicinal purposes. The main psychotropic component in marijuana, Δ9-tetrahydrocannabinol (THC), has also been shown to mediate potent anti-inflammatory properties. Whether the immunomodulatory activity of THC is mediated by epigenetic regulation has not been investigated previously. In this study, we employed ChIP-Seq technology to examine the in vivo effect of THC on global histone methylation in lymph node cells of mice immunized with a superantigen, staphylococcal enterotoxin B. We compared genome-wide histone H3 Lys-4, Lys-27, Lys-9, and Lys-36 trimethylation and histone H3 Lys-9 acetylation patterns in such cells exposed to THC or vehicle. Our results showed that THC treatment leads to the association of active histone modification signals to Th2 cytokine genes and suppressive modification signals to Th1 cytokine genes, indicating that such a mechanism may play a critical role in the THC-mediated switch from Th1 to Th2. At the global level, a significant portion of histone methylation and acetylation regions were altered by THC. However, the overall distribution of these histone methylation signals among the genomic features was not altered significantly by THC, suggesting that THC activates the expression of a subset of genes while suppressing the expression of another subset of genes through histone modification. Functional classification of these histone marker-associated genes showed that these differentially associated genes were involved in various cellular functions, from cell cycle regulation to metabolism, suggesting that THC had a pleiotropic effect on gene expression in immune cells. Altogether, the current study demonstrates for the first time that THC may modulate immune response through epigenetic regulation involving histone modifications. 相似文献
18.
Background
Magnesium is known to lower the risk of cardiovascular disease. However, studies on its relationship with hypertension, a single and common cause of various chronic diseases, are limited and their findings are not consistent. The purpose of the present study is to identify the relationship between magnesium intake and high blood pressure (HBP) risk in Koreans.Methods
This research is a cross-sectional study based on the 2007~2009 Korean National Health and Nutritional Examination Survey data. This study investigated 11,685 adults aged over 20 to examine their general characteristics, anthropometry and blood pressure. Daily magnesium intake was analyzed using the 24-hour dietary recall method. To calculate the odds ratio (OR) of HBP risk (130/85 mmHg or over) according to the quartile of magnesium intake (mg/1000kcal) together with its 95% confidence interval (CI), multivariable logistic regression analysis was performed.Results
No significant association between dietary magnesium intake and the risk of HBP was found. In obese women, particularly, after adjusting relevant factors, the adjusted odds ratio of HBP prevalence in the highest magnesium intake quartile was 0.40 compared with the lowest magnesium intake quartile (95% CI = 0.25~0.63, P for trend = 0.0014). Women, especially obese women, were found to have a negative relationship of magnesium intake with HBP.Conclusions
The present results indicate that sufficient magnesium intake could be useful in decreasing the high blood pressure risk of obese women. 相似文献19.
Thomas John Bender Matthew E. Wise Okey Utah Anne C. Moorman Umid Sharapov Jan Drobeniuc Yury Khudyakov Marielle Fricchione Mary Beth White-Comstock Nicola D. Thompson Priti R. Patel 《PloS one》2012,7(12)