| 1. |
- Aartsen, M. G., et al.
(författare)
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Multiwavelength follow-up of a rare IceCube neutrino multiplet
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 607
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Tidskriftsartikel (refereegranskat)abstract
- On February 17, 2016, the IceCube real-time neutrino search identified, for the first time, three muon neutrino candidates arriving within 100 s of one another, consistent with coming from the same point in the sky. Such a triplet is expected once every 13.7 years as a random coincidence of background events. However, considering the lifetime of the follow-up program the probability of detecting at least one triplet from atmospheric background is 32%. Follow-up observatories were notified in order to search for an electromagnetic counterpart. Observations were obtained by Swift's X-ray telescope, by ASAS-SN, LCO and MASTER at optical wavelengths, and by VERITAS in the very-high-energy gamma-ray regime. Moreover, the Swift BAT serendipitously observed the location 100 s after the first neutrino was detected, and data from the Fermi LAT and HAWC observatory were analyzed. We present details of the neutrino triplet and the follow-up observations. No likely electromagnetic counterpart was detected, and we discuss the implications of these constraints on candidate neutrino sources such as gamma-ray bursts, core-collapse supernovae and active galactic nucleus flares. This study illustrates the potential of and challenges for future follow-up campaigns.
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| 2. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 3. |
- Song, Fei, et al.
(författare)
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The prevalence and determinants of hypothyroidism in hospitalized patients with type 2 diabetes mellitus
- 2017
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 55:1, s. 188-194
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the prevalence of hypothyroidism among hospitalized patients with type 2 diabetes mellitus and its related factors, and to assess the prevalence of macrovascular and microvascular diseases among type 2 diabetes mellitus inpatients with hypothyroidism and euthyroidism. A total of 1662 type 2 diabetes mellitus inpatients hospitalized at the Metabolic Diseases Hospital, Tianjin Medical University from 1 January 2008 to 1 March 2013 were included in this study. Information on demographic and anthropometric factors and additional variables related to hypothyroidism were collected from medical records. Prevalence rates were calculated and standardized using direct method based on the age-specific and sex-specific structure of all participants. Data were analyzed using binary logistic regression with adjustment for potential confounders. The prevalence of hypothyroidism among type 2 diabetes mellitus inpatients was 6.8 %, and 77.0% of the patients with hypothyroidism had subclinical hypothyroidism. The prevalence of hypothyroidism increased with age, and was higher in women (10.8 %) than in men (3.4 %). Older age (odds ratio, 1.74; 95% confidence interval, 1. 05 to 2.89), female gender (odds ratio, 2.02; 95% confidence interval, 1.05 to 3.87), and positive thyroid peroxidase antibody (odds ratio, 4.99; 95% confidence interval, 2.83 to 8.79) were associated with higher odds of hypothyroidism among type 2 diabetes mellitus inpatients. The type 2 diabetes mellitus inpatients with hypothyroidism had higher prevalence of cerebrovascular diseases than those with euthyroidism after adjustment for age and gender. The prevalence of hypothyroidism among type 2 diabetes mellitus inpatients was 6.8 %, and most patients had subclinical hypothyroidism. Older age, female gender, and positive thyroid peroxidase antibody could be indicators for detecting hypothyroidism in type 2 diabetes mellitus inpatients.
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| 4. |
- Wheeler, Eleanor, et al.
(författare)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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| 5. |
- Zhang, Hua, et al.
(författare)
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Relation of socioeconomic status to overweight and obesity : a large population-based study of Chinese adults
- 2017
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Ingår i: Annals of Human Biology. - : Informa UK Limited. - 0301-4460 .- 1464-5033. ; 44:6, s. 495-501
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Tidskriftsartikel (refereegranskat)abstract
- Background: China has been going through significant changes in social and economical aspects and with great socioeconomic disparity in different regions. However, data on the association between socioeconomic status (SES) and obesity are not available in Tianjin, China.Aim: This study aimed to investigate the association between SES and high adiposity among the adult population in Tianjin.Subjects and methods: A total of 7351 individuals aged 20-79 were included in this study. Socioeconomic information was collected through an interview following a structured questionnaire. Waist circumference, body weight and height were measured following standard procedures. Overweight and obesity were defined according to the criteria of the Working Group on Obesity in China. Data were analysed using multinomial logistic regression with adjustment for potential confounders.Results: Stratified analysis showed that higher monthly income and education were related to decreased odds of abdominal overweight/ obesity in women, while high education was associated with increased odds of general overweight/obesity in men. Retirement increased the odds of abdominal overweight and obesity and non-manual work was associated with low odds of abdominal obesity in women.Conclusions: SES was associated with general and abdominal overweight/obesity and sex may play a role in such an association.
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| 6. |
- Bergström, Joakim, et al.
(författare)
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Epitope-Specific Suppression of IgG Responses by Passively Administered Specific IgG : Evidence of Epitope Masking
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Specific IgG, passively administered together with particulate antigen, can completely prevent induction of antibody responses to this antigen. The ability of IgG to suppress antibody responses to sheep red blood cells (SRBCs) is intact in mice lacking Fc gamma Rs, complement factor 1q, C3, or complement receptors 1 and 2, suggesting that Fc-dependent effector functions are not involved. Two of the most widely discussed explanations for the suppressive effect are increased clearance of IgG-antigen complexes and/or that IgG "hides" the antigen from recognition by specific B cells, so-called epitope masking. The majority of data on how IgG induces suppression was obtained through studies of the effects on IgM-secreting single spleen cells during the first week after immunization. Here, we show that IgG also suppresses antigen-specific extrafollicular antibody-secreting cells, germinal center B-cells, longlived plasma cells, long-term IgG responses, and induction of memory antibody responses. IgG anti-SRBC reduced the amount of SRBC in the spleens of wild-type, but not of Fc gamma R-deficient mice. However, no correlation between suppression and the amount of SRBC in the spleen was observed, suggesting that increased clearance does not explain IgG-mediated suppression. Instead, we found compelling evidence for epitope masking because IgG anti-NP administered with NP-SRBC suppressed the IgG anti-NP, but not the IgG anti-SRBC response. Vice versa, IgG anti-SRBC administered with NP-SRBC, suppressed only the IgG anti-SRBC response. In conclusion, passively transferred IgG suppressed all measured parameters of an antigen-specific antibody/B cell response and an important mechanism of action is likely to be epitope masking.
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| 7. |
- Pan, K-Y., et al.
(författare)
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Work-related psychosocial stress and the risk of type 2 diabetes in later life
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:6, s. 601-610
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Although work-related psychosocial stress and type 2 diabetes mellitus (T2DM) have been investigated, the association between lifelong work stress and T2DM in later life remains unclear. This study examined whether high work stress increased the risk of T2DM risk in later life, accounting also for other sources of stress outside work, such as burden from household chores.Methods: From the population-based prospective study SNAC-K, 2719 diabetes-free participants aged 60 years were identified and followed up for 6 years. T2DM was ascertained by glycated haemoglobin level, self-report, hypoglycaemic medication use and clinical records. Levels of job control and demands over the whole working life were assessed by a validated matrix. Household chores load was assessed by hours spent on such chores. Multivariate logistic regression models were used to estimate the association between job strain and T2DM.Results: During the 6-year follow-up, 154 incident cases of T2DM were identified. High job strain was associated with T2DM occurrence amongst the 60-year-old cohort (OR = 3.14, 95% CI: 1.27-7.77), and only amongst women (OR = 6.18, 95% CI: 1.22-31.26), but not in men. When taking into account household chores load, a more pronounced risk of T2DM was associated with high job strain in combination with heavy household chores load in women aged 60 years at baseline (OR = 9.45, 95% CI: 1.17-76.53).Conclusion: Work-related psychosocial stress may increase the risk of T2DM only amongst women in their early 60s. The risk can be amplified by high household chores load.
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| 8. |
- Sun, Xu, et al.
(författare)
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Elevated heparanase expression is associated with poor prognosis in breast cancer : a study based on systematic review and TCGA data
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:26, s. 43521-43535
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Forskningsöversikt (refereegranskat)abstract
- Heparanase promotes tumorigenesis, angiogenesis, and metastasis. Here, we conducted a study based on systematic review and the Cancer Genome Atlas (TCGA) data that examined heparanase expression in clinical samples to determine its prognostic value. According to the meta-analysis and TCGA data, we found that heparanase expression was up-regulated in most breast cancer specimens, and elevated heparanase expression was associated with increased lymph node metastasis, larger tumor size, higher histological grade, and poor survival. These results suggest that targeting heparanase might improve treatments for breast cancer patients.
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| 9. |
- Wang, Xunying, et al.
(författare)
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La0.1SrxCa0.9-xMnO3-δ -Sm0.2Ce0.8O1.9 composite material for novel low temperature solid oxide fuel cells
- 2017
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Ingår i: International journal of hydrogen energy. - : Elsevier. - 0360-3199 .- 1879-3487. ; 42:27, s. 17552-17558
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Tidskriftsartikel (refereegranskat)abstract
- Lowering the operating temperature of the solid oxide fuel cells (SOFCs) is one of the world R&D tendencies. Exploring novel electrolytes possessing high ionic conductivity at low temperature becomes extremely important with the increasing demands of the energy conversion technologies. In this work, perovskite La0.1SrxCa0.9-xMnO3-δ (LSCM) materials were synthesized and composited with the ionic conductor Sm0.2Ce0.8O1.9 (SDC). The LSCM-SDC composite was sandwiched between two nickel foams coated with semiconductorNi0.8Co0.15Al0.05LiO2- δ (NCAL) to form the fuel cell device. The strontium content in theLSCM and the ratios of LSCM to SDC in the LSCM-SDC composite have significant effects on the electrical properties and fuel cell performances. The best performance has been achieved from LSCM-SDC composite with a weight ratio of 2:3. The fuel cells showed OCV over 1.0 V and excellent maximum output power density of 800 mW/cm2 at 550 ºC. Device processes and ionic transport processes were also discussed.
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| 10. |
- Wu, Cheng-Guo, et al.
(författare)
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PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis
- 2017
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Ingår i: Cell Discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase; it forms diverse heterotrimeric holoenzymes that counteract kinase actions. Using a peptidome that tiles the disordered regions of the human proteome, we identified proteins containing [LMFI]xx[ILV]xEx motifs that serve as interaction sites for B'-family PP2A regulatory subunits and holoenzymes. The B'-binding motifs have important roles in substrate recognition and in competitive inhibition of substrate binding. With more than 100 novel ligands identified, we confirmed that the recently identified LxxIxEx B'α-binding motifs serve as common binding sites for B' subunits with minor variations, and that S/T phosphorylation or D/E residues at positions 2, 7, 8 and 9 of the motifs reinforce interactions. Hundreds of proteins in the human proteome harbor intrinsic or phosphorylation-responsive B'-interaction motifs, and localize at distinct cellular organelles, such as midbody, predicting kinase-facilitated recruitment of PP2A-B' holoenzymes for tight spatiotemporal control of phosphorylation at mitosis and cytokinesis. Moroever, Polo-like kinase 1-mediated phosphorylation of Cyk4/RACGAP1, a centralspindlin component at the midbody, facilitates binding of both RhoA guanine nucleotide exchange factor (epithelial cell transforming sequence 2 (Ect2)) and PP2A-B' that in turn dephosphorylates Cyk4 and disrupts Ect2 binding. This feedback signaling loop precisely controls RhoA activation and specifies a restricted region for cleavage furrow ingression. Our results provide a framework for further investigation of diverse signaling circuits formed by PP2A-B' holoenzymes in various cellular processes.
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