Polimorfizm rs10830963 w genie receptora melatoniny 1B a cukrzyca ciążowa w populacji chińskiej — metaanaliza badań

Introduction: Studies have been conducted to investigate the association between rs10830963 of MTNR1B and the risk of gestational diabetes mellitus (GDM), but with inconclusive results. We aimed to clarify these controversies, especially with regard to the association in the Chinese population. Material and methods: A systemic literature reference search inclusive to August 12, 2016 yielded 35 articles, from which 11 studies met the inclusion criteria for the final meta-analysis, including 3889 patients with GDM and 6708 controls. Results: We found statistically significant associations between rs10830963 and GDM using odds ratios (ORs) and 95% confidence intervals (CIs) [GG genotype vs. CC genotype: OR = 1.70, 95% CI: 1.38–2.10; G allele vs C allele: OR = 1.27, 95% CI: 1.20–1.36; GG+CG vs. CC (dominant model): OR = 1.31, 95% CI: 1.20–1.44; GG vs CG+CC (recessive model): OR = 1.41, 95% CI: 1.26–1.58]. In subgroup analyses stratified by ethnicity, we also observed rs10830963 to be associated with significantly increased risk of GDM in all genetic models in the Chinese population. Conclusions: Our meta-analysis indicated that the rs10830963 polymorphism might serve as a risk factor of GDM in the Chinese population.Wstęp: Wyniki dotychczas badań przeprowadzonych w celu ustalenia związku między polimorfizmem rs10830963 w genie MTNR1B a ryzykiem cukrzycy ciążowej (gestational diabetes mellitus, GDM) nie pozwoliły na sformułowanie jednoznacznych wniosków. Niniejsze badanie przeprowadzono w celu wyjaśnienia tych kontrowersji, zwłaszcza w odniesieniu do występowania tych związków w populacji chińskiej. Materiał i metody: W wyniku przeszukania w sposób systematyczny piśmiennictwa obejmującego okres do 12 sierpnia 2016 roku wytypowano 35 artykułów, spośród których 11 badań spełniało kryteria włączenia do metaanalizy. Obejmowały one 3889 chorych z GDM i 6708 osób kontrolnych. Wyniki: Autorzy stwierdzili statystycznie istotny związek między polimorfizmem rs10830963 a GDM, obliczając ilorazy szans (odds ratio, OR) i 95-procentowe przedziały ufności (confidence interval, CI) [genotyp GG vs. genotyp CC: OR = 1,70; 95% CI: 1,38–2,10; allel G vs. allel C: OR = 1,27; 95% CI: 1,20–1,36; GG+CG vs CC (model dominujący): OR = 1,31; 95% CI: 1,20–1,44; GG vs. CG+CC (model recesywny): OR = 1,41; 95% CI: 1,26–1,58]. W analizach podgrup wydzielonych na podstawie pochodzenia etnicznego również stwierdzono, że polimorfizm rs10830963 wiąże się z istotnie wyższym ryzykiem GDM we wszystkich modelach genetycznych w populacji chińskiej. Wnioski: Przeprowadzona przez autorów metaanaliza wskazuje, że polimorfizm rs10830963 może być uważany za czynnik ryzyka GDM w populacji chińskiej

Control of Cotton Fibre Elongation by a Homeodomain Transcription Factor GhHOX3

Cotton fibres are unusually long, single-celled epidermal seed trichomes and a model for plant cell growth, but little is known about the regulation of fibre cell elongation. Here we report that a homeodomain-leucine zipper (HD-ZIP) transcription factor, GhHOX3, controls cotton fibre elongation. GhHOX3 genes are localized to the 12th homoeologous chromosome set of allotetraploid cotton cultivars, associated with quantitative trait loci (QTLs) for fibre length. Silencing of GhHOX3 greatly reduces (\u3e80%) fibre length, whereas its overexpression leads to longer fibre. Combined transcriptomic and biochemical analyses identify target genes of GhHOX3 that also contain the L1-box cis-element, including two cell wall loosening protein genes GhRDL1 and GhEXPA1. GhHOX3 interacts with GhHD1, another homeodomain protein, resulting in enhanced transcriptional activity, and with cotton DELLA, GhSLR1, repressor of the growth hormone gibberellin (GA). GhSLR1 interferes with the GhHOX3–GhHD1 interaction and represses target gene transcription. Our results uncover a novel mechanism whereby a homeodomain protein transduces GA signal to promote fibre cell elongation

Single crystal of a one-dimensional metallo-covalent organic framework.

Although polymers have been studied for well over a century, there are few examples of covalently linked polymer crystals synthesised directly from solution. One-dimensional (1D) covalent polymers that are packed into a framework structure can be viewed as a 1D covalent organic framework (COF), but making a single crystal of this has been elusive. Herein, by combining labile metal coordination and dynamic covalent chemistry, we discover a strategy to synthesise single-crystal metallo-COFs under solvothermal conditions. The single-crystal structure is rigorously solved using single-crystal electron diffraction technique. The non-centrosymmetric metallo-COF allows second harmonic generation. Due to the presence of syntactic pendant amine groups along the polymer chains, the metallopolymer crystal can be further cross-linked into a crystalline woven network

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer's Disease

Protein phosphatase 2A (PP2A) inhibition causes hyperphosphorylation of tau and APP in Alzheimer's disease (AD). However, the mechanisms underlying the downregulation of PP2A activity in AD brain remain unclear. We demonstrate that Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is overexpressed in AD brain. CIP2A-mediated PP2A inhibition drives tau/APP hyperphosphorylation and increases APP beta-cleavage and A beta production. Increase in CIP2A expression also leads to tau mislocalization to dendrites and spines and synaptic degeneration. In mice, injection of AAV-CIP2A to hippocampus induced AD-like cognitive deficits and impairments in long-term potentiation (LTP) and exacerbated AD pathologies in neurons. Indicative of disease exacerbating the feedback loop, we found that increased CIP2A expression and PP2A inhibition in AD brains result from increased A beta production. In summary, we show that CIP2A overexpression causes PP2A inhibition and AD-related cellular pathology and cognitive deficits, pointing to CIP2A as a potential target for AD therapy

Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma

BACKGROUND: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants