Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.

A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations

An effective gauge-Higgs operators analysis of new physics associated with the Higgs

We study the new physics(NP) related to the recent discovered 125 GeV Higgs by employing an important subset of the standard model(SM) gauge invariant dimension-six operators constructed by the the SM Higgs and gauge fields. Explicitly, we perform a model-independent study on the production and decays of the Higgs, the electric dipole moments(EDM) of the neutron and the electron, and we take into account the anomalous magnetic dipole moments of muon and electron as well. We find that, even all Higgs decay channels agree with the SM predictions, the SM theoretical uncertainties provide a lot of room to host NP associated with the 125 GeV boson. A linear relation is revealed in our numerical study that $\mu_{ZZ}\simeq \mu_{WW}$ and $0.6 \lesssim \mu_{ZZ,WW} \lesssim 1.4$ at 95% CL with or without the EDM's constraints. The neutron and electron EDM's severely constrain the relevant Wilson coefficients. Therefore the CP violating components in the $h\rightarrow WW, ZZ$ channels are too small, $\sim{\cal O}(10^{-5})$, to be detected at LHC. However, we point out that even the parity of the 125GeV boson has been largely determined to be even in the $h\to ZZ$ channel, one should pay special attention to the potentially large CP violation in the $h\to \gamma\gamma$ and $h\to \gamma Z$ channels. This should be seriously checked in the future spin correlation experiments.Comment: 32 pages, 11 figures; UV complete model section revised, typos corrected, and refernces adde

DC-SIGN promotes Japanese encephalitis virus transmission from dendritic cells to T cells via virological synapses.

Skin-resident dendritic cells (DCs) likely encounter incoming viruses in the first place, and their migration to lymph nodes following virus capture may promote viral replication. However, the molecular mechanisms underlying these processes remain unclear. In the present study, we found that compared to cell-free viruses, DC-bound viruses showed enhanced capture of JEV by T cells. Additionally, JEV infection was increased by co-culturing DCs and T cells. Blocking the C-type lectin receptor DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) with neutralizing antibodies or antagonists blocked JEV transmission to T cells. Live-cell imaging revealed that DCs captured and transferred JEV viral particles to T cells via virological synapses formed at DC-T cell junctions. These findings indicate that DC-SIGN plays an important role in JEV transmission from DCs to T cells and provide insight into how JEV exploits the migratory and antigen-presenting capabilities of DCs to gain access to lymph nodes for dissemination and persistence in the host

NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants

Salicylic acid (SA) is a plant immune signal produced upon pathogen challenge to induce systemic acquired resistance (SAR). It is the only major plant hormone for which the receptor has not been firmly identified. SAR in Arabidopsis requires the transcription cofactor NPR1 (nonexpresser of PR genes 1), whose degradation serves as a molecular switch for SAR. Here we show that NPR1 paralogues, NPR3 and NPR4, are SA receptors that bind SA with different affinities and function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the npr3 npr4 mutant accumulates higher levels of NPR1 and is insensitive to SAR induction. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge

Microsatellite discovery in an insular amphibian (Grandisonia alternans) with comments on cross-species utility and the accuracy of locus identification from unassembled Illumina data

The Seychelles archipelago is unique among isolated oceanic islands because it features an endemic radiation of caecilian amphibians (Gymnophiona). In order to develop population genetics resources for this system, we identified microsatellite loci using unassembled Illumina MiSeq data generated from a genomic library of Grandisonia alternans, a species that occurs on multiple islands in the archipelago. Applying a recently described method (PALFINDER) we identified 8001 microsatellite loci that were potentially informative for population genetics analyses. Of these markers, we screened 60 loci using five individuals, directly sequenced several amplicons to confirm their identity, and then used eight loci to score allele sizes in 64 G. alternans individuals originating from five islands. A number of these individuals were sampled using non-lethal methods, demonstrating the efficacy of non-destructive molecular sampling in amphibian research. Although two loci satisfied our criteria as diploid, neutrally evolving loci with the statistical power to detect population structure, our success in identifying reliable loci was very low. Additionally, we discovered some issues with primer redundancy and differences between Illumina and Sanger sequences that suggest some Illumina-inferred loci are invalid. We investigated cross-species utility for eight loci and found most could be successfully amplified, sequenced and aligned across other species and genera of caecilians from the Seychelles. Thus, our study in part supported the validity of using PALFINDER with unassembled reads for microsatellite discovery within and across species, but importantly identified major limitations to applying this approach to small datasets (ca. 1 million reads) and loci with small tandem repeat sizes

Unique electronic and optical properties of stacking-modulated bilayer graphene under external magnetic fields

This study delves into the magneto-electronic and magneto-optical properties of stacking-modulated bilayer graphene. By manipulating domain walls (DWs) across AB-BA domains periodically, we unveil oscillatory Landau subbands and the associated optical excitations. The DWs act as periodic potentials, yielding fascinating 1D spectral features. Our exploration reveals 1D phenomena localized to Bernal stacking, DW regions, and stacking boundaries, highlighting the intriguing formation of Landau state quantization influenced by the commensuration between the magnetic length and the system. The stable quantized localization within different regions leads to the emergence of unconventional quantized subbands. This study provides valuable insights into the essential properties of stacking-modulated bilayer graphene.Comment: 31 pages, 7 figures, 43 conference