Disruption of Vitamin D and Calcium Signaling in Keratinocytes Predisposes to Skin Cancer.

1,25 dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, and calcium regulate epidermal differentiation. 1,25(OH)2D exerts its effects through the vitamin D receptor (VDR), a transcription factor in the nuclear hormone receptor family, whereas calcium acts through the calcium sensing receptor (Casr), a membrane bound member of the G protein coupled receptor family. We have developed mouse models in which the Vdr and Casr have been deleted in the epidermis ((epid) Vdr (-∕-) and (epid) Casr (-∕-)). Both genotypes show abnormalities in calcium induced epidermal differentiation in vivo and in vitro, associated with altered hedgehog (HH) and β-catenin signaling that when abnormally expressed lead to basal cell carcinomas (BCC) and trichofolliculomas, respectively. The Vdr (-∕-) mice are susceptible to tumor formation following UVB or chemical carcinogen exposure. More recently we found that the keratinocytes from these mice over express long non-coding RNA (lncRNA) oncogenes such as H19 and under express lncRNA tumor suppressors such as lincRNA-21. Spontaneous tumors have not been observed in either the (epid) Vdr (-∕-) or (epid) Casr (-∕-). But in mice with epidermal specific deletion of both Vdr and Casr ((epid) Vdr (-∕-)/(epid) Casr (-∕-) [DKO]) tumor formation occurs spontaneously when the DKO mice are placed on a low calcium diet. These results demonstrate important interactions between vitamin D and calcium signaling through their respective receptors that lead to cancer when these signals are disrupted. The roles of the β-catenin, hedgehog, and lncRNA pathways in predisposing the epidermis to tumor formation when vitamin D and calcium signaling are disrupted will be discussed

On the zeros of solutions of any order of derivative of second order linear differential equations taking small functions

In this paper, we investigate the hyper-exponent of convergence of zeros of $f^{(j)}(z)-\varphi(z) (j\in N)$, where $f$ is a solution of second or $k(\geq2)$ order linear differential equation, $\varphi(z)\not\equiv0$ is an entire function satisfying $\sigma(\varphi)<\sigma(f)$ or $\sigma_{2}(\varphi)<\sigma_{2}(f)$. We obtain some precise results which improve the previous results in [3, 5] and revise the previous results in [11, 13]. More importantly, these results also provide us a method to investigate the hyper-exponent of convergence of zeros of $f^{(j)}(z)-\varphi(z)(j\in N)$

Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Stroke among Patients with Hypertension

Background: Dysregulations ofAQP7andAQP9were found to be related to lipid metabolism abnormality, which had been provento be one of the mechanisms of stroke. However, limited epidemiological studies explore the associations betweenAQP7andAQP9and the risk of stroke among patients with hypertension in China. Aims: We aimed to investigate the associations between genetic variants in AQP7andAQP9and the risk of stroke among patients with hypertension, as well as to explore gene-gene andgene-environment interactions. Methods: Baseline blood samples were drawn from 211 cases with stroke and 633 matched controls. Genomic DNA was extracted by a commercially available kit. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs2542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes. Results: Participants with the rs2989924 GG genotype were found to be with a 1.74-fold increased risk of stroke compared to those with the AA+AG genotype, and this association remained significant after adjustment for potential confounders (odds ratio (OR): 1.74, 95% confidence interval (CI): 1.23-2.46). The SNP rs3758269 CC+TT genotype was found to be with a 33% decreased risk of stroke after multivariate adjustment (OR: 0.67, 95% CI: 0.45-0.99) compared to the rs3758269 CC genotype. The significantly increased risk of stroke was prominent among males, patients aged 60 or above, and participants who were overweight and with a harbored genetic variant in SNP rs2989924. After adjusting potential confounders, the SNP rs3758269 CT+TT genotype was found to be significantly associated with a decreased risk of stroke compared to the CC genotype among participants younger than 60 years old or overweight. No statistically significant associations were observed between genotypes of rs2542743, rs57139208, or rs16939881 with the risk of stroke. Neither interactions nor linkage disequilibrium had been observed in this study. Conclusions: This study suggests that SNPs rs2989924 and rs3758269 are associated with the risk of stroke among patients with hypertension, while there were no statistically significant associations between rs2542743, rs57139208, and rs16939881 and the risk of stroke being observed

Self-absorption in the solar transition region

Transient brightenings in the transition region of the Sun have been studied for decades and are usually related to magnetic reconnection. Recently, absorption features due to chromospheric lines have been identified in transition region emission lines raising the question of the thermal stratification during such reconnection events. We analyse data from the Interface Region Imaging Spectrograph (IRIS) in an emerging active region. Here the spectral profiles show clear self-absorption features in the transition region lines of Si\,{\sc{iv}}. While some indications existed that opacity effects might play some role in strong transition region lines, self-absorption has not been observed before. We show why previous instruments could not observe such self-absorption features, and discuss some implications of this observation for the corresponding structure of reconnection events in the atmosphere. Based on this we speculate that a range of phenomena, such as explosive events, blinkers or Ellerman bombs, are just different aspects of the same reconnection event occurring at different heights in the atmosphere.Comment: Accepted for publication in Ap

Antiviral treatment alters the frequency of activating and inhibitory receptor-expressing natural killer cells in chronic Hepatitis B virus infected patients

Natural killer (NK) cells play a critical role in innate antiviral immunity, but little is known about the impact of antiviral therapy on the frequency of NK cell subsets. To this aim, we performed this longitudinal study to examine the dynamic changes of the frequency of different subsets of NK cells in CHB patients after initiation of tenofovir or adefovir therapy. We found that NK cell numbers and subset distribution differ between CHB patients and normal subjects; furthermore, the association was found between ALT level and CD158b+ NK cell in HBV patients. In tenofovir group, the frequency of NK cells increased during the treatment accompanied by downregulated expression of NKG2A and KIR2DL3. In adefovir group, NK cell numbers did not differ during the treatment, but also accompanied by downregulated expression of NKG2A and KIR2DL3. Our results demonstrate that treatment with tenofovir leads to viral load reduction, and correlated with NK cell frequencies in peripheral blood of chronic hepatitis B virus infection. In addition, treatments with both tenofovir and adefovir in chronic HBV infected patients induce a decrease of the frequency of inhibitory receptor+ NK cells, which may account for the partial restoration of the function of NK cells in peripheral blood following treatment