OSMRβ mutants enhance basal keratinocyte differentiation via inactivation of the STAT5/KLF7 axis in PLCA patients

Dear Editor, Primary localized cutaneous amyloidosis (PLCA) is a skin-limited disorder characterized by deposition of amyloid material in the superficial dermis.According to clinical characteristics,PLCA is divided into lichen,macular,and nodular amyloidosis.PLCA is found worldwide but has a higher incidence in South America and Southeast Asia,such as in Brazil and China (Chang et al.,2014;Tey et al.,2016).     

Prediction of Drug-Target Interactions for Drug Repositioning Only Based on Genomic Expression Similarity

Small drug molecules usually bind to multiple protein targets or even unintended off-targets. Such drug promiscuity has often led to unwanted or unexplained drug reactions, resulting in side effects or drug repositioning opportunities. So it is always an important issue in pharmacology to identify potential drug-target interactions (DTI). However, DTI discovery by experiment remains a challenging task, due to high expense of time and resources. Many computational methods are therefore developed to predict DTI with high throughput biological and clinical data. Here, we initiatively demonstrate that the on-target and off-target effects could be characterized by drug-induced in vitro genomic expression changes, e.g. the data in Connectivity Map (CMap). Thus, unknown ligands of a certain target can be found from the compounds showing high gene-expression similarity to the known ligands. Then to clarify the detailed practice of CMap based DTI prediction, we objectively evaluate how well each target is characterized by CMap. The results suggest that (1) some targets are better characterized than others, so the prediction models specific to these well characterized targets would be more accurate and reliable; (2) in some cases, a family of ligands for the same target tend to interact with common off-targets, which may help increase the efficiency of DTI discovery and explain the mechanisms of complicated drug actions. In the present study, CMap expression similarity is proposed as a novel indicator of drug-target interactions. The detailed strategies of improving data quality by decreasing the batch effect and building prediction models are also effectively established. We believe the success in CMap can be further translated into other public and commercial data of genomic expression, thus increasing research productivity towards valid drug repositioning and minimal side effects.     

Chromosome‐level reference genome of X12, a highly virulent race of the soybean cyst nematode Heterodera glycines

Soybean cyst nematode (SCN, Heterodera glycines) is a major pest of soybean that is spreading across major soybean production regions worldwide. Increased SCN virulence has recently been observed in both the United States and China. However, no study has reported a genome assembly for H. glycines at the chromosome scale. Herein, the first chromosome‐level reference genome of X12, an unusual SCN race with high infection ability, is presented. Using whole‐genome shotgun (WGS) sequencing, Pacific Biosciences (PacBio) sequencing, Illumina paired‐end sequencing, 10X Genomics linked reads and high‐throughput chromatin conformation capture (Hi‐C) genome scaffolding techniques, a 141.01‐megabase (Mb) assembled genome was obtained with scaffold and contig N50 sizes of 16.27 Mb and 330.54 kilobases (kb), respectively. The assembly showed high integrity and quality, with over 90% of Illumina reads mapped to the genome. The assembly quality was evaluated using Core Eukaryotic Genes Mapping Approach and Benchmarking Universal Single‐Copy Orthologs. A total of 11,882 genes were predicted using de novo, homolog and RNAseq data generated from eggs, second‐stage juveniles (J2), third‐stage juveniles (J3) and fourth‐stage juveniles (J4) of X12, and 79.0% of homologous sequences were annotated in the genome. These high‐quality X12 genome data will provide valuable resources for research in a broad range of areas, including fundamental nematode biology, SCN–plant interactions and co‐evolution, and also contribute to the development of technology for overall SCN management.     

Fruit and vegetable consumption,cardiovascular disease,and all-cause mortality in China

Science China Life Sciences - Evidence about the response patterns of fruit and vegetable consumption with the risk of cardiovascular disease (CVD) and all-cause mortality was inconsistent. These...     

纳豆激酶的研究与应用

纳豆激酶是一种枯草芽孢杆菌产生的丝氨酸蛋白酶 ,具有强烈的纤溶活性 ,有望开发成为新型口服溶栓药。综述了纳豆激酶的生化特性、生物学活性、结构与功能及开发应用前景等。     

绝经对血液单核细胞基因表达谱的影响:基因芯片初步研究

绝经是女性一生中很重要的生理现象之一,它能增加一系列复杂免疫、神经退化、新陈代谢和心血管方面的疾病。血液单核细胞能分化成各种各样的细胞,这些细胞在组织形态发生和免疫应答方面起着很重要的作用。本研究中采用了包含大约14,500个基因探针的Affymetrix Human U133A基因芯片来研究健康的绝经前和绝经后女性外周血液单核细胞中的基因表达谱。样本之间的对比分析表明有20个基因上调,20个基因下调。其中的28个基因根据它们的生物过程如细胞繁殖、免疫应答、细胞代谢等等被分成了6个主要的GO类别;剩下的12个基因其生物学功能还没有被鉴定。研究结果支持了我们的假设:血液单核细胞的功能状态确实受到绝经的影响,而且由此带来的改变可能是由全基因组范围的基因表达谱而决定的。本研究中鉴定的一些差异表达基因有可能作为以后研究与绝经相关的系统免疫、神经退化和心血管疾病的候选基因研究。此工作是这个研究方向的第一次尝试,为将来的进一步研究奠定了基础。     

Roles of Apolipoprotein E (ApoE) and Inducible Nitric Oxide Synthase (iNOS) in Inflammation and Apoptosis in Preeclampsia Pathogenesis and Progression

Objectives

To investigate potential roles of inducible nitric oxide synthase (iNOS) and apolipoprotein (apoE) in inflammation and apoptosis promoting pathological changes in preeclampsia in pregnant mice with apoE and/or iNOS knock out.

Methods

B6.129 mice were crossed to produce WT, apoE^−/−, apoE^+/−, iNOS^−/−, iNOS^+/− and apoE^−/−iNOS^−/− groups. Variants were confirmed by PCR. Serum lipid parameters (triglycerides, TG; total cholesterol, TC; high density lipoprotein, HDL; and low density lipoprotein, LDL), NO levels and placental electronic microscopic ultrastructures were evaluated, and blood pressure (BP), 24-hour urine protein and pregnancy outcomes were recorded for pregnant F1 generation mice. Placental expressions of inflammatory (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; nuclear factor-κB, NF-κb) and apoptotic markers (Bcl-2 associated X protein, Bax, B-cell lymphoma/leukemia-2, Bcl-2, and Caspase-3) were evaluated via Western blot.

Results

Serum lipids, BP and 24-hour urine protein levels were shown to be significantly higher and parturition and placenta weights were lower in apoE^−/− and apoE^−/−iNOS^−/− groups (p<0.05). NO levels were lower in the apoE^−/−iNOS^−/− group. In addition, inflammatory/apoptosis parameters, including TNF-α, IL-6, NF-κb, Bax, Bcl-2 and Caspase-3 in the apoE^−/−iNOS^−/− group (p<0.01), as well as in the apoE^−/− group (p<0.05), and NF-κB, Bax in iNOS^−/− group (p<0.05) were higher compared with WT group. However, most of the inflammatory/apoptosis parameters in the iNOS^+/− and the apoE^+/− groups (p>0.05) showed no differences. In addition, placenta vascular endothelial and trophoblast cell morphological changes were demonstrated in both the apoE^−/−iNOS^−/− and apoE^−/− groups.

Conclusion

Elevated lipid metabolism and inflammatory/apoptosis parameters suggest a potentially significant role of apoE in preeclampsia pathology, as well as a relationship between iNOS and preeclampsia progression.