使用DNA微阵列分析研究系统性血管炎潜在的基因靶点

本研究旨在确定系统性血管炎中关键基因,从而获得新的潜在的基因靶向位点来治疗系统性血管炎。从Gene Expression Omnibus数据库中下载了GSE16945的双色cDNA微阵列数据,由来自13名系统性血管炎患者和16名健康对照组成员的外周单核细胞标本组成。通过BRB Array Tools,在系统性血管炎中筛选差异表达基因(DEG),随后使用cluster Profiler包构建蛋白质-蛋白质相互作用(PPI)网络以及选择显著功能相互作用(FI)模块。此外,预测了确定的DEG之间的转录因子(TF),并构建了转录调控网络。鉴定了总共173个上调基因和93个下调的基因,主要与免疫应答途径相关。FBJ小鼠骨肉瘤病毒基因同源物(FOS),泛素B(UBB),信号转导和转录激活因子1(STAT1)和MX dynamin样GTPase 1(MX1)在PPI网络中被鉴定为中枢蛋白。此外,UBB、FOS和STAT1分别是三个确定的FI模块中的中枢蛋白。在DEGs中总共预测了9个转录因子。在预测为转录因子的DEG中,鉴定了相互作用的STAT1,v-maf禽类肌肉痉挛性纤维肉瘤癌基因同源物B(MAFB)和酪氨酸3-单加氧酶/色氨酸5-单加氧酶活化蛋白Z(YWHAZ),这些转录因子作为靶点进一步调节其他DEGs。包括FOS、UBB、MX1、STAT1、MAFB和YWHAZ在内的各种基因可能是用于治疗系统性血管炎的潜在靶标。

Identification of Prosaposin as a Novel Interaction Partner for Rhox5

Prosaposin （Psap） has multiple cellular functions. It is involved in the development of the reproductive system, nervous system, and prostate cancer as well as in the regulation of sphingolipid catabolism by activating several lysosomal hydrolases involved in the metabolism of various sphingolipids. In this research, it was found to be a novel interaction partner for Rhox5 using yeast two-hybrid screening. The interaction between Rhox5 and the full-length prosapsoin （the transcript without exon 8） as well as the C-terminal domain of prosaposin, was further confirmed in both yeast two hybrid analysis and in vitro assay. It suggested that the C-terminal domain of prosaposin may be critical for the Rhox5-prosaposin interaction. Given the important roles played by both Rhox5 and prosaposin in maintaining the differentiation of male reproductive organs, spermatogenesis, and fertilization, the interaction between Rhox5 and prosaposin might regulate the development of male reproductive organs dynamically.

Theoretical Studies on Interaction Between Methanol and Functionalized Single-Walled Carbon Nanotubes

We study the adsorption of a methanol molecule on single-walled carbon nanotubes （SWCNTs） with various diameters and chiral angles by using the density functional theory based calculations. We find that methanol prefers to be adsorbed physically on the exterior surface of chiral nanotubes in comparison to the armchair and zigzag tubes with binding energy of about -2.76 kcal/mol, which is consistent with recent experimental and theoretical investigation results. We further consider the adsorption of methanol on the exterior surface and edge site of functionalized SWCNTs. The obtained results indicate that the binding energy of methanol is significantly increased for adsorption on the sidewall of functionalized nanotubes. It is also found that the adsorption of methanol at the edge site of both functionalized and pristine SWCNT is remarkably different （chemisoption process） in comparison to the exterior sidewall of the tubes. Furthermore, the electronic structures and Mulliken charge population of the considered complexes at their ground state are discussed within the context.

Multifunctionality of the linker histones： an emerging role for protein-protein interactions

Linker histones, e.g., H1, are best known for their ability to bind to nucleosomes and stabilize both nucleosome structure and condensed higher-order chromatin structures. However, over the years many investigators have reported specific interactions between linker histones and proteins involved in important cellular processes. The purpose of this review is to highlight evidence indicating an important alternative mode of action for H1, namely protein-protein interactions. We first review key aspects of the traditional view of linker histone action, including the importance of the H1 C-terminal domain. We then discuss the current state of knowledge of linker histone interactions with other proteins, and, where possible, highlight the mechanism of linker histone-mediated protein-protein interactions. Taken together, the data suggest a combinatorial role for the linker histones, functioning both as primary chromatin architectural proteins and simultaneously as recruitment hubs for proteins involved in accessing and modifying the chromatin fiber.

AIMP1生物学活性的研究进展

氨基酰tRNA合成酶相互作用多功能蛋白质1(AIMP1)最早是被发现位于一个巨大的氨基酰tRNA合成酶复合物(MSC)的中心位置,并作为一种非酶类辅助蛋白参与该复合物的形成。AIMP1不仅在维持MSC的结构上具有关键性作用,还可以作为分泌蛋白,发挥多种生物学功能,参与血稳态调节、免疫调控、新生血管形成、创伤愈合、炎症调控、凋亡调控及神经系统发育等多种体内生理反应。因此,该蛋白质在肿瘤、创伤、自身免疫性疾病及一些新生血管性疾病与炎症、凋亡瀑布激活密切相关的眼科疾病领域中具有巨大的研究价值和应用前景。

An Investigation into Disease Progression and the Correlation between Diabetes Mellitus and Hepatocellular Carcinoma

Diabetes mellitus has been associated with anincreased risk of hepatocellular carcinoma in recent studies ofpatients. At the same time, advanced hepatocellular carcinomaitself can cause glucose intolerance and can aggravate diabetes.Diabetes mellitus inducing hepatocellular carcinoma may resultin changes in the following aspects: dysfunction of organism,endocrine hormone balance and interactions, endothelins andso on. One way, diabetes mellitus may induce hepatocellularcarcinoma through the effects of chemotherapeutics and otheradjuvant drugs. This review outlines the relationship betweendiabetes mellitus and the risk of hepatocellular carcinoma as wellas treatments for hepatocellular carcinoma, which may be helpfulfor clinicians.

A Paradoxical Way of Communication in Children With Autism Spectrum Disorders Syndrome

This paper seeks to exemplify some of the intentional and unintentional nonverbal communication attempts expressea Dy children with Autism Spectrum Disorder （ASD） syndrome. It demonstrates that such interactions with the rest of the world are trying to establish some semiotic functions, in an effort behaviorally to overcome the children＇s disability. The author＇s aim is to analyze such a paradoxical way of communicational interaction of such a subject vs. a given objectively perceivable reality, thus attempting to reveal paradoxical social contexts. The focus is on interpersonal communication abilities and/or disabilities, thus allowing semiotically distinguishable units as an object of analysis. The problem of mental disorders, such as ASD, requires a multi-dimensional approach--e.g., biological, medical, and other related fields. In conclusion, by applying a semiotic analysis, it becomes necessary to communicate with such children in a whole new way which, by processes of transformation, can bring about a state of awareness of a paradoxical and/or abnormal phenomenon.

Soil Removal Efficacy of Catholyte on Polyamide 6.6 Fabric

This study determined the detergency properties of Catholyte, an electrochemically activated medium, on polyamide 6.6 as a possible alternative to conventional laundering detergents. Undyed polyamide 6.6 was used and soiled with keltex, corn starch, mineral oil, oleic acid, morpholine, vegetable fat, butanol, solvesso 150 and water. Some soiled fabric was retained as control and not laundered. Soiled fabric was laundered at 30 ~C as well as 40 ~C with either, distilled water, Catholyte, non-phosphate detergent, a 50/50 solution of Catholyte and non-phosphate detergent, or a 50/50 solution of Catholyte and phosphate detergent. Data were analyzed descriptively by using analysis of variance （ANOVA）, which fitted the factors of treatment and temperature, as well as all two-factor interactions between these variables. A probability value of 0.05 or less indicated significance. Catholyte was effective in removing soil and reached a/XE＊ value of 59.30, but was statistically different from the phosphate detergent. Temperature did not have a significant effect on soil removal from the fabric, but the interaction with a treatment had significant effects. Treatment alone had a significant soil removal effect on the fabric. Thus, the temperature was dependent on an interaction with the treatment. The non-phosphate detergent was efficient in removing soil from the fabric and slightly more efficient than either 50/50 Catholyte solution. The 50/50 Catholyte/non-phosphate detergent solution was slightly less effective than its phosphate containing counterpart. When considering the interaction between treatment and temperature, the 50/50 Catholyte/phosphate and 50/50 Catholyte/non-phosphate solutions were more efficient at 40 ~C. Thus the interaction between the solution and higher temperature proved to be a better combination. This was also the case for the Catholyte and the non-phosphate wash liquors. Catholyte, an environmentally friendly washing agent, is an attractive alternative to conventional laundry detergents because it removes soil efficiently from polyamide 6.6 fabric.

Identifying and annotating human bifunctional RNAs reveals their versatile functions

Bifunctional RNAs that possess both protein-coding and noncoding functional properties were less explored and poorly understood. Here we systematically explored the characteristics and functions of such human bifunctional RNAs by integrating tandem mass spectrometry and RNA-seq data. We first constructed a pipeline to identify and annotate bifunctional RNAs,leading to the characterization of 132 high-confidence bifunctional RNAs. Our analyses indicate that bifunctional RNAs may be involved in human embryonic development and can be functional in diverse tissues. Moreover, bifunctional RNAs could interact with multiple miRNAs and RNA-binding proteins to exert their corresponding roles. Bifunctional RNAs may also function as competing endogenous RNAs to regulate the expression of many genes by competing for common targeting miRNAs. Finally,somatic mutations of diverse carcinomas may generate harmful effect on corresponding bifunctional RNAs. Collectively,our study not only provides the pipeline for identifying and annotating bifunctional RNAs but also reveals their important gene-regulatory functions.

Layer by layer surface engineering of poly (lactide-co-glycolide) nanoparticles:A versatile tool for nanoparticle engineering for targeted drug delivery

Recent work regarding the Layer by Layer （LbL） engineering of poly（lactide-co-glycolide） nanoparticles （PLGA NPs） is reviewed here. The LbL engineering of PLGA NPs is applied as a means of generating advanced drug delivery devices with tailored recognition, protection, cargo and release properties. LbL in combination with covalent chemistry is used to attach PEG and folic acid to control cell uptake and direct it towards cancer cells. LbL coatings composed of chitosan and alginate show low protein interactions and can be used as an alternative to Pegylation. The assembly on top of LbL coatings of lipid layers composed of variable percentages of 1,2-dioleoyl-sn-glycero-3-choline （DOPC） and 1,2-dioleoyl-sn-glycero-3-phospho- L-serine （DOPS） increases NP uptake and directs the NPs towards the endoplasmic reticulum. The antibody anti-TNF-ct is encapsulated forming a complex with alginate that is assembled LbL on top of PLGA NPs. The antibody is released in cell culture following first order kinetics. The release kinetics of encapsulated molecules inside PLGA NPs are studied when the PLGA NPs are coated via LbL with different polyelectrolytes. The intracellular release of encapsulated Doxorubicin is studied in the HepG2 cell line by means of Fluorescence Lifetime Imaging.

α-secretase ADAM IO physically interacts with β-secretase BACE1 in neurons and regulates CHL1 proteolysis

α-secretase and β-secretase are known to compete for amyloid precursor protein （APP） processing and thus play a vital role in Alzheimer＇s disease pathogenesis. A disintegrin and metaUoproteinase 10 （ADAM10） and β-site APP cleaving enzyme 1 （BACE1） mediate the major activities of α-secretase and β-secretase in brain and share various common substrates. However, whether they function separately or together is poorly understood. Here, we show that ADAM10 and BACE1 co-localize in the neurites of mouse primary neurons. Co-immunoprecipitation and fluorescence resonance energy transfer analysis revealed that ADAM10 and BACE1 interact with each other under both endogenous and exogenous conditions. In addition, we found that ADAMIO enhances the proteolysis of neural cell adhesion molecule close homolog of L1 （CHL1） by BACE1. Further studies found that ADAM10-BACE1 interaction interfering peptide LT52 attenuates the regulation of ADAM10 on BACEl-mediated cleavage of CHL1. Our data indicate that ADAM10-BACE1 interaction regulates the proteolysis of some specific substrates and may play a potential role in brain function.

Cytoplasmic dynein:a key player in neurodegenerative and neurodevelopmental diseases

Cytoplasmic dynein is the most important molecular motor driving the movement of a wide range of cargoes towards the minus ends of microtubules.As a molecular motor protein,dynein performs a variety of basic cellular functions including organelle transport and centrosome assembly.In the nervous system,dynein has been demonstrated to be responsible for axonal retrograde transport.Many studies have revealed direct or indirect evidence of dynein in neurodegenerative diseases such as amyotrophic lateral sclerosis,Charcot-Marie-Tooth disease,Alzheimer’s disease,Parkinson’s disease and Huntington’s disease.Among them,a number of mutant proteins involved in various neurodegenerative diseases interact with dynein.Axonal transport disruption is presented as a common feature occurring in neurodegenerative diseases.Dynein heavy chain mutant mice also show features of neurodegenerative diseases.Moreover,defects of dynein-dependent processes such as autophagy or clearance of aggregation-prone proteins are found in most of these diseases.Lines of evidence have also shown that dynein is associated with neurodevelopmental diseases.In this review,we focus on dynein involvement in different neurological diseases and discuss potential underlying mechanisms.

Fsh-Pc-Sce complex mediates active transcription of Cubitus interruptus （Ci）

The Hedgehog （Hh） signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus （Ci）. Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile （1） homeotic （Fsh）, a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh, Sex combs extra （Sce）, and Polycomb （Pc）. Functional assays further showed that both Pc and Sce are required for Ci expression, which is not likely mediated by the derepression of Engraited （En）, a repressor of Ci, in Pc or Sce mutant cells. Finally, we provide evidence showing that Pc/Sce facilitates the binding of Fsh at Ci locus and that the physical interaction between Fsh and Pc is essential for Fsh-mediated Ci transcription. Taken together, we not only uncover that Ci is transcriptionally regulated by Fsh-Pc-Sce complex but also provide evidence for the coordination between Fsh and PcG proteins in transcriptional regulation.

Viral proteomics: The emerging cutting-edge of virus research

Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in host cells.Viral genomes were chronologically the first to be sequenced.However,the corresponding viral proteomes,the alterations of host proteomes upon viral infection,and the dynamic nature of proteins,such as post-translational modifications,enzymatic cleavage,and activation or destruction by proteolysis,remain largely unknown.Emerging high-throughput techniques,in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes,have been applied to define viruses and their interactions with their hosts.Here,we review the major areas of viral proteomics,including virion proteomics,structural proteomics,viral protein interactomics,and changes to the host cell proteome upon viral infection.