Semen as a rich source of diagnostic biomarkers for prostate cancer: latest evidence and implications

Molecular and Cellular Biochemistry - Prostate cancer (PCa) is one of the most common cancers in men and the cause of numerous cancer deaths in the world. Nowadays, based on diagnostic criteria,...     

纳米技术在抗白色念珠菌感染中的应用

白色念珠菌(Candida albicans,C.albicans)在引发血源性感染的病原微生物中位列第四,全国每年由C.albicans引起的各类感染性疾病高达千万例.该菌极易附着于植入医疗器械的表面,形成坚固生物被膜阻碍药物和免疫系统的进攻,给治疗带来了极大难度.同时,近年来C.albicans的高流行率和不断增强...     

桉树种植对林地土壤丛枝菌根真菌群落结构及多样性的影响

桉树(Eucalyptus spp.)种植所产生的生态争议已受到广泛关注。丛枝菌根真菌(Arbuscular Mycorrhizal Fungi, AM真菌)是土壤微生物的重要组成部分,与根系共生后可促进植物的养分运输、提高植物逆境生存能力等。然而,桉树种植对土壤AM真菌群落结构和功能的影响尚不清楚。研究比较了次生林改种桉树后不同年限(2年/5年/10年)的土壤理化性质、AM真菌种类、群落组成及多样性的变化。结果表明,桉树种植显著改变了土壤理化性质,具体表现为2年生和10年生桉树林中土壤pH和有机碳显著降低(P0.05);AM真菌的孢子密度在桉树林土壤中显著低于次生林土壤(其中在5年生土壤中最低);AM真菌的种丰度随种植年份的增加逐渐下降,在10年生桉树林土壤中有所恢复; 5年生桉树的菌根侵染率最高,10年生桉树侵染率最低。AM真菌群落组成和结构发生显著变化,优势种Funneliforms geosporus的丰度在2年生和10年生林地中显著降低;而Septoglomus deserticola的丰度在2年生和10年生林地中显著增加。另外,冗余分析(Redundancy analysis, RDA)结果表明,土壤AM真菌群落结构主要受土壤pH值(解释率:89.88%)变化的影响。研究揭示了次生林改种桉树林后土壤AM真菌的群落变化特征,为桉树林的栽培管理和环境修复提供了数据支撑。     

Molecular basis of ligand recognition and activation of human V2 vasopressin receptor

Dear Editor, Vasopressin type 2 receptor(V2R)belongs to the vasopressin(VP)/oxytocin(OT)receptor subfamily of G protein-coupled receptors(GPCRs),which comprises...     

Anchorage‐dependent binding of integrin I‐domain to adhesion ligands

The dynamic interactions between leukocyte integrin receptors and ligands in the vascular endothelium, extracellular matrix, or invading pathogens result in leukocyte adhesion, extravasation, and phagocytosis. This work examined the mechanical strength of the connection between iC3b, a complement component that stimulates phagocytosis, and the ligand‐binding domain, the I‐domain, of integrin α_Mβ₂. Single‐molecule force measurements of α_M I‐domain–iC3b complexes were conducted by atomic force microscope. Strikingly, depending on loading rates, immobilization of the I‐domain via its C‐terminus resulted in a 1.3‐fold to 1.5‐fold increase in unbinding force compared with I‐domains immobilized via the N‐terminus. The force spectra (unbinding force versus loading rate) of the I‐domain–iC3b complexes revealed that the enhanced mechanical strength is due to a 2.4‐fold increase in the lifetime of the I‐domain–iC3b bond. Given the structural and functional similarity of all integrin I‐domains, our result supports the existing allosteric regulatory model by which the ligand binding strength of integrin can be increased rapidly when a force is allowed to stretch the C‐terminus of the I‐domain. This type of mechanism may account for the rapid ligand affinity adjustment during leukocyte migration. Copyright © 2015 John Wiley & Sons, Ltd.     

Integrating multiple references for single-cell assignment

Efficient single-cell assignment is essential for single-cell sequencing data analysis. With the explosive growth of single-cell sequencing data, multiple single-cell sequencing data sources are available for the same kind of tissue, which can be integrated to further improve single-cell assignment; however, an efficient integration strategy is still lacking due to the great challenges of data heterogeneity existing in multiple references. To this end, we present mtSC, a flexible single-cell assignment framework that integrates multiple references based on multitask deep metric learning designed specifically for cell type identification within tissues with multiple single-cell sequencing data as references. We evaluated mtSC on a comprehensive set of publicly available benchmark datasets and demonstrated its state-of-the-art effectiveness for integrative single-cell assignment with multiple references.     

Fast bilayer-micelle fusion mediated by hydrophobic dipeptides

To understand the transition from inanimate matter to life, we studied a process that directly couples simple metabolism to evolution via natural selection, demonstrated experimentally by Adamala and Szostak. In this process, dipeptides synthesized inside precursors of cells promote absorption of fatty acid micelles to vesicles, inducing their preferential growth and division at the expense of other vesicles. The process is explained on the basis of coarse-grained molecular dynamics simulations, each extending for tens of microseconds, carried out to model fusion between a micelle and a membrane, both made of fatty acids in the absence and presence of hydrophobic dipeptides. In all systems with dipeptides, but not in their absence, fusion events were observed. They involve the formation of a stalk made by hydrophobic chains from the micelle and the membrane, similar to that postulated for vesicle-vesicle fusion. The emergence of a stalk is facilitated by transient clusters of dipeptides, side chains of which form hydrophobic patches at the membrane surface. Committor probability calculations indicate that the size of a patch is a suitable reaction coordinate and allows for identifying the transition state for fusion. Free-energy barrier to fusion is greatly reduced in the presence of dipeptides to only 4–5 kcal/mol, depending on the hydrophobicity of side chains. The mechanism of mediated fusion, which is expected to apply to other small peptides and hydrophobic molecules, provides a robust means by which a nascent metabolism can confer evolutionary advantage to precursors of cells.     

一种可药物筛选及体内检测的新型慢病毒基因治疗载体的构建

为实现基因治疗过程中的有效药物筛选及体内检测, 首次利用核糖体内部进入位点(IRES)构建了同时携带O6-烷基鸟嘌呤-DNA烷基转移酶(MGMT)的突变型P140K基因和荧光素酶(Luciferase)基因的慢病毒载体pBobi-MIL。RT-PCR、免疫荧光、药物筛选克隆形成及化学发光检测等实验结果表明感染重组慢病毒L-MIL的细胞能同时表达MGMT及Luciferase。构建成功的新型慢病毒载体为今后的基因治疗奠定了基础, 也为慢病毒滴度的确定提供了一种新的可能。     

Bioimaging nitric oxide in activated macrophages in vitro and hepatic inflammation in vivo based on a copper–naphthoimidazol coordination compound

Nitric oxide (NO) serves as a messenger for cellular signaling and physiological reactions such as inflammatory responses in vivo. Fluorescent bioimaging of nitric oxide is a very useful tool in NO functional research. Although many encouraging results have been achieved in the field of NO fluorescent detection, there is rarely satisfying result in inflammatory NO imaging in vivo. Here we report that fluorescent 5′-chloro-2-(2′-hydroxyphenyl)-1H-naphtho[2,3-d]imidazol can coordinate with Cu(II) to form a non-fluorescent coordination compound, which is able to directly and quickly image NO in cellular system or in vivo inflammation system with a turn-on fluorescence, based on a redox action of Cu(II). It was used to image NO produced by inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS) activated murine macrophages. More importantly, it could image the NO production in an acute severe hepatic injury (ASHI) model of BALB/c mice induced by integrative LPS and d-galactosamine (GalN) treatment. The results prove that the 5′-chloro-2-(2′-hydroxyphenyl)-1H-naphtho[2,3-d]imidazol coordinated with cupric ions can serve as an excellent NO bioimaging agent in different biological systems especially in inflammation related systems, and it may be valuable for diagnostic and pathological studies of NO related diseases.     

Synaptosomes secrete and uptake functionally active microRNAs via exocytosis and endocytosis pathways

In this study, we first characterized synaptosome microRNA (miRNA) profiles using microarray and qRT‐PCR. MicroRNAs were detected in isolated synaptic vesicles, and Ago2 immunoprecipitation studies revealed an association between miRNAs and Ago2. Second, we found that miR‐29a, miR‐99a, and miR‐125a were significantly elevated in synaptosome supernatants after depolarization. MiRNA secretion by the synaptosome was Ca²⁺‐dependent and was inhibited by the exocytosis inhibitor, okadaic acid. Furthermore, application of nerve growth factor increased miRNA secretion without altering the spontaneous release of miRNAs. Conversely, kainic acid decreased miRNA secretion and enhanced the spontaneous release of miRNAs. These results indicate that synaptosomes could secrete miRNAs. Finally, synthesized miRNAs were taken up by synaptosomes, and the endocytosis inhibitor Dynasore blocked this process. After incubation with miR‐125a, additional miR‐125a was bound to Ago2 in the synaptosome, and expression of the miR‐125a target gene (PSD95 mRNA) was decreased; these findings suggest that the ingested miRNAs were assembled in the RNA‐induced silencing complex, resulting in the degradation of target mRNAs. To our knowledge, this is the first study that demonstrates the secretion of miRNAs by synaptosomes under physiological stimulation and demonstrates that secreted miRNAs might be functionally active after being taken up by the synaptic fraction via the endocytic pathway.