Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2

New-onset diabetes mellitus has a rough correlation with pancreatic cancer (PaC), but the underlying mechanism remains unclear. This study aimed to explore the exosomal microRNAs and their potential role in PaC-induced β-cell dysfunction. The pancreatic β cells were treated with isolated exosomes from PaC cell lines, SW1990 and BxPC-3, before measuring the glucose-stimulated insulin secretion (GSIS), validating that SW1990 and BxPC-3 might disrupt GSIS of both β cell line MIN6 and primary mouse pancreatic islets. The difference in expression profiles between exosomes and exosome-free medium of PaC cell lines was further defined, revealing that miR-19a secreted by PaC cells might be an important signaling molecule in this process. Furthermore, adenylyl cyclase 1 (Adcy1) and exchange protein directly activated by cAMP 2 (Epac2) were verified as the direct targets of exogenous miR-19a, which was involved in insulin secretion. These results indicated that exosomes might be an important mediator in the pathogenesis of PaC-DM, and miR-19a might be the effector molecule. The findings shed light on the pathogenesis of PaC-DM.     

Absence of mutations in the coding regions of follicle-stimulating hormone receptor gene in Singapore Chinese women with premature ovarian failure and polycystic ovary syndrome.

Normal gonadal function is critically dependent on the integrity of pituitary-gonadal axis, where follicle-stimulating hormone (FSH) plays a key role. In the female, FSH is required for follicular growth, estrogen production and oocyte maturation. Its function is mediated by its specific receptor (FSHR), and defective FSHR has been shown to affect folliculogenesis and ovarian function. In this study, we screened the entire coding region of FSHR gene for pathogenic mutations in women with premature ovarian failure (POF) (n = 16) and polycystic ovary syndrome (PCOS) (n = 124) and found no mutations in these patients. Two known polymorphisms, Thr307Ala and Ser680Asn showed similar distributions of the allelic variations and protein isoforms in PCOS and normal control subjects (n = 236). It appears from this study that mutations in the coding regions of FSHR gene are not a causative factor of the above clinical manifestations in Chinese Singapore women.     

First cervical vertebra (atlas) fracture mechanism studies using finite element method.

Injury mechanisms and stress distribution patterns are important in the clinical evaluation of spinal injuries. Recognition and interpretation of the failure patterns help to determine spinal instability and consequently the choice of treatment. Although, the biomechanics responses of the atlas have received much attention, it has not been investigated using theoretical modeling. Mathematical techniques such as finite element model will provide further understanding to the injury mechanisms of the atlas, which is important for the prevention, diagnosis, and treatment of spinal injuries. In the present study, a detailed three-dimensional finite element model of the human atlas (C1) was constructed, with the geometrical data obtained using a three-dimensional digitizer. Anterior arch, superior/inferior articular processes, transverse processes, posterior arch and posterior tubercule were modeled using eight-noded brick elements. Using the material properties from literature, the 7808-finite element model was exercised under three simulated axial compressive mode of pressure loading and boundary conditions to investigate the sites of failure reported in vivo and in vitro. This report demonstrates high concentration of localized stress at the anterior and posterior archs of the atlas, which agrees well with those reported in the literature. Furthermore, under simulated hyperextension, our results agreed well with the experimental findings, which show that the groove of the posterior arch is subjected to enormous bending moment. The close agreement of the failure location provided confidence to perform further analysis and in vitro experiments. These results may be potentially used to supplement experimental research in understanding the clinical biomechanics of the atlas.     

A review of the catfish genus Pterocryptis (Siluridae) in Vietnam, with the description of two new species

Of the silurid catfish genus Pterocryptis in Vietnam, a total of four species are recognized as valid, of which Pterocryptis crenula and P. verecunda are described here as new. The type locality of P. cochinchinensis is restricted to central Vietnam, and the species is redescribed from topotypic material. Pterocryptis crenula (from northeastern Vietnam) can be differentiated from its congeners in having visibly confluent anal and caudal fins while P. verecunda (from Cat Ba Island in northeastern Vietnam) can be differentiated from its congeners in having the genital papilla concealed behind the anus. Notes on the identity of other nominal Pterocryptis species are also provided.     

Bt毒素蛋白基因的PCR鉴定及定位

利用合成的cryI、cryIII和cryV基因专一性引物 ,检测了从土壤中分离到的 56株苏云金芽孢杆菌菌株所含的晶体毒素蛋白基因。含有cryI基因的有 7株 ,含有cryIII基因的有 2株 ,同时含有cryI和cryV基因的有 2 1株。斑点杂交及Southern杂交分析表明 ,cryV基因定位于 1 50MD的大质粒上。     

Purification and characterization of charantin, a napin-like ribosome-inactivating peptide from bitter gourd (Momordica charantia) seeds.

A peptide designated charantin, with a molecular mass of 9.7 kDa, was isolated from bitter gourd seeds. The procedure comprised affinity chromatography on Affi-gel blue gel, ion-exchange chromatography on Mono S and gel filtration on Superdex 75. The N-terminal sequence of charantin exhibited marked similarity to that of the 7.8-kDa napin-like peptide previously isolated from bitter gourd seeds. Charantin inhibited cell-free translation in a rabbit reticulocyte lysate system with an IC50 of 400 nm, a potency lower than that of the previously reported small ribosome-inactivating protein gamma-momorcharin (IC50 = 55 nm) which also exhibited an abundance of arginine and glutamate/glutamine residues. Charantin reacted positively in the N-glycosidase assay, yielding a band similar to that formed by the small ribosome-inactivating proteins gamma-momorcharin and luffin S.     

Dockers at the crossroads.

The family of docker proteins containing phosphotyrosine-binding (PTB) domains appears to represent a family of critically positioned and exquisitely controlled signalling proteins that relay signals from the activated receptors to downstream pathways. These proteins all have a membrane attachment domain, a PTB domain that targets the protein to a subset of receptors and a number of phosphorylatable tyrosines that dock other signalling proteins. Evidence is accruing that suggests that the PTB domain has evolved from a pleckstrin homology (PH) domain to bind to a range of sequences that, while bestowing specificity, allows switching of the docker protein between receptors or signalling systems. The history of the PTB domain and how it influences the participation of docker protein in various signalling pathways are discussed.     

Regulation of K+ current in human airway epithelial cells by exogenous and autocrine adenosine

The regulatory actions ofadenosine on ion channel function are mediated by four distinctmembrane receptors. The concentration of adenosine in the vicinity ofthese receptors is controlled, in part, by inwardly directed nucleosidetransport. The purpose of this study was to characterize the effects ofadenosine on ion channels in A549 cells and the role of nucleosidetransporters in this regulation. Ion replacement and pharmacologicalstudies showed that adenosine and an inhibitor of human equilibrative nucleoside transporter (hENT)-1, nitrobenzylthioinosine, activated K⁺ channels, most likely Ca²⁺-dependentintermediate-conductance K⁺ (I_K)channels. A₁ but not A₂ receptor antagonistsblocked the effects of adenosine. RT-PCR studies showed that A549 cellsexpressed mRNA for I_K-1 channels as well asA₁, A_2A, and A_2B but notA₃ receptors. Similarly, mRNA for equilibrative (hENT1 andhENT2) but not concentrative (hCNT1, hCNT2, and hCNT3) nucleosidetransporters was detected, a result confirmed in functional uptakestudies. These studies showed that adenosine controls the function ofK⁺ channels in A549 cells and that hENTs play a crucialrole in this process.