Elevated intracellular cyclic-di-GMP level in Shewanella oneidensis increases expression of c-type cytochromes

Electrochemically active biofilms are capable of exchanging electrons with solid electron acceptors and have many energy and environmental applications such as bioelectricity generation and environmental remediation. The performance of electrochemically active biofilms is usually dependent on c-type cytochromes, while biofilm development is controlled by a signal cascade mediated by the intracellular secondary messenger bis-(3ʹ-5ʹ) cyclic dimeric guanosine monophosphate (c-di-GMP). However, it is unclear whether there are any links between the c-di-GMP regulatory system and the expression of c-type cytochromes. In this study, we constructed a S. oneidensis MR-1 strain with a higher cytoplasmic c-di-GMP level by constitutively expressing a c-di-GMP synthase and it exhibited expected c-di-GMP-influenced traits, such as lowered motility and increased biofilm formation. Compared to MR-1 wild-type strain, the high c-di-GMP strain had a higher Fe(III) reduction rate (21.58 vs 11.88 pM of Fe(III)/h cell) and greater expression of genes that code for the proteins involved in the Mtr pathway, including CymA, MtrA, MtrB, MtrC and OmcA. Furthermore, single-cell Raman microspectroscopy (SCRM) revealed a great increase of c-type cytochromes in the high c-di-GMP strain as compared to MR-1 wild-type strain. Our results reveal for the first time that the c-di-GMP regulation system indirectly or directly positively regulates the expression of cytochromes involved in the extracellular electron transport (EET) in S. oneidensis, which would help to understand the regulatory mechanism of c-di-GMP on electricity production in bacteria.     

Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss

Changes in mitochondrial dynamics (fusion and fission) are known to occur during stem cell differentiation; however, the role of this phenomenon in tissue aging remains unclear. Here, we report that mitochondrial dynamics are shifted toward fission during aging of Drosophila ovarian germline stem cells (GSCs), and this shift contributes to aging‐related GSC loss. We found that as GSCs age, mitochondrial fragmentation and expression of the mitochondrial fission regulator, Dynamin‐related protein (Drp1), are both increased, while mitochondrial membrane potential is reduced. Moreover, preventing mitochondrial fusion in GSCs results in highly fragmented depolarized mitochondria, decreased BMP stemness signaling, impaired fatty acid metabolism, and GSC loss. Conversely, forcing mitochondrial elongation promotes GSC attachment to the niche. Importantly, maintenance of aging GSCs can be enhanced by suppressing Drp1 expression to prevent mitochondrial fission or treating with rapamycin, which is known to promote autophagy via TOR inhibition. Overall, our results show that mitochondrial dynamics are altered during physiological aging, affecting stem cell homeostasis via coordinated changes in stemness signaling, niche contact, and cellular metabolism. Such effects may also be highly relevant to other stem cell types and aging‐induced tissue degeneration.     

Deleterious cardiovascular effect of exosome in digitalis‐treated decompensated congestive heart failure

Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis.     

The protective effects of grape seed procyanidin B2 against asporin mediates glycated low‐density lipoprotein induced‐cardiomyocyte apoptosis and fibrosis

The progression of diabetic cardiomyopathy is related to cardiomyocyte dysfunction and apoptosis. Our previous studies showed that asporin (ASPN) was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of ASPN in the heart of db/db mice. We report here that ASPN played a critical role in glycated low‐density lipoproteins (gly‐LDL) induced‐cardiomyocyte apoptosis. We found that gly‐LDL upregulated ASPN expression. ASPN increased H9C2 cardiomyocyte apoptosis with down‐regulation of Bcl‐2, upregulation of transforming growth factor‐β1, Bax, collagen III, fibronectin, and phosphorylation of smad2 and smad3. However, GSPB2 treatment reversed ASPN‐induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against ASPN injury, and thus suggest a new target for fighting against diabetic cardiomyopathy.     

Permeabilized Escherichia coli Whole Cells Containing Co‐Expressed Two Thermophilic Enzymes Facilitate the Synthesis of scyllo‐Inositol from myo‐Inositol

Scyllo‐inositol (SI), a stereoisomer of inositol, is regarded as a promising therapeutic agent for Alzheimer's disease. Here, an in vitro cofactor‐balance biotransformation for the production of SI from myo‐inositol (MI) by thermophilic myo‐inositol 2‐dehydrogenase (IDH) and scyllo‐inositol 2‐dehydrogenase (SIDH) is presented. These two enzymes (i.e., IDH and SIDH from Geobacillus kaustophilus) are co‐expressed in Escherichia coli BL21(DE3), and E. coli cells containing the two enzymes are permeabilized by heat treatment as whole‐cell catalysts to convert MI to SI. After condition optimizations about permeabilized temperature, reaction temperature, and initial MI concentration, about 82 g L^?1 of SI is produced from 250 g L^?1 of MI within 24 h without any cofactor supplementation. This final titer of SI produced is the highest to the authors’ limited knowledge. This study provides a promising method for the large‐scale industrial production of SI.     

miRNA和lncRNA在动物脂肪沉积中的研究进展

微小RNA(MicroRNA,miRNA)是一类由18–25个核苷酸组成的高度保守的核苷酸序列,它可以特异性结合信使RNA (mRNA)的3′-非编码区域,进而发挥降解mRNA或阻遏mRNA翻译的负调控作用。长链非编码RNA (Long non-coding RNA,lncRNA)是一类长度超过200个核苷酸、不能编码蛋白质或只能编码蛋白质微肽的核苷酸序列,它可以在表观遗传、转录水平和转录后水平调控基因表达。脂肪作为一种重要的储能物质,在调节动物体能量平衡过程中发挥着重要的作用,并与动物产肉量、肉品质等产肉性状密切相关。而脂肪功能的紊乱可导致高血脂、Ⅱ型糖尿病以及一系列心血管疾病发生,因此动物脂肪沉积的分子调控机制备受人们关注。近年来,越来越多的研究发现miRNA和lncRNA在动物脂肪沉积中发挥重要作用。文中就现阶段miRNA和lncRNA在动物脂肪沉积中的研究进展进行综述,以期为进一步揭示动物脂肪沉积的分子调控机制提供理论指导和新思路。