Comparison of complete genome sequences of dog rabies viruses isolated from China and Mexico reveals key amino acid changes that may be associated with virus replication and virulence

Rabies is a global problem, but its impact and prevalence vary across different regions. In some areas, such as parts of Africa and Asia, the virus is prevalent in the domestic dog population, leading to epidemic waves and large numbers of human fatalities. In other regions, such as the Americas, the virus predominates in wildlife and bat populations, with sporadic spillover into domestic animals. In this work, we attempted to investigate whether these distinct environments led to selective pressures that result in measurable changes within the genome at the amino acid level. To this end, we collected and sequenced the full genome of two isolates from divergent environments. The first isolate (DRV-AH08) was from China, where the virus is present in the dog population and the country is experiencing a serious epidemic. The second isolate (DRV-Mexico) was taken from Mexico, where the virus is present in both wildlife and domestic dog populations, but at low levels as a consequence of an effective vaccination program. We then combined and compared these with other full genome sequences to identify distinct amino acid changes that might be associated with environment. Phylogenetic analysis identified strain DRV-AH08 as belonging to the China-I lineage, which has emerged to become the dominant lineage in the current epidemic. The Mexico strain was placed in the D11 Mexico lineage, associated with the West USA-Mexico border clade. Amino acid sequence analysis identified only 17 amino acid differences in the N, G and L proteins. These differences may be associated with virus replication and virulence–for example, the short incubation period observed in the current epidemic in China.     

Modulation of LPS-Stimulated Pulmonary Inflammation by Borneol in Murine Acute Lung Injury Model

The object of our study is to investigate the protective effects of Borneol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. To determine the effects of Borneol on the histopathological changes in mice with ALI, inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. Next, cytokine production induced by LPS in BALF and RAW 264.7 cells was measured by enzyme-linked imunosorbent assay (ELISA). To further study the mechanism of Borneol-protective effects on ALI, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways were investigated. In the present study, Borneol obviously alleviated pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, Borneol significantly suppressed phosphorylation of NF-κB/P65, IκBa, p38, JNK, and ERK. Taken together, our results suggest that Borneol suppressed inflammatory responses in LPS-induced acute lung injury through inhibition of the NF-κB and MAPKs signaling pathways. Borneol may be a promising potential preventive agent for acute lung injury treatment.     

Mesoaccumbens dopamine signaling alteration underlies behavioral transition from tolerance to sensitization to morphine rewarding properties during morphine withdrawal

Although the firing activity of dopamine (DA) neurons in the ventral tegmental area (VTA) and the behavioral response to morphine rewarding properties alter as opiate withdrawal, little is known about the dynamic changes in DA signal pathway from the VTA to the nucleus accumbens (NAc) during prolonged withdrawal, and whether the changes are indicative of vulnerability to relapse of drug abuse. Here we report that morphine spontaneously withdrawn (SW) rats are incapable of responding to small dose of morphine-induced conditioned place preference (CPP) from 24h-SW to 30d-SW, but recover response at 45d-SW. Interestingly, mesoaccumbens DA signaling, including the firing of DA neurons in the VTA, contents of DA and its metabolic ratio, and the membrane level of dopamine D₁ receptor in the NAc elicited by morphine challenge, display a similar pattern of time-dependent changes during morphine withdrawal. Moreover, blockade of D₁ receptor abolishes this behavioral transition. In addition, a strong correlation was found between % change in CPP score and membrane D₁ receptor level induced by morphine challenge. These results indicate a time-dependent behavioral switch from tolerance to sensitization during the prolonged withdrawal, which could offer a window for therapeutic intervention via manipulations of D₁ receptors.     

视听联合刺激诱发事件相关电位的时变源分析

目的 运用偶极子源分析方法分析视（V）、听（A）单独刺激和视听（VA）联合刺激早期阶段脑功能区的动态变化.方法 采用64道脑电采集系统,记录14例志愿者在视觉、听觉和视听联合刺激下诱发的事件相关电位（ERPs）,并将这3种任务的早期阶段分成不同子时间段进行偶极子源分析.结果 视觉、听觉刺激诱发的早期偶极子源定位在特定脑皮层功能区,并且偶极子的位置和强度随时间发生变化.结论 脑功能区在视听刺激的早期阶段（＜150 ms）对感觉信息存在动态的处理过程.     

Arkadia在TGF-β/Smad信号转导通路中的作用

转化生长因子-β（TGF-β）是一种多功能蛋白,具有调节细胞增殖、分化、迁移及凋亡等多种细胞生物学效应.已有研究证实,TGF-β是重要的促纤维化细胞因子之一,且与肿瘤的发展密切相关.Smad信号是其发挥作用的主要通路.而近年研究发现,E3泛素连接酶Arkadia通过Smad信号能起到增强TGF-β信号通路生物学效应的作用,因而日益引起人们的关注.拟对TGF-β信号转导通路中Arkadia的作用作一综述.     

STK11 Domain XI Mutations: Candidate Genetic Drivers Leading to the Development of Dysplastic Polyps in Peutz–Jeghers Syndrome

Peutz–Jeghers syndrome (PJS) is a rare hereditary disorder resulting from mutations in serine/threonine kinase 11 (STK11) and characterized by gastrointestinal (GI) hamartomatous polyps, mucocutaneous pigmentation, and an increased risk for specific cancers. Little is known about the genetic implications of specific STK11 mutations with regard to their role in dysplastic and malignant transformation of GI polyps. Peripheral blood genomic DNA samples from 116 Chinese PJS patients from 52 unrelated families were investigated for STK11 mutations. Genotype–phenotype correlations were investigated. The mutation detection rate was 67.3% (51.9% point mutations, 15.4% large deletions). Fourteen out of the 25 point mutations identified were novel. Nearly one‐third of all mutations, 8/27 (29.6%), were in exon 7, the shortest out of the nine exons. Strikingly, mutations affecting protein kinase domain XI, encoded in part by exon 7, correlated with a 90% (9/10) incidence of GI polyp dysplasia. In contrast, only two out of 17 (11.8%) nondomain XI mutations were linked to polyp dysplasia (P = 0.0001). The extent of the association between dysplasia and the development of GI‐related cancers is currently unknown but our results highlight a novel STK11 genotype–phenotype association as the basis for future genetic counseling and basic research studies.     

A Conjugated Random Copolymer of Benzodithiophene‐Difluorobenzene‐Diketopyrrolopyrrole with Full Visible‐Light Absorption for Bulk‐Heterojunction Solar Cells

Stille coupling polymerization is used to synthesize a new donor–acceptor (D–A) conjugated random copolymer (PBDT‐DFB‐DPP) that comprises an electron‐rich benzodithiophene (BDT) unit in conjugation with electron‐deficient 2,5‐difluorobenzene (DFB) and diketopyrrolopyrrole (DPP) moieties, which have complementary light‐absorption behavior. The thermal, photophysical, and electrochemical properties of the polymer are investigated using thermogravimetric analysis, UV–vis absorption spectroscopy, and cyclic voltammetry. The random copolymer exhibits both broad light absorption and a low‐lying highest occupied molecular orbital (HOMO) level, which contribute to enhancement of the short‐circuit current density (J_sc) and open‐circuit voltage (V_oc). A bulk‐heterojunction polymer solar cell fabricated from PBDT‐DFB‐DPP and PC₆₀BM exhibits a promising power conversion efficiency (PCE) of 2.50%.