Endogenous Hydrogen Sulfide is Involved in Asymmetric Dimethylarginine-induced Protection Against Neurotoxicity of 1-Methyl-4-phenyl-pyridinium Ion

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is profoundly protective against 1-methy-4-phenylpyridinium ion (MPP⁺)-induced neurotoxicity. Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of MPP⁺; while hydrogen sulfide (H₂S) is a pivotal endogenous antioxidant. This study is to assess the potential role of endogenous H₂S in the neuroprotection of ADMA against MPP⁺-induced toxicity in PC12 cells. We showed that ADMA prevented MPP⁺-induced inhibition of endogenous H₂S generation through inhibiting the down-regulation of cystathionine-β-synthetase (CBS, the major enzyme responsible for endogenous H₂S generation in PC12 cells) expression and activity elicited by MPP⁺. ADMA obviously attenuated MPP⁺-triggered accumulation of intracellular ROS, dissipation of mitochondrial membrane potential (MMP), release of cytochrome c (Cyt-c), and downregulation of Bcl-2 protein expression in PC12 cells. Inhibition of CBS activity by amino-oxyacetate and CBS silencing with a short hairpin RNA vector targeting rat CBS gene reversed the protective action of ADMA against MPP⁺-caused cytotoxicity, ROS overproduction, and MMP loss in PC12 cells. These results indicate that the protection of ADMA against MPP⁺-mediated neurotoxicity involves the melioration of MPP⁺-induced inhibition of endogenous H₂S generation. Our findings suggest that modulation of H₂S production provide new therapeutic targets for the treatment of neurodegenerative disease, such as Parkinson’s disease.     

Different Long-Term Outcomes of Abdominal Aortic Aneurysm and Intracranial Aneurysm Models: Hemodynamic Change may also Play an Essential Role in the Initiation and Progression of Abdominal Aortic Aneurysm in Rabbits

Self-healing phenomenon was found in the periarterial elastase-induced abdominal aortic aneurysm (AAA) in rabbit. This kind of aneurysm model does not progress and heals spontaneously in the long term, which is quite different from the performance of AAA disease in human. In order to better mimic human AAA and overcome this shortcoming of traditional AAA model in rabbit, we studied the pathogenesis of cerebral aneurysm (CA) model in small animal, which shows an excellent long-term patency and progressive enlargement. We found that hemodynamic conditions, such as turbulence flow, high blood flow, and shear stress, play an important role in the formation and progression of CA. So, we hypothesize that hemodynamic change may also play an essential role in the initiation and progression of rabbit AAA, and self-healing will be overcome if hemodynamic condition changes by coarctation of infra-renal aorta after elastase incubation.     

金黄色葡萄球菌基因表达的DNA扣除法

[目的]金黄色葡萄球菌作为一种分布广泛的致病微生物和研究革兰氏阳性菌遗传背景的模式菌株,利用real-time RT PCR对相关毒素及调控基因进行表达定量分析,在生物、医学、食品检测等领域具有较大研究价值.[方法]对制备好的反转录(RT,含有cDNA和DNA)和非反转录(RTˉ,仅含DNA)样品进行Real-time PCR检测,根据经典(1 E)ˉ△△Ct相对定量算法并结合PCR效率公式建立一种基因表达相对定量分析的DNA扣除法,将得到的Ct值转换为各样品含量,从RT样品中扣除RTˉ样品的量,无需DNaseⅠ酶解处理就可以去除DNA的影响,RTˉ样品的检测结果还可同时作为稳定的DNA内参.[结果]采用以上方法分析金黄色葡萄球菌肠毒素A基因(sea)、16S rRNA和RNA Ⅲ的表达情况,在含有葡萄糖的NB培养基中sea的相对转录水平随着葡萄糖浓度的增大而升高,RNAⅢ的相对转录水平随葡萄糖浓度的变化而产生小幅度的波动,16S rRNA在菌体生长初期时的表达量较为稳定;与绝对定量法比较,结果差异较小(均小于15%),且差异不显著(p＞0.05).[结论]这种基于DNA扣除法的Real-time RT PCR相对定量方法可以有效的对金黄色葡萄球菌的基因表达进行分析.     

安徽南陵下三叠统青龙组鲎类足迹化石的发现

这是在我国首次发现的鲎类足迹化石,标本采自安徽南陵下三叠统青龙组薄层灰岩。除对它们的形态特征加以描述、分析和比较外,还就其形成环境及保存特点作了初步的探讨。     

The genomic basis of high-elevation adaptation in wild house mice (Mus musculus domesticus) from South America

Understanding the genetic basis of environmental adaptation in natural populations is a central goal in evolutionary biology. The conditions at high elevation, particularly the low oxygen available in the ambient air, impose a significant and chronic environmental challenge to metabolically active animals with lowland ancestry. To understand the process of adaptation to these novel conditions and to assess the repeatability of evolution over short timescales, we examined the signature of selection from complete exome sequences of house mice (Mus musculus domesticus) sampled across two elevational transects in the Andes of South America. Using phylogenetic analysis, we show that house mice colonized high elevations independently in Ecuador and Bolivia. Overall, we found distinct responses to selection in each transect and largely nonoverlapping sets of candidate genes, consistent with the complex nature of traits that underlie adaptation to low oxygen availability (hypoxia) in other species. Nonetheless, we also identified a small subset of the genome that appears to be under parallel selection at the gene and SNP levels. In particular, three genes (Col22a1, Fgf14, and srGAP1) bore strong signatures of selection in both transects. Finally, we observed several patterns that were common to both transects, including an excess of derived alleles at high elevation, and a number of hypoxia-associated genes exhibiting a threshold effect, with a large allele frequency change only at the highest elevations. This threshold effect suggests that selection pressures may increase disproportionately at high elevations in mammals, consistent with observations of some high-elevation diseases in humans.     

Outgrowth promoting factor for the inner cell mass of the mouse blastocyst

When cultured individually, isolated inner cell masses (ICMs) of the mouse blastocyst form an outer layer of endoderm and remain in suspension as spherical structures for several days. Conditioned media from certain teratocarcinoma- and blastocyst-derived cell lines contain one or more outgrowth promoting factors (OPF) which facilitate attachment and outgrowth of ICMs, in some cases prior to endoderm formation. OPF adheres to culture dishes and presumably promotes ICM cell outgrowth by alteration of the substratum. Analyses indicate that the active material is a nondialyzable protein which is stable to freezing and thawing, a wide range of pH, and extended incubation at 37°C. However, inactivation takes place at 60°C for 20 min. Although these properties of OPF are in some ways similar to those of various proteins which have been implicated in cell adhesion and spreading, differences between OPF and most of these other proteins are evident. The detection of OPF activity in conditioned medium from primary cultures of embryonic and some extraembryonic cell types suggests that the factor is biologically significant, perhaps, for example, in the spreading of parietal endoderm cells along the surface of the trophoblast layer.     

Environmental footprints of British Columbia wood pellets from a simplified life cycle analysis

Purpose  

Environmental footprints of wood pellets produced in British Columbia (BC) of Canada are to be estimated based on industry surveys and published emission factor data.     

Isoliquiritigenin ameliorates caerulein‐induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages

Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone‐type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein‐induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF‐κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti‐inflammatory and anti‐fibrotic therapeutic agent for CP.