Essential role for collectrin in renal amino acid transport

Angiotensin -converting enzyme 2 (ACE2) is a regulator of the renin angiotensin system involved in acute lung failure, cardiovascular functions and severe acute respiratory syndrome (SARS) infections in mammals. A gene encoding a homologue to ACE2, termed collectrin (Tmem27), has been identified in immediate proximity to the ace2 locus. The in vivo function of collectrin was unclear. Here we report that targeted disruption of collectrin in mice results in a severe defect in renal amino acid uptake owing to downregulation of apical amino acid transporters in the kidney. Collectrin associates with multiple apical transporters and defines a novel group of renal amino acid transporters. Expression of collectrin in Xenopus oocytes and Madin-Darby canine kidney (MDCK) cells enhances amino acid transport by the transporter B(0)AT1. These data identify collectrin as a key regulator of renal amino acid uptake.     

SARS相关冠状病毒刺突糖蛋白的研究(综述)

概述了SARS—CoV的S蛋白的结构及功能相关研究。严重急性呼吸综合症相关的冠状病毒(SARS-CoV)引起2003年我国南方非典型肺炎爆发流行，波及多个国家和地区。目前全球许多学对SARS-CoV进行了广泛的研究，发现S蛋白是病毒表面的主要蛋白，它构成冠状病毒科特征性的冠状样结构，在严重急性呼吸综合症的发病机制起着关键性作用，可介导表达相关受体的宿主细胞感染。现已鉴定出SARS-CoV的S蛋白相关受体，同时它在抗病毒感染中是一个关键靶蛋白。     

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.     

Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV.     

Angiotensin-converting enzyme 2 is an essential regulator of heart function

Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.     

Bioinformatic Analysis of Putative Gene Products Encoded in SARS—HCoV Genome

The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus named as SARS-HCoV. Using bioinformatic methods, we have performed a detailed domain search. In addition to the viral structure proteins, we have found that several putative polypeptides share sequence similarity to known domains or proteins. This study may provide a basis for future studies on the infection and replication process of this notorious virus.     

新生儿胎粪吸入综合征的临床分型与治疗

目的：探讨新生儿胎粪吸入综合征（ＭＡＳ）的临床分型与治疗的关系。方法：对１８６例ＭＡＳ患儿临床资料进行回顾性分析,根据临床症状、体征及辅助检查结果,将ＭＡＳ患儿分为无症状型、普通型、急性呼吸窘迫综合征（ＡＲＤＳ）型、肺动脉高压（ＰＰＨＮ）型及肺出血型等５种临床类型;根据病情严重程度分为轻型、重型和极重型等３种临床类型。结果：在１８６例ＭＡＳ患儿中,普通型、无症状型、ＰＰＨＮ型、肺出血型及ＡＲＤＳ型     

用计算流体力学方法研究非典型肺炎病毒颗粒的分布

通过分析非典型肺炎（SARS）病毒颗粒在空气中随气流绕过建筑物后的运动过程和分布情况，研究了病毒颗粒在空气中的扩散、聚集和分布情况，得到了病毒颗粒在空气中的动态流型、相关的影响区范围以及主要扩散方向．提供了在受到病毒污染的建筑物后面设置有效隔离带的计算流体力学（CFD）研究数据，给出了一种建筑物群位置合理排列的CFD研究方法．     

AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration

The vasopressor angiotensin II regulates vascular contractility and blood pressure through binding to type 1 angiotensin II receptors (AT1; refs 1, 2). Bradykinin, a vasodepressor, is a functional antagonist of angiotensin II (ref. 3). The two hormone systems are interconnected by the angiotensin-converting enzyme, which releases angiotensin II from its precursor and inactivates the vasodepressor bradykinin. Here we show that the AT1 receptor and the bradykinin (B2) receptor also communicate directly with each other. They form stable heterodimers, causing increased activation of G alpha(q) and G alpha(i) proteins, the two major signalling proteins triggered by AT1. Furthermore, the endocytotic pathway of both receptors changed with heterodimerization. This is the first example of signal enhancement triggered by heterodimerization of two different vasoactive hormone receptors.     

ACE2、AT2R、eNOS基因与原发性高血压相关性研究

原发性高血压（EH）是一种由遗传因素和环境因素共同作用导致的严重危害人类健康的心血管疾病。高血压疾病基因的研究有助于高血压发病机制的探讨,对其早期预防和及时治疗具有十分重要的理论意义和巨大的临床应用前景。至今研究者们已经发现有一百多种基因与原发性高血压的发病有关,特别是内皮型一氧化氮合酶（eNOS）更是研究的热点。已经确定肾素血管紧张素系统（RAS）在调控心血管功能时发挥重要作用,最近又在该系统中新发现了两个成员——血管紧张素转换酶2（ACE2）和血管紧张素Ⅱ2型受体（AT2R）,但是对其研究报道较少。文章分别从eNOS,ACE2和AT2R的生物学特性和作用机制的情况,探讨其与原发性高血压的相关性。     

Regulation by angiotensin II of its receptors in resistance blood vessels

The sensitivity of blood vessels to the vasoconstrictor effects of the hormone angiotensin II appears to be modulated by the activity of the renin-angiotensin system. Elevation of circulating angiotensin II levels by sodium depletion or renal artery stenosis is associated with a diminished pressor response to infused angiotensin II (refs 1-3). Conversely, the vasocontrictor response to the hormone is enhanced when endogenous angiotensin II levels are reduced by sodium loading or nephrectomy. The mechanisms of these varying effects are not known, but physiological and pharmacological experiments suggest involvement of the vascular smooth receptor for angiotensin II (refs 5-8). Modification of the interaction between angiotensin II and its vascular receptor, resulting in altered responsiveness to the hormone, could occur either via 'prior occupancy' of receptors by elevated levels of endogenous angiotensin II resulting in fewer free receptors available to respond to circulating angiotensin II (ref. 5), or, elevated levels of angiotensin II could result in a decrease in receptor affinity for the hormone or a decrease in total receptor number in the vascular smooth muscle cell. We now report the first direct evidence, by radioligand binding assay, that angiotensin II regulates the number of its own receptors in resistance vasculature.     

Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor

Angiotensin II is an important effector molecule controlling blood pressure and volume in the cardiovascular system. Its importance is manifested by the efficacy of angiotensin-converting enzyme inhibitors in the treatment of hypertension and congestive heart failure. Angiotensin II interacts with two pharmacologically distinct subtypes of cell-surface receptors, AT1 and AT2. AT1 receptors seem to mediate the major cardiovascular effects of angiotensin II. Here we report the isolation by expression cloning of a complementary DNA encoding a unique protein with the pharmacological specificity of a vascular AT1 receptor. Hydropathic modelling of the deduced protein suggests that it shares the seven-transmembrane-region motif with the G protein-coupled receptor superfamily. Knowledge of the AT1 receptor primary sequence should now permit structural analysis, definition of the angiotensin II receptor gene family and delineation of the contribution of AT receptors to the genetic component of hypertension.     

传染性非典型肺炎病毒核蛋白的表达与活性检测

用PCR方法，人工合成传染性非典型肺炎病毒(SARS-CoV)核蛋白(N)全编码基因，并构建原核表达载体．在大肠杆菌中进行表达．结果重组N蛋白表达产量占菌体总蛋白的40％以上，主要以可溶形式存在．用SARS患者急性期血清进行蛋白印迹检测，表明可溶形式和包含体形式均有明显活性．包含体形式的重组蛋白经纯化后纯度可达90％以上，活性与纯化前相当，可作为SARS抗体诊断试剂盒的抗原原料．     

SARS的研究进展

2003年3月,发现SARS病原是一种从未在人类或动物中发现过的新的冠状病毒.其基因组结构与其他的冠状病毒相似,由29727核苷酸组成,有11个开放阅读框.通过多基因分析序列比较说明,SARS冠状病毒与已知的冠状病毒无关.针对SARS冠状病毒的各种特征及研究进展进行了综述.     

冠状病毒主蛋白酶及其化学抑制剂研究进展

一个新的冠状病毒已经被鉴定为急性呼吸道综合症(SARS)的病原体,控制该病毒复制复合体活性的主蛋白酶(Mpro或3CLpro)将很可能成为开发针对SARS特效治疗药物的靶位点.综述了人冠状病毒株229E(HCoV 229E)和一种在猪体内引发传染性胃肠炎的病毒(TGEV)的Mpro的晶体结构以及以此为基础构建的SARS冠状病毒(SARS-CoV)同源蛋白酶的空间结构模型.通过对这些同源蛋白酶的结构及其与已知的蛋白酶化学抑制剂的结合特征进行分析后发现Mpro的底物结合位点具有惊人的保守性,这种保守性也被重组SARS-CoV Mpro能介导的TGEV Mpro的底物剪切实验所进一步证实.分子模型表明已有的鼻病毒3Cpro抑制剂经过改进后或许能用于SARS的治疗.     

引起人非典型性肺炎的冠状病毒基因组与其它冠状病毒基因组的初步比较

一种在世界范围内突然爆发的致命流行病——急性呼吸窘迫综合症(SARS)击倒了数干人，一种全新的冠状病毒被认为是其病原．5个SARS相关冠状病毒的全基因组序列已经完成．我们进行了SARS相关冠状病毒和其它冠状病毒的基因组进化分析和序列比较，结果显示：1．SARS相关冠状病毒不直接来自于任何已知的冠状病毒；2．E蛋白的基因可能是在近期从其它病毒横向转移到SARS病毒中来的；3．Sl和S2基因发生了较大范围的缺失或插入突变．这些基因横向转移和突变改变了SARS相关病毒的表面结构和抗原性，极有可能是导致其获得侵染人类细胞的主要原因．     

Captopril (SQ 14225) depresses drinking and aldosterone in rats lacking vasopressin.

Angiotensin II is dipsogenic, and vasopressin (ADH) regulates renal water excretion. Together, these hormones govern overall mammalian water balance. The Brattleboro rat with inherited diabetes insipidus (DI) lacks ADH and is therefore a convenient model with which to elucidate mechanisms regulating water metabolism. In the present studies, angiotensin II has also been removed from DI rats by the administration of an inhibitor (captopril, SQ 14225; D-2-methyl-3-mercaptopropanoyl-L-proline) of the enzyme which converts angiotensin I, the relatively inert component of the renin-angiotensin system, to angiotensin II, the biologically active substance. SQ 14225 reduced the drinking rates, and after 6 days lowered peripheral plasma aldosterone concentrations were associated with hyperkalaemia. We conclude that the polydipsia of diabetes insipidus partly results from elevated plasma renin activities and angiotensin II concentrations seen in this syndrome. Further, the apparent hypoaldosteronism of DI Brattleboro rats reflects differences in both tissue usage of the steroid and adrenocortical sensitivities associated with polyuria, hyperosmolarity and possibly potassium wasting.     

全球冠状病毒科研态势及研究热点分析

 2019年12月以来，一种新型冠状病毒感染引起的急性呼吸道传染病蔓延全球。新型冠状病毒是目前已知的第7种可以感染人的冠状病毒，20世纪以来已知的另外2种可以引起比较严重人类疾病的冠状病毒为2003年爆发的严重急性呼吸综合征冠状病毒和2012年的中东呼吸综合征冠状病毒。自冠状病毒发现以来，国内外学者针对冠状病毒已进行了大量研究，本文基于文献计量、内容分析等方法，对全球冠状病毒的研究态势进行揭示，并对冠状病毒的研究热点及研究趋势进行分析。     

Protein Subcellular Localization Prediction and Genomic Polymorphism Analysis of the SARS Coronavirus

Introduction In March 2003, a novel coronavirus (CoV) was dis-covered in association with the outbreak of severe acute respiratory syndrome (SARS)[1-3]. The complete genome sequence of several SARS-CoV isolates was soon determined and characterized[4,5]. Comparison of variant SARS-CoV genome sequences has identified certain genetic signatures that can be used to trace sources of infection[6]. Vaccines are now being devel-oped and molecular modeling has suggested that modi-fied rhinovir…     

A Coordination Model of Gene Sequences for SARS-CoV and its Receptor

IntroductionFrom the emergence of SARS CoV, manystudies havebeen done on its biological medicine aspects, such aspathogeny characteristics, mechanisms of causing disease,clinic diagnosis and treatment, bacterin development andthe spreading rules. At the level of molecule biology,studies have been done on its genome sequences characteristics, structures and functions of the translatedproteins, and the evolution relationships in sequences[1 5].The caus…