Kinematic Analysis of Trunk-to-trunk Leaping in <Emphasis Type="Italic">Callimico goeldii</Emphasis>

Leaping to and from vertical trunks is a pattern of locomotor behavior that characterizes the positional repertoire of several prosimian and neotropical primate species. We examined the kinematics of leaping in a group of 6 captive Goeldis monkeys. We introduced a set of 2 wooden, fixed, non-compliant vertical supports in their enclosure and used 2 video cameras set at right angles to document leaping. The supports are 2.5, 6, or 15 cm in diameter and were placed at distances of between 1 and 2 m. We conducted frame-by-frame analyses of 122 leaps. The results indicate that irrespective of distance leaped and the diameter of takeoff and landing substrates, the forelimbs of {Callimico} contacted the landing platform in advance of the hind limbs. Moreover, even when leaping a horizontal distance of 2 m, {Callimico} experienced a downward vertical displacement of only 0.17 m. Several features of the shoulder and forelimb of {Callimico} appear to be associated with enhanced stability at the humeral head and radioulnar joint, and are consistent with the ability to withstand large compressive forces generated when landing on noncompliant substrates. Based on a series of kinematic equations provided by Warren and Crompton (1998a), the mechanical cost of transport in {Callimico} (5.4 m/s^–2) is greater than those of prosimian vertical clingers and leapers. However, compared to other callitrichine primates, {Callimico goeldii} is behaviorally and anatomically specialized for leaping between vertical trunks in the lowest layers of the forest understory.     

Structure conservation in cytochromes P450

The recent availability of crystal structures for several diverse cytochromes P450 (CYPs) offers the possibility to perform an up-to-date comparative analysis to identify the degree of structure conservation among this superfamily of enzymes specially relevant for their involvement in drug metabolism and toxicity. A set of 9 CYPs sharing between 10% and 27% sequence identity was selected, including 7 class I (CYP 101, 107, 108, 119, 121, 51, and 55) and two class II (CYP 102, and 2C5) structures. After obtaining a multiprotein structure superimposition, a structure-based sequence alignment was derived. Mapping the level of three-dimensional structural conservation onto the sequence alignment revealed that over 28% of the alignment positions have the Calpha carbons of their residues within a root-mean-square deviation (RMSD) of 2 A. This degree of structure conservation is found to be generally preserved, even when the structure undergoes dramatic conformational changes. Performing the analysis on 4 members of the CYP2 family (CYP 2B4, 2C5, 2C8, and 2C9), the percentage of alignment positions within 2 A RMSD amounted to 73%, increasing to over 85% when only structures in a closed conformation are considered. The present findings suggest that it should be plausible to derive models of overall good quality for the major CYP2 metabolizing forms (CYP 2A6, 2C19, 2D6, and 2E1), whereas high levels of uncertainty are still likely to be expected in models for the remaining 2 major P450 metabolizing forms (CYP 1A2 and 3A4), with the corresponding implications for their potential applicability in drug design activities.     

An observation of non-superimposable stereogeometrical features in a non-chiral one-component beta-Ala model peptide

This paper describes the chemical synthesis and crystal molecular conformation of a non-chiral beta-Ala containing model peptide Boc-beta-Ala-Acc5-OCH3. The analysis revealed the existence of two crystallographically independent molecules A and B, in the asymmetric unit. Unexpectedly, while the magnitudes of the backbone torsion angles in both molecules are remarkably similar, the signs of the corresponding torsion angles are reverse therefore, inclining us to suggest the existence of non-superimposable stereogeometrical features in a non-chiral one-component beta-Ala model system. The critical mu torsion angle around CbetaH2-CalphaH2 bond of the beta-Ala residue represents a typical gauche orientation i.e., mu = 67.7 degrees in A and mu = -61.2 degrees in B, providing the molecule an overall crescent shaped topology. The observed conformation contrasts markedly to those determined for the correlated non-chiral model peptides: Boc-beta-Ala-Acc6-OCH3 and Boc-beta-Ala-Aib-OCH3 signifying the role of stereocontrolling elements since the stereochemically constrained Calpha, alpha-disubstituted glycyl residues (e.g., Acc5, Acc6, and the prototype Aib) are known to strongly restrict the peptide backbone conformations in the 3(10)/alpha-helical-regions ( phi approximately +/-60+/-20 degrees, psi approximately +/-30+/-20 degrees) of the Ramachandran map. Unpredictably, the preferred, phi, psi torsion angles of the Acc5 residue fall outside the helical regions of the Ramachandran map and exhibit opposite-handed twists for A and B. The implications of the semi-extended conformation of the Acc5 residue in the construction of backbone-modified novel scaffolds and peptides of biological relevance are highlighted. Taken together, the results indicate that in short linear beta-Ala containing peptides specific structural changes can be induced by selective substitution of non-coded linear- or cyclic symmetrically Calpha,alpha-disubstituted glycines, reinstating the hypothesis that in addition to conformational restrictions, the chemical nature of the neighboring side-chain substituents and local environments collectively influences the stabilization of folding-unfolding behavior of the two methylene units of a beta-Ala residue.     

侵袭性曲霉菌病13例临床特点分析

目的分析侵袭性肺曲霉病(IPA)的临床特点,提高对本病的认识。方法对13例确诊的IPA患者的临床资料进行回顾性分析。结果 IPA患者中存在基础疾病或危险因素者占69.2%(9/13);临床表现包括咳嗽、黄痰(13/13)、高热(11/13)、胸闷或呼吸困难(7/13)和咯血(2/13)等;92.3%(12/13)患者有高白细胞血症,WBC大多为(15~30)×109;10例G试验检测的患者中有9例出现阳性;影像学检查:肺内多发空洞及"空气新月征"9例(69.2%),"晕轮征"2例(15.4%),支气管炎表现6例(46.2%),胸腔积液3例(23.1%),颅内播散病灶1例;气管镜检查以粘膜水肿、脓痰、管腔坏死物为主;9例患者痰培养或肺泡灌洗液培养阳性(占69.2%),所有患者病理检查均见曲霉菌丝。所有患者均接受抗真菌药物治疗,4例好转出院,9例恶化放弃治疗或死亡。结论 IPA是临床严峻挑战;掌握该病的临床特点、实验室检查和胸部影像特征,及时的气管镜、组织病理检查有助于IPA确诊。临床医师应高度重视曲霉病。     

Morphogenesis as a macroscopic self-organizing process

We start from reviewing different epistemological constructions used for explaining morphogenesis. Among them, we explore the explanatory power of a law-centered approach which includes top-down causation and the basic concepts of a self-organization theory. Within such a framework, we discuss the morphomechanical models based upon the presumption of feedbacks between mechanical stresses imposed onto a given embryo part from outside and those generated within the latter as a kind of active response. A number of elementary morphogenetic events demonstrating that these feedbacks are directed towards hyper-restoration (restoration with an overshoot) of the initial state of mechanical stresses are described. Moreover, we show that these reactions are bound together into the larger scale feedbacks. That permits to suggest a reconstruction of morphogenetic successions in early Metazoan development concentrated around two main archetypes distinguished by the blastopores geometry. The perspectives of applying the same approach to cell differentiation are outlined. By discussing the problem of positional information we suggest that the developmental pathway of a given embryo part depends upon its preceded deformations and the corresponding mechanical stresses rather than upon its static position at any moment of development.     

Designing allosteric modulators for active conformational state of m-glutamate G-protein coupled receptors

G-protein coupled receptors (GPCRs) are found to be attractive drug targets for the treatment of various neuronal diseases. Allosteric modulators have their role in enhancing or suppressing the effect of glutamate on mGluRs. Structure of mGluR1 was generated with the help of Modeller software by considering human B2-adrenergic GPCR protein as template. Structure of various already known drug molecules were used for similarity search in the ZINC database and a large number of similar molecules were obtained, than filtering of these molecules were done by applying drug features. Molecules were screened by Molegro Virtual Docking program and numbers of novel molecules were generated by using LigBuilder software. Finally 16 novel drug candidates were selected, which were showing better results than the seed molecule and previously known modulators. These results will help in designing and synthesis of better drugs against diseases like Epilepsy and Parkinson's.     

地枫皮营养器官解剖结构特征及其叶片结构的生态适应性

为了明确地枫皮的结构特征及其在石灰岩山顶和山腰疏林间两种环境下生长的叶片解剖结构的差异,本研究采用石蜡切片和半薄切片对地枫皮营养器官进行解剖观察并评价了叶片结构对不同生态环境的响应。结果表明:地枫皮根中次生维管组织发达,木射线和韧皮射线明显。老茎的次生构造中,皮层贮藏物质丰富,内有大的石细胞群,韧皮射线和木射线明显;而髓细胞内含有大量晶簇和少量单晶。在叶片横切面观上,叶为异面叶,表皮细胞一层,上表皮无气孔分布,主脉中薄壁细胞中分散有石细胞。叶片解剖结构显示,随海拔高度上升,地枫皮趋向于旱生植物的特点,其主要表现在叶片表皮细胞外壁角质层加厚,栅海比增加、海绵组织排列由紧密变疏松。另外,根皮、茎皮和叶肉中都分布有大量油细胞。     

秦岭水灾迹地油松和华山松更新种群数量特征

 不同植物种群种间比较研究利于揭示种群的形成机制和影响因素。该文研究了秦岭地区蔡玉河流域范家庄段水灾迹地恢复17年后群落优势种油松(Pinus tabulaeformis) 和华山松(P. armandii)的种群数量特征。水灾灾后第一年（1989年）就有油松和华山松个体进入迹地,由于较大的高生长速度和侧生长速度,油松种群的平均高度和地径高于华山松,占据了较大的垂直和水平空间。相对来说, 油松和华山松高度结构和径级结构模式不同,二者均是小个体数量居多,大个体数量极少,但油松中等大小个体多于华山松。油松和华山松种群的年龄结构模式不同,油松的为单峰右偏曲线,华山松的则近似于正态分布。坡向对油松的年龄结构模式没有影响,但对华山松种 群有影响。油松和华山松种群不同高度级、径级和年龄级之间存在显著正或负相关关系,缺少一致性,表明种群大小结构不一定反映年龄结构。油松和华山松种群的密度动态和存活曲线类型一致,均为Ⅱ型,表明二者具有相同的种群动态。总体上说,油松和华山松具有不同的树种生物学特性,使得种群的大小结构和年龄结构不同,但对种群更新存活动态没有影响。     

Non-masticatory uses of anterior teeth of Sima de los Huesos individuals (Sierra de Atapuerca, Spain)

In this study we examine the labial and occlusal surfaces of incisors and canines of hominins recovered from the Sima de los Huesos (SH), middle Pleistocene site, in order to establish the possible extra-masticatory use of anterior teeth. We have compared the microwear of these fossils with microwear from the anterior teeth of Australian Aborigines, a population characterized by ethnographic evidence of the use of their teeth as a third hand. These two samples of teeth were microscopically analyzed using Scanning Electron Microscopy (SEM). Our results support the “cultural” origin of microwear observed on fossil teeth: we conclude that the SH hominins used their anterior teeth as a “third hand” for para- or extra-masticatory activities.     

HIV and tuberculosis in India

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities, risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India.