Neurophysiological mechanisms underlying face processing within and beyond the temporal cortical visual areas.

The ways in which information about faces is represented and stored in the temporal lobe visual areas of primates, as shown by recordings from single neurons in macaques, are considered. Some neurons that respond primarily to faces are found in the cortex in the anterior part of the superior temporal sulcus (in which neurons are especially likely to be tuned to facial expression and to face movement involved in gesture), and in the TE areas more ventrally forming the inferior temporal gyrus (in which neurons are more likely to have responses related to the identity of faces). Quantitative studies of the responses of the neurons that respond differently to the faces of different individuals show that information about the identity of the individual is represented by the responses of a population of neurons, that is, ensemble encoding rather than 'grandmother cell' encoding is used. It is argued that this type of tuning is a delicate compromise between very fine tuning, which has the advantage of low interference in neuronal network operations but the disadvantage of losing the useful properties (such as generalization, completion and graceful degradation) of storage in neuronal networks, and broad tuning, which has the advantage of allowing these properties of neuronal networks to be realized but the disadvantage of leading to interference between the different memories stored in an associative network. There is evidence that the responses of some of these neurons are altered by experience so that new stimuli become incorporated in the network. It is shown that the representation that is built in temporal cortical areas shows considerable invariance for size, contrast, spatial frequency and translation. Thus the representation is in a form which is particularly useful for storage and as an output from the visual system. It is also shown that one of the representations that is built is object based, which is suitable for recognition and as an input to associative memory, and that another is viewer centred, which is appropriate for conveying information about gesture. Ways are considered in which such cortical representations might be built by competitive self-organization aided by back projections in the multi-stage cortical processing hierarchy which has convergence from stage to stage.     

Cytoplasmic localization of the ORF2 protein of hepatitis E virus is dependent on its ability to undergo retrotranslocation from the endoplasmic reticulum

Hepatitis E virus (HEV) is a positive-strand RNA virus that is prevalent in much of the developing world. ORF2 is the major capsid protein of HEV. Although ORF2 is an N-linked glycoprotein, it is abundantly located in the cytoplasm in addition to having membrane and surface localization. The mechanism by which ORF2 protein obtains access to the cytoplasm is unknown. In this report, we prove that initially all ORF2 protein is present in the endoplasmic reticulum and a fraction of it becomes retrotranslocated to the cytoplasm. The ability of ORF2 to be retrotranslocated is dependent on its glycosylation status and follows the canonical dislocation pathway. However, in contrast to general substrates of the dislocation pathway, retrotranslocated ORF2 protein is not a substrate of the 26S proteasome complex and is readily detectable in the cytoplasm in the absence of any protease inhibitor, suggesting that the retrotranslocated protein is stable in the cytoplasm. This study thus defines the pathway by which ORF2 obtains access to the cytoplasm.     

Cysteinesulfonate and beta-sulfopyruvate metabolism. Partitioning between decarboxylation, transamination, and reduction pathways

L-Cysteinesulfonate (L-cysteate) is present in plasma, urine, and tissues in concentrations comparable to that of L-cysteinesulfinate, the primary oxidative metabolite of L-cysteine. Although cysteinesulfonate is known to be decarboxylated to taurine by cysteinesulfinate decarboxylase, the occurrence and importance of other metabolisms has not been examined. The present studies indicate that cysteinesulfonate partitions in vivo between decarboxylation and transamination; the latter reaction is catalyzed by aspartate aminotransferase and yields beta-sulfopyruvate. Whereas beta-sulfinylpyruvate, the product of cysteinesulfinate transamination, decomposes spontaneously, beta-sulfopyruvate is stable and is reduced by malate dehydrogenase to beta-sulfolactate. When L-[1-14C]cysteinesulfonate is given to mice, 60-75% is decarboxylated to taurine and about 25% is excreted in the urine as beta-sulfolactate. beta-Sulfo[1-14C] pyruvate is found to partition about equally between beta-sulfolactate and cysteinesulfonate formation; greater than 90% of the latter is decarboxylated. Parenterally administered beta-sulfo[1-14C]lactate is mostly excreted in the urine, but 12% is metabolized via beta-sulfopyruvate and cysteinesulfonate to 14CO2 and taurine. beta-Sulfopyruvate is not excreted, and only traces of sulfoacetate, perhaps formed by oxidative decarboxylation, are detected. These studies establish that cysteinesulfonate, beta-sulfopyruvate, and beta-sulfolactate are reversibly interconverted in vivo. Since only cysteinesulfonate is directly metabolized to CO2, the rate of 14CO2 formation from L-[1-14C]cysteinesulfonate is a valid measure of total cysteinesulfinate decarboxylase activity in vivo; use of this assay permits inhibitor effects to be accurately determined in intact mice. Thus, whereas in vitro assays indicate that beta-methyleneaspartate inhibits brain, liver, and kidney cysteinesulfinate decarboxylase by 0, greater than 60, and 90%, respectively, in vivo studies with L-[1-14C]cysteinesulfonate show net metabolic inhibition is about 40%.     

Children as means and ends in large-scale medical research

This paper considers the often-expressed fear that medical research may use children merely as means, and not respect them as ends in themselves - especially insofar as they are deemed less able to consent than adults. The main focus is on large-scale genetic, socio-medical and epidemiological research. The theoretical starting point of the paper is that to be treated as an end in oneself is to be regarded as - and to act as - a participant in cooperative endeavours. This participatory status is certainly connected with individual authority to consent and dissent; and there is no doubt that consent plays an important role when adults participate in many research projects. However, insofar as consent is located within structures of human cooperation, the authority to consent is not a straightforward privilege. Rather, consent is bound up with responsibility for one's choices and commitment to shared terms of cooperation. Given this understanding, it is argued that consent should not be our principal concern when we involve children in research. This is not because of children's (possible) incompetence to consent as such, but rather because children are still learning how to respect and assess the cooperative terms involved in our institutional lives. Instead, our leading concern should be with the terms regulating their involvement in research. Given suitable safeguards, research is one way in which children may learn what it is to bear responsibilities and to act as an end in oneself - that is, to cooperate with others on reasonable terms and for worthy ends.     

ATR dependent activation of Chk2

ATM and ATR are essential regulators of DNA damage checkpoints in mammalian cells through their respective effectors, Chk2 and Chk1. Cross regulation of the ATM-Chk2 and ATR-Chk1 pathways is very limited, although ATM and ATR show overlapping function in a partnership and time-dependent manner. In this study, we report that Chk2 is a substrate of ATR in response to ionizing and ultraviolet radiation. ATR activation induced by ionizing radiation (IR) is weak in ATM+/+ cells. However, when ATM is inhibited by caffeine, ATR activation is markedly enhanced. Total Chk2 and Chk2 Thr68 are also hyperphosphorylated in the presence of caffeine. Both ATM+/+ and ATM-/- cells display normal ATR activation in response to UV radiation-induced DNA damage, which is caffeine sensitive. In two lines of ATM-deficient, as well as in an ATM siRNA silencing cell line, ATR is activated when the cells are exposed to IR and is able to phosphorylate Chk2 in vitro. These observations suggest that ATR is one of the kinases that is likely involved in phosphorylation of Chk2 in response to IR when ATM is deficient.     

Valoración funcional en la demencia grave

Severe dementia is currently one of the main causes of dependence and is defined as cognitive impairment that interferes with the performance of basic activities of daily living. However, in clinical practice severe dementia is difficult to define.Assessment of the ability to perform activities of daily living is a key factor in patients with severe dementia, since functional impairment is a defining feature. Assessment allows an accurate prognosis to be made and a care plan to be established, as well as the effectiveness of the intervention to be evaluated, when necessary.Functional assessment in dementia is complex, since functional status is the expression of multiple interactions, especially in geriatric patients. Functional status is measured by functional scales. In severe dementia, these scales must evaluate basic activities of daily living in the different types of dementia with high sensitivity to changes and strong discriminatory capacity. They should also be culturally adapted and validated in the community and institutional settings. Consensus should be established on the use of these instruments to allow them to be standardized and their results to be compared.     

Vitamin C. Biosynthesis, recycling and degradation in mammals

Vitamin C, a reducing agent and antioxidant, is a cofactor in reactions catalyzed by Cu(+)-dependent monooxygenases and Fe(2+)-dependent dioxygenases. It is synthesized, in vertebrates having this capacity, from d-glucuronate. The latter is formed through direct hydrolysis of uridine diphosphate (UDP)-glucuronate by enzyme(s) bound to the endoplasmic reticulum membrane, sharing many properties with, and most likely identical to, UDP-glucuronosyltransferases. Non-glucuronidable xenobiotics (aminopyrine, metyrapone, chloretone and others) stimulate the enzymatic hydrolysis of UDP-glucuronate, accounting for their effect to increase vitamin C formation in vivo. Glucuronate is converted to l-gulonate by aldehyde reductase, an enzyme of the aldo-keto reductase superfamily. l-Gulonate is converted to l-gulonolactone by a lactonase identified as SMP30 or regucalcin, whose absence in mice leads to vitamin C deficiency. The last step in the pathway of vitamin C synthesis is the oxidation of l-gulonolactone to l-ascorbic acid by l-gulonolactone oxidase, an enzyme associated with the endoplasmic reticulum membrane and deficient in man, guinea pig and other species due to mutations in its gene. Another fate of glucuronate is its conversion to d-xylulose in a five-step pathway, the pentose pathway, involving identified oxidoreductases and an unknown decarboxylase. Semidehydroascorbate, a major oxidation product of vitamin C, is reconverted to ascorbate in the cytosol by cytochrome b(5) reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Transmembrane electron transfer systems using ascorbate or NADH as electron donors serve to reduce semidehydroascorbate present in neuroendocrine secretory vesicles and in the extracellular medium. Dehydroascorbate, the fully oxidized form of vitamin C, is reduced spontaneously by glutathione, as well as enzymatically in reactions using glutathione or NADPH. The degradation of vitamin C in mammals is initiated by the hydrolysis of dehydroascorbate to 2,3-diketo-l-gulonate, which is spontaneously degraded to oxalate, CO(2) and l-erythrulose. This is at variance with bacteria such as Escherichia coli, which have enzymatic degradation pathways for ascorbate and probably also dehydroascorbate.     

北京山区与城区植物组成比较

通过典型抽样法对北京山区与城区植物物种进行了调查,结果表明北京山区有植物种1283种,隶属于127科,538属,北京城区(五环内)共有维管束植物99科,307属,536种。含25种以上的科的数量在北京山区和城区都比较少,含5种以下的科的数量在北京山区和城区都比较多,而城区只含有1种植物的科要比山区多一些。植物种在属上的分布与其在科上的分布相似。城区植物中乔木、灌木和多年生草本和一年生草本的比例相差不大,而在山区,多年生草本植物优势极为明显,也是山区和城区植物种数差异的主要来源。在属级水平上,植物区系中温带成分在北京山区和城区均占有绝对优势,二者的差异主要表现在城区植物的热带成分明显高于山区,而温带成分的比例则要稍低于山区。山区和城区共有植物有329种,隶属于72科,201属。主要集中在菊科、禾本科、蔷薇科等世界性大科中。     

The fate of di-(3,5-di-tert.-butyl-4-hydroxyphenyl)methane (Ionox 22) in the rat

1. A large proportion of a single oral dose of [(14)C]Ionox 220 to rats is eliminated in 24 days: 89.3-97.4% of the label is excreted in the faeces (much of this is eliminated in the first 4 days after dosage), 1% in the urine and less than 0.1% in the expired gases; 4.06% of (14)C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 2. About 87% of (14)C in the faeces is due to unchanged antioxidant, 5% to the quinone methide, 5% to the free acid and 3% to an unidentified polar constituent. Three-fifths of (14)C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid and the remainder to the ester glucuronide. In three individual animals, one-half of (14)C in the bile is due to the free acid, one-quarter to the ester glucuronide and the remainder to unchanged antioxidant, whereas in another all of (14)C in the bile is due to Ionox 220. About 97% of (14)C in the body fat is due to unchanged antioxidant and the remainder to the free acid. 3. Up to 20% of a single oral dose of Ionox 220 is absorbed in rats: 13-14% is metabolized. 3,5-Di-tert.-butyl-4-hydroxybenzoic acid accounts for just over 5% of a dose of Ionox 220, 3,5-di-tert.-butyl-4-hydroxybenzoyl-beta-d-glucopyranosiduronic acid for less than 0.4%, the quinone methide for just over 5% and an unidentified compound for less than 3%. 4. The physiological and biochemical implications of ingesting Ionox 220 are discussed.     

Dynamic Monte Carlo simulations of globular protein folding. Model studies of in vivo assembly of four helix bundles and four member beta-barrels

As part of an ongoing series of dynamic Monte Carlo simulations of globular protein folding, the nature of the folding pathway, of model four-member beta-barrels and four-helix bundles, under highly idealized conditions in vivo, has been examined. The ribosome is crudely modeled as an inert hard wall on to which the model protein chain is attached. Three cases are considered in detail. The first corresponds to post-translational assembly in which the fully synthesized chain is tethered to the wall and starts out under strongly denaturing conditions. The system is cooled down, and the chain is allowed to fold. Interestingly, the helical motif prefers to assemble parallel to the wall, whereas the beta-barrel, predominantly assembles with its principal axis perpendicular to the wall. In the former case, the dominant intermediate, the helical hairpin, is different from that in free solution, a three-helix bundle. The wall acts to reduce the expanse of configuration space that must be searched and aids in folding. Two situations that might lead to co-translational folding are also simulated. In the first case, to eliminate wall effects, the chain is slowly synthesized in free solution, and in the second case, it is slowly synthesized from the wall. In all cases, the chains are observed to fold post-translationally. While partially folded intermediates are observed during synthesis, they lack the stability to survive until chain synthesis is complete. The implications of these results for the folding in vivo of real protein chains is discussed, and a model of multiple domain protein folding is proposed.     

Xanthine oxidoreductase is present in bile ducts of normal and cirrhotic liver

Xanthine oxidoreductase (XOR) is a widely distributed enzyme, involved in the metabolism of purines, which generates superoxide and is thought to be involved in free radical-generated tissue injury. It is present at high concentrations in the liver, from where it may be released during liver injury into the circulation, binding to vascular endothelium and causing vascular dysfunction. The cellular localization of the enzyme, essential to understanding its function, is, however, still debated. The present study has used a highly specific mouse monoclonal antibody to define the cellular distribution of XOR in normal and cirrhotic human liver. As shown previously, XOR is present in hepatocytes. However, the novel finding of this study is that XOR is present in bile duct epithelial cells, where it is concentrated toward the luminal surface. Moreover, in liver disease, proliferating bile ducts are also strongly positive for XOR. These findings suggest that the enzyme is secreted into bile, and this was confirmed by analysis of human and rat bile. Xanthine oxidase activity was 10 to 20-fold higher in liver tissue obtained from patients with liver disease, than in healthy liver. We conclude that XOR is expressed primarily in hepatocytes, but is also present in bile duct epithelial cells and is secreted into bile. Its role in bile is unknown but it may be involved in innate immunity of the bowel muscosa.     

扬子鳄视觉器官组织学研究

本文用光镜和电镜研究了扬子鳄(Alligator sinensis)的组织学,同时测量了其眼球的一些光学参数.扬子鳄眼球呈扁圆球形,角膜径与球径的比值为1:1.44;晶状体与角膜的比值为1:1.40。角膜内具鲍氏膜;虹膜内的括约肌、睫状体内的睫状肌均属横纹肌,视细胞椭圆体内线粒体嵴突与线粒体长轴相平行,这与报道的其它鳄类不同。虹膜内未见扩瞳肌纤维,角膜缘缺巩膜小骨片,晶状体环垫薄,因而其视觉调节能力仍然很弱。视网膜中视细胞由视杆细胞、单锥细胞、双锥细胞组成,其中以视杆细胞占多数。视细胞与神经节细胞核比值平均为2.5:1,表明扬子鳄的组织结构与其弱光视觉相适应。     

The yeast inositol-sensitive upstream activating sequence, UASINO, responds to nitrogen availability

The INO1 gene of yeast is expressed in logarithmically growing, wild-type cells when inositol is absent from the medium. However, the INO1 gene is repressed when inositol is present during logarithmic growth and it is also repressed as cells enter stationary phase whether inositol is present or not. In this report, we demonstrate that transient nitrogen limitation also causes INO1 repression. The repression of INO1 in response to nitrogen limitation shares many features in common with repression in response to the presence of inositol. Specifically, the response to nitrogen limitation is dependent upon the presence of a functional OPI1 gene product, it requires ongoing phosphatidylcholine biosynthesis and it is mediated by the repeated element, UASINO, found in the promoter of INO1 and other co-regulated genes of phospholipid biosynthesis. Thus, we propose that repression of INO1 in response to inositol and in response to nitrogen limitation occurs via a common mechanism that is sensitive to the status of ongoing phospholipid metabolism.     

Quantitative Estimation of Phloem Regeneration in Coleus Internodes

Phloem regeneration in Coleus internodes, earlier wounded so that one or more phloem bundles were severed, is estimated quantitatively by microscopic examination of permanent slides prepared in the following way: The wounded internode is removed from the plant after a given regeneration period, is fixed in Craf III for 24 hr and is transferred to 85% lactic acid for 12-24 hr. While still in lactic acid, a “strip”, which is composed of the phloem and all tissues peripheral to it in the internode, is peeled from the internode, leaving only the xylem-pith cylinder. The strip is stained for 6-12 hr in 0.1% aniline blue in 85% lactic acid, then is transferred to 60% alcohol containing 0.5% HCI. While in the latter solution, the epidermis, scar tissue, and most of the cortical tissue is carefully dissected from the strip while it is observed in a dissecting microscope. The strip is restained for an hour or more and is passed through two 5-10 min changes each of acidified 60% alcohol, absolute alcohol, and xylene, and is then mounted on a glass slide in damar-xylene. Counts of regenerated, interfascicular phloem strands, governed by a counting convention, which were shown to bear a fairly constant relationship to the actual number of regenerated sieve tube members, are made while examining under low and high power magnifications. This method is presently being used to study the physiology of phloem differentiation and its regulation in Coleus.     

脉压、脉压指数对肥胖预测的前瞻性队列研究

目的:分析成都地区1992年时非肥胖中年居民脉压(PP)、脉压指数(PPI)对该人群15年后(2007年)肥胖发生的预测价值。方法:本研究纳入1992年时年龄处于45～60岁且BMI正常者1017人,依据PP(PP≤60mmHg及PP>60mmHg)及PP(I PPI≤0.450及PPI>0.450)分为PP/PPI正常组及增高组,分析两组人群在15年后(2007年)BMI分布特征及肥胖的患病情况。结果:①1992年PP/PPI增高人群2007年时BMI皆高于PP/PPI正常人群,t检验示BMI组间差异有统计学意义。2007年肥胖患病率亦呈类似BMI的特点,亦为PP/PPI增高组高于PP/PPI正常组,经x2检验,肥胖患病率的组间差异有统计学意义。②根据该队列人群1992年的PP增高与否计算2007年的肥胖患病率的相对危险度(RR)为4.109,P值为0.000,95%可信区间为2.874～8.847;1992年PPI与2007年肥胖患病的RR为4.998,P值为0.000,95%可信区间为2.876～8.687。③使用logistic回归模型分析1992年基线PP/PPI对2007年肥胖患病的影响,在调整了SBP、WC、BMI、HR、TG后,PP、PPI的相对危险度仍为1.040及1.044。其各自相应95%CI分别为1.017～1.065、1.025～1.063。结论:脉压、脉压指数的异常与肥胖的发生关系密切,脉压、脉压指数可以预测肥胖的发生。     

Two distinct mechanisms segregate Prospero in the longitudinal glia underlying the timing of interactions with axons

Prospero is required in dividing longitudinal glia (LG) during axon guidance; initially to enable glial division in response to neuronal contact, and subsequently to maintain glial precursors in a quiescent state with mitotic potential. Only Prospero-positive LG respond to neuronal ablation by over-proliferating, mimicking a glial-repair response. Prospero is distributed unequally through the progeny cells of the longitudinal glioblast lineage. Just before axon contact the concentration of Prospero is higher in two of the four progeny cells, and after axon guidance Prospero is present only in six out of ten progeny LG. Here we ask how Prospero is distributed unequally in these two distinct phases. We show that before neuronal contact, longitudinal glioblasts undergo invaginating divisions, perpendicular to the ectodermal layer. Miranda is required to segregate Prospero asymmetrically up to the four glial-progeny stage. After neuronal contact, Prospero is present in only the LG that activate Notch signalling in response to Serrate provided by commissural axons, and Numb is restricted to the glia that do not contain Prospero. As a result of this dual regulation of Prospero deployment, glia are coupled to the formation and maintenance of axonal trajectories.     

Degradation of L-glutamate dehydrogenase from Escherichia coli: allosteric regulation of enzyme stability.

L-glutamate dehydrogenase (GDH) is stable in exponentially growing Escherichia coli cells but is degraded at a rate of 20-30% per hour in cells starved for either nitrogen or carbon. GDH degradation is energy-dependent, and mutations in ATP-dependent proteases, ClpAP or Lon lead to partial stabilization. Degradation is inhibited by chloramphenicol and is completely blocked in relA mutant cells, suggesting that ribosome-mediated signaling may facilitate GDH degradation. Purified GDH has a single tight site for NADPH binding. Binding of NADPH in the absence of other ligands leads to destabilization of the enzyme. NADPH-induced instability and sensitivity to proteolysis is reversed by tri- and dicarboxylic acids or nucleoside di- and triphosphates. GTP and ppGpp bind to GDH at an allosteric site and reverse the destabilizing effects of NADPH. Native GDH is resistant to degradation by several purified ATP-dependent proteases: ClpAP, ClpXP, Lon, and ClpYQ, but denatured GDH is degraded by ClpAP. Our results suggest that, in vivo, GDH is sensitized to proteases by loss of a stabilizing ligand or interaction with an destabilizing metabolite that accumulates in starving cells, and that any of several ATP-dependent proteases degrade the sensitized protein.     

维吾尔族的体质特征研究

１９９１年５月,对新疆伊梨维吾尔族５２９人（男２７１,女２５８）进行了活体观察和测量。观察２９项,测量９２项。维吾尔族的主要特征是：黑直发,黑褐色眼,眉毛较浓密,大都有上眼脸皱褶,鼻根中等偏高,大多为直形鼻,鼻尖向前,鼻基部下垂,大多有达尔文结节,耳垢湿型。头面部指数分型,属于特短头型,阔头型和高头型。身材中等偏高,平均身高男１６８．６毫米,女１５７８．８毫米。