人类乙型肝炎样病毒核心蛋白中第7位疏水性氨基酸重复肚段区域的突变可以抑制病毒核衣壳的组装

人类乙型肝炎病毒的核衣壳由核心蛋白的二聚体所组成．但是,核心蛋白亚单位与亚单位之间相互作用的机制至今尚不清楚．研究发现,在人类乙型肝炎样病毒──土拨鼠肝炎病毒（WHV）核心蛋白的氨基端,存在着4个保守的疏水氨基酸残基（氨基酸位置101～102）．它们分别是亮氨酸101,亮氨酸108,缬氨酸115和苯丙氨酸122．这4个疏水氨基酸残基以每隔6个氨基酸残基而重复出现1次．它们被称为“第7位疏水性氨基酸重复肽段（hhr）”．由于蛋白质中的疏水键往往在蛋白质的相互作用中起重要作用,因此就在培养细胞系统中研究WHV核心蛋白的hhr区域在…     

The forecasting attributes of trend- and difference-stationary representations for macroeconomic time series

We analyse the forecasting attributes of trenc and diffence-stationary representations of the U.S. macroeconomic time series sudied by Nelson and Plosser (1982). Predictive densities based on models estimated for these series (which terminate in 1970) are compared with subsequent realizations compiled by Schotman and van Dijk (1991) which terminate in (1988). Predictive densities obtained using the, extended series are also derived to assess the impact of the subsequent realization on long-range forecasts. Of particular interest are comparisons of the average intervals of predictive densities corresponding to the competing specifications In general, we find that coverage intervals based on diference-stationary specifications are far wider than those based or. trend-stationary specifications for the real series, and slightly wider for the nominal series. This additional width is often a virtue in forecasting nuninal series over the 1971-1988 period, as the inflation experienced durnig this time was unprecedented in the 1900s. However, the evolution of the real series has been relatively stable in the 1900s, hence the uncertainty associated with difference-stationary specifications generally seems excessive for these data.     

An efficient algorithm for supertrees

Givenk rooted binary treesA ₁, A₂, ..., A_k, with labeled leaves, we generateC, a unique system of lineage constraints on common ancestors. We then present an algorithm for constructing the set of rooted binary treesB, compatible with all ofA ₁, A₂, ..., A_k. The running time to obtain one such supertree isO(k ² n²), wheren is the number of distinct leaves in all of the treesA ₁, A₂, ..., A_k.     

Industry funds in universities: new guidelines emerge from Pajaro Dunes

The Pajaro Dunes conference, organized at the suggestion of Stanford University president Donald Kennedy, brought the presidents and selected faculty members of Stanford, Harvard, MIT, the University of California, and the California Institute of Technology together with senior executives from biotechnology companies which sponsor university research. It produced agreement on an 11-page statement of principles which marks an initial attempt to establish a national consensus on collaboration between universities and industry. The participants have been sent a letter, signed by 25 other university researchers and some prominent union and consumer spokesmen, calling for a second conference to explore additional points of view.     

Morphology and contact mechanics influence adhesive characteristics of Dung Beetle’s bristle and Gecko’s setae

Geckos (Gekko gecko) use their hairy setae to adhere on various solid surfaces and dung beetles (Copris ochus Motschulsky) use their hairy bristles to anti-adhere in sticky environments. We study why two hairy systems express a conflict in functions by using SEM, histological approaches and functional experiments. Adhesion models and various parameters were collected and analyzed. Based on the morphological data and functional experimental results carried out by natural and denatured gecko setae and beetle bristles, we first demonstrated that the stiffness along the hair is 1000 to 30000 times that perpendicular to the hair. This stiffness difference is the key factor leading to the two hairy systems’ functional differences. Slope of gecko setae reduces contact stiffness, increases contact points and real contact area that results in amazing adhesive abilities. On the other hand, stiff bristles in a beetle have higher contact stiffness, which reduces the real contact area and decreases the adhesion between two contact surfaces. Deformation of gecko setae destroys the hierarchical structure, increases the contact stiffness and results in a decrease of adhesion forces. Similarly, deformation of beetle bristles destroys the erect structure of the hair, interconnects the separated bristles and thus decreases the anti-adhesive functions. These observations inspire us in designing anti-adhesive and adhesive biomimetic systems.     

New evidence for human occupation of the northern Tibetan Plateau, China during the Late Pleistocene

The described stone artifacts are recovered from the 70 m-high terrace (4600 m a.s.l.) at the southeastern shore of the Siling Co on the northern Tibetan Plateau. The terrace was formed during the Interstadial period before the LGM, ca. 40-30 ka B.P. based on paleoenvironmental research. The Paleoliths from the Siling Co provide evidence for early human occupation of the northern Tibetan Plateau. They show technological and typological affinities with the European Middle Paleolithic suggesting that the early human occupation here might relate to migratory waves during the Late Pleistocene that dispersed humans across the Old World.     

Differentially methylated forms of histone H3 show unique association patterns with inactive human X chromosomes.

Studies of histone methylation have shown that H3 can be methylated at lysine 4 (Lys4) or lysine 9 (Lys9). Whereas H3-Lys4 methylation has been correlated with active gene expression, H3-Lys9 methylation has been linked to gene silencing and assembly of heterochromatin in mouse and Schizosaccharomyces pombe. The chromodomain of mouse HP1 (and Swi6 in S. pombe) binds H3 methylated at Lys9, and methylation at this site is thought to mark and promote heterochromatin assembly. We have used a well-studied model of mammalian epigenetic silencing, the human inactive X chromosome, to show that enrichment for H3 methylated at Lys9 is also a distinguishing mark of facultative heterochromatin. In contrast, H3 methylated at Lys4 is depleted in the inactive X chromosome, except in three 'hot spots' of enrichment along its length. Chromatin immunoprecipitation analyses further show that Lys9 methylation is associated with promoters of inactive genes, whereas Lys4 methylation is associated with active genes on the X chromosome. These data demonstrate that differential methylation at two distinct sites of the H3 amino terminus correlates with contrasting gene activities and may be part of a 'histone code' involved in establishing and maintaining facultative heterochromatin.     

Resculpting the binding pocket of APC superfamily LeuT-fold amino acid transporters

Amino acid transporters are essential components of prokaryote and eukaryote cells, possess distinct physiological functions, and differ markedly in substrate specificity. Amino acid transporters can be both drug targets and drug transporters (bioavailability, targeting) with many monogenic disorders resulting from dysfunctional membrane transport. The largest collection of amino acid transporters (including the mammalian SLC6, SLC7, SLC32, SLC36, and SLC38 families), across all kingdoms of life, is within the Amino acid-Polyamine-organoCation (APC) superfamily. The LeuT-fold is a paradigm structure for APC superfamily amino acid transporters and carriers of sugars, neurotransmitters, electrolytes, osmolytes, vitamins, micronutrients, signalling molecules, and organic and fatty acids. Each transporter is specific for a unique sub-set of solutes, specificity being determined by how well a substrate fits into each binding pocket. However, the molecular basis of substrate selectivity remains, by and large, elusive. Using an integrated computational and experimental approach, we demonstrate that a single position within the LeuT-fold can play a crucial role in determining substrate specificity in mammalian and arthropod amino acid transporters within the APC superfamily. Systematic mutation of the amino acid residue occupying the equivalent position to LeuT V104 titrates binding pocket space resulting in dramatic changes in substrate selectivity in exemplar APC amino acid transporters including PAT2 (SLC36A2) and SNAT5 (SLC38A5). Our work demonstrates how a single residue/site within an archetypal structural motif can alter substrate affinity and selectivity within this important superfamily of diverse membrane transporters.