Mathematical Insights in Evaluating State Dependent Effectiveness of HIV Prevention Interventions

Mathematical models have been used to simulate HIV transmission and to study the use of preexposure prophylaxis (PrEP) for HIV prevention. Often a single intervention outcome over 10 years has been used to evaluate the effectiveness of PrEP interventions. However, different metrics express a wide variation over time and often disagree in their forecast on the success of the intervention. We develop a deterministic mathematical model of HIV transmission and use it to evaluate the public-health impact of oral PrEP interventions. We study PrEP effectiveness with respect to different evaluation methods and analyze its dynamics over time. We compare four traditional indicators, based on cumulative number or fractions of infections prevented, on reduction in HIV prevalence or incidence and propose two additional methods, which estimate the burden of the epidemic to the public-health system. We investigate the short and long term behavior of these indicators and the effects of key parameters on the expected benefits from PrEP use. Our findings suggest that public-health officials considering adopting PrEP in HIV prevention programs can make better informed decisions by employing a set of complementing quantitative metrics.     

Identifying foldable regions in protein sequence from the hydrophobic signal

Structural genomics initiatives aim to elucidate representative 3D structures for the majority of protein families over the next decade, but many obstacles must be overcome. The correct design of constructs is extremely important since many proteins will be too large or contain unstructured regions and will not be amenable to crystallization. It is therefore essential to identify regions in protein sequences that are likely to be suitable for structural study. Scooby-Domain is a fast and simple method to identify globular domains in protein sequences. Domains are compact units of protein structure and their correct delineation will aid structural elucidation through a divide-and-conquer approach. Scooby-Domain predictions are based on the observed lengths and hydrophobicities of domains from proteins with known tertiary structure. The prediction method employs an A*-search to identify sequence regions that form a globular structure and those that are unstructured. On a test set of 173 proteins with consensus CATH and SCOP domain definitions, Scooby-Domain has a sensitivity of 50% and an accuracy of 29%, which is better than current state-of-the-art methods. The method does not rely on homology searches and, therefore, can identify previously unknown domains.     

西双版纳片断热带雨林土壤动物组成的比较

本文对西双版纳国家自然保护区勐仑片和城子,曼峨,曼养广傣族“龙山”４个热带雨林片断土壤动物群落组成及其季节性变动规律进行了比较研究。调查方法：在每片森林沿直角线路布设７个样点,每点取５０ｃｍ×５０ｃｍ面积的枯枝落叶及表层土,用于漏斗法收集土壤动物。干季和雨季各取样１人,统计单面积个体数理。     

Relationship between leaf photosynthetic function at grain filling stage and yield in super high-yielding hybrid rice (<Emphasis Type="Italic">Oryza sativa</Emphasis>. L)

The characteristics of dry matter production before and after heading and the relationships between photosynthesis of flag leaves and dry matter accumulation in panicles were investigated on super high-yielding rice cv. Xieyou 9308 (the yield of up to 12 t/ha) with rice cv. Xieyou 63 as a control. The results showed that (i) the capacity of dry matter production before and after heading in Xieyou 9308, i.e. biomass and daily dry matter production, was remarkably higher than that in Xieyou 63, especially after heading; (ii) CO₂ assimilation capacity in flag leaves in Xieyou 9308, namely Leaf Source Capacity (LSC), was also significantly higher than that in Xieyou 63, and the supply of photosynthate in leaves and the demand of grain filling were completely synchronous in Xieyou 9308, but photosynthetic function in flag leaves in Xieyou 63 declined sharply 20 days after heading and it was not enough to meet the demand of grain filling. These results confirmed that high efficient photosynthetic function in leaves after heading and its complete synchronization with grain filling are the key approaches to super high yield of rice.     

Cryo-electron microscopy structure of the intact photosynthetic light-harvesting antenna-reaction center complex from a green sulfur bacterium

The photosynthetic reaction center complex (RCC) of green sulfur bacteria (GSB) consists of the membrane-imbedded RC core and the peripheric energy transmitting proteins called Fenna–Matthews–Olson (FMO). Functionally, FMO transfers the absorbed energy from a huge peripheral light-harvesting antenna named chlorosome to the RC core where charge separation occurs. In vivo, one RC was found to bind two FMOs, however, the intact structure of RCC as well as the energy transfer mechanism within RCC remain to be clarified. Here we report a structure of intact RCC which contains a RC core and two FMO trimers from a thermophilic green sulfur bacterium Chlorobaculum tepidum at 2.9 Å resolution by cryo-electron microscopy. The second FMO trimer is attached at the cytoplasmic side asymmetrically relative to the first FMO trimer reported previously. We also observed two new subunits (PscE and PscF) and the N-terminal transmembrane domain of a cytochrome-containing subunit (PscC) in the structure. These two novel subunits possibly function to facilitate the binding of FMOs to RC core and to stabilize the whole complex. A new bacteriochlorophyll (numbered as 816) was identified at the interspace between PscF and PscA-1, causing an asymmetrical energy transfer from the two FMO trimers to RC core. Based on the structure, we propose an energy transfer network within this photosynthetic apparatus.     

Effect of self-association on the structural organization of partially folded proteins: inactivated actin

The propensity to associate or aggregate is one of the characteristic properties of many nonnative proteins. The aggregation of proteins is responsible for a number of human diseases and is a significant problem in biotechnology. Despite this, little is currently known about the effect of self-association on the structural properties and conformational stability of partially folded protein molecules. G-actin is shown to form equilibrium unfolding intermediate in the vicinity of 1.5 M guanidinium chloride (GdmCl). Refolding from the GdmCl unfolded state is terminated at the stage of formation of the same intermediate state. An analogous form, known as inactivated actin, can be obtained by heat treatment, or at moderate urea concentration, or by the release of Ca(2+). In all cases actin forms specific associates comprising partially folded protein molecules. The structural properties and conformational stability of inactivated actin were studied over a wide range of protein concentrations, and it was established that the process of self-association is rather specific. We have also shown that inactivated actin, being denatured, is characterized by a relatively rigid microenvironment of aromatic residues and exhibits a considerable limitation in the internal mobility of tryptophans. This means that specific self-association can play an important structure-forming role for the partially folded protein molecules.     

Tumorhead, a Xenopus gene product that inhibits neural differentiation through regulation of proliferation

Tumorhead (TH) is a novel maternal gene product from Xenopus laevis containing several basic domains and a weak coiled-coil. Overexpression of wild-type TH resulted in increased proliferation of neural plate cells, causing expansion of the neural field followed by neural tube and craniofacial abnormalities. Overexpressed TH protein repressed neural differentiation and neural crest markers, but did not inhibit the neural inducers, pan-neural markers or mesodermal markers. Loss of function by injection of anti-TH antibody inhibited cell proliferation. Our data are consistent with a model in which tumorhead functions in regulating differentiation of the neural tissues but not neural induction or determination through its effect on cell proliferation.     

Effects of structure on inhibitory activity in a series of mechanism-based inhibitors of human neutrophil elastase

A structurally-diverse series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-one 1,1 dioxide scaffold were synthesized and used to probe the S′ subsites of human neutrophil elastase (HNE) and neutrophil proteinase 3 (Pr 3). Several compounds are potent inhibitors of HNE but devoid of inhibitory activity toward Pr 3, suggesting that the S′ subsites of HNE exhibit significant plasticity and can, unlike Pr 3, tolerate various large hydrophobic groups. The results provide a promising framework for the design of highly selective inhibitors of the two enzymes.