Distribution, abundance, and utilization of wild berries by the gwich’in people in the Mackenzie River Delta region

This paper examines the abundance and Aboriginal use of botanical non-timber forest products in the Gwich’in Settlement Area in the Northwest Territories, Canada. Informants indicated that wild berries are important to Gwich’in diets and an important factor in culture and traditional land use. People collected mostly cloudberries (Rubus chamaemorus), blueberries (Vaccinium uliginosum), and lingonberries (Vaccinium vitisidaea). The total quantities collected were estimated to be greater than other published accounts of berry gathering by northern Aboriginal peoples in North America. The total collected by the 450 households in the year 2000 was about 16,000 L. Inventories of wild berries on the landscape suggest that substantial quantities could be collected for commercial production, although the between-year supply can show considerable variation.     

Risk of Cardiovascular Disease from Antiretroviral Therapy for HIV: A Systematic Review

Background

Recent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease.

Purpose

We performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI).

Data Sources

We searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts.

Study Selection

Eligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes.

Data Extraction

Eligibility screening, data extraction, and quality assessment were performed independently by two investigators.

Data Synthesis

Random effects methods and Fisher’s combined probability test were used to summarize evidence.

Findings

Twenty-seven studies met inclusion criteria, with 8 contributing to a formal meta-analysis. Findings based on two observational studies indicated an increase in risk of MI for patients recently exposed (usually defined as within last 6 months) to abacavir (RR 1.92, 95% CI 1.51–2.42) and protease inhibitors (PI) (RR 2.13, 95% CI 1.06–4.28). Our analysis also suggested an increased risk associated with each additional year of exposure to indinavir (RR 1.11, 95% CI 1.05–1.17) and lopinavir (RR 1.22, 95% CI 1.01–1.47). Our findings of increased cardiovascular risk from abacavir and PIs were in contrast to four published meta-analyses based on secondary analyses of randomized controlled trials, which found no increased risk from cardiovascular disease.

Conclusion

Although observational studies implicated specific drugs, the evidence is mixed. Further, meta-analyses of randomized trials did not find increased risk from abacavir and PIs. Our findings that implicate specific ARTs in the observational setting provide sufficient evidence to warrant further investigation of this relationship in studies designed for that purpose.     

鄱阳湖湿地景观恢复的物种选择及其对环境因子的响应

湿地是重要的生态系统,对人类和野生生物都具有极其重要的价值。由于自然因素的变化和人类活动的干扰,湿地退化严重。近年来,湿地恢复已成为世界环境问题改善的重要工具之一。选择适用的湿地植物是退化湿地恢复的关键途径。本文以鄱阳湖湿地为研究对象,通过专家赋值、野外调查、定位观测等方法,筛选了苦草、野菱、芦苇、苔草等25种鄱阳湖常见植物作为湿地景观恢复的优先物种。对苦草、黑藻、菹草、菖蒲、芦苇等5种植物对环境因子的响应进行观测。结果表明,苦草在清水环境130-140cm处的生长最好;黑藻在清水环境中100-110cm处的生长最好;菹草在不同水深(50-160cm)下都能够生长,菹草高度随水深增加而增加;菖蒲具有一定的耐淹能力(< 80cm),但完全淹水(水深100-120cm)明显影响到菖蒲根状茎萌发、幼苗生长和生物量的积累;芦苇根状茎萌发对水深要求严格,土壤要湿润且透气性良好才是芦苇萌发的最好条件,芦苇根状茎萌发前淹水超过20 cm其萌发将会受到明显抑制,淹水超过30 cm则无法萌发。通过对沉水植物的透明度研究表明,植物对水质的透明度都有一定的要求,透明度较好更利于湿地植物的生长发育。     

Engineering Anthrax Toxin Variants That Exclusively Form Octamers and Their Application to Targeting Tumors

Anthrax toxin protective antigen (PA) delivers its effector proteins into the host cell cytosol through formation of an oligomeric pore, which can assume heptameric or octameric states. By screening a highly directed library of PA mutants, we identified variants that complement each other to exclusively form octamers. These PA variants were individually nontoxic and demonstrated toxicity only when combined with their complementary partner. We then engineered requirements for activation by matrix metalloproteases and urokinase plasminogen activator into two of these variants. The resulting therapeutic toxin specifically targeted cells expressing both tumor associated proteases and completely stopped tumor growth in mice when used at a dose far below that which caused toxicity. This scheme for obtaining intercomplementing subunits can be employed with other oligomeric proteins and potentially has wide application.     

Evaluation of amidoxime derivatives as prodrug candidates of potent bis-cationic antimalarials

Plasmodium falciparum is responsible for most of the cases of malaria and its resistance to established antimalarial drugs is a major issue. Thus, new chemotherapies are needed to fight the emerging multi-drug resistance of P. falciparum malaria, like choline analogues targeting plasmodial phospholipidic metabolism. Here we describe the synthesis of amidoxime derivatives as prodrug candidates of reverse-benzamidines and hybrid compounds able to mimic choline, as well as the design of a new series of asymmetrical bis-cationic compounds. Bioconversion studies were conducted on amidoximes in asymmetrical series and showed that amidoxime prodrug strategy could be applied on C-alkylamidine moieties, like benzamidines and that N-substituents did not alter the bioconversion of amidoximes. The antimalarial activity of the three series of compounds was evaluated in vitro against P. falciparum and in vivo against P. vinckei petteri in mice.     

Drawbacks in the use of unconventional hydrophobic anhydrides for histone derivatization in bottom‐up proteomics PTM analysis

MS‐based proteomics has become the most utilized tool to characterize histone PTMs. Since histones are highly enriched in lysine and arginine residues, lysine derivatization has been developed to prevent the generation of short peptides (<6 residues) during trypsin digestion. One of the most adopted protocols applies propionic anhydride for derivatization. However, the propionyl group is not sufficiently hydrophobic to fully retain the shortest histone peptides in RP LC, and such procedure also hampers the discovery of natural propionylation events. In this work we tested 12 commercially available anhydrides, selected based on their safety and hydrophobicity. Performance was evaluated in terms of yield of the reaction, MS/MS fragmentation efficiency, and drift in retention time using the following samples: (i) a synthetic unmodified histone H3 tail, (ii) synthetic modified histone peptides, and (iii) a histone extract from cell lysate. Results highlighted that seven of the selected anhydrides increased peptide retention time as compared to propionic, and several anhydrides such as benzoic and valeric led to high MS/MS spectra quality. However, propionic anhydride derivatization still resulted, in our opinion, as the best protocol to achieve high MS sensitivity and even ionization efficiency among the analyzed peptides.     

Modeling and analysis of protein design under resource constraints.

The potency, or fitness, of a protein-based drug can be enhanced by changing the sequence of its underlying protein. We present a novel stochastic model for the sequence-fitness relation, and estimate its four parameters from industrial data. Using this model, we formulate and analyze two variants of the protein design problem. In the single-period design problem, the designer needs to decide under capacity constraints which set of sequences to screen in order to maximize the expected fitness of the best sequence in the set. In the more general two-period design problem, the designer can afford two screening rounds and needs to allocate resources optimally across the two periods to maximize the same objective function. Analytical and simulation results allow us to assess the utility of the proposed design strategies for various parameter regimes.     

Essential gene acquisition destabilizes plasmid inheritance

Extra-chromosomal genetic elements are important drivers of evolutionary transformations and ecological adaptations in prokaryotes with their evolutionary success often depending on their ‘utility’ to the host. Examples are plasmids encoding antibiotic resistance genes, which are known to proliferate in the presence of antibiotics. Plasmids carrying an essential host function are recognized as permanent residents in their host. Essential plasmids have been reported in several taxa where they often encode essential metabolic functions; nonetheless, their evolution remains poorly understood. Here we show that essential genes are rarely encoded on plasmids; evolving essential plasmids in Escherichia coli we further find that acquisition of an essential chromosomal gene by a plasmid can lead to plasmid extinction. A comparative genomics analysis of Escherichia isolates reveals few plasmid-encoded essential genes, yet these are often integrated into plasmid-related functions; an example is the GroEL/GroES chaperonin. Experimental evolution of a chaperonin-encoding plasmid shows that the acquisition of an essential gene reduces plasmid fitness regardless of the stability of plasmid inheritance. Our results suggest that essential plasmid emergence leads to a dose effect caused by gene redundancy. The detrimental effect of essential gene acquisition on plasmid inheritance constitutes a barrier for plasmid-mediated lateral gene transfer and supplies a mechanistic understanding for the rarity of essential genes in extra-chromosomal genetic elements.