A high level interface to SCOP and ASTRAL implemented in Python

Background  

Benchmarking algorithms in structural bioinformatics often involves the construction of datasets of proteins with given sequence and structural properties. The SCOP database is a manually curated structural classification which groups together proteins on the basis of structural similarity. The ASTRAL compendium provides non redundant subsets of SCOP domains on the basis of sequence similarity such that no two domains in a given subset share more than a defined degree of sequence similarity. Taken together these two resources provide a 'ground truth' for assessing structural bioinformatics algorithms. We present a small and easy to use API written in python to enable construction of datasets from these resources.     

Shr of group A streptococcus is a new type of composite NEAT protein involved in sequestering haem from methaemoglobin

A growing body of evidence suggests that surface or secreted proteins with NEAr Transporter (NEAT) domains play a central role in haem acquisition and trafficking across the cell envelope of Gram‐positive bacteria. Group A streptococcus (GAS), a β‐haemolytic human pathogen, expresses a NEAT protein, Shr, which binds several haemoproteins and extracellular matrix (ECM) components. Shr is a complex, membrane‐anchored protein, with a unique N‐terminal domain (NTD) and two NEAT domains separated by a central leucine‐rich repeat region. In this study we have carried out an analysis of the functional domains in Shr. We show that Shr obtains haem in solution and furthermore reduces the haem iron; this is the first report of haem reduction by a NEAT protein. More specifically, we demonstrate that both of the constituent NEAT domains of Shr are responsible for binding haem, although they are missing a critical tyrosine residue found in the ligand‐binding pocket of other haem‐binding NEAT domains. Further investigations show that a previously undescribed region within the Shr NTD interacts with methaemoglobin. Shr NEAT domains, however, do not contribute significantly to the binding of methaemoglobin but mediate binding to the ECM components fibronectin and laminin. A protein fragment containing the NTD plus the first NEAT domain was found to be sufficient to sequester haem directly from methaemoglobin. Correlating these in vitro findings to in vivo biological function, mutants analysis establishes the role of Shr in GAS growth with methaemoglobin as a sole source of iron, and indicates that at least one NEAT domain is necessary for the utilization of methaemoglobin. We suggest that Shr is the prototype of a new group of NEAT composite proteins involved in haem uptake found in pyogenic streptococci and Clostridium novyi.     

Exploration of potential prodrug approach of the bis-thiazolium salts T3 and T4 for orally delivered antimalarials

We report here the synthesis and biological evaluation of a series of 37 compounds as precursors of potent antimalarial bis-thiazolium salts (T3 and T4). These prodrugs were either thioester, thiocarbonate or thiocarbamate type and were synthesized in one step by reaction of an alkaline solution of the parent drug with the appropriate activated acyl group. Structural variations affecting physicochemical properties were made in order to improve oral activity. Twenty-five of them exhibited potent antimalarial activity with IC₅₀ lower than 7 nM against Plasmodium falciparum in vitro. Notably, 3 and 22 showed IC₅₀ = 2.2 and 1.8 nM, respectively. After oral administration 22 was the most potent compound clearing the parasitemia in Plasmodium vinckei infected mice with a dose of 1.3 mg/kg.     

Effects of Hygiene and Defecation Behavior on Helminths and Intestinal Protozoa Infections in Taabo,C?te d’Ivoire

Background

More than 1 billion people are currently infected with soil-transmitted helminths and schistosomes. The global strategy to control helminthiases is the regular administration of anthelmintic drugs to at-risk populations. However, rapid re-infection occurs in areas where hygiene, access to clean water, and sanitation are inadequate.

Methodology

In July 2011, inhabitants from two villages and seven hamlets of the Taabo health demographic surveillance system in south-central Côte d’Ivoire provided stool and urine samples. Kato-Katz and ether-concentration methods were used for the diagnosis of Schistosoma mansoni, soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura, and hookworm), and intestinal protozoa. Urine samples were subjected to a filtration method for the diagnosis of Schistosoma haematobium. A questionnaire was administered to households to obtain information on knowledge, attitude, practice, and beliefs in relation to hygiene, sanitation, and defecation behavior. Logistic regression models were employed to assess for associations between questionnaire data and parasitic infections.

Principal Findings

A total of 1,894 participants had complete data records. Parasitological examinations revealed prevalences of hookworm, S. haematobium, T. trichiura, S. mansoni, and A. lumbricoides of 33.5%, 7.0%, 1.6%, 1.3% and 0.8%, respectively. Giardia intestinalis and Entamoeba histolytica/E. dispar were detected in 15.0% and 14.4% of the participants, respectively. Only one out of five households reported the presence of a latrine, and hence, open defecation was common. Logistic regression analysis revealed that age, sex, socioeconomic status, hygiene, and defecation behavior are determinants for helminths and intestinal protozoa infections.

Conclusions/Significance

We found that inadequate sanitation and hygiene behavior are associated with soil-transmitted helminths and intestinal protozoa infections in the Taabo area of south-central Côte d’Ivoire. Our data will serve as a benchmark to monitor the effect of community-led total sanitation and hygiene education to reduce the transmission of helminthiases and intestinal protozoa infections.     

Whole-genome analysis of Malawian Plasmodium falciparum isolates identifies possible targets of allele-specific immunity to clinical malaria

Individuals acquire immunity to clinical malaria after repeated Plasmodium falciparum infections. Immunity to disease is thought to reflect the acquisition of a repertoire of responses to multiple alleles in diverse parasite antigens. In previous studies, we identified polymorphic sites within individual antigens that are associated with parasite immune evasion by examining antigen allele dynamics in individuals followed longitudinally. Here we expand this approach by analyzing genome-wide polymorphisms using whole genome sequence data from 140 parasite isolates representing malaria cases from a longitudinal study in Malawi and identify 25 genes that encode possible targets of naturally acquired immunity that should be validated immunologically and further characterized for their potential as vaccine candidates.     

Phosphorus supply drives rapid turnover of membrane phospholipids in the diatom Thalassiosira pseudonana

In low-phosphorus (P) marine systems, phytoplankton replace membrane phospholipids with non-phosphorus lipids, but it is not known how rapidly this substitution occurs. Here, when cells of the model diatom Thalassiosira pseudonana were transferred from P-replete medium to P-free medium, the phospholipid content of the cells rapidly declined within 48 h from 45±0.9 to 21±4.5% of the total membrane lipids; the difference was made up by non-phosphorus lipids. Conversely, when P-limited T. pseudonana were resupplied with P, cells reduced the percentage of their total membrane lipids contributed by a non-phosphorus lipid from 43±1.5 to 7.3±0.9% within 24 h, whereas the contribution by phospholipids rose from 2.2±0.1 to 44±3%. This dynamic phospholipid reservoir contained sufficient P to synthesize multiple haploid genomes, suggesting that phospholipid turnover could be an important P source for cells. Field observations of phytoplankton lipid content may thus reflect short-term changes in P supply and cellular physiology, rather than simply long-term adjustment to the environment.     

Seed germination temperatures of eight Mexican Agave species with economic importance

The genetic diversity of Agave plants is threatened by clonal commercial reproduction and climatic change. Sexual reproduction is uncommon and research on seed germination is scarce. The present study evaluated the seed germination of Agave lechuguilla, Agave striata, Agave americana var. marginata, Agave asperrima, Agave cupreata, Agave duranguesis, Agave angustifolia ssp. tequilana and Agave salmiana at constant temperatures (10, 15, 20, 25, 30, 35 and 40°C). Initial imbibition (after the first 12 h) was significantly variable among species, positively correlated with seed weight (r = 0.6560, P < 0.001) and increased with temperature (from 35% at 10°C to 66% at 40°C). Temperature affected maximum imbibition (83–150%) for A. asperrima, A. lechuguilla, A. salmiana and A. striata; other species averaged 110%. Most germination kinetics best fitted a logistic model, whereas only a few treatments fit a Weibull model. The time to germination onset diminished (P < 0.05) from 125–173 h at 15°C to 68–84 h at 25°C, and then ascended to 84–196 h at 35°C. The mean germination rate and seed germination percentage after 312 h peaked at 25°C (0.50–0.95% seeds/h and 85–99%, respectively) and fell (P < 0.05) to near zero at 10 and 40°C. Temperatures of 10, 35 and 40°C were partially lethal to A. asperrima, A. duranguensis and A. salmiana seeds. The time to germination onset, seed germination percentage after 312 h and mean germination rate are best described by a Gaussian distribution, with its optimum at approximately 25°C. Thus, optimum temperatures are related to the ecological characteristics of each species area.