Functional and Structural Properties of a Novel Protein and Virulence Factor (Protein sHIP) in Streptococcus pyogenes

Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment, enabling bacterial interactions with the host. In the present study, we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice with a non-virulent strain. Particularly, one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal histidine-rich glycoprotein-interacting protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP suggest a role for the protein in S. pyogenes pathogenesis.     

3D reconstruction techniques of human coronary bifurcations for shear stress computations

Background

Heterogeneity in plaque composition in human coronary artery bifurcations is associated with blood flow induced shear stress. Shear stress is generally determined by combing 3D lumen data and computational fluid dynamics (CFD). We investigated two new procedures to generate 3D lumen reconstructions of coronary artery bifurcations for shear stress computations.

Methods

We imaged 10 patients with multislice computer tomography (MSCT) and intravascular ultrasound (IVUS). The 3D reconstruction of the main branch was based on the fusion of MSCT and IVUS. The proximal part of side branch was reconstructed using IVUS data or MSCT data, resulting in two different reconstructions of the bifurcation region. The distal part of the side branch was based on MSCT data alone. The reconstructed lumen was combined with CFD to determine the shear stress. Low and high shear stress regions were defined and shear stress patterns in the bifurcation regions were investigated.

Results

The 3D coronary bifurcations were successfully generated with both reconstruction procedures. The geometrical features of the bifurcation region for the two reconstruction procedures did not reveal appreciable differences. The shear stress maps showed a qualitative agreement, and the low and high shear stress regions were similar in size and average shear stress values were identical. The low and high shear stress regions showed an overlap of approximately 75%.

Conclusion

Reconstruction of the side branch with MSCT data alone is an adequate technique to study shear stress and wall thickness in the bifurcation region. The reconstruction procedure can be applied to further investigate the effect of shear stress on atherosclerosis in coronary bifurcations.     

Latitudinal variation in thermal reaction norms of post‐winter pupal development in two butterflies differing in phenological specialization

Latitudinal clines in thermal reaction norms of development are a common phenomenon in temperate insects. Populations from higher latitudes often develop faster throughout the range of relevant temperatures (i.e countergradient variation) because they must be able to complete their life cycle within a shorter seasonal time window compared to populations at lower latitudes. In the present study, we experimentally demonstrate that two species of butterflies Anthocharis cardamines (L.) and Pieris napi (L.) instead show a cogradient variation in thermal reaction norms of post‐winter pupal development so that lower latitude populations develop faster than higher latitude populations. The two species share host plants but differ in the degree of phenological specialization, as well as in the patterns of voltinism. We suggest that the pattern in A. cardamines, a univoltine phenological specialist feeding exclusively on flowers and seedpods, is the result of selection for matching to the phenological pattern of its local host plants. The other species, P. napi, is a phenological generalist feeding on the leaves of the hosts and it shows a latitudinal cline in voltinism. Because the latitudinal pattern in P. napi was an effect of slow development in a fraction of the pupae from the most northern population, we hypothesize that this population may include both bivoltine and univoltine genotypes. Consequently, although the two species both showed cogradient patterns in thermal reaction norms, it appears likely that this was for different reasons. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 113 , 981–991.     

High Parasitological Failure Rate of Visceral Leishmaniasis to Sodium Stibogluconate among HIV Co-infected Adults in Ethiopia

Background

Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.

Objectives

This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).

Methods

Retrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.

Results

The study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7).

Conclusion

SSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.     

Visceral Leishmaniasis and HIV Coinfection in East Africa

Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.     

QM/MM Molecular Dynamics Study of the Galactopyranose → Galactofuranose Reaction Catalysed by Trypanosoma cruzi UDP-Galactopyranose Mutase

The enzyme UDP-Galactopyranose Mutase (UGM) catalyses the conversion of galactopyranose into galactofuranose. It is known to be critical for the survival and proliferation of several pathogenic agents, both prokaryotic and eukaryotic. Among them is Trypanosoma cruzi, the parasite responsible for Chagas'' disease. Since the enzyme is not present in mammals, it appears as a promising target for the design of drugs to treat this illness. A precise knowledge of the mechanism of the catalysed reaction would be crucial to assist in such design. In this article we present a detailed study of all the putative steps of the mechanism. The study is based on QM/MM free energy calculations along properly selected reaction coordinates, and on the analysis of the main structural changes and interactions taking place at every step. The results are discussed in connection with the experimental evidence and previous theoretical studies.     

The Contribution of Paraserianthes (Albizia) falcataria to Sustainable Swidden Management Practices among The Baduy of West Java

There is a prohibition on the use of modern external inputs, such as chemical fertilizers, in Baduy swidden farming. Ordinarily, the consequence of this in a situation of acute forest pressure would be a decrease in fallow times, and an inevitable depletion of soil fertility. The Baduy (particularly Outer Baduy) have several ways of alleviating this problem, one of which is the introduction of Paraserianthes (Albizia) falcataria. By alternating this commercially valuable perennial leguminous tree with rice, soil fertility is maintained and the socio-economic position of the Baduy improved. As a result, swidden farming, which is considered by the Baduy to be central to their cultural identity, continues to be viable, despite increasing population density and the continuing depletion of mature forest.     

The search for common anthropogenic impacts on biodiversity: a global network

We introduce an initiative to assess and compare landscape changes related to human activities on a global scale, using a single group of invertebrates. The GLOBENET programme uses common field methodology (pitfall trapping), to appraise assemblages of ground beetles (Coleoptera, Carabidae) in visually-similar land-mosaics (urban-rural gradients). Carabids were selected as the focal taxon as they are sufficiently varied (both taxonomically and ecologically), abundant and sensitive to the environment. However, work on other taxa is comparable with the GLOBENET framework. The continuum of decreasing human pressure from city centres into the surrounding countryside was selected to represent human-caused disturbance for this initial stage of GLOBENET because these gradients can be found virtually all over the world. Through the broad-scale assessment envisioned in the GLOBENET programme, we seek to separate general, repeated effects on biodiversity from those that depend on local environments or particular biotic assemblages. Based on this understanding we aim to develop simple tools and protocols for assessing ecological effects of human-caused landscape changes, which could help to sustainably manage landscapes for biodiversity and for human requirements. For instance, the response of different functional groups of carabids to these landscape changes may help guide management practices. Further GLOBENET developments and information are available at our website: http://www.helsinki.fi/science/globenet/     

Costs of sporophyte production in the moss,Dicranum polysetum

We investigated the cost of sporophyte production in the moss Dicranum polysetum both by examining patterns of growth and reproduction in unmanipulated shoots and by experimentally manipulating sexual reproduction.The estimated proportion of total carbon investment allocated to sexual reproduction in sporophyte-producing shoots over the study period was 74.8%. Unmanipulated shoots that aborted all sporophytes had a significantly higher growth in the top shoots than shoots that produced sporophytes. In sporophyte-producing shoots, total apical growth decreased proportionately with the number of sporophytes.Experimental prevention of sporophyte development resulted in significantly higher total apical growth of the gametophytes. Shoots where current perichaetia were lacking when marked had a mass increase in the top shoots similar to manipulated sporophytic shoots whereas sporophytic control shoots grew significantly less than these two categories.The difference between control shoots and manipulated shoots in the mass of vegetative apical growth was mainly because of different length increments whereas mass per unit length was similar between groups. The probability to reproduce sexually in the year after the manipulation, and the biomass allocated to this reproduction, were not affected by the experimental treatment.