Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis C virus E2 envelope glycoprotein

Hepatitis C virus (HCV) remains a significant threat to the general health of the world's population, and there is a pressing need for the development of new treatments and preventative vaccines. Here, we describe the generation of retrovirus-based pseudoparticles (HCVpp) incorporating a panel of full-length E1E2 clones representative of the major genotypes 1 through 6, and their application to assess the reactivity and neutralizing capability of antisera and monoclonal antibodies raised against portions of the HCV E2 envelope protein. Rabbit antisera raised against either the first hypervariable region or ectodomain of E2 showed limited and strain specific neutralization. By contrast, the monoclonal antibody (MAb) AP33 demonstrated potent neutralization of infectivity against HCVpp carrying E1E2 representative of all genotypes tested. The concentration of AP33 required to achieve 50% inhibition of infection by HCVpp of diverse genotypes ranged from 0.6 to 32 mug/ml. The epitope recognized by MAb AP33 is linear and highly conserved across different genotypes of HCV. Thus, identification of a broadly neutralizing antibody that recognizes a linear epitope is likely to be of significant benefit to future vaccine and therapeutic antibody development.     

Antimicrobial and antioxidative potential of free and immobilised cellobiose dehydrogenase isolated from wood degrading fungi

Cellobiose dehydrogenase (CDH, EC 1.1.99.18) is a glycoprotein having many biotechnological applications. In the present study, CDHs isolated from Phlebia lindtneri (PlCDH), Phanerochaete chrysosporium (PchCDH), Cerrena unicolor (CuCDH), and Pycnoporus sanguineus (PsCDH) were studied the first time for their ability to generate antioxidant and antimicrobial agents. The aim of the research was to evaluate the antioxidant and antimicrobial activity of systems composed of four CDHs and lactose or cellobiose as a reaction substrate. The free radical scavenging effect of free and immobilised enzymes was evaluated using the DPPH method. The lowest values of EC₅₀ (10.04 ± 0.75 $\text{μg}$/ml) was noted for PlCDH/lactose and for PlCDH/cellobiose (12.06 ± 1.35 $\text{μg}$/ml). The EC₅₀value reached 12.6 ± 1.51 $\text{μg}$/ml in the case of PsCDH/lactose and 15.96 ± 1.35 for PsCDH. The CDH preparations were also effectively immobilised in alginate (the immobilisation efficiency expressed as a protein yield ranged from 61.6 to 100 %). The operational stability expressed as a scavenging effect showed the possibility of using the alginate beads 4 times. Both the free and immobilised CDHs as well as the CDH/substrate were tested against Gram-negative Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Gram-positive Staphylococcus aureus ATCC 25923 bacteria. All samples, except PlCDH, were potentially effective in suppression of bacterial growth. The highest percentage of inhibition (100 %) was obtained for S. aureus bacteria using PsCDH and PchCDH with lactose as a substrate, whereas a slightly lesser effect was observed for E. coli and P. aeruginosa bacterial cells, i.e. 64.1 % and 86.5 % (PsCDH) and 94.1 % and 41.4 % (PchCDH), respectively. Furthermore, the concentrations of the reaction products (aldonic acids and hydrogen peroxide) were quantified and the surface morphology of the alginate beads was analysed using SEM visualisation.     

PfAlbas constitute a new eukaryotic DNA/RNA-binding protein family in malaria parasites

In Plasmodium falciparum, perinuclear subtelomeric chromatin conveys monoallelic expression of virulence genes. However, proteins that directly bind to chromosome ends are poorly described. Here we identify a novel DNA/RNA-binding protein family that bears homology to the archaeal protein Alba (Acetylation lowers binding affinity). We isolated three of the four PfAlba paralogs as part of a molecular complex that is associated with the P. falciparum-specific TARE6 (Telomere-Associated Repetitive Elements 6) subtelomeric region and showed in electromobility shift assays (EMSAs) that the PfAlbas bind to TARE6 repeats. In early blood stages, the PfAlba proteins were enriched at the nuclear periphery and partially co-localized with PfSir2, a TARE6-associated histone deacetylase linked to the process of antigenic variation. The nuclear location changed at the onset of parasite proliferation (trophozoite-schizont), where the PfAlba proteins were also detectable in the cytoplasm in a punctate pattern. Using single-stranded RNA (ssRNA) probes in EMSAs, we found that PfAlbas bind to ssRNA, albeit with different binding preferences. We demonstrate for the first time in eukaryotes that Alba-like proteins bind to both DNA and RNA and that their intracellular location is developmentally regulated. Discovery of the PfAlbas may provide a link between the previously described subtelomeric non-coding RNA and the regulation of antigenic variation.     

Etiology and Epidemiology of Diarrhea in Hospitalized Children from Low Income Country: A Matched Case-Control Study in Central African Republic

Background

In Sub-Saharan Africa, infectious diarrhea is a major cause of morbidity and mortality. A case-control study was conducted to identify the etiology of diarrhea and to describe its main epidemiologic risk factors among hospitalized children under five years old in Bangui, Central African Republic.

Methods

All consecutive children under five years old hospitalized for diarrhea in the Pediatric Complex of Bangui for whom a parent’s written consent was provided were included. Controls matched by age, sex and neighborhood of residence of each case were included. For both cases and controls, demographic, socio-economic and anthropometric data were recorded. Stool samples were collected to identify enteropathogens at enrollment. Clinical examination data and blood samples were collected only for cases.

Results

A total of 333 cases and 333 controls was recruited between December 2011 and November 2013. The mean age of cases was 12.9 months, and 56% were male. The mean delay between the onset of first symptoms and hospital admission was 3.7 days. Blood was detected in 5% of stool samples from cases. Cases were significantly more severely or moderately malnourished than controls. One of the sought-for pathogens was identified in 78% and 40% of cases and controls, respectively. Most attributable cases of hospitalized diarrhea were due to rotavirus, with an attributable fraction of 39%. Four other pathogens were associated with hospitalized diarrhea: Shigella/EIEC, Cryptosporidium parvum/hominis, astrovirus and norovirus with attributable fraction of 9%, 10%, 7% and 7% respectively. Giardia intestinalis was found in more controls than cases, with a protective fraction of 6%.

Conclusions

Rotavirus, norovirus, astrovirus, Shigella/EIEC, Cryptosporidium parvum/hominis were found to be positively associated with severe diarrhea: while Giardia intestinalis was found negatively associated. Most attributable episodes of severe diarrhea were associated with rotavirus, highlighting the urgent need to introduce the rotavirus vaccine within the CAR’s Expanded Program on Immunization. The development of new medicines, vaccines and rapid diagnostic tests that can be conducted at the bedside should be high priority for low-resource countries.     

Coral reefs in a high-latitude,siliciclastic barrier island setting: reef framework and sediment production at Inhaca Island,southern Mozambique

Inhaca Island (southern Mozambique) is located in a high-latitude setting along the seaward margins of the estuarine Maputo Bay and is subject to fluctuations in temperature and salinity, and high sedimentation and turbidity levels. Coral reefs are developed sporadically along the margins of intertidal channels, but framework development is severely restricted. Coral growth is bathymetrically limited (never exceeding 6-m depth), and framework accumulation is only present in the upper 1–2 m. Massive Porites sp. produce a basic reef structure, with other coral genera (mainly Acropora sp., Favia sp., Platygyra sp., Pocillopora sp., and Montipora sp.) colonizing available substrata. Sediment samples also indicate restricted carbonate sediment production, with siliciclastics (mainly quartz) a major sediment contributor (often >90%) and carbonate grain assemblages differing from those normally associated with lower-latitude reefs. Although corals, molluscs and coralline algae (including rhodoliths) represent dominant grain constituents, Halimeda is absent and there is a low diversity (four species identified) of benthic foraminifera (mainly Amphistegina sp.). Grain associations are therefore somewhat transitional in character, comprising elements of both tropical (chlorozoan) and temperate (foramol) grain assemblages. These patterns of reef and associated carbonate production emphasize the marginal character of these reef environments, which form one end member in a broad spectrum of marginal reef systems that are now being identified in a range of both high- and low-latitude settings.     

Description of the immature stages of two Mononychus species (Coleoptera: Curculionidae: Ceutorhynchinae) and a study of the host preferences of M. punctumalbum for Iris species in central Europe

Last larval instars and pupae of Mononychus punctumalbum (Herbst, 1784) and Mononychus schoenherri Kolenati, 1859 (Curculionidae, Ceutorhynchinae) are described in detail for the first time. No immatures of other species of this genus had previously been described. The immatures of Mononychus were compared with available data on immatures of all genera in the subfamily Ceutorhynchinae. Both the larvae and pupae of the two Mononychus species are very distinctive, having distinct characters from other genera in the subfamily Ceutorhynchinae. New bionomic data for M. punctumalbum concerning its host preferences for Iris species in central Europe can be used to verify literature data indicating the important role of the iris weevil in the dramatic decline in the plant's abundance in natural habitats as well as in gardens and other anthropogenic associations.     

Combination of fuzzy-AHP and GIS techniques in land suitability assessment for wheat (Triticum aestivum) cultivation

Land suitability classification is a useful management practice to ensure planned and sustainable use of agricultural lands according to their potentials. The main purposes of this study were to analyze land suitability for bread wheat (Triticum aestivum) cultivation and generate a land suitability map for wheat by integrating the analytical hierarchy (AHP)-fuzzy algorithm with the Geographical Information System (GIS) in the Tozanlı sub-basin located in the upper part of Yeşilırmak Basin, Turkey. Topographic (elevation, slope, aspect) characteristics of the basin and some of physical and chemical properties of soils (texture, pH, electrical conductivity, lime, organic matter, and soil depth) were used as criteria in determining the suitability classes. Ninety-two disturbed soil samples were collected from 0 to 20 cm depth in October 2017 using random sampling method. Weighted overlay spatial analysis in GIS was used to combine different thematic layers to identify areas suitable for wheat production. The fuzzy-AHP suitability assessment model was adapted to determine the weights for topographic and soil properties. The highest specific weights were obtained for soil depth (0.232) and elevation (0.218), while the lowest weight was calculated for aspect (0.042). Highly, moderately, and marginally suitable lands for wheat cultivation cover 2.63, 9.85 and 32.59% of the study area, respectively. In addition, the results indicated that 54.92% of the total area is permanently unsuitable for wheat cultivation. The results revealed that integration of AHP-fuzzy algorithm and GIS techniques is a useful method for accurate evaluation of land suitability in planning for specific crop production and decreasing the negative environmental impacts of agricultural practices.     

Three dimensional modeling of the cerebrospinal fluid dynamics and brain interactions in the aqueduct of sylvius

A computational fluid dynamics (CFD) method is presented to investigate the flow of cerebro-spinal fluid (CSF) in the cerebral aqueduct. In addition to former approaches exhibiting a rigid geometry, we propose a model which includes a deformable membrane as the wall of this flow channel. An anatomical shape of the aqueduct was computed from magnetic resonance images (MRI) and the resulting meshing was immersed in a marker-and-cell (MAC) staggered grid for to take into account fluid-structure interactions. The time derivatives were digitized using the Crank-Nicolson scheme. The equation of continuity was modified by introducing an artificial compressibility and digitized by a finite difference scheme. Calculations were validated with the simulation of laminar flow in a rigid tube. Then, comparisons were made between simulations of a rigid aqueduct and a deformable one. We found that the deformability of the walls has a strong influence on the pressure drop for a given flow.