Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes

The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.     

Mapping Current and Potential Distribution of Non-Native Prosopis juliflora in the Afar Region of Ethiopia

We used correlative models with species occurrence points, Moderate Resolution Imaging Spectroradiometer (MODIS) vegetation indices, and topo-climatic predictors to map the current distribution and potential habitat of invasive Prosopis juliflora in Afar, Ethiopia. Time-series of MODIS Enhanced Vegetation Indices (EVI) and Normalized Difference Vegetation Indices (NDVI) with 250 m² spatial resolution were selected as remote sensing predictors for mapping distributions, while WorldClim bioclimatic products and generated topographic variables from the Shuttle Radar Topography Mission product (SRTM) were used to predict potential infestations. We ran Maxent models using non-correlated variables and the 143 species- occurrence points. Maxent generated probability surfaces were converted into binary maps using the 10-percentile logistic threshold values. Performances of models were evaluated using area under the receiver-operating characteristic (ROC) curve (AUC). Our results indicate that the extent of P. juliflora invasion is approximately 3,605 km² in the Afar region (AUC  = 0.94), while the potential habitat for future infestations is 5,024 km² (AUC  = 0.95). Our analyses demonstrate that time-series of MODIS vegetation indices and species occurrence points can be used with Maxent modeling software to map the current distribution of P. juliflora, while topo-climatic variables are good predictors of potential habitat in Ethiopia. Our results can quantify current and future infestations, and inform management and policy decisions for containing P. juliflora. Our methods can also be replicated for managing invasive species in other East African countries.     

Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma

Background

The naked mole-rat (NMR) is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M.

Results

Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL) and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL) in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma.

Conclusion

We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the anti-aging mechanisms in the NMR.     

High Mortality from Blood Stream Infection in Addis Ababa,Ethiopia, Is Due to Antimicrobial Resistance

Background

Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa.

Methods

Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co-resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time.

Results

Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38–25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3–164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3^rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3–4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32–7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole.

Conclusion

Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae-infected patients with isolates resistant to third generation cephalosporins. Strong and significant resistance covariation between 3^rd. generation cephalosporins, chloramphenicol, gentamicin, and co-trimoxazole was identified. Pronounced pancytopenia was common and associated with increased mortality. HIV positive patients had no excess mortality.     

Improving Microstructured TiO2 Photoanodes for Dye Sensitized Solar Cells by Simple Surface Treatment

TiCl₄ surface treatment studies of porous electrode structure of TiO₂ aggregates synthesized using an acidic precursor and CTAB as a templating agent are carried out in order to understand and improve upon recombination kinetics in the photonanode film matrix, together with enhancing the intrinsic light scattering. The key beneficial features of the photoanode included high surface roughness, necessary for superior dye adsorption, nanocrystallite aggregates leading to diffuse light scattering within the film matrix, and a hierarchical macro‐ and mesopore structure allowing good access of electrolyte to the dye, thereby assisting in dye regeneration (enhanced charge transfer). Pre‐treatment of the TiO₂ electrodes reduced recombination at the fluorine‐doped tin oxide (FTO)/electrolyte interface. The post‐treatment study showed enhanced surface roughness through the deposition of a thin overlayer of amorphous TiO₂ on the film structure. This led to a notable improvement in both dye adsorption and inherent light scattering effects by the TiO₂ aggregates, resulting in enhanced energy harvesting. The thin TiO₂ overlayer also acted as a barrier in a core‐shell configuration within the porous TiO₂ matrix, and thereby reduced recombination. This allowed the hierarchical macro‐ and mesoporosity of the film matrix to be utilized more effectively for enhanced charge transfer during dye regeneration. Post‐treatment of the aggregated TiO₂ matrix resulted in a 36% enhancement in power conversion efficiency from 4.41% of untreated cells to 6.01%.     

CO2‐Mediated H2 Storage‐Release with Nanostructured Catalysts: Recent Progresses,Challenges, and Perspectives

It has increasingly become clear that economic growth worldwide based on fossil fuel energy supply cannot be sustained; thus, alternative, renewable energy sources and carriers must be urgently developed to maintain growth. Dihydrogen (H₂), which can produce energy without generating environmental pollutants, can play a major role in this endeavor. However, to use H₂ in renewable energy systems, systems and materials that can store and transport it, or convert it into easier‐to‐handle/transport synthetic fuels, need to be developed. In this article, first, many of the issues related to both homogeneous and heterogeneous catalysts that are being developed to help H₂'s use as energy carrier are discussed. More focus is then given to heterogeneous nanocatalysts that are developed for reversible CO₂‐mediated hydrogenation and dehydrogenation reactions involving chemical hydrogen carriers and delivery systems, mainly formic acid/CO₂ and formate/bicarbonate. The challenges associated with the development of nanocatalysts based on earth‐abundant elements for dehydrogenation and hydrogenation reactions of these compounds for H₂ storage and release are emphasized in the discussions. Finally, the pressing research questions and major issues that need to be addressed in the near future to help the realization of the “hydrogen economy” are outlined.     

Cytotoxicity of mesoporous silica nanomaterials

We here measure the toxicity of MCM-41, a mesoporous silica nanomaterial, two of its functionalized analogs, AP-T, which has grafted aminopropyl groups and MP-T, which has grafted mercaptopropyl groups, and spherical silica nanoparticles (SiO₂), toward human neuroblastoma (SK-N-SH) cells. Since the particles studied are not soluble in aqueous media, the metric used to report the cytotoxicity of these materials is a new quantity, Q₅₀, which is the number of particles required to inhibit normal cell growth by 50%. Determining the number of particles per gram of material applied to the cells required both the calculated and experimentally determined surface areas of these nanomaterials. This study shows that Q₅₀ increases in the order, MCM-41 < MP-T < AP-T ≈ SiO₂, showing that on a per particle basis, MCM-41 is the most cytotoxic material studied. For the three mesoporous silica materials in this study, cytotoxicity appears related to the adsorptive surface area of the particle, although the nature of the functional group cannot be ruled out. Silica nanospheres have the lowest surface area of the particles studied but since they exhibit a Q₅₀ value similar to that of AP-T, shape may also be important in the cytotoxicity of these materials.     

Oocyte aging in a marine protostome worm: The roles of maturation‐promoting factor and extracellular signal regulated kinase form of mitogen‐activated protein kinase

The roles of maturation‐promoting factor (MPF) and an extracellular signal regulated kinase form of mitogen‐activated protein kinase (ERK MAPK) are analyzed during oocyte aging in the marine protostome worm Cerebratulus. About a day after removal from the ovary, unfertilized metaphase‐I‐arrested oocytes of Cerebratulus begin to flatten and swell before eventually lysing, thereby exhibiting characteristics of a necroptotic mode of regulated cell death. Based on immunoblots probed with phospho‐specific antibodies, MPF and ERK are initially active in freshly mature specimens. However, as oocytes age, both kinase activities decline, with ERK deactivation occurring well before MPF downregulation. Experiments using pharmacological modulators indicate that oocyte degradation is promoted by the maturation‐initiated activation of ERK as well as by the deactivation of MPF that occurs in extensively aged specimens. The potential significance of these findings is discussed relative to previously published results for apoptotic eggs and oocytes of echinoderm and vertebrate deuterostomes.