The β-Hemolysin and Intracellular Survival of Streptococcus agalactiae in Human Macrophages

S. agalactiae (group B streptococci, GBS) is a major microbial pathogen in human neonates and causes invasive infections in pregnant women and immunocompromised individuals. The S. agalactiae β-hemolysin is regarded as an important virulence factor for the development of invasive disease. To examine the role of β-hemolysin in the interaction with professional phagocytes, the THP-1 monocytic cell line and human granulocytes were infected with a serotype Ia S. agalactiae wild type strain and its isogenic nonhemolytic mutant. We could show that the nonhemolytic mutants were able to survive in significantly higher numbers than the hemolytic wild type strain, in THP-1 macrophage-like cells and in assays with human granulocytes. Intracellular bacterial multiplication, however, could not be observed. The hemolytic wild type strain stimulated a significantly higher release of Tumor Necrosis Factor-α than the nonhemolytic mutant in THP-1 cells, while similar levels of the chemokine Interleukin-8 were induced. In order to investigate bacterial mediators of IL-8 release in this setting, purified cell wall preparations from both strains were tested and found to exert a potent proinflammatory stimulus on THP-1 cells. In conclusion, our results indicate that the β-hemolysin has a strong influence on the intracellular survival of S. agalactiae and that a tightly controlled regulation of β-hemolysin expression is required for the successful establishment of S. agalactiae in different host niches.     

The greenhouse effect: the impacts of carbon dioxide (CO2), ultraviolet-B (UV-B) radiation and ozone (O3) on vegetation (crops)

Man's influence on the greenhouse effect, the heating of the atmosphere due to increasing concentrations of tropospheric trace gases, is of much international concern. Among the climatic variables, elevated levels of carbon dioxide (CO₂), ultraviolet-B (UV-B) radiation and ozone (O₃) are known to have a direct effect on vegetation. Our current knowledge of these effects is mainly based on studies involving single stress mode. Thus, the joint effects of CO₂, UV-B and O₃ on vegetation are poorly understood. Nevertheless, based on the literature analysis of plant response to individual stress factors, it can be concluded that sorghum, pea, bean, potato, oat, lettuce, cucumber, rice and tomato are among the crop species potentially sensitive to the joint effects of the aforementioned three variables. Similar information for tree species is essentially lacking.At least with some climatic variables such as O₃, present modeling efforts of cause-effect relationships have proven to be controversial. While at a regional geographic scale ambient CO₂ concentrations appear to be relatively homogeneous, ambient concentrations of O₃ exhibit significant temporal and spatial variability. Because of the protective action of O₃ against UV-B, similar but inverse temporal and spatial variability is expected in the surface levels of UV-B. Thus, future experimental designs should consider these exposure dynamics and modeling cuase-effect relationships should be directed to stochastic processes.     

Lifelong exercise and stroke.

OBJECTIVES--To examine the potential of lifelong patterns of increased physical activity to prevent stroke. DESIGN--Case-control study. SETTING--11 general practices in west Birmingham. SUBJECTS--125 men and women who had just had their first stroke and were aged 35-74 and 198 controls frequency matched for age and sex recruited over 24 months during 1988-90. Exclusion criteria were a previous history of stroke, mitral valvular heart disease combined with atrial fibrillation, primary or metastatic cerebral neoplasm, or coagulation disorder or myeloproliferative disease. MAIN OUTCOME MEASURES--Odds ratios for stroke related to lifetime history of exercise after 15 years of age. RESULTS--A history of vigorous exercise during the ages 15-25 appeared to protect from stroke: odds ratio adjusted for age and sex 0.33 (95% confidence interval 0.2 to 0.6). This effect was independent of other potential risk factors. Increasing years of participation in vigorous exercise between the ages of 15 and 55 produced an increasing protection from stroke (p < 0.001). In the 65 cases and 169 controls who were free of cardiac ischaemia, peripheral vascular disease, and poor health recent vigorous exercise and walking were protective against stroke: odds ratios of 0.41 (0.2 to 1.0) for recent vigorous exercise and 0.30 (0.1 to 0.7) for recent walking. CONCLUSIONS--Appreciable protection from stroke in later life is conferred by vigorous exercise in early adulthood. This increased level of physical activity should, if possible, be continued lifelong.     

Correlation of encystment and division in Schizopyrenus russelli.

Schizopyrenus russelli, a free-living soil ameba, grows and encysts in the presence of bacteria. The encystment occurs with decline in the division rate. This is accompanied by incorporation of [U-14C] glucose into cyst cellulose. The degree of multiplication (but not of encystment) is a function of bacterial concentration. Berenil, a trypanocidal drug, while allowing excystment, completely inhibited multiplication of emerged amebae and their encystment. Addition of this drug after 24 hr, when amebae had gone into a phase of active division failed to check encystment, although it still inhibited further multiplication of the amebae. The findings suggest that a phase of cell division may be a prerequisite for encystment.     

Movement of Endotoxin Through Soil Columns

Land treatment of wastewater is an attractive alternative to conventional sewage treatment systems and is gaining widespread acceptance. Although land application systems prevent surface water pollution and augment the available water supplies, the potential dangers to human health should be evaluated. Since sewage may contain high amounts of bacterial endotoxin, the removal of endotoxin from sewage by percolation through soil was investigated. It was found that 90 to 99% of the endotoxin was removed after travel of sewage through 100 to 250 cm of loamy sand soil. When distilled water was allowed to infiltrate into the soil to simulate rainfall, the endotoxin was mobilized and moved in a concentrated band through the soil column. On testing samples from actual land treatment sites, as much as 480 ng of endotoxin per milliliter was found in some groundwater samples. The presence of endotoxin in potable water is known to be a potential problem under some circumstances, but the importance of endotoxin in water supplies has not been fully assessed. Therefore, the design, operation, and management of land application systems should take into account the fate of endotoxin in groundwater beneath the sites.     

Development of Dopant‐Free Organic Hole Transporting Materials for Perovskite Solar Cells

There has been considerable progress over the last decade in development of the perovskite solar cells (PSCs), with reported performances now surpassing 25.2% power conversion efficiency. Both long‐term stability and component costs of PSCs remain to be addressed by the research community, using hole transporting materials (HTMs) such as 2,2′,7,7′‐tetrakis(N,N′‐di‐pmethoxyphenylamino)‐9,9′‐spirbiuorene(Spiro‐OMeTAD) and poly[bis(4‐phenyl)(2,4,6‐trimethylphenyl)amine] (PTAA). HTMs are essential for high‐performance PSC devices. Although effective, these materials require a relatively high degree of doping with additives to improve charge mobility and interlayer/substrate compatibility, introducing doping‐induced stability issues with these HTMs, and further, additional costs and experimental complexity associated with using these doped materials. This article reviews dopant‐free organic HTMs for PSCs, outlining reports of structures with promising properties toward achieving low‐cost, effective, and scalable materials for devices with long‐term stability. It summarizes recent literature reports on non‐doped, alternative, and more stable HTMs used in PSCs as essential components for high‐efficiency cells, categorizing HTMs as reported for different PSC architectures in addition to use of dopant‐free small molecular and polymeric HTMs. Finally, an outlook and critical assessment of dopant‐free organic HTMs toward commercial application and insight into the development of stable PSC devices is provided.     

A nanoformulation of siRNA and its role in cancer therapy: In vitro and in vivo evaluation

Overexpression of anti-apoptotic Bcl-2 is often observed in a wide variety of human cancers. It prevents the induction of apoptosis in neoplastic cells and contributes to resistance to chemotherapy. RNA interference has emerged as an efficient and selective technique for gene silencing. The potential to use small interfering RNA (siRNA) as a therapeutic agent for the treatment of cancer has elicited a great deal of interest. However, insufficient cellular uptake and poor stability have limited its therapeutic applications. The purpose of this study was to prepare chitosan nanoparticles via ionic gelation of chitosan by tripolyphosphate for effective delivery of siRNA to silence the anti-apoptotic Bcl-2 gene in neoplastic cells. Chitosan nanoparticles loaded with siRNA were in the size range 190 to 340 nm with a polydispersive index ranging from 0.04 to 0.2. They were able to completely bind with siRNA, provide protection against nuclease degradation, and enhance the transfection. Cell culture studies revealed that nanoparticles with entrapped siRNA could efficiently silence the antiapoptotic Bcl-2 gene. Studies on Swiss albino mice showed that siRNA could be effectively delivered through nanoparticles. There was significant decrease in the tumor volume. Blocking the expression of anti-apoptotic Bcl-2 can enhance the sensitivity of cancerous cells to anti-cancer drugs and the apoptosis rate. Therefore, nanoformulations with siRNA can be promoted as an adjuvant therapy in combination with anti-cancer drugs.     

Execution of programmed cell death by singlet oxygen generated inside the chloroplasts of Arabidopsis thaliana

Protoplasma - Absorption of excess excitation energy induces overproduction of singlet oxygen (1O2) in plants. The major sources of singlet oxygen production are chlorophyll and its intermediates...