A minimalistic tetrapeptide amphiphile scaffold for transmembrane pores with a preference for sodium

Synthetic channels or pores that are easy to synthesize, stable and cation-selective are extremely attractive for the development of therapeutics and materials. Herein, we report a pore developed from a small tetrapeptide scaffold that shows a preference for sodium over lithium/potassium. The sodium selectivity is attributed to the appended oligoether tail at the C-terminus. A peptide dimer is proposed as the predominant cation-transporting pore. Such pyridine containing stable pores can be potentially utilized for the pH modulated ion transport.     

Comparison of Newly Diagnosed and Relapsed Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide: Insight into Mechanisms of Resistance

There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL) in comparison with newly diagnosed cases (NAPL). We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO) based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022). The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38%) of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92), cell survival (n=50), immune regulation (n=74) and stem cell regulation (n=51). Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001) in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR) to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens.     

Fatty Aldehydes in Cyanobacteria Are a Metabolically Flexible Precursor for a Diversity of Biofuel Products

We describe how pathway engineering can be used to convert a single intermediate derived from lipid biosynthesis, fatty aldehydes, into a variety of biofuel precursors including alkanes, free fatty acids and wax esters. In cyanobacteria, long-chain acyl-ACPs can be reduced to fatty aldehydes, and then decarbonylated to alkanes. We discovered a cyanobacteria class-3 aldehyde-dehydrogenase, AldE, that was necessary and sufficient to instead oxidize fatty aldehyde precursors into fatty acids. Overexpression of enzymes in this pathway resulted in production of 50 to 100 fold more fatty acids than alkanes, and the fatty acids were secreted from the cell. Co-expression of acyl-ACP reductase, an alcohol-dehydrogenase and a wax-ester-synthase resulted in a third fate for fatty aldehydes: conversion to wax esters, which accumulated as intracellular lipid bodies. Conversion of acyl-ACP to fatty acids using endogenous cyanobacterial enzymes may allow biofuel production without transgenesis.     

Arsenic hazards: strategies for tolerance and remediation by plants

Arsenic toxicity has become a global concern owing to the ever-increasing contamination of water, soil and crops in many regions of the world. To limit the detrimental impact of arsenic compounds, efficient strategies such as phytoremediation are required. Suitable plants include arsenic hyperaccumulating ferns and aquatic plants that are capable of completing their life cycle in the presence of high levels of arsenic through the concerted action of arsenate reduction to arsenite, arsenite complexation, and vacuolar compartmentalization of complexed or inorganic arsenic. Tolerance can also be conferred by lowering arsenic uptake by suppression of phosphate transport activity, a major pathway for arsenate entry. In many unicellular organisms, arsenic tolerance is based on the active removal of cytosolic arsenite while limiting the uptake of arsenate. Recent molecular studies have revealed many of the gene products involved in these processes, providing the tools to improve crop species and to optimize phytoremediation; however, so far only single genes have been manipulated, which has limited progress. We will discuss recent advances and their potential applications, particularly in the context of multigenic engineering approaches.     

Rural,Urban and Migrant Differences in Non-Communicable Disease Risk-Factors in Middle Income Countries: A Cross-Sectional Study of WHO-SAGE Data

Background

Understanding how urbanisation and rural-urban migration influence risk-factors for non-communicable disease (NCD) is crucial for developing effective preventative strategies globally. This study compares NCD risk-factor prevalence in urban, rural and migrant populations in China, Ghana, India, Mexico, Russia and South Africa.

Methods

Study participants were 39,436 adults within the WHO Study on global AGEing and adult health (SAGE), surveyed 2007–2010. Risk ratios (RR) for each risk-factor were calculated using logistic regression in country-specific and all country pooled analyses, adjusted for age, sex and survey design. Fully adjusted models included income quintile, marital status and education.

Results

Regular alcohol consumption was lower in migrant and urban groups than in rural groups (pooled RR and 95%CI: 0.47 (0.31–0.68); 0.58, (0.46–0.72), respectively). Occupational physical activity was lower (0.86 (0.72–0.98); 0.76 (0.65–0.85)) while active travel and recreational physical activity were higher (pooled RRs for urban groups; 1.05 (1.00–1.09), 2.36 (1.95–2.83), respectively; for migrant groups: 1.07 (1.0 -1.12), 1.71 (1.11–2.53), respectively). Overweight, raised waist circumference and diagnosed diabetes were higher in urban groups (1.19 (1.04–1.35), 1.24 (1.07–1.42), 1.69 (1.15–2.47), respectively). Exceptions to these trends exist: obesity indicators were higher in rural Russia; active travel was lower in urban groups in Ghana and India; and in South Africa, urban groups had the highest alcohol consumption.

Conclusion

Migrants and urban dwellers had similar NCD risk-factor profiles. These were not consistently worse than those seen in rural dwellers. The variable impact of urbanisation on NCD risk must be considered in the design and evaluation of strategies to reduce the growing burden of NCDs globally.     

Mega2: data-handling for facilitating genetic linkage and association analyses

Mega2, the manipulation environment for genetic analysis, transparently allows users to process genetic data for family-based or case/control studies accurately and efficiently. In addition to data validation checks, Mega2 provides analysis setup capabilities for a broad choice of commonly used genetic analysis programs, including SimWalk2, ASPEX, GeneHunter, SLINK, SIMULATE, S.A.G.E., SOLAR, Vitesse, Allegro, PREST, PAP, Loki, Merlin and MENDEL. AVAILABILITY: http://watson.hgen.pitt.edu/register/     

Effect of carbofuran on the growth and nodulation ofVigna radiata

Effect of carbofuran on the growth, nodulation, phytomass, chlorophyll and carotene ofVigna radiata Roxb., was studied. Out of different concentrations of carbofuranviz., 0, 5, 10, 25, 50 and 100 ppm, the concentration of 5 ppm carbofuran revealed no toxic effect, instead the growth, number of nodules, phytomass and chlorophyll were increased in comparison to control. However, 10, 25 and 50 ppm carbofuran proved to be toxic. The plants showed inhibition of growth. While 100 ppm of carbofuran was found to be fatal for the growth of plants.