A complete transition to clean household energy can save one–quarter of the healthy life lost to particulate matter pollution exposure in India

Exposure to fine particulate matter (PM _2.5 ) is a leading contributor to the disease burden in India, largely due to widespread household solid fuel use. The transition from solid to clean fuels in households has the potential to substantially improve public health. India has implemented large initiatives to promote clean fuel access, but how these initiatives will reduce PM _2.5 exposure and the associated health benefits have not yet been established. We quantified the impacts of a transition of household energy from solid fuel use to liquefied petroleum gas (LPG) on public health in India from ambient and household PM _2.5 exposure. We estimate that the transition to LPG would reduce ambient PM _2.5 concentrations by 25%. Reduced exposure to total PM _2.5 results in a 29% reduction in the loss of healthy life, preventing 348 000 (95% uncertainty interval, UI: 284 000–373 000) premature mortalities every year. Achieving these benefits requires a complete transition to LPG. If access to LPG is restricted to within 15 km of urban centres, then the health benefits of the clean fuel transition are reduced by 50%. If half of original solid fuel users continue to use solid fuels in addition to LPG, then the health benefits of the clean fuel transition are reduced by 75%. As the exposure–outcome associations are non–linear, it is critical for air pollution studies to consider the disease burden attributed to total PM _2.5 exposure, and not only the portion attributed to either ambient or household PM _2.5 exposure. Our work shows that a transition to clean household energy can substantially improve public health in India, however, these large public health benefits are dependent on the complete transition to clean fuels for all

Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy

Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers

Subunit organization and Rab interactions of Vps-C protein complexes that control endolysosomal membrane traffic

The Vps-C complexes, CORVET and HOPS, are key regulators of membrane traffic through late endosomes and lysosomes. In this study Vps-C intersubunit contacts, domain architecture, and interactions with Rab G proteins are systematically dissected using genetic and biochemical approaches