Does Revolution Work? Evidence from Nepal’s People’s War

In 2015, after a decade-long conflict and nine years of negotiation, Nepal promulgated a constitution that replaced its 240-year-old monarchy by a federal republic. The subsequent 2017 local elections ushered more than 30,000 first-time politicians into office. Using a census of 3.68 million Nepalis (2.56 million of whom are of voting age) covering eleven districts, party nomination lists and party candidate selection committee surveys, electoral data and information on conflict incidence, we document that castes that were historically excluded from political representation achieved representation without a significant representation-ability trade-off: improved social representation among politicians is accompanied by positive selection on education and income. Triangulating across multiple data sources, we show that the entry of the revolutionary Maoist group as a post-conflict mainstream party played an important role. Finally, political representation of non-elite castes improved their policy inclusion as measured by individual access to earthquake reconstruction transfers. These gains, however, vary with the extent of social connections to the elected mayor and point to a continuing need to balance power by supporting institutions that provide all citizens political voice

Effective Delivery of PEGylated siRNA-Containing Lipoplexes to Extraperitoneal Tumours following Intraperitoneal Administration

Intraperitoneal (i.p.) administration of small interfering RNA (siRNA) has, to date, shown promise in treating tumours located within the peritoneal cavity. The ability of these siRNA molecules to reach extraperitoneal tumours following i.p. administration is, however, yet to be investigated. Here, we examined the impact of PEGylation on the biodistribution of i.p. administered nucleic acids-containing lipoplexes. We showed that in contrast to non-PEGylated liposomes, PEGylated liposomes can deliver siRNA efficiently to extraperitoneal tumours following i.p. administration, resulting in a 45% reduction in tumour size when the oncogene-targeted siRNA was used. This difference was likely contributed by the decreased uptake of PEGylated lipoplexes in the first-pass organs, and, in particular, we observed a 10-fold decrease in the macrophage uptake of these particles compared to non-PEGylated counterparts. Overall, our results indicated the potential of using PEGylated liposomes to deliver siRNA for the treatment of i.p. localized cancer with coexisting extraperitoneal metastasis

1st International Conference on Bioresource Technology for Bioenergy, Bioproducts & Environmental Sustainability (BIORESTEC)

With growing global interest in bioenergy, biobased product and environmental sustainability, the first International Conference on Bioresource Technology for Bioenergy, Bioproducts & Environmental Sustainability (BIORESTEC) was organized from October 2326, 2016 in Sitges, Barcelona in Spain. The conference was organized in association with Elseviers premier journal Bioresource Technology (BITE), with an aim to provide a shared forum for researchers, academicians, industries, and policymakers, to discuss the current state-of-the-art and the emerging trends in biotechnology, bioenergy, and biobased products. The 1st BIORESTEC conference received tremendous response from all over the globe with 754 abstracts submitted. The scientific committee consisted of 13 eminent scientists from 11 countries. The committee then screened and selected 54 abstracts for oral and 166 abtsracts for poster presentations. Besides, there were 19 invited speakers from 14 countries. Apart from the scientific presentations, a workshop on How to write a scientific paper and get published was also organized for early career researchers by Elsevier. This special issue of the journal contain 29 papers (all presented at the BIORESTEC conference) after peer-review process. These papers broadly cover areas such as biomass pretreatment, algal and lignocellulose biorefinery, biological waste treatment, white biotechnology and biomass policies, LCA and techno-economics and classified as below.info:eu-repo/semantics/publishedVersio

Short interfering RNA induced generation and translation of stable 5' mRNA cleavage intermediates

Sequence-specific degradation of homologous mRNA is the main mechanism by which short-interfering RNAs (siRNAs) suppress gene expression. Generally, it is assumed that the mRNA fragments resulting from Ago2 cleavage are rapidly degraded, thus making the transcript translation-incompetent. However, the molecular mechanisms involved in the post-cleavage mRNA decay are not completely understood and the fate of cleavage intermediates has been poorly studied. Using specific siRNAs and short-hairpin RNAs (shRNAs) we show that the 5′ and 3′ mRNA cleavage fragments of human papilloma virus type 16 (HPV-16) E6/7 mRNA, over-expressed in cervical malignancies, are unevenly degraded. Intriguingly, the 5′ mRNA fragment was more abundant and displayed a greater stability than the corresponding 3′ mRNA fragment in RNAi-treated cells. Further analysis revealed that the 5′ mRNA fragment was polysome-associated, indicating its active translation, and this was further confirmed by using tagged E7 protein to show that C-terminally truncated proteins were produced in treated cells. Overall, our findings provide new insight into the degradation of siRNA-targeted transcripts and show that RNAi can alter protein expression in cells as a result of preferential stabilization and translation of the 5′ cleavage fragment. These results challenge the current model of siRNA-mediated RNAi and provide a significant step forward towards understanding non-canonical pathways of siRNA gene silencing

Aberrant DNA Methylation Reprogramming During Induced Pluripotent Stem Cell Generation is Dependent on the Choice of Reprogramming Factors

The conversion of somatic cells into pluripotent stem cells via overexpression of reprogramming factors involves epigenetic remodeling. DNA methylation at a significant proportion of CpG sites in induced pluripotent stem cells (iPSCs) differs from that of embryonic stem cells (ESCs). Whether different sets of reprogramming factors influence the type and extent of aberrant DNA methylation in iPSCs differently remains unknown. In order to help resolve this critical question, we generated human iPSCs from a common fibroblast cell source using either the Yamanaka factors (OCT4, SOX2, KLF4 and cMYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28), and determined their genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all our iPSCs, we identified Yamanaka-iPSC (Y-iPSC)-specific and Thomson-iPSC (T-iPSC)-specific recurrent aberrations. Strikingly, not only were the genomic locations of the aberrations different but also their types: reprogramming with Yamanaka factors mainly resulted in failure to demethylate CpGs, whereas reprogramming with Thomson factors mainly resulted in failure to methylate CpGs. Differences in the level of transcripts encoding DNMT3b and TET3 between Y-iPSCs and T-iPSCs may contribute partially to the distinct types of aberrations. Finally, de novo aberrantly methylated genes in Y-iPSCs were enriched for NANOG targets that are also aberrantly methylated in some cancers. Our study thus reveals that the choice of reprogramming factors influences the amount, location, and class of DNA methylation aberrations in iPSCs. These findings may provide clues into how to produce human iPSCs with fewer DNA methylation abnormalities

Month of birth and child height in 40 countries

Lokshin and Radyakin (2012) present evidence that month of birth affects child physical growth in India. We replicate these correlations using the same data and demonstrate that they are the result of a spurious relationship between month of birth, age-at-measurement and child growth patterns in developing countries. We repeat the analysis on 39 additional countries and show that there is no evidence of seasonal birth effects in child height-for-age z-score in any country. Furthermore, we demonstrate that the Demographic and Health Survey data used to estimate the correlation is not suitable for the task due to a previously unrecognized source of measurement error in child month of birth. We document results from several papers that should be re-interpreted in light of this issue

Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis

Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection

A Study of the Feasibility and Potential Implementation of Metro-Based Freight Transportation in Newcastle upon Tyne

The concept of using a metropolitan railway network to transport freight directly to a city centre from the surrounding businesses has been the subject of much research. This paper looks in depth at the Tyne and Wear Metro system, situated in Newcastle upon Tyne, to determine if such a scheme would be feasible. Through research into the modes of transport available, along with a review of literature and case studies, it was found that the current method of transporting the majority of freight by road is unsustainable and damaging to both the environment and local communities. Other options for the transportation of freight have been reviewed, and results showed that a modal shift will be necessary in the near future. The system was then modelled using software provided by the Department for Transport, which demonstrated that the implementation of such a scheme would provide vast accident savings, a reduction in the number of casualties on the road, and a monetary saving as a result of the lower casualty rate. The conclusion was reached that the scheme is viable, however further research and study is necessary before implementation

Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos

Transcriptional enhancers are a primary mechanism by which tissue-specific gene expression is achieved. Despite the importance of these regulatory elements in development, responses to environmental stresses, and disease, testing enhancer activity in animals remains tedious, with a minority of enhancers having been characterized. Here, we have developed ‘enhancer-FACS-Seq’ (eFS) technology for highly parallel identification of active, tissue-specific enhancers in Drosophila embryos. Analysis of enhancers identified by eFS to be active in mesodermal tissues revealed enriched DNA binding site motifs of known and putative, novel mesodermal transcription factors (TFs). Naïve Bayes classifiers using TF binding site motifs accurately predicted mesodermal enhancer activity. Application of eFS to other cell types and organisms should accelerate the cataloging of enhancers and understanding how transcriptional regulation is encoded within them

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers