Perturbation of the P-Body Component Mov10 Inhibits HIV-1 Infectivity

Exogenous retroviruses are obligate cellular parasites that co-opt a number of host proteins and functions to enable their replication and spread. Several host factors that restrict HIV and other retroviral infections have also recently been described. Here we demonstrate that Mov10, a protein associated with P-bodies that has a putative RNA-helicase domain, when overexpressed in cells can inhibit the production of infectious retroviruses. Interestingly, reducing the endogenous Mov10 levels in virus-producing cells through siRNA treatment also modestly suppresses HIV infectivity. The actions of Mov10 are not limited to HIV, however, as ectopic expression of Mov10 restricts the production of other lentiviruses as well as the gammaretrovirus, murine leukemia virus. We found that HIV produced in the presence of high levels of Mov10 is restricted at the pre-reverse transcription stage in target cells. Finally, we show that either helicase mutation or truncation of the C-terminal half of Mov10, where a putative RNA-helicase domain is located, maintained most of its HIV inhibition; whereas removing the N-terminal half of Mov10 completely abolished its activity on HIV. Together these results suggest that Mov10 could be required during the lentiviral lifecycle and that its perturbation disrupts generation of infectious viral particles. Because Mov10 is implicated as part of the P-body complex, these findings point to the potential role of cytoplasmic RNA processing machinery in infectious retroviral production

Al Qaeda, Islamists and Terrorism in Southeast Asia: A Lesson from the Past

 This article aims to explore the involvement of the Al-Qaeda network in Southeast Asia at the beginning of the 21st century. As an international terrorist organization with sufficient financial and human resources, Al-Qaeda's arrival in Southeast Asia came as a major shock to the local communities affected by it—an injustice caused by the capitalist regimes in the region. The methods used in writing this article are case studies and historical analysis. This article will provide specific examples of Al-Qaeda involvement in several countries in Southeast Asia, such as the case in Poso, Indonesia, where Al-Qaeda members Omar Bandon and Jusuf Galan from Spain provided military training and funding to militant Islamic groups in Malaysia. This article will also discuss Al-Qaeda's involvement in the Philippines, where they formed cells and networks with the Abu Sayyaf and other extreme Islamic groups. The results of this research show that the entry of the Al-Qaeda network in this area has caused terrorism problems and resulted in quite large losses in the form of property and lives. It is hoped that this article will provide new insights and policy recommendations to strengthen counterterrorism efforts in the future.  

Hubungan antara Karakteristik, Antropometrik, Kebiasaan, Status Psikososial, dan Gambaran Radiografis Responden dengan Kejadian Spondylogenic Low Back Pain

Background : Low Back Pain is a patient’s complaint that frequently come to the orthopaedic surgeon. Plenty of studies about Low Back Pain worldwide are related to the risk factors or radiographical image, but similar study are yet to be found in Indonesia. Considering the sociocultural diversity on Indonesia people, a proper study about risk factors and radiographical image need to be done in Indonesia. Aim of this study : To find out the correlation between risk factors, radiographical images, psychosocial status, with the occurrence of spondylogenic Low Back Pain. Method : Analytic Observational study with case control design on 96 people consist of 48 patients with Low Back Pain who came to the orthopaedic and medical rehabilitation clinics of Dr Soetomo General Hospital, Surabaya and 48 respondents without Low Back Pain complaint. Evaluation was done with questionnaire, physical examination, 6 positions of lumbosacral x-ray imaging and MRI evaluation of some of the Low Back Pain patients. Result: A meaningful correlation was found between type of working chair with spondylogenic low back pain (p=0,004). The condition of the patient’s psychosocial status had a meaningful correlation with spondylogenic low back pain (p=0,02).Radiographical image of spondylolisthesis also had a meaningful correlation with spondylogenic low back pain (p=0,016). Meanwhile other factors namely characteristics such as age, sex, antropometrics measurement such as body weight or BMI, habit of lifting weight, duration of standing, type of house chair, cross-leg sitting, type of bed and smoking didn’t show any correlation with spondylogenic low back pain. Conclusion : A meaningful correlation was found between type of working chair (p=0,004) and condition of psychosocial status (p=0,02) with spondylogenic low back pain. Radiographical image that correlate with spondylogenic low back pain is spondylolisthesis (p=0,016)

Gerakan Kebersihan Lingkungan dan Pencegahan Bencana melalui Program Kali Bersih (PROKASI)

Kebersihan lingkungan merupakan faktor utama dalam mewujudkan masyarakat yang sehat. Salah satu unsur lingkungan yang perlu dijaga adalah kebersihan sungai. Permasalahan kebersihan sungai selalu menjadi masalah utama dalam kebersihan lingkungan.  Selain itu, dalam menciptakan lingkungan yang bersih dan untuk mencegah terjadinya bencana, diperlukan Gerakan yang berkelanjutan. Program Kali Bersih (PROKASI) adalah salah satu upaya untuk menjaga kebersihan lingkungan di Desa Kalipare, Kabupaten Malang. Program pengabdian kepada masyarakat ini menekankan pada gerakan kebersihan berkelanjutan dan sosialisasi pentingnya menjaga kebersihan lingkungan.  Langkah-langkah yang dilaksanakan dalam pelaksanaan program ini adalah Gerakan bersih-bersih di beberapa titik sungai di desa tersebut, serta sosialisasi pentingnya menjaga kebersihan kepada warga desa. Berbagai langkah ini dilakukan dalam jangka waktu tiga minggu dan mendapat sambutan baik dari warga desa. Diharapkan berbagai kegiatan yang dilakukan tersebut dapat memberikan pemahaman yang lebih baik dan menumbuhkan kesadaran warga Desa Klalipare tentang pentingnya kebersihan lingkungan dan kebiasaan menjaga lingkungan sebagai upaya untuk mewujudkan masyarakat desa yang sehat

Effects of fuel content and density on the smoldering characteristics of cellulose and hemicellulose

Smoldering combustion in wildland fires poses hazards for both ecosystems and humans by destroying biomass, transitioning to flaming combustion, and releasing significant quantities of pollution. Understanding the parameters that control smoldering is necessary to help predict and potentially mitigate these hazards. A challenge in identifying these parameters is the wide variety of biomasses which occur in nature. The objective of this study is to identify the effects of density and fuel concentration on the smoldering characteristics of cellulose and hemicellulose mixtures. These fuels were considered because they are some of the major organic constituents within biomass. To this end, downward smoldering propagation velocities were measured for 50%, 75%, and 100% cellulose content at densities varying from 170 to 400 kg/m(3). The horizontal smoldering propagation velocities and temperature distributions were also determined for loosely packed samples ranging from 100% to 0% cellulose (with residual hemicellulose). Additionally, horizontal smoldering propagation velocities were determined for systematically varied ratios of cellulose (50-100%) and densities (200-400 kg/m(3)). The fuel was burned in an insulated reactor box. An infrared camera measured the horizontal propagation velocity, and thermocouples measured the downward propagation. A one-dimensional reactive porous media model with reduced chemistry was used to identify key processes causing the observed sensitivities. At constant packing density, the propagation velocity increased as cellulose content decreased because of decreased heat release with increased cellulose content and the earlier onset of hemicellulose pyrolysis. The propagation velocity decreased with respect to packing density when the fuel content was constant because of reduced oxygen diffusion. The propagation velocity increased with cellulose content when the fuel was loosely packed because of the decreasing density. (C) 2018 The Combustion Institute. Published by Elsevier Inc. All rights reserved

A Stable Human-Cell System Overexpressing Cystic Fibrosis Transmembrane Conductance Regulator Recombinant Protein at the Cell Surface

Recent human clinical trials results demonstrated successful treatment for certain genetic forms of cystic fibrosis (CF). To extend treatment opportunities to those afflicted with other genetic forms of CF disease, structural and biophysical characterization of CF transmembrane conductance regulator (CFTR) is urgently needed. In this study, CFTR was modified with various tags, including a His10 purification tag, the SUMOstar (SUMO*) domain, an extracellular FLAG epitope, or an enhanced green fluorescent protein (EGFP), each alone or in various combinations. Expressed in HEK293 cells, recombinant CFTR proteins underwent complex glycosylation, compartmentalized with the plasma membrane, and exhibited regulated chloride-channel activity with only modest alterations in channel conductance and gating kinetics. Surface CFTR expression level was enhanced by the presence of SUMO* on the N-terminus. Quantitative mass-spectrometric analysis indicated approximately 10% of the total recombinant CFTR (SUMO*-CFTRFLAG-EGFP) localized to the plasma membrane. Trial purification using dodecylmaltoside for membrane protein extraction reproducibly recovered 178 ± 56 μg SUMO*-CFTRFLAG-EGFP per billion cells at 80% purity. Fluorescence size-exclusion chromatography indicated purified CFTR was monodisperse. These findings demonstrate a stable mammalian cell expression system capable of producing human CFTR of sufficient quality and quantity to augment futrure CF drug discovery efforts, including biophysical and structural studies

Barrier-to-Autointegration Factor Proteome Reveals Chromatin-Regulatory Partners

Nuclear lamin filaments and associated proteins form a nucleoskeletal (“lamina”) network required for transcription, replication, chromatin organization and epigenetic regulation in metazoans. Lamina defects cause human disease (“laminopathies”) and are linked to aging. Barrier-to-autointegration factor (BAF) is a mobile and essential component of the nuclear lamina that binds directly to histones, lamins and LEM-domain proteins, including the inner nuclear membrane protein emerin, and has roles in chromatin structure, mitosis and gene regulation. To understand BAF's mechanisms of action, BAF associated proteins were affinity-purified from HeLa cell nuclear lysates using BAF-conjugated beads, and identified by tandem mass spectrometry or independently identified and quantified using the iTRAQ method. We recovered A- and B-type lamins and core histones, all known to bind BAF directly, plus four human transcription factors (Requiem, NonO, p15, LEDGF), disease-linked proteins (e.g., Huntingtin, Treacle) and several proteins and enzymes that regulate chromatin. Association with endogenous BAF was independently validated by co-immunoprecipitation from HeLa cells for seven candidates including Requiem, poly(ADP-ribose) polymerase 1 (PARP1), retinoblastoma binding protein 4 (RBBP4), damage-specific DNA binding protein 1 (DDB1) and DDB2. Interestingly, endogenous BAF and emerin each associated with DDB2 and CUL4A in a UV- and time-dependent manner, suggesting BAF and emerin have dynamic roles in genome integrity and might help couple DNA damage responses to the nuclear lamina network. We conclude this proteome is a rich source of candidate partners for BAF and potentially also A- and B-type lamins, which may reveal how chromatin regulation and genome integrity are linked to nuclear structure

Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types