Imaging Single Retrovirus Entry through Alternative Receptor Isoforms and Intermediates of Virus-Endosome Fusion

A large group of viruses rely on low pH to activate their fusion proteins that merge the viral envelope with an endosomal membrane, releasing the viral nucleocapsid. A critical barrier to understanding these events has been the lack of approaches to study virus-cell membrane fusion within acidic endosomes, the natural sites of virus nucleocapsid capsid entry into the cytosol. Here we have investigated these events using the highly tractable subgroup A avian sarcoma and leukosis virus envelope glycoprotein (EnvA)-TVA receptor system. Through labeling EnvA pseudotyped viruses with a pH-sensitive fluorescent marker, we imaged their entry into mildly acidic compartments. We found that cells expressing the transmembrane receptor (TVA950) internalized the virus much faster than those expressing the GPI-anchored receptor isoform (TVA800). Surprisingly, TVA800 did not accelerate virus uptake compared to cells lacking the receptor. Subsequent steps of virus entry were visualized by incorporating a small viral content marker that was released into the cytosol as a result of fusion. EnvA-dependent fusion with TVA800-expressing cells occurred shortly after endocytosis and delivery into acidic endosomes, whereas fusion of viruses internalized through TVA950 was delayed. In the latter case, a relatively stable hemifusion-like intermediate preceded the fusion pore opening. The apparent size and stability of nascent fusion pores depended on the TVA isoforms and their expression levels, with TVA950 supporting more robust pores and a higher efficiency of infection compared to TVA800. These results demonstrate that surface receptor density and the intracellular trafficking pathway used are important determinants of efficient EnvA-mediated membrane fusion, and suggest that early fusion intermediates play a critical role in establishing low pH-dependent virus entry from within acidic endosomes

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Enabling advanced inference on sensor nodes through the direct use of compressively-sensed signals

Abstract-Nowadays, sensor networks are being used to monitor increasingly complex physical systems, necessitating advanced signal analysis capabilities as well as the ability to handle large amounts of network data. For the first time, we present a methodology to enable advanced decision support on a lowpower sensor node through the direct use of compressively-sensed signals in a supervised-learning framework; such signals provide a highly efficient means of representing data in the network, and their direct use overcomes the need for energy-intensive signal reconstruction. Sensor networks for advanced patient monitoring are representative of the complexities involved. We demonstrate our technique on a patient-specific seizure detection algorithm based on electroencephalograph (EEG) sensing. Using data from 21 patients in the CHB-MIT database, our approach demonstrates an overall detection sensitivity, latency, and false alarm rate of 94.70%, 5.83 seconds, and 0.199 per hour, respectively, while achieving data compression by a factor of 10×. This compares well with the state-of-the-art baseline detector with corresponding results being 96.02%, 4.59 seconds, and 0.145 per hour, respectively

Enabling advanced inference on sensor nodes through the direct use of compressively-sensed signals

Abstract-Nowadays, sensor networks are being used to monitor increasingly complex physical systems, necessitating advanced signal analysis capabilities as well as the ability to handle large amounts of network data. For the first time, we present a methodology to enable advanced decision support on a lowpower sensor node through the direct use of compressively-sensed signals in a supervised-learning framework; such signals provide a highly efficient means of representing data in the network, and their direct use overcomes the need for energy-intensive signal reconstruction. Sensor networks for advanced patient monitoring are representative of the complexities involved. We demonstrate our technique on a patient-specific seizure detection algorithm based on electroencephalograph (EEG) sensing. Using data from 21 patients in the CHB-MIT database, our approach demonstrates an overall detection sensitivity, latency, and false alarm rate of 94.70%, 5.83 seconds, and 0.199 per hour, respectively, while achieving data compression by a factor of 10×. This compares well with the state-of-the-art baseline detector with corresponding results being 96.02%, 4.59 seconds, and 0.145 per hour, respectively

Distal foot reconstruction using distally based fi rst web fl ap: A case series

Background: The reconstruction of distal foot for various defects or contractures mainly over or near the toes has always been a diffi cult task. A fl ap distally based on fi rst web space is dependent upon a perforator arising from the the distal communicating artery between the fi rst dorsal and plantar metatarsal arteries, can be used for the coverage of the toe or the distal foot defects.Method: An observational study was conducted with the study period from August 2016 till August 2018. 10 patients with toe defects and contractures at the dorsum of the distal foot were operated using distally based fl ap elevated from fi rst webspace. Patient’s demographic data were collected and evaluated in terms of various factors.</p