A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection

The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734–736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo

In vitro anti-HIV activity of some Indian medicinal plant extracts

Background Human Immunodeficiency Virus (HIV) persists to be a significant public health issue worldwide. The current strategy for the treatment of HIV infection, Highly Active Antiretroviral Therapy (HAART), has reduced deaths from AIDS related disease, but it can be an expensive regime for the underdeveloped and developing countries where the supply of drugs is scarce and often not well tolerated, especially in persons undergoing long term treatment. The present therapy also has limitations of development of multidrug resistance, thus there is a need for the discovery of novel anti-HIV compounds from plants as a potential alternative in combating HIV disease. Methods Ten Indian medicinal plants were tested for entry and replication inhibition against laboratory adapted strains HIV-1IIIB, HIV-1Ada5 and primary isolates HIV-1UG070, HIV-1VB59 in TZM-bl cell lines and primary isolates HIV-1UG070, HIV-1VB59 in PM1 cell lines. The plant extracts were further evaluated for toxicity in HEC-1A epithelial cell lines by transwell epithelial model. Results The methanolic extracts of Achyranthes aspera, Rosa centifolia and aqueous extract of Ficus benghalensis inhibited laboratory adapted HIV-1 strains (IC80 3.6–118 μg/ml) and primary isolates (IC80 4.8–156 μg/ml) in TZM-bl cells. Methanolic extract of Strychnos potatorum, aqueous extract of Ficus infectoria and hydroalcoholic extract of Annona squamosa inhibited laboratory adapted HIV-1 strains (IC80 4.24–125 μg/ml) and primary isolates (IC80 18–156 μg/ml) in TZM-bl cells. Methanolic extracts of Achyranthes aspera and Rosa centifolia, (IC801-9 μg/ml) further significantly inhibited HIV-1 primary isolates in PM1cells. Methanolic extracts of Tridax procumbens, Mallotus philippinensis, Annona reticulate, aqueous extract of Ficus benghalensis and hydroalcoholic extract of Albizzia lebbeck did not exhibit anti-HIV activity in all the tested strains. Methanolic extract of Rosa centifolia also demonstrated to be non-toxic to HEC-1A epithelial cells and maintained epithelial integrity (at 500 μg/ml) when tested in transwell dual-chamber. Conclusion These active methanolic extracts of Achyranthes aspera and Rosa centifolia, could be further subjected to chemical analysis to investigate the active moiety responsible for the anti-HIV activity. Methanolic extract of Rosa centifolia was found to be well tolerated maintaining the epithelial integrity of HEC-1A cells in vitro and thus has potential for investigating it further as candidate microbicide

Modeling the effects of information-dependent vaccination behavior on meningitis transmission

We propose a mathematical model to investigate the effects of information–dependent vaccination behavior on meningitis transmission. The information is represented by means of information index as early proposed by d'Onofrio et al. (Theor. Popul. Biol., 2007). We perform a qualitative analysis based on stability theory, focusing to the global stability of the disease-free equilibrium (DFE) and the related transcritical bifurcation taking place at the threshold for the DFE. Finally, we assess the role of epidemiological and information parameters in the model dynamics through numerical simulations. Our simulations suggests that the impact of the parameters that are related to human behavior critically depend on the average information delay. For example, it can induce recurrent epidemics, provided that transfer rate from the carrier to the infectious state is over a threshold. Otherwise, the endemic equilibrium is (at least) locally stable

Detailed Magnetic Study of the Red Sea Propagator within Afar, Ethiopia: Implications for the Transitioning from Continental Rifting to Sea Floor Spreading

A detailed magnetic study across the Tendaho Graben (the Red Sea propagator within the Afar Depression, Ethiopia) revealed features that can best be interpreted as a continental rift undergoing oceanization. This NW-trending extensional structure is ~50 km wide and it is confined within well-developed NW-trending boarder faults that deform the 2 km thick and ~ 2 Ma basalt flows of the Afar Stratoids. Faults within the graben are inward dipping and the deformed blocks show inward tilting. The age of the basaltic flows becomes progressively younger inward from the boarder faults until it reaches ~30,000 years close to the rift axis. The rift is filled with up to 2 km lacustrine sediments. A gravity analysis has indicated a gravity maximum over the center and thickest part of the graben that is caused by a thick zone of mafic dikes that extends into the basement rocks. Total-field magnetic measurements over the same region as the gravity study indicates that the central part of the Tendaho Graben has a 10 km wide magnetic minimum, which exhibits a narrow zone (~3 km) of a relatively higher magnetic values that coincides with the region of hydrothermal activities. This magnetic geometry is similar in dimension and magnitude to that observed from magnetic stripes of typical mid-ocean ridges. Forward modeling of the magnetic data (combined with geochronological data) shows that the basaltic rocks within the magnetic trough were crystallized after 0.78 Ma under normal magnetic polarity. Finally, the width of the magnetic trough (10 km) and the age of basaltic rocks ( \u3c 0.78 Ma) indicate a spreading rate of ~ 0.64 cm/year. However, to achieve the ~50 km width of the Tendaho Graben which started opening ~1.6 Ma, a 2.4 cm/year spreading rate is needed between 1.6 and 0.78 Ma. This suggests that the spreading rate with Tendaho Graben is slowing down and extension within Afar is taken somewhere else

Production model to improve the efficiency of a peruvian cotton knitwear export company using 5s, standardization of operations and autonomous maintenance

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado.Nowadays, organizations in the cotton knitwear industry have had to adapt to a client who is not willing to pay an additional cost for activities that do not add value to the product. In Peru, many companies that export cotton knitwear closes every year since they cannot compete with countries such as China and Hong Kong due to their high production costs. This paper introduces a production management model based on Lean Manufacturing techniques and standardization of operations to reduce waste in the production flow, thus improving quality, and reducing production time and costs. So, a Production and Continuous improvement model (PDCA) were implemented. The validation was performed in a representative Peruvian company that exports cotton knitwear, resulting in an efficiency improvement of 10%, reduction of defective products of 20%, and generating savings of almost 5,000 soles monthly

Surgical data strengthening in Ethiopia: results of a Kirkpatrick framework evaluation of a data quality intervention

Background: One key challenge in improving surgical care in resource-limited settings is the lack of high-quality and informative data. In Ethiopia, the Safe Surgery 2020 (SS2020) project developed surgical key performance indicators (KPIs) to evaluate surgical care within the country. New data collection methods were developed and piloted in 10 SS2020 intervention hospitals in the Amhara and Tigray regions of Ethiopia. Objective: To assess the feasibility of collecting and reporting new surgical indicators and measure the impact of a surgical Data Quality Intervention (DQI) in rural Ethiopian hospitals. Methods: An 8-week DQI was implemented to roll-out new data collection tools in SS2020 hospitals. The Kirkpatrick Method, a widely used mixed-method evaluation framework for training programs, was used to assess the impact of the DQI. Feedback surveys and focus groups at various timepoints evaluated the impact of the intervention on surgical data quality, the feasibility of a new data collection system, and the potential for national scale-up. Results: Results of the evaluation are largely positive and promising. DQI participants reported knowledge gain, behavior change, and improved surgical data quality, as well as greater teamwork, communication, leadership, and accountability among surgical staff. Barriers remained in collection of high-quality data, such as lack of adequate human resources and electronic data reporting infrastructure. Conclusions: Study results are largely positive and make evident that surgical data capture is feasible in low-resource settings and warrants more investment in global surgery efforts. This type of training and mentorship model can be successful in changing individual behavior and institutional culture regarding surgical data collection and reporting. Use of the Kirkpatrick Framework for evaluation of a surgical DQI is an innovative contribution to literature and can be easily adapted and expanded for use within global surgery