Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics

Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes

Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new therapeutics as well as provide potential insight into the trafficking and entry mechanism of other filoviruses

Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

Background Ebolaviruses cause a severe and often fatal haemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently, the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission. Results To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naïve animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage. Conclusions Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV

Ebolavirus Is Internalized into Host Cells via Macropinocytosis in a Viral Glycoprotein-Dependent Manner

Ebolavirus (EBOV) is an enveloped, single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever with mortality rates of up to 90% in humans and nonhuman primates. Previous studies suggest roles for clathrin- or caveolae-mediated endocytosis in EBOV entry; however, ebolavirus virions are long, filamentous particles that are larger than the plasma membrane invaginations that characterize clathrin- or caveolae-mediated endocytosis. The mechanism of EBOV entry remains, therefore, poorly understood. To better understand Ebolavirus entry, we carried out internalization studies with fluorescently labeled, biologically contained Ebolavirus and Ebolavirus-like particles (Ebola VLPs), both of which resemble authentic Ebolavirus in their morphology. We examined the mechanism of Ebolavirus internalization by real-time analysis of these fluorescently labeled Ebolavirus particles and found that their internalization was independent of clathrin- or caveolae-mediated endocytosis, but that they co-localized with sorting nexin (SNX) 5, a marker of macropinocytosis-specific endosomes (macropinosomes). Moreover, the internalization of Ebolavirus virions accelerated the uptake of a macropinocytosis-specific cargo, was associated with plasma membrane ruffling, and was dependent on cellular GTPases and kinases involved in macropinocytosis. A pseudotyped vesicular stomatitis virus possessing the Ebolavirus glycoprotein (GP) also co-localized with SNX5 and its internalization and infectivity were affected by macropinocytosis inhibitors. Taken together, our data suggest that Ebolavirus is internalized into cells by stimulating macropinocytosis in a GP-dependent manner. These findings provide new insights into the lifecycle of Ebolavirus and may aid in the development of therapeutics for Ebolavirus infection

Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions

Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus

Pagpupumiglas: An Analysis of the Motivation, Discourse, and Impact of the Social Media Movement #Tumindig Using the Virtual Collective Consciousness by Neil M. Alperstein

The #Tumindig social movement brought upon a collective call for change under the utilization of Philippine Twitter in standing up against the country’s social issues. Since this is a relatively new topic, there is a lack of studies regarding the #Tumindig social movement. The present study seeks to analyze and understand the different factors that greatly influence the social movement which focuses on the motivation, discourse, and impact through using the Virtual Collective Consciousness framework by Neil M. Alperstein. With these—the motivation, discourse, and impact—behind the #Tumindig may provide insights regarding how exposure to social movements online, gain support and how Filipino Twitter users respond to the movement. The researchers utilizes a humanities inquiry approach by gathering 121 tweets using the aforementioned framework. These tweets were interpreted using content analysis which aims to analyze and interpret the meaning of qualitative data. It was found that the supporters of the movement contributed in addressing issues in the Philippine landscape through discourse, contesting ideologies, performing activism, in which perspectives are openly expressed by them to open more channels for engagement due to the “shared relevance” experienced by various groups, organizations, and individuals, they were able to be connected through the help of the hashtag, which mobilized them for social change. This demonstrates how social movements operate in both a celebrity (being them as forerunners) and leader-less environment driven by the virtual collective consciousness in the idea of solidarity against oppressive systems in the Philippines

DEVELOPMENT OF DIGITAL HUMAN BODY TRACKIER ALARM SYSTEM USING GPS AND TRANSCEIVER FOR CATASTROPHIC EVENTS' RESCUE OPERATION

Catastrophic events especially natural disasters are one of the most devastating events countries around the world normally experience nowadays. One major problem is that disasters leave some countries with a massive destruction and most of the time it kills and destroys the life of the people. After such said event, the lives of the people would become unpredictable because some of them have might survive would die instantly. This is where the researchers thought of conducting a study that would be useful every time these catastrophic events will occur. The study focused on the development of digital human body tracker alarm system (DHBT AS). The DHBT AS is a device to be monitored by the rescuers who will help the survivors during tragedy. The device is incorporated with GPS and transceiver to locate the survivors. The location in the form of latitude and longitude coordinates will be displayed on the LCD monitor of the DHBT AS. Using the coordinates at wiki map, it would be easier for the rescuers to locate the survivors with respect to the location of the DHBT AS. The device is also incorporated with a buzzer to alarm the rescuers the respective distance between the device and the survivor. The more abrupt the sound of the buzz is, the nearer is the rescuer to the survivor. The DHBT AS has its partner which is the rescue and operation device (ROP) which is to be worn by the victim; According to the tracked number of ROPs, the rescuers will be able to track the location and know the number of persons who still have a chance to live or survive within the 100m radius of the DHBT AS location. Moreover, the Rap device has its button that is to be pushed by the victim to inform the rescuers that they badly needed assistance or help as soon as possible. Pushing the button will allow the rescuers prioritize the need of the respective Rap wearer. The overall system trials gave an average delay of 2.4 seconds waiting time before the GPS satellite locator can give exact location

MICROCONTROLLER-BASED FLOOD WARNING SYSTEM WITH SHORT MESSAGE SERVICE NOTIFIER

Floods are the most common natural disaster and the leading cause of natural disaster fatalities worldwide. Particularly, Philippines is the most-exposed country to typhoons in the world. The most recent typhoons that hit the Philippines are Typhoon Haiyan (Yolanda), Bopha (Pablo), and Washi (Sendong). Each of the typhoons gave destructive effects as it hit the Philippines. In the case of tropical storm Washi, it brought long hours of rapid falling rains that triggered flash flood all over Mindanao. Such flood affected almost 132,000 families (NDRRMC, 2012). The researchers who were all residents of Iligan City, took the high level damage to properties and significant number of lost lives due to flood caused by typhoon Sendong, not only in Iligan City but all over Mindanao last December 2011, as the most important underlying factor to consider the design and development of the Microcontroller - Based Flood Warning System with SMS Notifier (MB-FWSSN) as shown in fig. 1. If only someone could have alarmed everybody that there is an incoming flash flood at that time then lives could have been saved. Thus, this system is focused on providing a forecasting system to the locality through warning devices like light indicators, buzzing sound, and issuing a text message every time the sensors at different water level readings at low, average and high levels are triggered by the water. Text messages are received as shown in fig.2. A graphical user interface as a desktop application for the control center is also added in the system to monitor the water level and serve as a database for the cellular telephone numbers of the affected registered residents. With these adequate components for early warning, this system will aid the residents and local authorities to make necessary precautions before and during the flood. The designed MB-FWSSN prototype for Mandulog River of Iligan City indeed turned on the light indicators, produces a buzzing sound and issued a text message to individuals upon different water level readings at only 5sec to 6.5sec delay from actual water reading

BRS 137: cultivar de soja para cultivo no Sul do Brasil BRS 137: soybean cultivar for southern Brazil

A liberação de cultivares de elevado potencial produtivo e com resistência a doenças é fundamental para continuar agregando rendimento na produção brasileira de soja. A cultivar BRS 137 é resultado do programa de melhoramento de soja desenvolvido pela Embrapa. A cultivar apresentou rendimento médio de grãos 2% superior ao da cultivar IAS 5, em 24 ambientes, no Rio Grande do Sul. É resistente à pústula-bacteriana (Xanthomonas axonopodis pv. glycines), ao cancro-da-haste (Diaporthe phaseolorum f. sp. meridionalis), à podridão-parda-da-haste (Phialophora gregata), à mancha-olho-de-rã (Cercospora sojina) e ao oídio (Microsphaera diffusa). É indicada para cultivo no Rio Grande do Sul, em semeaduras realizadas a partir de meados de outubro até fim de novembro, com população máxima de 300.000 plantas/ha.<br>The goals of the soybean breeding program for the release of a new cultivar include high yield potential and resistance to diseases in order to improve Brazilian production. The cultivar BRS 137 is a result of the soybean breeding program of Embrapa (Brazil). Prior to its release, the cultivar had shown a mean grain yield potential 2% higher than the cultivar IAS 5 in 24 environments in the State of Rio Grande do Sul, Brazil. Moreover, it is resistant to bacterial pustule (Xanthomonas axonopodis pv. glycines), soybean stem canker (Diaporthe phaseolorum f. sp. meridionalis), brown stem rot (Phialophora gregata), frogeye leaf spot (Cercospora sojina), and powdery mildew (Microsphaera diffusa). The cultivar is being indicated to be cropped in the Rio Grande do Sul state for sowing from mid October to the end of November with a maximum population of 300,000 plants/ha