Competitive endothelial adhesion between Plasmodium falciparum isolates under physiological flow conditions

<p>Abstract</p> <p>Background</p> <p>Sequestration of parasitized red blood cells in the microvasculature of major organs involves a sequence of events that is believed to contribute to the pathogenesis of severe falciparum malaria. <it>Plasmodium falciparum </it>infections are commonly composed of multiple subpopulations of parasites with varied adhesive properties. A key question is: do these subpopulations compete for adhesion to endothelium? This study investigated whether, in a laboratory model of cytoadherence, there is competition in binding to endothelium between pRBC infected with <it>P. falciparum </it>of variant adhesive phenotypes, particularly under flow conditions.</p> <p>Methods</p> <p>Four different <it>P. falciparum </it>isolates, of known adherence phenotypes, were matched in pairs, mixed in different proportions and allowed to bind to cultured human endothelium. Using <it>in vitro </it>competitive static and flow-based adhesion assays, that allow simultaneous testing of the adhesive properties of two different parasite lines, adherence levels of paired <it>P. falciparum </it>isolates were quantified and analysed using either non-parametric Wilcoxon's paired signed rank test or Student paired test.</p> <p>Results</p> <p>Study findings show that <it>P. falciparum </it>parasite lines show marked differences in the efficiency of adhesion to endothelium.</p> <p>Conclusion</p> <p><it>Plasmodium falciparum </it>variants will compete for adhesion to endothelia and variants can be ranked by their efficiency of binding. These findings suggest that variants from a mixed infection will not show uniform cytoadherence and so may vary in their ability to cause disease.</p

Sexual and reproductive health and human rights of women living with HIV

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/1/jia20834-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/2/jia20834.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/3/jia20834-sup-0002.pd

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Karakteristik Geokimia Basal Alkali Formasi Manamas di Sungai Bihati, Baun, Pulau Timor

Batuan beku Formasi Manamas di Sungai Bihati, Baun merupakan salah satu singkapan batuan beku di Pulau Timor yang belum banyak diteliti berdasarkan karakter geokimia. Penelitian ini bertujuan untuk mengetahui genesa dan proses yang terjadi pada batuan beku Formasi Manamas dalam kerangka tektonik yang terjadi di Pulau Timor berdasarkan analisis petrografi dan geokimia. Analisis geokimia dilakukan dengan menggunakan X-ray Fluorescence (XRF) dan Inductively Coupled Plasma-mass Spectrometery (ICP-MS) untuk mengetahui senyawa utama, unsur jejak, dan unsur tanah jarang. Batuan beku Formasi Manamas berupa intrusi basal dengan afinitas alkali yang menunjukkan pola pengayaan unsur tanah jarang yang identik dengan Ocean Island Basalt (OIB). Penelitian ini membuktikan adanya dua mekanisme pengayaan unsur yang berbeda yaitu fluid related enrichment yang berkaitan dengan aktifitas subduksi lempeng Samudra Hindia di bawah Busur Banda dan melt related enrichment yang diperkirakan berasal dari sisa lempeng Samudra Hindia yang patah yang masuk kedalam zona reservoir OIB. Kedua magma lalu bercampur dan mengalami underplating di bawah Busur Banda

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Software Startup Education : Gamifying Growth Hacking

Marketing is a vital activity for software startups as they seek high growth. A specific type of digital marketing, growth hacking, in particular has attracted a lot of attention in software startups. Growth hacking is about utilizing low-cost marketing practices and existing platforms to rapidly increase the user count of a service. Though topics related to growth hacking such as marketing on a general level have been extensively studied in the past, growth hacking has not seen much direct interest in the academia thus far. As a result, we currently have few tools to teach growth hacking in startup education. In this chapter, we present two board games intended to serve as an introduction to growth hacking.peerReviewe