Decoy ACE2-expressing extracellular vesicles that competitively bind SARS-CoV-2 as a possible COVID-19 therapy

© 2020 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND - https://creativecommons.org/licenses/by-nc-nd/4.0/).The novel strain of coronavirus that appeared in 2019, SARS-CoV-2, is the causative agent of severe respiratory disease, COVID-19, and the ongoing pandemic. As for SARS-CoV that caused the SARS 2003 epidemic, the receptor on host cells that promotes uptake, through attachment of the spike (S) protein of the virus, is angiotensin-converting enzyme 2 (ACE2). In a recent article published by Batlle et al. (Clin. Sci. (Lond.) (2020) 134, 543-545) it was suggested that soluble recombinant ACE2 could be used as a novel biological therapeutic to intercept the virus, limiting the progression of infection and reducing lung injury. Another way, discussed here, to capture SARS-CoV-2, as an adjunct or alternative, would be to use ACE2+-small extracellular vesicles (sEVs). A competitive inhibition therapy could therefore be developed, using sEVs from engineered mesenchymal stromal/stem cells (MSCs), overexpressing ACE2.Peer reviewedFinal Published versio

AlxGa1-xN-based avalanche photodiodes with high reproducible avalanche gain

Cataloged from PDF version of article.The authors report high performance solar-blind photodetectors with reproducible avalanche gain as high as 1560 under ultraviolet illumination. The solar-blind photodetectors have a sharp cutoff around 276 nm. The dark currents of the 40 m diameter devices are measured to be lower than 8 fA for bias voltages up to 20 V. The responsivity of the photodetectors is 0.13 A/W at 272 nm under 20 V reverse bias. The thermally limited detectivity is calculated as D*=1.4 1014 cm Hz1/2 W−1 for a 40 m diameter device

PENGEMBANGAN BUKU SAKU UNTUK KESEHATAN PRIBADI BAGI SISWA KELAS ATAS DI SEKOLAH DASAR NEGERI SUMBERARUM 1 KECAMATAN TEMPURAN KABUPATEN MAGELANG

Tujuan penelitian adalah: (1) mengembangkan buku saku kesehatan pribadi sebagi sumber belajar siswa kelas atas di Sekolah Dasar Negeri Sumberarum 1 Kecamatan Tempuran, Kabupaten Magelang, (2) mengetahui penilaian kualitas buku saku kesehatan pribadi oleh ahli materi dan media, (3) mengetahui penilaian kualitas produk buku saku kesehatan pribadi oleh siswa kelas atas. Penelitian ini merupakan penelitian Research and Development (R&D) yang berorientasi pada produk. Pengembangan buku saku ini melalui tahap mengidentifikasi potensi dan masalah, mengumpulkan data, mendesain dan membuat produk awal, validasi oleh ahli materi dan ahli media. Produk diujicobakan kepada siswa di Sekolah Dasar Negeri Sumberarum 1 Kecamatan Tempuran, Kabupaten Magelang. Data dikumpulkan melalui kuesioner yang diberikan kepada siswa. Data berupa hasil penilaian mengenai kualitas produk, saran untuk perbaikan produk, serta data kualitatif lainnya. Data kuantitatif dianalisis dengan statistik deskriptif. Hasil penelitian dan pengembangan ini dihasilkan sebuah buku saku sumber belajar kesehatan khususnya kesehatan pribadi yang dapat digunakan sebagai sumber belajar oleh siswa Sekolah Dasar kelas atas. Kualitas produk yang dikembangkan menurut penilaian ahli materi ”Sangat Baik” dengan rerata skor 4,73, menurut ahli media ” Baik” dengan rerata skor 4,00. Sedangkan uji coba lapangan persiapan pada buku saku kesehatan pribadi yang diujikan kepada siswa menunjukkan kriteria “ sangat baik” dengan rerata sekor 4,48 dan untuk uji coba lapangan utama pada buku saku kesehatan pribadi yang diujikan kepada siswa menunjukan kriteria “ sangat baik” dengan rerata 4,37. Dapat disimpulkan bahwa pengembangan buku saku kesehatan pribadi layak digunakan sebagai sarana sumber belajar siswa dalam pelajaran kesehatan di sekolah

Plasma mEV levels in Ghanain malaria patients with low parasitaemia are higher than those of healthy controls, raising the potential for parasite markers in mEVs as diagnostic targets

This study sought to measure medium-sized extracellular vesicles (mEVs) in plasma, when patients have low Plasmodium falciparum early in infection. We aimed to define the relationship between plasma mEVs and: (i) parasitaemia, (ii) period from onset of malaria symptoms until seeking medical care (patient delay, PD), (iii) age and (iv) gender. In this cross-sectional study, n = 434 patients were analysed and Nanosight Tracking Analysis (NTA) used to quantify mEVs (vesicles of 150–500 nm diameter, isolated at 15,000 × g, β-tubulin-positive and staining for annexin V, but weak or negative for CD81). Overall plasma mEV levels (1.69 × 1010 mEVs mL−1) were 2.3-fold higher than for uninfected controls (0.51 × 1010 mEVs mL−1). Divided into four age groups, we found a bimodal distribution with 2.5- and 2.1-fold higher mEVs in infected children (10 mEVs mL−1) and the elderly (>45 yo) (median:1.92 × 1010 mEVs mL−1), respectively, compared to uninfected controls; parasite density varied similarly with age groups. There was a positive association between mEVs and parasite density (r = 0.587, p p p = 0.667). Parasite density was also exponentially related to patient delay. Gender (p = 0.667) had no effect on plasma mEV levels. During periods of low parasitaemia (PD = 72h), mEVs were 0.93-fold greater than in uninfected controls. As 75% (49/65) of patients had low parasitaemia levels (20–500 parasites µL−1), close to the detection limits of microscopy of Giemsa-stained thick blood films (5–150 parasites µL−1), mEV quantification by NTA could potentially have early diagnostic value, and raises the potential of Pf markers in mEVs as early diagnostic targets

Organic Electrochemical Transistors

Organic electrochemical transistors (OECTs) leverage ion injection from an electrolyte into an organic semiconductor film to yield compelling advances in biological interfacing, printed logic circuitry and neuromorphic devices. Their defining characteristic is the coupling between electronic and ionic charges within the volume of an organic film. In this review we discuss the mechanism of operation and the materials that are being used, overview the various form factors, fabrication technologies and proposed applications, and take a critical look at the future of OECT research and development

Pengamatan Post-mortem Kualitas Kulit Kambing Di Kota Manado

Kulit ternak merupakan hasil ikutan ternak yang memiliki nilai ekonomis sebagai bahan baku utama berbagai produk industri kulit. Kualitas kuli tsegar dapat mengalami penurunan pada saat ternak masih hidup maupun setelah lepas dari tubuh ternak. Penyembelihan ternak kambing di Kota Manado cukup banyak namun belum memperhatikan kualitas kulitnya. Penelitian ini bertujuan untuk mengetahui seberapa jauh kualitas post-mortem kulit kambing di Kota Manado. Pengambilan data dilakukan di tempat pemotongan hewan pasar bersehati Kota Manado menggunakan metode observasi terhadap beberapa variabel yaitu cacat irisan, cacat penyakit kulit, dan cacat flek darah. Pengambilan sampel melalui purposive sampling serta penyajian data menggunakan statistik deskriptif. Hasil pengamatan menunjukkan bahwa cacat pada kulit kambing post mortem yang terbanyak adalah cacat irisan dan cacat penyakit kulit (± 60%) dan cacat flek darah paling sedikit (± 13,3%). Cacat yang ditemui terbanyak pada daerah D (daerah badan)

Complement C2 Receptor Inhibitor Trispanning Confers an Increased Ability to Resist Complement-Mediated Lysis in Trypanosoma cruzi

The ability to resist complement differs between theYand Colombiana Trypanosoma cruzi strains.Wefound that the Y strain of T. cruzi was more able to resist the classical and lectin pathways of complement activation than the Colombiana strain. The complement C2 receptor inhibitor trispanning gene (CRIT) is highly conserved in both strains. At the protein level, CRIT is expressed only in stationary-phase epimastigotes of the Y but not the Colombiana strain and is expressed in infectious metacyclic trypomastigotes of both strains. Y strain epimastigotes with an overexpressed CRIT gene (pTEX-CRIT) had higher survival in normalhumanserum (NHS). Overexpression of the Y strain CRIT gene in Colombiana epimastigote forms increased the parasite's resistance to lysis mediated by the classical and lectin pathways but not to lysis mediated by alternative pathways. CRIT involvement on the parasite surface was confirmed by showing that the lytic activity ofNHSagainst epimastigotes could be restored by adding excess C

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 and moesin protein levels, as well as on cell invasion. The PAD3 inhibitor was most effective in modulating EVs to anti-oncogenic signatures (reduced miR21 and miR210, and elevated miR126), to reduce cell invasion and to modulate protein expression of pro-GBM proteins in LN229 cells, while the PAD2 and PAD4 inhibitors were more effective in LN18 cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins relating to cancer, metabolism and inflammation differed between the two GBM cell lines. Our findings highlight roles for the different PAD isozymes in the heterogeneity of GBM tumours and the potential for tailored PAD-isozyme specific treatment

Evolutionary game of coalition building under external pressure

We study the fragmentation-coagulation (or merging and splitting) evolutionary control model as introduced recently by one of the authors, where $N$ small players can form coalitions to resist to the pressure exerted by the principal. It is a Markov chain in continuous time and the players have a common reward to optimize. We study the behavior as $N$ grows and show that the problem converges to a (one player) deterministic optimization problem in continuous time, in the infinite dimensional state space