Novel HIV-1 Knockdown Targets Identified by an Enriched Kinases/Phosphatases shRNA Library Using a Long-Term Iterative Screen in Jurkat T-Cells

HIV-1 is a complex retrovirus that uses host machinery to promote its replication. Understanding cellular proteins involved in the multistep process of HIV-1 infection may result in the discovery of more adapted and effective therapeutic targets. Kinases and phosphatases are a druggable class of proteins critically involved in regulation of signal pathways of eukaryotic cells. Here, we focused on the discovery of kinases and phosphatases that are essential for HIV-1 replication but dispensable for cell viability. We performed an iterative screen in Jurkat T-cells with a short-hairpin-RNA (shRNA) library highly enriched for human kinases and phosphatases. We identified 14 new proteins essential for HIV-1 replication that do not affect cell viability. These proteins are described to be involved in MAPK, JNK and ERK pathways, vesicular traffic and DNA repair. Moreover, we show that the proteins under study are important in an early step of HIV-1 infection before viral integration, whereas some of them affect viral transcription/translation. This study brings new insights for the complex interplay of HIV-1/host cell and opens new possibilities for antiviral strategies

The state of capacity development evaluation in biodiversity conservation and natural resource management

Capacity development is critical to long-term conservation success, yet we lack a robust and rigorous understanding of how well its effects are being evaluated. A comprehensive summary of who is monitoring and evaluating capacity development interventions, what is being evaluated and how, would help in the development of evidence-based guidance to inform design and implementation decisions for future capacity development interventions and evaluations of their effectiveness. We built an evidence map by reviewing peer-reviewed and grey literature published since 2000, to identify case studies evaluating capacity development interventions in biodiversity conservation and natural resource management. We used inductive and deductive approaches to develop a coding strategy for studies that met our criteria, extracting data on the type of capacity development intervention, evaluation methods, data and analysis types, categories of outputs and outcomes assessed, and whether the study had a clear causal model and/or used a systems approach. We found that almost all studies assessed multiple outcome types: most frequent was change in knowledge, followed by behaviour, then attitude. Few studies evaluated conservation outcomes. Less than half included an explicit causal model linking interventions to expected outcomes. Half of the studies considered external factors that could influence the efficacy of the capacity development intervention, and few used an explicit systems approach. We used framework synthesis to situate our evidence map within the broader literature on capacity development evaluation. Our evidence map (including a visual heat map) highlights areas of low and high representation in investment in research on the evaluation of capacity development

The chemistry and biological activity of the Hyacinthaceae

Covering: 1914 to 2012The Hyacinthaceae (sensu APGII), with approximately 900 species in about 70 genera, can be divided into three main subfamilies, the Hyacinthoideae, the Urgineoideae and the Ornithogaloideae, with a small fourth subfamily the Oziroëoideae, restricted to South America. The plants included in this family have long been used in traditional medicine for a wide range of medicinal applications. This, together with some significant toxicity to livestock has led to the chemical composition of many of the species being investigated. The compounds found are, for the most part, subfamily-restricted, with homoisoflavanones and spirocyclic nortriterpenoids characterising the Hyacinthoideae, bufadienolides characterising the Urgineoideae, and cardenolides and steroidal glycosides characterising the Ornithogaloideae. The phytochemical profiles of 38 genera of the Hyacinthaceae will be discussed as well as any biological activity associated with both crude extracts and compounds isolated. The Hyacinthaceae of southern Africa were last reviewed in 2000 (T. S. Pohl, N. R. Crouch and D. A. Mulholland, Curr. Org. Chem., 2000, 4, 1287-1324; ); the current contribution considers the family at a global level

Diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: a multicenter study (vol 12, pg 1104, 2021)

Transplantation and immunomodulatio

Etude des répercussions de la pollution industrielle sur la riziculture dans la plaine de Laniera à Antananarivo, Madagascar

Face au développement urbain à Antananarivo, l'agriculture urbaine et péri-urbaine est exposée à la pollution industrielle. Les industries spécialisées dans le textile déversent leurs eaux usées dans le système d'irrigation, et polluent directement les champs de rizières à proximité des zones industrielles. Après 3 ans de suivi, l'effet de la pollution est variable et fonction de la situation et du processus industriel. Pendant la saison sèche, la pollution est très prononcée, alors que pendant la saison de pluie, les effets de dilution ont des impacts très importants sur la qualité de l'eau d'irrigation. Les effluents sont généralement colorés en bleu par le procédé de lavage de jeans, et sont riches en matières organiques en suspension. La qualité des effluents varie dans la journée : le pH de 3,9 à 10,6 et la conductivité électrique de 452 à 3620 μS / cm. Notre étude a pour but d’analyser la qualité de l'eau d'irrigation et d’observer les effets de la pollution sur les sols, les compositions chimiques des plants de riz et sur la production. En début de la saison culturale, l’effluent résulte une diminution du pH et une forte salinité dans les rizières. Le complexe absorbant du sol est chargé lentement en sodium. L'analyse de la paille montre un déséquilibre nutritionnel dans le plant de riz, notamment l'accumulation de potassium : K (14,5 à 22%), N (0,44 à 0,7%), du Ca (0,42 à 3%), Mg (0,02 à 0,95%), Na (0,35 à 0,8%), P (200 à 561 ppm). Quand la pollution est très élevée, on observe un allongement du cycle et une forte nutrition azotée. Le rendement en riz obtenu est faible (< 2t/ha), tandis que le rendement recueilli dans la plaine de Laniera peut atteindre jusqu’à 5t/ha.Mots-Clés: pollution, eau d’irrigation, industries textiles, pollution des sols, rizière, Laniera.Study of the repercussion of industrial pollution on rice production in plain of LANIERA in Antananarivo, Madagascar Faced to urban development in Antananarivo, urban and peri-urban agriculture is exposed on industrial pollution. Specialized textile industries discharge their wastewater into the circulating irrigation system, and pollute directly the rice fields near the industrial area. After 3 years of monitoring, the effect of pollution is variable and depending on the situation and the industrial process. During the dry season, the pollution is very high. But during the rainy season, dilution effects are very important to the quality of irrigation water. The effluents are usually colored in blue, from the activity for the jeans washing process and riches of suspended organic matters. The effluents quality varies on day, the pH from 3.9 to 10.6 and the electrical conductivity from 452 to 3620 μS/cm. Our study focused on the water irrigation quality and observed the effect on soil, the rice plant chemical compositions and on the production. At the first of the cropping cycle, effluents caused a lower pH and a high salinity in the rice fields. The absorbent complex is slowly charged in sodium concentration. Straw analysis provides the instability absorption of minerals nutriment in the rice, enriched by potassium accumulation: K (14.5 to 22 %), N (0.44 to 0.7 %), Ca (0,42 to 3 %), Mg (0.02 to 0.95 %), Na (0.35 to 0.8 %), and P (200 to 561 ppm). When pollution is very high, we observed an elongation cycle and a strong nitrogenous nutrition. The yield of paddy rice decreased (<2 t / ha), while the average yield collected in the plain of Laniera can be achieved to 5t/ha of paddy.Keywords: pollution, water irrigation, textiles industries, pollution of soil, rice field, Laniera

Isolation of <em>Clostridium septicum</em> during a Blackleg Outbreak in Madagascar

Blackleg outbreaks have been reported at various locations in Vakinankaratra area (Madagascar) in 1996 and 1997, and caused the death of 588 head of cattle within seven months. Even animals that had been vaccinated between April and August 1996 were not spared from the disease. After performing bacteriological investigations on samples in March 1997, another blackleg agent, Clostridium septicum, was isolated, and its presence was reported in the country for the first time. The Institute for Applied Biotechnology in the Tropics of Goettingen (Germany) confirmed the diagnosis by the gas chromatography technique in May. An experimental vaccine was developed from that strain in order to fill the lacking valence in the conventional product. The isolation of C. septicum occurred 28 years after the first outbreaks of blackleg caused by Clostridium chauvoei. Its origin is briefly discussed

Provider-initiated HIV testing and counselling for TB in low HIV prevalence settings: is it worthwhile?

We assessed the HIV-positive yield of offering provider-initiated HIV testing and counselling (PITC) for TB and the costs, in Madagascar, which has a low HIV prevalence and a high TB burden

Antiproliferative Compounds from <i>Cleistanthus boivinianus</i> from the Madagascar Dry Forest

The two new lignans 3α-<i>O</i>-(β-d-glucopyranosyl)­desoxypodophyllotoxin (<b>1</b>) and 4-<i>O</i>-(β-d-glucopyranosyl)­dehydropodophyllotoxin (<b>2</b>) were isolated from <i>Cleistanthus boivinianus</i>, together with the known lignans deoxypicropodophyllotoxin (<b>3</b>), (±)-β-apopicropodophyllin (<b>4</b>), (−)-desoxypodophyllotoxin (<b>5</b>), (−)-yatein (<b>6</b>), and β-peltatin-5-<i>O</i>-β-d-glucopyranoside (<b>7</b>). The structures of all compounds were characterized by spectroscopic techniques. Compounds <b>1</b>, <b>4</b>, and <b>5</b> showed potent antiproliferative activities against the A2780 ovarian cancer cell line, with IC₅₀ values of 33.0 ± 3.6, 63.1 ± 6.7, and 230 ± 1 nM, respectively. Compounds <b>2</b> and <b>7</b> showed only modest A2780 activities, with IC₅₀ values of 2.1 ± 0.3 and 4.9 ± 0.1 μM, respectively, while compounds <b>3</b> and <b>6</b> had IC₅₀ values of >10 μM. Compound <b>1</b> also had potent antiproliferative activity against the HCT-116 human colon carcinoma cell line, with an IC₅₀ value of 20.5 nM, and compound <b>4</b> exhibited modest antiproliferative activity against the A2058 human caucasian metastatic melanoma and MES-SA human uterine sarcoma cell lines, with IC₅₀ values of 4.6 and 4.0 μM, respectively

Neolignans and Other Metabolites from <i>Ocotea cymosa</i> from the Madagascar Rain Forest and Their Biological Activities1

Ten new neolignans including the 6′-oxo-8.1′-lignans cymosalignans A (<b>1a</b>), B (<b>2</b>), and C (<b>3</b>), an 8.O.6′-neolignan (<b>4a</b>), ococymosin (<b>5a</b>), didymochlaenone C (<b>6a</b>), and the bicyclo[3.2.1]­octanoids <b>7</b>–<b>10</b> were isolated along with the known compounds 3,4,5,3′,5′-pentamethoxy-1′-allyl-8.O.4′-neolignan, 3,4,5,3′-tetramethoxy-1′-allyl-8.O.4′-neolignan, didymochlaenone B, virologin B, ocobullenone, and the unusual 2′-oxo-8.1′-lignan sibyllenone from the stems or bark of the Madagascan plant <i>Ocotea cymosa</i>. The new 8.O.6′-neolignan <b>4a</b>, dihydrobenzofuranoid <b>5a</b>, and the bicyclo[3.2.1]­octanoid <b>7a</b> had in vitro activity against <i>Aedes aegypti</i>, while the new compounds <b>5a</b>, <b>7a</b>,<b> 8</b>, and <b>10a</b> and the known virolongin B (<b>4b</b>) and ocobullenone (<b>10b</b>) had antiplasmodial activity. We report herein the structure elucidation of the new compounds on the basis of spectroscopic evidence, including 1D and 2D NMR spectra, electronic circular dichroism, and mass spectrometry, and the biological activities of the new and known compounds