Inhibitory effects of commercial and enriched green tea extracts on the growth of Brochothrix thermosphacta, Pseudomonas putida and Escherichia coli

The major catechin found in green tea, called epigallocatechin gallate (EGCG), have been reported to have antimicrobial properties. In this study, we examined in vitro the antimicrobial effects of a commercial green tea extract sold in a capsule form, and two prepared green tea extracts enriched in catechins against Brochothrix thermosphacta, Pseudomonsas putida and Escherichia coli which have been associated with meat spoilage. The antimicrobial activity of the different tea extracts was evaluated by Spot-On-Lawn and Well Diffusion assays and the Minimum Inhibitory Concentration (MIC) was also determined in Brain Heart Infusion broth. The three methods used showed an inhibition of Brochothrix thermosphacta, whereas the inhibition of Pseudomonas putida and Escherichia coli was only detected with the MIC assay. The determination of the MIC in broth culture appeared to be the most reliable method to determine the inhibitory activity of catechin compounds

Social drivers forewarn of marine regime shifts

Some ecosystems can undergo regime shifts to alternative compositions of species. Although ecological indicators can identify approaching regime shifts, we propose that rapid changes in the social drivers underlying ecosystem change may provide additional and potentially earlier indicators of impending shifts. We demonstrate this by reconstructing the underlying social drivers of four iconic marine regime shifts: Pacific kelp forests, Northwest Atlantic continental shelf, Jamaican coral reefs, and the Chesapeake Bay estuary. In all cases, a range of social drivers – including opening of lucrative markets, technological innovations, and policies that enhanced the driver – ultimately prompted these ecosystem shifts. Drawing on examples emerging from environmental management practice, we present three practical recommendations for using social drivers as early indicators: monitor social change, determine social trigger points, and identify policy responses. We argue that accounting for the underlying social drivers of ecosystem change could improve decision making

Heat flux-based strategies for the thermal monitoring of sub-fumarolic areas: Examples from Vulcano and La Soufrière de Guadeloupe

Although it is relatively easy to set-up, the monitoring of soil temperature in sub-fumarolic areas is quite rarely used to monitor the evolution of hydrothermal systems. Indeed, measurements are highly sensitive to environmental conditions, in particular daily and seasonal variations of atmospheric temperatures and rainfalls, which can be only partially filtered by the established statistical analysis. In this paper, we develop two innovative processingmethods, both based on the computation of the heat flux in the soil. The upward heat flux method (UHF), designed for dry environments, consists in computing both the conductive and convective components of the heat flux between two thermocouples placed vertically. In the cases of wet environments, the excess of total heat method (ETH) allows the integration of rain gauges data in order to correct the heat balance fromthe superficial cooling effect of the precipitations. The performances of both processing techniques are faced to established methods (temperature gradient and coefficient of determination) on soil temperature time series from two test volcanoes. At La Fossa di Vulcano (Italy), the UHF method undoubtedly detects three thermal crises between 2009 and 2012, enabling to quantify not only the intensity but also the precise timing of the heat flux increase with respect to corresponding geochemical and seismic crises. At La Soufrière de Guadeloupe (French Lesser Antilles), despite large rainfalls dramatically influencing the thermal behavior of the soil, a constant geothermal heat flux is retrieved by the ETH method, confirming the absence of fumarolic crisis during the observation period (February–August 2010). Being quantitative, robust, and usable in almost any context of sub-fumarolic zones, our two heat flux-based methods increase the potential of soil temperature for the monitoring, but also the general interpretation of fumarolic crises together with geochemical and seismological observations. A spreadsheet allowing direct computation of UHF and ETH is provided as supplemental material.Published122-1342V. Struttura e sistema di alimentazione dei vulcaniJCR Journa

Low seroprevalence of COVID-19 in Lao PDR, late 2020

Background In 2020 Lao PDR had low reported COVID-19 cases but it was unclear whether this masked silent transmission. A seroprevalence study was done August - September 2020 to determine SARS-CoV-2 exposure. Methods Participants were from the general community (n=2433) or healthcare workers (n=666) in five provinces and bat/wildlife contacts (n=74) were from Vientiane province. ELISAs detected anti- SARS-CoV-2 Nucleoprotein (N; n=3173 tested) and Spike (S; n=1417 tested) antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Controls were confirmed COVID-19 cases (n=15) and pre-COVID-19 samples (n=265). Seroprevalence for the general community was weighted to account for complex survey sample design, age and sex. Findings In pre-COVID-19 samples, 5·3%, [95% CI=3·1-8·7%] were anti-N antibody single-positive and 1·1% [0·3-3·5%] were anti-S antibody single positive. None were double positive. Anti-N and anti-S antibodies were detected in 5·2% [4·2-6·5%] and 2·1% [1·1-3·9%] of the general community, 2·0% [1·1-3·3%] and 1·4% [0·5-3·7%] of healthcare workers and 20·3% [12·6-31·0%] and 6·8% [2·8-15·3%] of bat/wildlife contacts. 0·1% [0·02-0·3%] were double positive for anti-N and anti-S antibodies (rapid test negative). Interpretation We find no evidence for significant SARS-CoV-2 circulation in Lao PDR before September 2020. This likely results from early decisive measures taken by the government, social behavior, and low population density. High anti-N /low anti-S seroprevalence in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses. Funding Agence Française de Développement. Additional; Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs (“PaReCIDS II”)

High-Throughput Drug Screening Identifies Pazopanib and Clofilium Tosylate as Promising Treatments for Malignant Rhabdoid Tumors

Summary: Rhabdoid tumors (RTs) are aggressive tumors of early childhood characterized by SMARCB1 inactivation. Their poor prognosis highlights an urgent need to develop new therapies. Here, we performed a high-throughput screening of approved drugs and identified broad inhibitors of tyrosine kinase receptors (RTKs), including pazopanib, and the potassium channel inhibitor clofilium tosylate (CfT), as SMARCB1-dependent candidates. Pazopanib targets were identified as PDGFRα/β and FGFR2, which were the most highly expressed RTKs in a set of primary tumors. Combined genetic inhibition of both these RTKs only partially recapitulated the effect of pazopanib, emphasizing the requirement for broad inhibition. CfT perturbed protein metabolism and endoplasmic reticulum stress and, in combination with pazopanib, induced apoptosis of RT cells in vitro. In vivo, reduction of tumor growth by pazopanib was enhanced in combination with CfT, matching the efficiency of conventional chemotherapy. These results strongly support testing pazopanib/CfT combination therapy in future clinical trials for RTs. : Rhabdoid tumors (RTs) are aggressive pediatric tumors characterized by SMARCB1 inactivation. Chauvin et al. identify two SMARCB1-dependent targeted therapies for RT: pazopanib, which inhibits PDGFR and FGFR2, and the potassium channel inhibitor clofilium tosylate, which induces endoplasmic reticulum stress. Combining both drugs induces cell apoptosis and reduces PDX tumor growth. Keywords: rhabdoid tumors, SMARCB1, pazopanib, clofilium tosylate, high-throughput drug screening, tyrosine kinase inhibitor

The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences

The PAZAR database unites independently created and maintained data collections of transcription factor and regulatory sequence annotation. The flexible PAZAR schema permits the representation of diverse information derived from experiments ranging from biochemical protein–DNA binding to cellular reporter gene assays. Data collections can be made available to the public, or restricted to specific system users. The data ‘boutiques’ within the shopping-mall-inspired system facilitate the analysis of genomics data and the creation of predictive models of gene regulation. Since its initial release, PAZAR has grown in terms of data, features and through the addition of an associated package of software tools called the ORCA toolkit (ORCAtk). ORCAtk allows users to rapidly develop analyses based on the information stored in the PAZAR system. PAZAR is available at http://www.pazar.info. ORCAtk can be accessed through convenient buttons located in the PAZAR pages or via our website at http://www.cisreg.ca/ORCAtk

Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms

Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes. JAK-STAT signaling differentially regulates CDC42-dependent HSC polarity, niche interaction and mutant cell expansion. Asymmetric HSC distribution causes differential BM niche remodeling: sinusoidal dilation in polycythemia vera and endosteal niche expansion in essential thrombocythemia. MPN development accelerates in a prematurely aged BM microenvironment, suggesting that the specialized niche can modulate mutant cell expansion. Finally, dissimilar HSC-niche interactions underpin variable clinical response to JAK inhibitor. Therefore, HSC-niche interactions influence the expansion rate and therapy response of cells carrying the same clonal hematopoiesis oncogenic driver

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry