Rapid succession drives spring community dynamics of small protists at Helgoland Roads, North Sea

The dynamics of diatoms and dinoflagellates have been monitored for many decades at the Helgoland Roads Long-Term Ecological Research site and are relatively well understood. In contrast, small-sized eukaryotic microbes and their community changes are still much more elusive, mainly due to their small size and uniform morphology, which makes them difficult to identify microscopically. By using next-generation sequencing, we wanted to shed light on the Helgoland planktonic community dynamics, including nano- and picoplankton, during a spring bloom. We took samples from March to May 2016 and sequenced the V4 region of the 18S rDNA. Our results showed that mixotrophic and heterotrophic taxa were more abundant than autotrophic diatoms. Dinoflagellates dominated the sequence assemblage, and several small-sized eukaryotic microbes like Haptophyta, Choanoflagellata, Marine Stramenopiles and Syndiniales were identified. A diverse background community including taxa from all size classes was present during the whole sampling period. Five phases with several communities were distinguished. The fastest changes in community composition took place in phase 3, while the communities from phases 1 to 5 were more similar to each other despite contrasting environmental conditions. Synergy effects of next-generation sequencing and traditional methods may be exploited in future long-term observations

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Incluye contenido parcial de los autoresBiological invasion is one of the main threats to native biodiversity. For a speciesto become invasive, it must be voluntarily or involuntarily introduced by humans into a nonna-tive habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this dataset, we make available occurrence and abundance data on mammal species that (1) transposeda geographical barrier and (2) were voluntarily or involuntarily introduced by humans into theNeotropics. Our data set is composed of 73,738 historical and current georeferenced recordson alien mammal species of which around 96% correspond to occurrence data on 77 speciesbelonging to eight orders and 26 families. Data cover 26 continental countries in the Neotrop-ics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Floridain the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 coun-tries of Caribbean islands. Our data set also includes neotropical species (e.g.,Callithrixsp.,Myocastor coypus,Nasua nasua)considered alien in particular areas of Neotropics. The mostnumerous species in terms of records are fromBossp. (n=37,782),Sus scrofa(n=6,730), andCanis familiaris(n=10,084); 17 species were represented by only one record (e.g., Syncerus caf-fer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of spe-cies in the data set (n=20 species), partly because of uncertainties regarding taxonomicidentification of the generaCallithrix,which includes the speciesCallithrix aurita, Callithrixflaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, andtheir hybrids. This unique data set will be a valuable source of information on invasion riskassessments, biodiversity redistribution and conservation-related research. There are no copy-right restrictions. Please cite this data paper when using the data in publications. We alsorequest that researchers and teachers inform us on how they are using the dat

Lycopene-rich extract from red guava ( Psidium guajava L.) displays cytotoxic effect against human breast adenocarcinoma cell line MCF-7 via an apoptotic-like pathway

This study investigated a lycopene-rich extract from red guava (LEG) for its chemical composition using spectrophotometry, mass spectrometry, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and computational studies. The cytotoxic activity of LEG and the underlying mechanism was studied in human breast adenocarcinoma cells (MCF-7), murine fibroblast cells (NIH-3T3), BALB/c murine peritoneal macrophages, and sheep blood erythrocytes by evaluating the cell viability with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry. Spectrophotometry analysis showed that LEG contained 20% of lycopene per extract dry weight. Experimental and theoretical ATR-FTIR suggests the presence of lycopene, whereas MS/MS spectra obtained after fragmentation of the molecular ion [M]+• of 536.4364 show fragment ions at m/z 269.2259, 375.3034, 444.3788, and 467.3658, corroborating the presence of lycopene mostly related to all-trans configuration. Treatment with LEG (1600 to 6.25μg/mL) for 24 and 72h significantly affected the viability of MCF-7 cells (mean half maximal inhibitory concentration [IC50]=29.85 and 5.964μg/mL, respectively) but not NIH-3T3 cells (IC50=1579 and 911.5μg/mL, respectively). Furthermore LEG at concentrations from 800 to 6.25μg/mL presented low cytotoxicity against BALB/c peritoneal macrophages (IC50≥800μg/mL) and no hemolytic activity. LEG (400 and 800μg/mL) caused reduction in the cell proliferation and induced cell cycle arrest, DNA fragmentation, modifications in the mitochondrial membrane potential, and morphologic changes related to granularity and size in MCF-7 cells; however, it failed to cause any significant damage to the cell membrane or display necrosis or traditional apoptosis. In conclusion, LEG was able to induce cytostatic and cytotoxic effects on breast cancer cells probably via induction of an apoptotic-like pathway.The authors acknowledge the computational time provided by CENAPAD/SP on the project proj697. Alexandra Plácido is gratefully to FCT by her grant SFRH/BD/97995/2013, financed by POPH–QREN–Tipologia 4.1–Formação Avançada, subsidized by Fundo Social Europeu and Ministério da Ciência, Tecnologia e Ensino Superior. The work at REQUIMTE/LAQV received financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT) through project UID/QUI/50006/2013. Adriany das G. N. Amorim is grateful to CAPES by for the doctoral fellowship process no. 99999.004236/2014-09 in Federal University of Piauí (UFPI). Eder A. Barbosa is grateful to PNPD/CAPES for its post-doctoral fellowship.info:eu-repo/semantics/publishedVersio

The RNA chaperone Hfq is essential for the virulence of Salmonella typhimurium

The RNA chaperone, Hfq, plays a diverse role in bacterial physiology beyond its original role as a host factor required for replication of Qβ RNA bacteriophage. In this study, we show that Hfq is involved in the expression and secretion of virulence factors in the facultative intracellular pathogen, Salmonella typhimurium. A Salmonella hfq deletion strain is highly attenuated in mice after both oral and intraperitoneal infection, and shows a severe defect in invasion of epithelial cells and a growth defect in both epithelial cells and macrophages in vitro. Surprisingly, we find that these phenotypes are largely independent of the previously reported requirement of Hfq for expression of the stationary phase sigma factor, RpoS. Our results implicate Hfq as a key regulator of multiple aspects of virulence including regulation of motility and outer membrane protein (OmpD) expression in addition to invasion and intracellular growth. These pleiotropic effects are suggested to involve a network of regulatory small non-coding RNAs, placing Hfq at the centre of post-transcriptional regulation of virulence gene expression in Salmonella. In addition, the hfq mutation appears to cause a chronic activation of the RpoE-mediated envelope stress response which is likely due to a misregulation of membrane protein expression

Early treatment versus expectative management of patent ductus arteriosus in preterm infants

_Background:_ Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. _Methods:_ This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA1.5mm. Early treatment (between 24 and 72h postnatal age) with the cyclooxygenase inhibitor(COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. _Discussion:_ As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36weeks

Technical recommendations for clinical translation of renal MRI: a consensus project of the Cooperation in Science and Technology Action PARENCHIMA

Purpose The potential of renal MRI biomarkers has been increasingly recognised, but clinical translation requires more standardisation. The PARENCHIMA consensus project aims to develop and apply a process for generating technical recommendations on renal MRI. Methods A task force was formed in July 2018 focused on fve methods. A draft process for attaining consensus was distributed publicly for consultation and fnalised at an open meeting (Prague, October 2018). Four expert panels completed surveys between October 2018 and March 2019, discussed results and refned the surveys at a face-to-face meeting (Aarhus, March 2019) and completed a second round (May 2019). Results A seven-stage process was defned: (1) formation of expert panels; (2) defnition of the context of use; (3) literature review; (4) collection and comparison of MRI protocols; (5) consensus generation by an approximate Delphi method; (6) reporting of results in vendor-neutral and vendor-specifc terms; (7) ongoing review and updating. Application of the process resulted in 166 consensus statements. Conclusion The process generated meaningful technical recommendations across very diferent MRI methods, while allowing for improvement and refnement as open issues are resolved. The results are likely to be widely supported by the renal MRI community and thereby promote more harmonisation

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver meta

Purpose: Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology: Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC. Expression of inhibitory molecules was also analyzed on leukocytes isolated from paired resected metastatic liver tumors, tumor-free liver tissues, and blood of patients with mismatch repair-proficient LM-CRC. The effects of blocking inhibitory pathways on tumor-infiltrating T-cell responses were studied in ex vivo functional assays. Results: Mismatch repair-proficient LM-CRC showed higher expression of inhibitory receptors on intra-tumoral T-cells and contained higher proportions of CD8+ T-cells, dendritic cells and monocytes than mismatch repair-proficient primary CRC and/or PM-CRC. Inhibitory receptors LAG3, PD-1, TIM3 and CTLA4 were higher expressed on CD8+ T-cells, CD4+ T-helper and/or regulatory T-cells in LM-CRC tumors compared with tumor-free liver and blood. Antibody blockade of LAG3 or PD-L1 increased proliferation and effector cytokine production of intra-tumoral T-cells isolated from LM-CRC in response to both polyclonal and autologous tumor-specific stimulations. Higher LAG3 expression on intra-tumoral CD8+ T-cells associated with longer progression-free survival of LM-CRC patients. Conclusion: Mismatch repair-proficient LM-CRC may be more sensitive to immune checkpoint inhibitors than mismatch repair-proficient primary CRC. Blocking LAG3 enhances tumor-infiltrating T-cell responses of mismatch repair-proficient LM-CRC, and therefore may be a new promising immunotherapeutic target for LM-CRC