Estudio de indicadores fisicoquímicos y toxicológicos del agua superficial del bajo río Paraná.

Capítulo de libroLos bioensayos de toxicidad en laboratorio constituyen una herramienta de diagnóstico realista, que se ajusta a las necesidades actuales facilitando la toma de decisiones frente a los problemas planteados por la contaminación.Fil: Peluso, Julieta. Laboratorio de Ecotoxicología, Instituto de Investigación e Ingeniería Ambiental (UNSAM)/CONICET, Argentina. Email: [email protected]: Aronzon, Carolina M.. Laboratorio de Ecotoxicología, Instituto de Investigación e Ingeniería Ambiental (UNSAM)/CONICET, Argentina. Email: [email protected]: Pérez Coll, Cristina S.. Laboratorio de Ecotoxicología, Instituto de Investigación e Ingeniería Ambiental (UNSAM)/CONICET, Argentina. Email: [email protected]

Structures of T7 bacteriophage portal and tail suggest a viral DNA retention and ejection mechanism

Double-stranded DNA bacteriophages package their genome at high pressure inside a procapsid through the portal, an oligomeric ring protein located at a unique capsid vertex. Once the DNA has been packaged, the tail components assemble on the portal to render the mature infective virion. The tail tightly seals the ejection conduit until infection, when its interaction with the host membrane triggers the opening of the channel and the viral genome is delivered to the host cell. Using high-resolution cryo-electron microscopy and X-ray crystallography, here we describe various structures of the T7 bacteriophage portal and fiber-less tail complex, which suggest a possible mechanism for DNA retention and ejection: a portal closed conformation temporarily retains the genome before the tail is assembled, whereas an open portal is found in the tail. Moreover, a fold including a seven-bladed β-propeller domain is described for the nozzle tail protein.This work was supported by the Ministry of Science, Innovation and Universities of Spain, grants BFU 2014-54181 (to J.L.C.), BFU 2014-53550-P and BFU2017-83720-P (to M.C.), and contracts SEV-2013-0347 (to A.C.) and RYC-2011-09071 (to C.M.). We acknowledge institutional funding through the Spanish Government Centres and Units of Excellence Severo Ochoa and Maria de Maeztu awards to IRB Barcelona (SEV-2015-0500) and IBMB Structural Biology Unit (MDM-2014-0435), respectively, and from the CERCA Programme of the Catalan Government to the IRB Barcelona. This work has also been supported by the European Commission, Horizon 2020 program through iNEXT project (grant number 653706)

Differential Uptake of Endosulfan in the South American Toad Under Sublethal Exposure

Agroecosystems are usually polluted with a wide variety of contaminants with pesticides being very frequently detected. Endosulfan, an organochlorine pesticide, has been shown to cause both lethal and sublethal effects on aquatic organisms such as amphibians and especially on its early developmental stages. In this context, the aim of this study was to evaluate the uptake of environmentally relevant concentrations of endosulfan and its correlation with differential sensitivity in the early development stages of the common South American toad, Rhinella arenarum. Embryos and larvae were exposed to sublethal concentrations of endosulfan for several periods of exposures. According to the developmental stage at which they were exposed, the uptake rate was different. Bioconcentration factors (BCFs) for embryos significantly decreased with exposure time and concentration (p < 0.05) reaching a BCF of ≤1679 for embryos at 96 h of exposure to 0.001 mg endosulfan L⁻¹. BCFs for larvae significantly increased with exposure time (p < 0.05) obtaining a maximum of 40 at 504 h. In our previous study, we reported that embryos were less sensitive to the effects of endosulfan than larvae, which is in line with the main tendency of embryos to bioconcentrate endosulfan as observed in this study.Facultad de Ciencias ExactasCentro de Investigaciones del Medioambient

Reliable Characterization of Organic & Pharmaceutical Compounds with High Resolution Monochromated EEL Spectroscopy

Organic and biological compounds (especially those related to the pharmaceutical industry) have always been of great interest for researchers due to their importance for the development of new drugs to diagnose, cure, treat or prevent disease. As many new API (active pharmaceutical ingredients) and their polymorphs are in nanocrystalline or in amorphous form blended with amorphous polymeric matrix (known as amorphous solid dispersion-ASD), their structural identification and characterization at nm scale with conventional X-Ray/Raman/IR techniques becomes difficult. During any API synthesis/production or in the formulated drug product, impurities must be identified and characterized. Electron energy loss spectroscopy (EELS) at high energy resolution by transmission electron microscope (TEM) is expected to be a promising technique to screen and identify the different (organic) compounds used in a typical pharmaceutical or biological system and to detect any impurities present, if any, during the synthesis or formulation process. In this work, we propose the use of monochromated TEM-EELS, to analyze selected peptides and organic compounds and their polymorphs. In order to validate EELS for fingerprinting (in low loss/optical region) and by further correlation with advanced DFT, simulations were utilized

Neuron-derived extracellular vesicles contain synaptic proteins, promote spine formation, activate TrkB-mediated signalling and preserve neuronal complexity

Extracellular vesicles (EVs) play an important role in intercellular communication as carriers of signalling molecules such as bioactive miRNAs, proteins and lipids. EVs are key players in the functioning of the central nervous system (CNS) by influencing synaptic events and modulating recipient neurons. However, the specific role of neuron-to-neuron communication via EVs is still not well understood. Here, we provide evidence that primary neurons uptake neuron-derived EVs in the soma, dendrites, and even in the dendritic spines, and carry synaptic proteins. Neuron-derived EVs increased spine density and promoted the phosphorylation of Akt and ribosomal protein S6 (RPS6), via TrkB-signalling, without impairing the neuronal network activity. Strikingly, EVs exerted a trophic effect on challenged nutrient-deprived neurons. Altogether, our results place EVs in the spotlight for synaptic plasticity modulation as well as a possible therapeutic tool to fight neurodegeneration

RTP801 is involved in mutant huntingtin-induced cell death

RTP801 expression is induced by cellular stress and has a pro-apoptotic function in non-proliferating differentiated cells such as neurons. In several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, elevated levels of RTP801 have been observed, which suggests a role for RTP801 in neuronal death. Neuronal death is also a pathological hallmark in Huntington's disease (HD), an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Currently, the exact mechanisms underlying mutant huntingtin (mhtt)-induced toxicity are still unclear. Here, we investigated whether RTP801 is involved in (mhtt)-induced cell death. Ectopic exon-1 mhtt elevated RTP801 mRNA and protein levels in nerve growth factor (NGF)-differentiated PC12 cells and in rat primary cortical neurons. In neuronal PC12 cells, mhtt also contributed to RTP801 protein elevation by reducing its proteasomal degradation rate, in addition to promoting RTP801 gene expression. Interestingly, silencing RTP801 expression with short hairpin RNAs (shRNAs) blocked mhtt-induced cell death in NGF-differentiated PC12 cells. However, RTP801 protein levels were not altered in the striatum of Hdh(Q7/Q111) and R6/1 mice, two HD models that display motor deficits but not neuronal death. Importantly, RTP801 protein levels were elevated in both neural telencephalic progenitors differentiated from HD patient-derived induced pluripotent stem cells and in the putamen and cerebellum of human HD postmortem brains. Taken together, our results suggest that RTP801 is a novel downstream effector of mhtt-induced toxicity and that it may be relevant to the human disease

Therapeutic Vaccination Refocuses T-cell Responses Towards Conserved Regions of HIV-1 in Early Treated Individuals (BCN 01 study)

Background Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy. Methods BCN01 trial was a phase I, open-label, non-randomized, multicenter study in HIV-1-positive individuals diagnosed and treated during early HIV-1 infection to evaluate two vaccination regimen arms, which differed in the time (8 versus 24 week) between the ChAdV63.HIVconsv prime and MVA.HIVconsv boost vaccinations. The primary outcome was safety. Secondary endpoints included frequencies of vaccine-induced IFN-γ+ CD8+ T cells, in vitro virus-inhibitory capacity, plasma HIV-1 RNA and total CD4+ T-cells associated HIV-1 DNA. (NCT01712425). Findings No differences in safety, peak magnitude or durability of vaccine-induced responses were observed between long and short interval vaccination arms. Grade 1/2 local and systemic post-vaccination events occurred in 22/24 individuals and resolved within 3 days. Weak responses to conserved HIV-1 regions were detected in 50% of the individuals before cART initiation, representing median of less than 10% of their total HIV-1-specific T cells. All participants significantly elevated these subdominant T-cell responses, which after MVA.HIVconsv peaked at median (range) of 938 (73-6,805) IFN-γ SFU/106 PBMC, representing on average 58% of their total anti-HIV-1 T cells. The decay in the size of the HIV-1 reservoir was consistent with the first year of early cART initiation in both arms

Presence of Blastocystis in the gut microbiota is associated with cognitive traits and decreased executive function

Growing evidence implicates the gut microbiome in cognition. Blastocystis is a common gut single-cell eukaryote parasite frequently detected in humans but its potential involvement in human pathophysiology has been poorly characterized. Here we describe how the presence of Blastocystis in the gut microbiome was associated with deficits in executive function and altered gut bacterial composition in a discovery (n = 114) and replication cohorts (n = 942). We also found that Blastocystis was linked to bacterial functions related to aromatic amino acids metabolism and folate-mediated pyrimidine and one-carbon metabolism. Blastocystis-associated shifts in bacterial functionality translated into the circulating metabolome. Finally, we evaluated the effects of microbiota transplantation. Donor's Blastocystis subtypes led to altered recipient's mice cognitive function and prefrontal cortex gene expression. In summary, Blastocystis warrant further consideration as a novel actor in the gut microbiome-brain axis