Intracellular and Extracellular Vesicle miRNA Signatures in Human iPSC-Derived Neural Stem Cells and Floor Plate Progenitors.

Refined control of intrinsic and extrinsic signals is critical for specific neuronal differentiation. Here, we differentiated human induced pluripotent stem cells (hiPSCs) from three different healthy donors into neural stem cells (NSCs) and floor plate progenitors (FPPs; progenitors of dopaminergic neurons) and further performed intracellular and extracellular vesicles' (EVs) miRNA profiling. While NSC and FPP cells differed significantly in levels of only 8 intracellular miRNAs, their differences were more evident in the EV miRNAs with 27 differentially expressed miRNAs.

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

Background & Aims: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19.

Methods: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America.

Mutant Allele-Specific CRISPR Disruption in DYT1 Dystonia Fibroblasts Restores Cell Function.

Most individuals affected with DYT1 dystonia have a heterozygous 3-bp deletion in the TOR1A gene (c.907_909delGAG). The mutation appears to act through a dominant-negative mechanism compromising normal torsinA function, and it is proposed that reducing mutant torsinA may normalize torsinA activity.

Navigating the Landscape of Tumor Extracellular Vesicle Heterogeneity.

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level.

Evidence of natural Zika virus infection in neotropical non-human primates in Brazil.

In Africa, Old World Primates are involved in the maintenance of sylvatic circulation of ZIKV. However, in Brazil, the hosts for the sylvatic cycle remain unknown. We hypothesized that free-living NHPs might play a role in urban/periurban ZIKV dynamics, thus we undertook an NHP ZIKV investigation in two cities in Brazil.

Extracellular Vesicles: Decoding a New Language for Cellular Communication in Early Embryonic Development.

The blastocyst inner cell mass (ICM) that gives rise to a whole embryo can be derived and cultured as embryonic stem cells (ESCs), which retain full developmental potential. ICM cells receive, from diverse sources, complex molecular and spatiotemporal signals that orchestrate the finely-tuned processes associated with embryogenesis. Those instructions come, continuously, from themselves and from surrounding cells, such as those present in the trophectoderm and primitive endoderm (PrE).

Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly.

X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression.

Mutant torsinA in the heterozygous DYT1 state compromises HSV propagation in infected neurons and fibroblasts.

Most cases of early onset torsion dystonia (DYT1) are caused by a 3-base pair deletion in one allele of the TOR1A gene causing loss of a glutamate in torsinA, a luminal protein in the nuclear envelope. This dominantly inherited neurologic disease has reduced penetrance and no other medical manifestations. It has been challenging to understand the neuronal abnormalities as cells and mouse models which are heterozygous (Het) for the mutant allele are quite similar to wild-type (WT) controls.

Extracellular RNAs: A New Awareness of Old Perspectives.

Extracellular RNA (exRNA) has recently expanded as a highly important area of study in biomarker discovery and cancer therapeutics. exRNA consists of diverse RNA subpopulations that are normally protected from degradation by incorporation into membranous vesicles or by lipid/protein association. They are found circulating in biofluids, and have proven highly promising for minimally invasive diagnostic and prognostic purposes, particularly in oncology.

Evidence of Extracellular Vesicles Biogenesis and Release in Mouse Embryonic Stem Cells.

Extracellular vesicles (EVs) released by mouse embryonic stem cells (mESCs) are considered a source of bioactive molecules that modulate their microenvironment by acting on intercellular communication. Either intracellular endosomal machinery or their derived EVs have been considered a relevant system of signal circuits processing. Herein, we show that these features are found in mESCs.

Zika detection: comparison of methodologies.

Many countries in the Americas have detected local transmission of multiple arboviruses that cause febrile illnesses. Therefore, laboratory testing has become an important tool for confirming the etiology of these diseases. The present study aimed to compare the sensitivity and specificity of three different Zika virus detection assays.

Clinical, laboratory and virological data from suspected ZIKV patients in an endemic arbovirus area.

Background: The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between the diseases caused by ZIKV, dengue (DENV) and chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. Brazilian authorities largely rely on clinical and epidemiological data for the epidemiological and clinical classifications of most ZIKV cases.

Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells.

Background: Glioblastoma (GBM), a highly aggressive brain tumor, contains a subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising target for GBM treatment. Our group identified the cellular prion protein (PrP) and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential target candidates due to their role in GBM tumorigenesis and in neural stem cell maintenance.

Revealing Annexin A2 and ARF-6 enrollment during Trypanosoma cruzi extracellular amastigote-host cell interaction.

Background: Invasion of host cells by Trypanosoma cruzi extracellular amastigotes is host actin polymerization-dependent. However, the role of proteins related to actin dynamics during invasion by amastigotes remains to be investigated. Here we describe the role of Annexin A2 and ARF-6 during extracellular amastigote-mammalian cell interactions.

Dengue-4 false negative results by Panbio® Dengue Early ELISA assay in Brazil.

Background: Dengue is a serious public health problem in numerous countries. The ability to rapidly diagnosis dengue is important for patient triage and management. Detection of dengue viral protein, NS1, represents a new approach to dengue diagnosis.

Recruitment of galectin-3 during cell invasion and intracellular trafficking of Trypanosoma cruzi extracellular amastigotes.

The invasion of host cells by the intracellular protozoan Trypanosoma cruzi requires interactions with host cell molecules, and the replication of the parasite requires escape from a parasitophorous vacuole into the host cell cytosol. Galectin-3, a member of β-galactosidase-binding lectin family, has numerous extracellular and intracellular functions. In this study, we investigated the role of galectin-3 during the invasion and intracellular trafficking of T.

The largest flying reptile from Gondwana: a new specimen of Tropeognathus cf. T. mesembrinus Wellnhofer, 1987 (Pterodactyloidea, Anhangueridae) and other large pterosaurs from the Romualdo Formation, Lower Cretaceous, Brazil.

A very large pterosaur (MN 6594-V) from the Romualdo Formation (Aptian/Albian), Santana Group, Araripe Basin, is described. The specimen is referred to Tropeognathus cf. T.

Natural intracellular peptides can modulate the interactions of mouse brain proteins and thimet oligopeptidase with 14-3-3ε and calmodulin.

Protein interactions are crucial for most cellular process. Thus, rationally designed peptides that act as competitive assembly inhibitors of protein interactions by mimicking specific, determined structural elements have been extensively used in clinical and basic research. Recently, mammalian cells have been shown to contain a large number of intracellular peptides of unknown function.

Identification of intracellular peptides in rat adipose tissue: Insights into insulin resistance.

Intracellular peptides generated by the proteasome and oligopeptidases have been suggested to function in signal transduction and to improve insulin resistance in mice fed a high-caloric diet. The aim of this study was to identify specific intracellular peptides in the adipose tissue of Wistar rats that could be associated with the physiological and therapeutic control of glucose uptake. Using semiquantitative mass spectrometry and LC/MS/MS analyses, we identified ten peptides in the epididymal adipose tissue of the Wistar rats; three of these peptides were present at increased levels in rats that were fed a high-caloric Western diet (WD) compared with rats fed a control diet (CD).

A glance at Listeria and Salmonella cell invasion: different strategies to promote host actin polymerization.

The facultative intracellular bacterial pathogens Listeria monocytogenes and Salmonella enterica have evolved multiple strategies to invade a large panel of mammalian cells. These pathogens use the host cell actin system for invasion and became a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. The key signaling component that these pathogens use to orchestrate actin remodeling is the Arp2/3 complex, which is related to polymerization of actin filaments.

Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study.

Objective: To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national introduction in El Salvador, a low-middle income country in Central America.

Design: Matched case-control study.

Setting: Seven hospitals in cities across El Salvador, January 2007 to June 2009.

Short report: serological evidence of West Nile virus activity in El Salvador.

Epizootics of encephalitis in El Salvador killed 203 equines between November 2001 and April 2003. During an investigation of the outbreaks, 18 (25%) of 73 serum samples collected from stablemates of deceased animals in 2003 had antibodies to West Nile virus. Ten of these infections were confirmed by plaque reduction neutralization tests, suggesting West Nile virus has extended its range and spread to Central America.