Search results for "MBL"

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation.

2016

Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications. Here, we determined that neonatal NET-inhibitory factor (nNIF) is an inhibitor of NET formation in umbilical cord blood. In human neonatal and adult neutrophils, nNIF inhi…

The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM

2018

The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aβ through endothelial cells. Late-onset AD risk fact…

Performance of a rapid diagnostic test for the detection of Cryptosporidium spp. in African children admitted to hospital with diarrhea

2020

Background Cryptosporidium is a protozoan parasite that causes mild to severe diarrhoeal disease in humans. To date, several commercial companies have developed rapid immunoassays for the detection of Cryptosporidium infection. However, the challenge is to identify an accurate, simple and rapid diagnostic tool for the estimation of cryptosporidiosis burden. This study aims at evaluating the accuracy of CerTest Crypto, a commercialized rapid diagnostic test (RDT) for the detection of Cryptosporidium antigens in the stool of children presenting with diarrhoea. Methods A cross-sectional study was conducted in four study sites in Sub-Saharan Africa (Gabon, Ghana, Madagascar, and Tanzania), from…

Phototherapy: Ruthenium-Containing Block Copolymer Assemblies: Red-Light-Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular…

2016

Detection of Viral −RNA and +RNA Strands in Enterovirus-Infected Cells and Tissues

2020

The current methods to study the distribution and dynamics of viral RNA molecules inside infected cells are not ideal, as electron microscopy and immunohistochemistry can only detect mature virions, and quantitative real-time PCR does not reveal localized distribution of RNAs. We demonstrated here the branched DNA in situ hybridization (bDNA ISH) technology to study both the amount and location of the emerging &minus

Whole Exome Sequencing Is the Preferred Strategy to Identify the Genetic Defect in Patients With a Probable or Possible Mitochondrial Cause

2018

Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused by pathogenic variants in mitochondrial genes. However, pathogenic variants in some of these genes can lead to clinical manifestations which overlap with other neuromuscular diseases, which can be caused by pathogenic variants in non-mitochondrial genes as well. Mitochondrial pathogenic variants can be found in the mitochondrial DNA (mtDNA) or in any of the 1,500 nuclear genes with a mitochondrial function. We have performed a two-step next-generation sequencing approach in a cohort of 117 patients, mostly children, in whom a mitochondrial disease-cause could likely or possibly explain the phe…

Archaeology and ichnology at Gombore II-2, Melka Kunture, Ethiopia: everyday life of a mixed age hominin group 700,000 years ago

2018

AbstractWe report the occurrence at 0.7 million years (Ma) of an ichnological assemblage at Gombore II-2, which is one of several archaeological sites at Melka Kunture in the upper Awash Valley of Ethiopia, 2000 m asl. Adults and children potentially as young as 12 months old left tracks in a silty substrate on the shore of a body of water where ungulates, as well as other mammals and birds, congregated. Furthermore, the same layers contain a rich archaeological and palaeontological record, confirming that knapping was taking place in situ and that stone tools were used for butchering hippo carcasses at the site. The site gives direct information on hominin landscape use at 0.7 Ma and may p…

MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity.

2017

We have studied theoretically the microRNA (miRNA) intercellular transfer through voltage-gated gap junctions in terms of a biophysically grounded system of coupled differential equations. Instead of modeling a specific system, we use a general approach describing the interplay between the genetic mechanisms and the single-cell electric potentials. The dynamics of the multicellular ensemble are simulated under different conditions including spatially inhomogeneous transcription rates and local intercellular transfer of miRNAs. These processes result in spatiotemporal changes of miRNA, mRNA, and ion channel protein concentrations that eventually modify the bioelectrical states of small multi…

Evolutionary stability of topologically associating domains is associated with conserved gene regulation

2018

AbstractBackgroundThe human genome is highly organized in the three-dimensional nucleus. Chromosomes fold locally into topologically associating domains (TADs) defined by increased intra-domain chromatin contacts. TADs contribute to gene regulation by restricting chromatin interactions of regulatory sequences, such as enhancers, with their target genes. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression.ResultsHere, we hypothesize that TADs represent essential functiona…

The ribosome assembly gene network is controlled by the feedback regulation of transcription elongation

2017

Ribosome assembly requires the concerted expression of hundreds of genes, which are transcribed by all three nuclear RNA polymerases. Transcription elongation involves dynamic interactions between RNA polymerases and chromatin. We performed a synthetic lethal screening in Saccharomyces cerevisiae with a conditional allele of SPT6, which encodes one of the factors that facilitates this process. Some of these synthetic mutants corresponded to factors that facilitate pre-rRNA processing and ribosome biogenesis. We found that the in vivo depletion of one of these factors, Arb1, activated transcription elongation in the set of genes involved directly in ribosome assembly. Under these depletion c…