Background: Decades of research and practice experience have led to an extensive body of evidence about effective home safety modifications. However, the benefits of safety modifications have not reached all segments of society. Poor quality housing in low-income neighborhoods, along with limited access to safety products and injury prevention information, can be significant barriers to child safety.
View Article and Find Full Text PDFThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.
View Article and Find Full Text PDFThe New World (NW) mammarenavirus group includes several zoonotic highly pathogenic viruses, such as Junin (JUNV) or Machupo (MACV). Contrary to the Old World mammarenavirus group, these viruses are not able to completely suppress the innate immune response and trigger a robust interferon (IFN)-I response via retinoic acid-inducible gene I (RIG-I). Nevertheless, pathogenic NW mammarenaviruses trigger a weaker IFN response than their nonpathogenic relatives do.
View Article and Find Full Text PDFThis paper presents a complete kinematic model of the tibiofemoral joint (TFJ) based on a RRPP + 4-SPS parallel mechanism, where R, P, and S stand for revolute, prismatic, and spherical joints, respectively. The model accounts for the contact between tibia and femur, and the four major ligaments: anterior cruciate, posterior cruciate, medial collateral, and lateral collateral, with anatomical significance in their length variations. An experimental flexion passive motion task is performed, and the kinematic model is tested to determine its capability to reproduce the workspace of the motion task.
View Article and Find Full Text PDFPLoS Negl Trop Dis
December 2020
A detailed understanding of the mechanisms underlying the capacity of a virus to break the species barrier is crucial for pathogen surveillance and control. New World (NW) mammarenaviruses constitute a diverse group of rodent-borne pathogens that includes several causative agents of severe viral hemorrhagic fever in humans. The ability of the NW mammarenaviral attachment glycoprotein (GP) to utilize human transferrin receptor 1 (hTfR1) as a primary entry receptor plays a key role in dictating zoonotic potential.
View Article and Find Full Text PDFThe zoonotic Old World mammarenavirus Lassa (LASV) causes severe hemorrhagic fever with high mortality and morbidity in humans in endemic regions. The development of effective strategies to combat LASV infections is of high priority, given the lack of a licensed vaccine and restriction on available treatment to off-label use of ribavirin. A better understanding of the fundamental aspects of the virus's life cycle would help to improve the development of novel therapeutic approaches.
View Article and Find Full Text PDFThe New World (NW) arenaviruses are a diverse group of zoonotic viruses, including several causative agents of severe hemorrhagic fevers in humans. All known human-pathogenic NW arenaviruses belong to clade B, where they group into sublineages with phylogenetically closely related nonpathogenic viruses, e.g.
View Article and Find Full Text PDFRecognition of functional receptors by viruses is a key determinant for their host range, tissue tropism, and disease potential. The highly pathogenic Lassa virus (LASV) currently represents one of the most important emerging pathogens. The major cellular receptor for LASV in human cells is the ubiquitously expressed and evolutionary highly conserved extracellular matrix receptor dystroglycan (DG).
View Article and Find Full Text PDFArenaviruses are a large family of emerging enveloped negative-strand RNA viruses that include several causative agents of viral hemorrhagic fevers. For cell entry, human-pathogenic arenaviruses use different cellular receptors and endocytic pathways that converge at the level of acidified late endosomes, where the viral envelope glycoprotein mediates membrane fusion. Inhibitors of arenavirus entry hold promise for therapeutic antiviral intervention and the identification of "druggable" targets is of high priority.
View Article and Find Full Text PDFViral hemorrhagic fevers caused by emerging RNA viruses of the Arenavirus family are among the most devastating human diseases. Climate change, global trade, and increasing urbanization promote the emergence and re-emergence of these human pathogenic viruses. Emerging pathogenic arenaviruses are of zoonotic origin and reservoir-to-human transmission is crucial for spillover into human populations.
View Article and Find Full Text PDFFatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
View Article and Find Full Text PDFThe family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly phyllostomid bats. Moreover, recent findings have documented a divergent group of arenaviruses in captive alethinophidian snakes. Human infections occur through mucosal exposure to aerosols or by direct contact of abraded skin with infectious materials.
View Article and Find Full Text PDFPeste des petits ruminants (PPR) is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV). Two recombinant replication-defective human adenoviruses serotype 5 (Ad5) expressing either the highly immunogenic fusion protein (F) or hemagglutinin protein (H) from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses.
View Article and Find Full Text PDFPeste des petits ruminants is a highly contagious disease of small ruminants caused by a Morbillivirus, peste des petits ruminants virus (PPRV). Two recombinant replication-defective human adenovirus serotype 5 (Ad5) containing the highly immunogenic fusion protein (F) and hemaglutinine protein (H) genes from PPRV were constructed. HEK293A cells infected with either virus (Ad5-PPRV-F or -H) express F and H proteins respectively.
View Article and Find Full Text PDFAmyloid-β peptide (Aβ)-membrane interactions have been implicated in the formation of toxic oligomers that permeabilize membranes, allowing an influx of calcium ions and triggering cell death in the pathogenesis of Alzheimer's disease (AD). Curcumin, a small dietary polyphenolic molecule, has been shown to reduce Aβ-induced toxicity and AD pathology. We investigate here the effect of curcumin on Aβ40-induced toxicity in cultured human neuroblastoma SH-SY5Y cells and test a novel neuroprotection mechanism in which curcumin reduces Aβ-membrane interactions and attenuates Aβ-induced membrane disruptions.
View Article and Find Full Text PDFLymphocytic choriomeningitis virus (LCMV) has contributed to unveil some of the molecular mechanisms of lethal mutagenesis, or loss of virus infectivity due to increased mutation rates. Here we review these developments, and provide additional evidence that ribavirin displays a dual mutagenic and inhibitory activity on LCMV that can be relevant to treatment designs. Using 5-fluorouracil as mutagenic agent and ribavirin either as inhibitor or mutagen, we document an advantage of a sequential inhibitor-mutagen administration over the corresponding combination treatment to achieve a low LCMV load in cell culture.
View Article and Find Full Text PDFBackground: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI) on progeny production of several RNA viruses under enhanced mutagenesis.
View Article and Find Full Text PDFThis study introduces the concept design and analysis of a robotic system for the assistance and rehabilitation of disabled people. Based on the statistical data of the most common types of disabilities in Spain and other industrialized countries, the different tasks that the device must be able to perform have been determined. In this study, different robots for rehabilitation and assistance previously introduced have been reviewed.
View Article and Find Full Text PDFArenaviruses include several important human pathogens, and there are very limited options of preventive or therapeutic interventions to combat these viruses. An off-label use of the purine nucleoside analogue ribavirin (1-β-d-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is the only antiviral treatment currently available for arenavirus infections. However, the ribavirin antiviral mechanism action against arenaviruses remains unknown.
View Article and Find Full Text PDFBackground & Aim: Melatonin is a molecule with antioxidative properties including direct free radical scavenging and indirect stimulatory actions on a variety of antioxidative enzymes which further promote its ability to reduce the toxicity of radicals and their associated reactants. Beer is an integral element of the diet of numerous people and is rich in antioxidants. We analyzed if melatonin is present in beer and if so, at what concentration.
View Article and Find Full Text PDFCombination of electrodes, such as aluminum and iron in a single electrochemical cell provide an alternative method for removal of arsenic from water by electrocoagulation. The removal process has been studied with a wide range of arsenic concentration (1-1000 ppm) at different pH (4-10). Analysis of the electrochemically generated by-products by XRD, XPS, SEM/EDAX, FT-IR, and Mössbauer Spectroscopy revealed the expected crystalline iron oxides (magnetite (Fe3O4), lepidocrocite (FeO(OH)), iron oxide (FeO)) and aluminum oxides (bayerite (Al(OH)3), diaspore (AlO(OH)), mansfieldite (AlAsO(4).
View Article and Find Full Text PDFArsenic contamination is an enormous worldwide problem. A large number of people dwelling in Comarca Lagunera, situated in the central part of northern México, use well water with arsenic in excess of the water standard regulated by the Secretary of Environment and Natural Resources of México (SEMARNAT), to be suitable for human health. Individuals with lifetime exposure to arsenic develop the classic symptoms of arsenic poisoning.
View Article and Find Full Text PDF