Neglected SARS-CoV-2 variants and potential concerns for molecular diagnostics: a framework for nucleic acid amplification test target site quality assurance.

Molecular tests like polymerase chain reaction were widely used during the COVID-19 pandemic but as the pandemic evolved, so did SARS-CoV-2. This virus acquired mutations, prompting concerns that mutations could compromise molecular test results and be falsely negative. While some manufacturers may have in-house programs for monitoring mutations that could impact their assay performance, it is important to promptly report mutations in circulating viral strains that could adversely impact a diagnostic test result.

Hunting for mpox (monkeypox) mimickers: Use of the Biofire meningitis/encephalitis panel on lesion swabs to support alternative viral diagnoses.

Background: Mpox (formerly monkeypox) is an emerging zoonotic disease of public health concern that presents as a rash mimicking other common viral exanthems. Unlike traditional testing algorithms relying on several assays, the BioFire FilmArray meningitis/encephalitis (ME) panel simultaneously detects common viruses causing rashes; however, Biofire ME is only licensed for testing on cerebral spinal fluid.

Objectives: This study evaluated use of the Biofire ME panel for detection and discrimination of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), human herpesviruses type 6 (HHV-6), enteroviruses (EVs), and human paraechoviruses (HPeVs) from a dermal or mucocutaneous swabs collected in universal transport media (UTM).

Characterization of Swine Influenza A(H1N2) Variant, Alberta, Canada, 2020.

Influenza strains circulating among swine populations can cause outbreaks in humans. In October 2020, we detected a variant influenza A subtype H1N2 of swine origin in a person in Alberta, Canada. We initiated a public health, veterinary, and laboratory investigation to identify the source of the infection and determine whether it had spread.

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease.

Enteroviruses are single-stranded positive-sense RNA viruses that primarily cause self-limiting gastrointestinal or respiratory illness. In some cases, these viruses can invade the central nervous system, causing life-threatening neurological diseases including encephalitis, meningitis and acute flaccid paralysis (AFP). As we near the global eradication of poliovirus, formerly the major cause of AFP, the number of AFP cases have not diminished implying a non-poliovirus etiology.

Dual RNA-Seq characterization of host and pathogen gene expression in liver cells infected with Crimean-Congo Hemorrhagic Fever Virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that can cause a hemorrhagic fever in humans, with a case fatality rate of up to 40%. Cases of CCHFV have been reported in Africa, Asia, and southern Europe; and recently, due to the expanding range of its vector, autochthonous cases have been reported in Spain. Although it was discovered over 70 years ago, our understanding of the pathogenesis of this virus remains limited.

The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease.

Multiple cell types and complex connection networks are an intrinsic feature of brain tissue. In this study we used expression profiling of specific microscopic regions of heterogeneous tissue sections isolated by laser capture microdissection (LCM) to determine insights into the molecular basis of brain pathology in prion disease. Temporal profiles in two mouse models of prion disease, bovine spongiform encephalopathy (BSE) and a mouse-adapted strain of scrapie (RML) were performed in microdissected regions of the CA1 hippocampus and granular layer of the cerebellum which are both enriched in neuronal cell bodies.

Isolation of Viral-Infected Brain Regions for miRNA Profiling from Formalin-Fixed Paraffin-Embedded Tissues by Laser Capture Microdissection.

Brain is a highly heterogeneous organ with numerous layers of specialized cells. Viral infection further adds complexity to downstream analysis because only a subpopulation of the brain is infected. In these instances, molecular changes that occur within infected cells are not truly reflected when whole tissue is used for downstream analysis.

MicroRNA-16 targets mRNA involved in neurite extension and branching in hippocampal neurons during presymptomatic prion disease.

The mechanisms that lead to neuronal death in neurodegenerative diseases are poorly understood. Prion diseases, like many more common disorders such as Alzheimer's and Parkinson's diseases, are characterized by the progressive accumulation of misfolded disease-specific proteins. The earliest changes observed in brain tissue include a reduction in synaptic number and retraction of dendritic spines, followed by reduced length and branching of neurites.

MicroRNA and mRNA Dysregulation in Astrocytes Infected with Zika Virus.

The Zika virus (ZIKV) epidemic is an ongoing public health concern. ZIKV is a flavivirus reported to be associated with microcephaly, and recent work in animal models demonstrates the ability of the virus to cross the placenta and affect fetal brain development. Recent findings suggest that the virus preferentially infects neural stem cells and thereby deregulates gene expression, cell cycle progression, and increases cell death.

DNA vaccination protects mice against Zika virus-induced damage to the testes.

Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm.

Correction: Induction of Multiple miR-200/182 Members in the Brains of Mice Are Associated with Acute Herpes Simplex Virus 1 Encephalitis.

[This corrects the article DOI: 10.1371/journal.pone.

Induction of Multiple miR-200/182 Members in the Brains of Mice Are Associated with Acute Herpes Simplex Virus 1 Encephalitis.

Important roles of microRNAs (miRNAs) in regulating the host response during viral infection have begun to be defined. However, little is known about the functional roles of miRNAs within an in vivo acute viral encephalitis model. We therefore identified global changes in miRNA expression during acute herpes simplex virus type 1 (HSV-1) encephalitis (HSVE) in mice.

Claudin 1 Expression Levels Affect miRNA Dynamics in Human Basal-Like Breast Cancer Cells.

Deemed a putative tumor suppressor in breast cancer, the tight junction protein claudin 1 has now been shown to be highly expressed in the basal-like molecular subtype. Moreover, recent in vitro studies show that claudin 1 can regulate breast cancer cell motility and proliferation. Herein, we investigated whether microRNA (miRNA) dysregulation is associated with alterations in the level of claudin 1.

MicroRNA abundance is altered in synaptoneurosomes during prion disease.

Discrepancy in synaptic structural plasticity is one of the earliest manifestations of the neurodegenerative state. In prion diseases, a reduction in synapses and dendritic spine densities is observed during preclinical disease in neurons of the cortex and hippocampus. The underlying molecular mechanisms of these alterations have not been identified but microRNAs (miRNAs), many of which are enriched at the synapse, likely regulate local protein synthesis in rapid response to stressors such as replicating prions.

[Visual and anatomical outcomes of three intravitreal aflibercept injections in eyes with neovascular form of age-related macular degeneration].

Purpose: To evaluate results of treatment of choroidal neovascularization due to age-related macular degeneration with aflibercept in a group of patients representative for Polish population.

Material And Methods: Three intravitreal injections of 2.0 mg of aflibercept were administrated to 48 eyes with active choroidal neovascularization at the four week intervals.

Activation of pro-survival CaMK4β/CREB and pro-death MST1 signaling at early and late times during a mouse model of prion disease.

Background: The signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis.

Microdissection and transcriptional profiling: a window into the pathobiology of preclinical prion disease.

Prion diseases share common features on a sub-cellular level with many neurodegenerative diseases including Alzheimer disease; the most prevalent neurodegenerative disease world-wide. The most obvious similarity is the accumulation of misfolded forms of the host proteins which forms aggregates in the brains of patients. Remarkably, one of the earliest pathological changes detected in degenerating brain tissue, well before clinical symptoms are observed, is synaptic dysfunction and loss.

Small RNA drugs for prion disease: a new frontier.

Introduction: Prion diseases, also known as transmissible spongiform encephalopathies, are a group of neurodegenerative diseases that are invariably incurable. In fact, intense laboratory and clinical research have failed to discover effective treatments, to date, which delay the onset or progression of any neurodegenerative conditions, including those caused by infectious prions. It has become clear that profound changes in the brains of patients are evident long before clinical signs and it is at this stage that the disease is reversible and presents 'druggable' targets.

The mtDNA rns gene landscape in the Ophiostomatales and other fungal taxa: twintrons, introns, and intron-encoded proteins.

Comparative sequence analysis of the mitochondrial small subunit ribosomal RNA (rns) gene among species of Ophiostoma, Grosmannia, Ceratocystiopsis and related taxa provides an overview of the types of introns that have invaded this gene within the ophiostomatoid fungi. The rns gene appears to be a reservoir for a number of group I and group II introns along with intron-associated open reading frames such as homing endonucleases and reverse transcriptases. This study uncovered two twintrons, one at position mS917 where a group ID intron encoding a LAGLIDADG ORF invaded another ORF-less group ID intron.

Early mechanisms of pathobiology are revealed by transcriptional temporal dynamics in hippocampal CA1 neurons of prion infected mice.

Prion diseases typically have long pre-clinical incubation periods during which time the infectious prion particle and infectivity steadily propagate in the brain. Abnormal neuritic sprouting and synaptic deficits are apparent during pre-clinical disease, however, gross neuronal loss is not detected until the onset of the clinical phase. The molecular events that accompany early neuronal damage and ultimately conclude with neuronal death remain obscure.

A user-friendly computational workflow for the analysis of microRNA deep sequencing data.

Second-generation high-throughput sequencing is a robust and inexpensive methodology that is becoming an increasingly common technique for the study of microRNA (miRNA) expression levels in the central nervous system. This method allows for the identification of both known and novel miRNAs, reporting on the qualitative and quantitative levels these RNA species represent in any given sample. Numerous bioinformatic programs are currently available to analyze deep sequencing data but many require at least a partial understanding of the command line interface.

Computational methodologies for studying non-coding RNAs relevant to central nervous system function and dysfunction.

Non-coding RNAs (ncRNAs) are a large and diverse group of transcripts that span the eukaryotic genome, of which less than 2% encodes proteins. Several distinct families of ncRNAs have been described and implicated in many aspects of central nervous system (CNS) function including translation, RNA metabolism, gene regulation, and development. The need to distinguish ncRNAs from sequence data, as well as potentially uncovering novel ncRNA families, has ignited the development of customized computational approaches and bioinformatic resources to handle these tasks.

Molecular evolution of the mtDNA encoded rps3 gene among filamentous ascomycetes fungi with an emphasis on the Ophiostomatoid fungi.

The mitochondrial ribosomal protein S3 (rps3) gene within the fungi is extremely diverse in location and organization, some versions of this gene have been incorporated into a group I intron, others appear to have gained large insertions, microsatellite expansions, or have been invaded by homing endonucleases. Among the ascomycetes fungi the group I intron encoded version of rps3 appears to have a rather complex evolutionary history including first the acquisition of rps3 by a group I intron (mL2449), the loss of the mL2499 intron and the establishment of rps3 as a free-standing gene, and the eventual loss of the intron derived version of rps3.

The sporadic occurrence of a group I intron-like element in the mtDNA rnl gene of Ophiostoma novo-ulmi subsp. americana.

The presence of group I intron-like elements within the U7 region of the mtDNA large ribosomal subunit RNA gene (rnl) was investigated in strains of Ophiostoma novo-ulmi subsp. americana from Canada, Europe and Eurasia, and in selected strains of O. ips, O.