RNA editing regulates glutamatergic synapses in the frontal cortex of a molecular subtype of Amyotrophic Lateral Sclerosis.

Background: Amyotrophic Lateral Sclerosis (ALS) is a highly heterogenous neurodegenerative disorder that primarily affects upper and lower motor neurons, affecting additional cell types and brain regions. Underlying molecular mechanisms are still elusive, in part due to disease heterogeneity. Molecular disease subtyping through integrative analyses including RNA editing profiling is a novel approach for identification of molecular networks involved in pathogenesis.

SIMOA Diagnostics on Alzheimer's Disease and Frontotemporal Dementia.

Background: Accurate diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) represents a health issue due to the absence of disease traits. We assessed the performance of a SIMOA panel in cerebrospinal fluid (CSF) from 43 AD and 33 FTD patients with 60 matching Control subjects in combination with demographic-clinical characteristics.

Methods: 136 subjects (AD: = 43, FTD: = 33, Controls: = 60) participated.

Establishment and maintenance of random monoallelic expression.

This Review elucidates the regulatory principles of random monoallelic expression by focusing on two well-studied examples: the X-chromosome inactivation regulator Xist and the olfactory receptor gene family. Although the choice of a single X chromosome or olfactory receptor occurs in different developmental contexts, common gene regulatory principles guide monoallelic expression in both systems. In both cases, an event breaks the symmetry between genetically and epigenetically identical copies of the gene, leading to the expression of one single random allele, stabilized through negative feedback control.

A Comparison of RML Prion Inactivation Efficiency by Heterogeneous and Homogeneous Photocatalysis.

Prions are proteinaceous pathogens responsible for a variety of devastating diseases in mammals, including scrapie in sheep and goats, chronic wasting disease in cervids, and Creutzfeldt-Jakob disease (CJD) in humans. They are characterized by their exceptional persistence to common inactivation procedures. This applies to all possible sources of prion contamination as prions may be present in the tissues and biological fluids of infected individuals.

Αnti-prion effects of anthocyanins.

Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, PrP, into the pathogenic isoform, PrP. Prion diseases are invariably fatal and despite ongoing research, no effective prophylactic or therapeutic avenues are currently available.

Photo-Fenton and TiO Photocatalytic Inactivation of Model Microorganisms under UV-A; Comparative Efficacy and Optimization.

Photocatalytic inactivation of pathogens in aqueous waste is gaining increasing attention. Several homogeneous and heterogeneous photocatalytic protocols exist using the Fenton's reagent and TiO, respectively. A comprehensive study of homogeneous and heterogeneous photocatalysis on a range of microorganisms will significantly establish the most efficient method.

Gene targeting in amyotrophic lateral sclerosis using causality-based feature selection and machine learning.

Background: Amyotrophic lateral sclerosis (ALS) is a rare progressive neurodegenerative disease that affects upper and lower motor neurons. As the molecular basis of the disease is still elusive, the development of high-throughput sequencing technologies, combined with data mining techniques and machine learning methods, could provide remarkable results in identifying pathogenetic mechanisms. High dimensionality is a major problem when applying machine learning techniques in biomedical data analysis, since a huge number of features is available for a limited number of samples.

Carnosic Acid and Carnosol Display Antioxidant and Anti-Prion Properties in In Vitro and Cell-Free Models of Prion Diseases.

Prion diseases are transmissible encephalopathies associated with the conversion of the physiological form of the prion protein (PrP) to the disease-associated (PrP). Despite intense research, no therapeutic or prophylactic agent is available. The catechol-type diterpene Carnosic acid (CA) and its metabolite Carnosol (CS) from Rosmarinus officinalis have well-documented anti-oxidative and neuroprotective effects.

A Systematic Review of Common and Brain-Disease-Specific RNA Editing Alterations Providing Novel Insights into Neurological and Neurodegenerative Disease Manifestations.

RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common type of mammalian RNA editing. It occurs as a nuclear co- and/or post-transcriptional event catalyzed by ADARs (Adenosine deaminases acting on RNA) and APOBECs (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like genes).

A physicochemical model for rationalizing SARS-CoV-2 concentration in sewage. Case study: The city of Thessaloniki in Greece.

Detection of SARS-CoV-2 in sewage has been employed by several researchers as an alternative early warning indicator of virus spreading in communities, covering both symptomatic and asymptomatic cases. A factor that can seriously mislead the quantitative measurement of viral copies in sewage is the adsorption of virus fragments onto the highly porous solids suspended in wastewater, making them inaccessible. This depends not only on the available amount of suspended solids, but also on the amount of other dissolved chemicals which may influence the capacity of adsorption.

Validation of Poly(Propylene Imine) Glycodendrimers Towards Their Anti-prion Conversion Efficiency.

Prion diseases, such as the sporadic Creutzfeldt-Jakob disease (sCJD), are a class of fatal neurodegenerative disorders. Currently, there is no efficient treatment or therapy available. Hence, the search for molecules that may inhibit the conversion of the cellular prion protein (PrP) into its pathological counterpart PrPScrapie (PrP) is of great urgency.

A Closed Chemobrionic System as a Biochemical Delivery Platform.

Inorganic cells bearing calcium silicate membranes were prepared and resembled closed chemical gardens. It was demonstrated that these inorganic cells can successfully be loaded with natural products, proteins and plasmid DNA, and their cargo can be released in a controlled manner. These cells demonstrated the ability of chemical gardens to act as platforms for the sustained delivery of biomolecules and are expected to introduce chemical gardens in the field of biosciences.

Cerebrospinal fluid neurofilament light in suspected sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. It is invariably fatal and displays a short clinical disease stage. The key event in sCJD is the propagation of a beta-sheet rich conformer of the physiological PrP protein, known as PrP.

MicroRNA Alterations in the Brain and Body Fluids of Humans and Animal Prion Disease Models: Current Status and Perspectives.

Prion diseases are transmissible progressive neurodegenerative conditions characterized by rapid neuronal loss accompanied by a heterogeneous neuropathology, including spongiform degeneration, gliosis and protein aggregation. The pathogenic mechanisms and the origins of prion diseases remain unclear on the molecular level. Even though neurodegenerative diseases, including prion diseases, represent distinct entities, their pathogenesis shares a number of features including disturbed protein homeostasis, an overload of protein clearance pathways, the aggregation of pathological altered proteins, and the dysfunction and/or loss of specific neuronal populations.

Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.

Introduction: Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown.

Methods: Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n = 122), mild cognitive impairment (n = 48), Alzheimer's disease (n = 108), dementia with Lewy bodies/Parkinson's disease dementia (n = 53), vascular dementia (n = 46), frontotemporal dementia (n = 41), sporadic Creutzfeldt-Jakob disease (sCJD, n = 132), and genetic prion diseases (n = 182).

Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis.

Increasing evidence indicates that microRNAs (miRNAs) are contributing factors to neurodegeneration. Alterations in miRNA signatures have been reported in several neurodegenerative dementias, but data in prion diseases are restricted to ex vivo and animal models. The present study identified significant miRNA expression pattern alterations in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) patients.

YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias.

Background: YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing.

Evaluation of α-synuclein as a novel cerebrospinal fluid biomarker in different forms of prion diseases.

Introduction: Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context.

Methods: We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease (n = 278), and in the neurologic control group (n = 111).

Results: An optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD).

Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells.

Scrapie, the prion disease of sheep and goats, is a devastating malady of small ruminants. Due to its infectious nature, epidemic outbreaks may occur in flocks/herds consisting of highly susceptible animals. Field studies identified scrapie-protective caprine PrP variants, harboring specific single amino acid changes (Met-142, Arg-143, Asp-146, Ser-146, His-154, Gln-211 and Lys-222).