Polymorphic pseudogenes in the human genome - a comprehensive assessment.

Background: Over the past decade, variations of the coding portion of the human genome have become increasingly evident. In this study, we focus on polymorphic pseudogenes, a unique and relatively unexplored type of pseudogene whose inactivating mutations have not yet been fixed in the human genome at the global population level. Thus, polymorphic pseudogenes are characterized by the presence in the population of both coding alleles and non-coding alleles originating from Loss-of-Function (LoF) mutations.

Critical Assessment of the Management of Unstable Angina in a Specialized Cardiology Emergency Room.

Background: The management of unstable angina (UA) presents a challenge due to its subjective diagnosis and limited representation in randomized clinical trials that inform current practices.

Objectives: This study aims to identify key factors associated with the indication for invasive versus non-invasive stratification in this population and to evaluate factors associated with stratification test results.

Methods: This retrospective cohort study included patients hospitalized with UA over a consecutive 20-month period.

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp.

Beta-Carotene Supplementation for Sows: Reproductive Parameters and Productive Performance of Piglets.

The rapid fetal development and the increased demand for milk result in a catabolic state and oxidative stress in hyperprolific sows. Despite animal defense mechanisms, the dietary supplementation of antioxidants is being evaluated to reduce the impacts of excess free radicals. The aim of this study was to evaluate the short- and long-term effects of beta-carotene supplementation for sows on the reproductive response and performance of suckling piglets.

Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses.

Introduction: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks.

ICARUS at the Fermilab Short-Baseline Neutrino program: initial operation.

The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV. After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation.

Automatic method based on deep learning to identify and account Rhipicephalus microplus larval hatching.

Reports of Rhipicephalus microplus resistant populations worldwide have increased extensively, making it difficult to control this ectoparasite. The adult immersion test, commonly used to screen for acaricide resistance, produces the results only after 40 days of the tick collection because it needs the eggs to be laid and larvae to hatch. The present study aims to develop an automatic method, based on deep learning, to predict the hatching of R.

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts.

Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae () capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood.

Complex interactions between p.His558Arg and linked variants in the sodium voltage-gated channel alpha subunit 5 (Na 1.5).

Common genetic polymorphisms may modify the phenotypic outcome when co-occurring with a disease-causing variant, and therefore understanding their modulating role in health and disease is of great importance. The polymorphic p.His558Arg variant of the sodium voltage-gated channel alpha subunit 5 (Na 1.

Hb F Levels in β-Thalassemia Carriers and Normal Individuals: Known and Unknown Quantitative Trait Loci in the β-Globin Gene Cluster.

In the already identified quantitative trait loci (QTL), modulating Hb F levels are -acting haplotypes of the β-globin gene cluster itself, although the single nucleotide polymorphisms (SNPs) accounting more for the association, remain uncertain. In this study, the role in Hb F production of previously reported candidate SNPs within the β-globin gene cluster was reexamined, along with a yet poorly studied variation in the gene. In a sample of β-thalassemia (β-thal) carriers, we succeeded in replicating the significant association between increased Hb F levels and rs7482144 (C>T) (I), which is the most well-established variation in the cluster influencing the trait.

Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example.

Over recent decades, the many functions of RNA have become more evident. This molecule has been recognized not only as a carrier of genetic information, but also as a specific and essential regulator of gene expression. Different RNA species have been identified and novel and exciting roles have been unveiled.

Laccase bioconjugate and multi-walled carbon nanotubes-based biosensor for bisphenol A analysis.

Bisphenol A (BPA) is an endocrine disruptor compound that has been detected in aquatic ecosystems. In this work, the development of an electrochemical biosensor for BPA determination based on laccase from Trametes versicolor is reported. A bioconjugate was optimized to maximize the biosensor electrocatalytic activity and stability, which for the first time involved the synergistic effect of this specific enzyme (6.

Genetic Variability of the Functional Domains of Chromodomains Helicase DNA-Binding (CHD) Proteins.

In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life.

Zebrafish as a model to study inflammation: A tool for drug discovery.

This study aims to demonstrate the applicability and importance of zebrafish (Danio rerio) model to study acute and chronic inflammatory responses induced by different stimuli: carrageenan phlogogen (nonimmune); acute infection by bacteria (immune); foreign body reaction (chronic inflammation by round glass coverslip implantation); reaction induced by xenotransplantation. In addition to the advantages of presenting low breeding cost, high prolificity, transparent embryos, high number of individuals belonging to the same spawning and high genetic similarity that favor translational responses to vertebrate organisms like humans, zebrafish proved to be an excellent tool, allowing the evaluation of edema formation, accumulation of inflammatory cells in the exudate, mediators, signaling pathways, gene expression and production of specific proteins. Our studies demonstrated the versatility of fish models to investigate the inflammatory response and its pathophysiology, essential for the successful development of studies to discover innovative pharmacological strategies.

Insights into the Middle Eastern paternal genetic pool in Tunisia: high prevalence of T-M70 haplogroup in an Arab population.

To obtain refreshed insights into the paternal lineages of Tunisian populations, Y-chromosome diversity was assessed in two populations belonging to an Arab genealogical lineage, Kairouan and Wesletia, as well as in four Tunisian Andalusian populations, Testour, Slouguia, Qalaat-El-Andalous and El Alia. The Arabs from Kairouan revealed 73.47% of E-M81 and close affinities with Berber groups, indicating they are likely arabized Berbers, clearly differentiated from the Arabs from Wesletia, who harbored the highest frequency (71.

Compensatory epistasis explored by molecular dynamics simulations.

A non-negligible proportion of human pathogenic variants are known to be present as wild type in at least some non-human mammalian species. The standard explanation for this finding is that molecular mechanisms of compensatory epistasis can alleviate the mutations' otherwise pathogenic effects. Examples of compensated variants have been described in the literature but the interacting residue(s) postulated to play a compensatory role have rarely been ascertained.

Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity.

Understanding the role of common polymorphisms in modulating the clinical phenotype when they co-occur with a disease-causing lesion is of critical importance in medical genetics. We explored the impact of apparently neutral common polymorphisms, using the gene encoding the urea cycle enzyme, ornithine transcarbamylase (OTC), as a model system. Distinct combinations of genetic backgrounds embracing two missense polymorphisms were created in cis with the pathogenic p.

Evolutionary dynamics of the human pseudoautosomal regions.

Recombination between the X and Y human sex chromosomes is limited to the two pseudoautosomal regions (PARs) that present quite distinct evolutionary origins. Despite the crucial importance for male meiosis, genetic diversity patterns and evolutionary dynamics of these regions are poorly understood. In the present study, we analyzed and compared the genetic diversity of the PAR regions using publicly available genomic sequences encompassing both PAR1 and PAR2.

Combination of entomopathogenic nematodes with acaricides or essential oil of Lippia triplinervis against Rhipicephalus microplus (Acari: Ixodidae).

This study aimed to evaluate the combination effect of Heterorhabditis bacteriophora HP88 and H. indica LPP1, with the acaricides deltamethrin, amitraz and chlorfenvinphos, and the essential oil (EO) of Lippia triplinervis, against engorged females of Rhipicephalus microplus. In order to verify the effect of acaricides and EO, the adult immersion test was used, and in the groups treated only with entomopathogenic nematodes (EPNs), 150 infective juveniles were used per female.

[Work at the cyclotron for radioisotope production: exposure risks and prevention measures].

In this article, there will be presented the main aspects of the radiation protection for a site dedicated to the production of radioisotopes by cyclotron for medical use. After analyzing the design parameters of the site for the operation from a point of view of the radiation protection of the operators, the population and the environment (shielding around the accelerator, ventilation system, chimney releases etc.), we will focus our attention to the handling of unsealed sources produced, with particular regard to the operating procedures.

[Exposure risk for workers and prevention measures in ordinary and emergency conditions].

The radiological risk assessment and the definition of the radioprotection physical surveillance program applied to a 250 kW (thermal power) research nuclear reactor operated by a large Italian public body. Useful elements for the prevention of personnel exposures, classification criteria for workers, risk reduction methods and optimization of exposures, most common criticalities in plant activities. Analysis of the main operations related to the activities of irradiation and scientific research with an eye to the needs of researchers and one to the indications of prevention.

Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation.

Objective: Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intestinal epithelial crypts (IEC-6).

Methods: IEC-6 cells were exposed to nutrient deprivation (no serum and no glutamine) and supplemented with retinyl palmitate or retinol at a range of 2 to 20 μM.

Efficacy and safety of glucose, glucose and polidocanol combination, liquid polidocanol and polidocanol foam in the treatment of reticular veins: A randomized study in rabbits.

Objective: To compare the efficacy and safety of sclerosing agents injected in dorsal veins of rabbit ears.

Methods: Sixty ears of 30 rabbits were randomly allocated in: 1% liquid polidocanol, 1% polidocanol foam, 0.2% polidocanol-glucose 70% solution, glucose 75% or 0.

Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach.

More than two thirds of Lysosomal Storage Diseases (LSDs) present central nervous system involvement. Nevertheless, only one of the currently approved therapies has an impact on neuropathology. Therefore, alternative approaches are under development, either addressing the underlying enzymatic defect or its downstream consequences.