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International Journal of Molecular... Jun 2024Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic...
Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic β-cells. The diagnosis of MODY still remains a challenge for clinicians, with many cases being misdiagnosed as type 1 or type 2 diabetes mellitus (T1DM/T2DM), and over 80% of cases remaining undiagnosed. With the introduction of modern technologies, important progress has been made in deciphering the molecular mechanisms and heterogeneous etiology of MD, including MODY. The aim of our study was to identify genetic variants associated with MODY in a group of patients with early-onset diabetes/prediabetes in whom a form of MD was clinically suspected. Genetic testing, based on next-generation sequencing (NGS) technology, was carried out either in a targeted manner, using gene panels for monogenic diabetes, or by analyzing the entire exome (whole-exome sequencing). -MODY 2 was the most frequently detected variant, but rare forms of -MODY 13, specifically, -MODY 1, were also identified. We have emphasized the importance of genetic testing for early diagnosis, MODY subtype differentiation, and genetic counseling. We presented the genotype-phenotype correlations, especially related to the clinical evolution and personalized therapy, also emphasizing the particularities of each patient in the family context.
Topics: Humans; Diabetes Mellitus, Type 2; Genetic Testing; Male; Female; Genetic Counseling; Adult; Precision Medicine; High-Throughput Nucleotide Sequencing; Adolescent; Potassium Channels, Inwardly Rectifying; Young Adult; Child; Hepatocyte Nuclear Factor 4; Exome Sequencing; Genetic Predisposition to Disease; Mutation
PubMed: 38928025
DOI: 10.3390/ijms25126318 -
International Journal of Molecular... Jun 2024Adipose tissue is conventionally recognized as a metabolic organ responsible for storing energy. However, a proportion of adipose tissue also functions as a thermogenic... (Review)
Review
Adipose tissue is conventionally recognized as a metabolic organ responsible for storing energy. However, a proportion of adipose tissue also functions as a thermogenic organ, contributing to the inhibition of weight gain and prevention of metabolic diseases. In recent years, there has been significant progress in the study of thermogenic fats, particularly brown adipose tissue (BAT). Despite this progress, the mechanism underlying thermogenesis in beige adipose tissue remains highly controversial. It is widely acknowledged that beige adipose tissue has three additional thermogenic mechanisms in addition to the conventional UCP1-dependent thermogenesis: Ca cycling thermogenesis, creatine substrate cycling thermogenesis, and triacylglycerol/fatty acid cycling thermogenesis. This paper delves into these three mechanisms and reviews the latest advancements in the molecular regulation of thermogenesis from the molecular genetic perspective. The objective of this review is to provide readers with a foundation of knowledge regarding the beige fats and a foundation for future research into the mechanisms of this process, which may lead to the development of new strategies for maintaining human health.
Topics: Thermogenesis; Humans; Adipocytes, Beige; Animals; Uncoupling Protein 1; Adipose Tissue, Brown; Energy Metabolism; Calcium; Fatty Acids; Triglycerides; Adipose Tissue, Beige
PubMed: 38928011
DOI: 10.3390/ijms25126303 -
International Journal of Molecular... Jun 2024Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional...
Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional communication plays a role in NPC proliferation and differentiation during development, but its relevance on postnatal age remains to be elucidated. In this work we aimed to evaluate the effect of the blockade of gap junctional communication on proliferation and cell fate of NPCs obtained from the SVZ of postnatal rats. NPCs were isolated and expanded in culture as neurospheres. Electron microscopy revealed the existence of gap junctions among neurosphere cells. Treatment of cultures with octanol, a broad-spectrum gap junction blocker, or with Gap27, a specific blocker for gap junctions formed by connexin43, produced a significant decrease in bromodeoxyuridine incorporation. Octanol treatment also exerted a dose-dependent antiproliferative effect on glioblastoma cells. To analyze possible actions on NPC fate, cells were seeded in the absence of mitogens. Treatment with octanol led to an increase in the percentage of astrocytes and oligodendrocyte precursors, whereas the percentage of neurons remained unchanged. Gap27 treatment, in contrast, did not modify the differentiation pattern of SVZ NPCs. Our results indicate that general blockade of gap junctions with octanol induces significant effects on the behavior of postnatal SVZ NPCs, by reducing proliferation and promoting glial differentiation.
Topics: Animals; Gap Junctions; Neural Stem Cells; Cell Proliferation; Cell Differentiation; Rats; Octanols; Neuroglia; Cells, Cultured; Lateral Ventricles; Connexin 43; Rats, Wistar; Astrocytes; Animals, Newborn; Humans
PubMed: 38927995
DOI: 10.3390/ijms25126288 -
Genes Jun 2024Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a...
Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: , , and . Using the Agena MassARRAY platform, 28 single-nucleotide polymorphisms (SNPs) across the three candidate genes were genotyped in a case-control cohort comprised of 182 migraine cases and 179 matched controls. Initial results identified significant associations between migraine and rs3776578 ( = 0.04) and rs16903247 ( = 0.05) genotypes within the gene, which encodes the EAAT1 glutamate transporter. These SNPs were subsequently genotyped in an independent cohort of 258 migraine cases and 290 controls using a high-resolution melt assay, and association testing supported the replication of initial findings-rs3776578 ( = 0.0041) and rs16903247 ( = 0.0127). The polymorphisms are in linkage disequilibrium and localise within a putative intronic enhancer region of . The minor alleles of both SNPs show a protective effect on migraine risk, which may be conferred via influencing the expression of .
Topics: Humans; Polymorphism, Single Nucleotide; Migraine Disorders; Female; Male; Excitatory Amino Acid Transporter 1; Adult; Case-Control Studies; Genetic Predisposition to Disease; Middle Aged; Genetic Association Studies
PubMed: 38927733
DOI: 10.3390/genes15060797 -
Genes Jun 2024Small auxin-upregulated RNAs (), as the largest family of early auxin-responsive genes, play important roles in plant growth and development processes, such as auxin...
Small auxin-upregulated RNAs (), as the largest family of early auxin-responsive genes, play important roles in plant growth and development processes, such as auxin signaling and transport, hypocotyl development, and tolerance to environmental stresses. However, the functions of few genes are known in the root development of sweet potatoes. In this study, an gene was cloned and functionally analyzed. The IbSAUR36 protein was localized to the nucleus and plasma membrane. The transcriptional level of this gene was significantly higher in the pencil root and leaf.This gene was strongly induced by indole-3-acetic acid (IAA), but it was downregulated under methyl-jasmonate(MeJA) treatment. The promoter of contained the core -elements for phytohormone responsiveness. Promoter β-glucuronidase (GUS) analysis in showed that is highly expressed in the young tissues of plants, such as young leaves, roots, and buds. -overexpressing sweet potato roots were obtained by an efficient -mediated root transgenic system. We demonstrated that overexpression of promoted the accumulation of IAA, upregulated the genes encoding IAA synthesis and its signaling pathways, and downregulated the genes encoding lignin synthesis and JA signaling pathways. Taken together, these results show that plays an important role in adventitious root (AR) development by regulating IAA signaling, lignin synthesis, and JA signaling pathways in transgenic sweet potatoes.
Topics: Ipomoea batatas; Plant Roots; Plants, Genetically Modified; Indoleacetic Acids; Gene Expression Regulation, Plant; Plant Proteins; Plant Growth Regulators; Promoter Regions, Genetic; Cyclopentanes
PubMed: 38927696
DOI: 10.3390/genes15060760 -
Genes Jun 2024In humans, the transient receptor potential vanilloid 1 () gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and...
In humans, the transient receptor potential vanilloid 1 () gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and endogenous (e.g., endocannabinoids, inflammatory factors, fatty acid metabolites, low pH) stimuli. It has been shown to be involved in several processes including nociception, thermosensation, and energy homeostasis. In this study, we investigated the association between gene variants, sensory perception (to capsaicin and PROP), and body composition (BMI and bioimpedance variables) in human populations. By comparing sequences deposited in worldwide databases, we identified two haplotype blocks (herein referred to as H1 and H2) that show strong stabilizing selection signals (MAF approaching 0.50, Tajima's D > +4.5) only in individuals with sub-Saharan African ancestry. We therefore studied the genetic variants of these two regions in 46 volunteers of sub-Saharan descent and 45 Italian volunteers (both sexes). Linear regression analyses showed significant associations between diplotypes and body composition, but not with capsaicin perception. Specifically, in African women carrying the H1-b and H2-b haplotypes, a higher percentage of fat mass and lower extracellular fluid retention was observed, whereas no significant association was found in men. Our results suggest the possible action of sex-driven balancing selection at the non-coding sequences of the gene, with adaptive effects on water balance and lipid deposition.
Topics: Adult; Female; Humans; Male; Middle Aged; Africa South of the Sahara; Black People; Body Composition; Haplotypes; Polymorphism, Single Nucleotide; Sub-Saharan African People; TRPV Cation Channels
PubMed: 38927688
DOI: 10.3390/genes15060752 -
Genes May 2024Zinc (Zn)- and iron (Fe)-regulating transport-like proteins (ZIPs) are a class of proteins crucial for metal uptake and transport in plants, particularly for Zn and Fe...
Zinc (Zn)- and iron (Fe)-regulating transport-like proteins (ZIPs) are a class of proteins crucial for metal uptake and transport in plants, particularly for Zn and Fe absorption and distribution. These proteins ensure the balance of trace elements essential for plant growth, development, and metabolic activities. However, the role of the rice () gene family in manganese (Mn) and selenium (Se) transport remains underexplored. This research conducted an all-sided analysis of the rice and identified 16 sequences. Phylogenetic analysis categorized the predominantly within the three subfamilies. The expression levels of in rice root and leaf subjected to Mn and Se toxicity stress were examined through quantitative real-time PCR (qRT-PCR). The findings revealed significant differential expression of many under these conditions, indicating a potential regulating effect in the response of rice to Mn and Se toxicity. This work lays a foundation for further functional studies of , enhancing our understanding of the response mechanisms of rice to Mn and Se toxicity and their roles in growth, development, and environmental adaptation.
Topics: Oryza; Selenium; Manganese; Plant Proteins; Gene Expression Regulation, Plant; Stress, Physiological; Phylogeny; Genome, Plant; Cation Transport Proteins; Plant Roots
PubMed: 38927632
DOI: 10.3390/genes15060696 -
Genes May 2024The Cosmonaut Sea is one of the least accessed regions in the Southern Ocean, and our knowledge about the fish biodiversity in the region is sparse. In this study, we...
The Cosmonaut Sea is one of the least accessed regions in the Southern Ocean, and our knowledge about the fish biodiversity in the region is sparse. In this study, we provided a description of demersal fish diversity in the Cosmonaut Sea by analysing cytochrome oxidase I () barcodes of 98 fish samples that were hauled by trawling during the 37th and 38th Chinese National Antarctic Research Expedition (CHINARE) cruises. Twenty-four species representing 19 genera and 11 families, namely, Artedidraconidae, Bathydraconidae, Bathylagidae, Channichthyidae, Liparidae, Macrouridae, Muraenolepididae, Myctophidae, Nototheniidae, Paralepididae and Zoarcidae, were discriminated and identified, which were largely identical to local fish occurrence records and the general pattern of demersal fish communities at high Antarctic shelf areas. The validity of a barcoding gap failed to be detected and confirmed across all species due to the indicative signals of two potential cryptic species. Nevertheless, DNA barcoding still demonstrated to be a very efficient and sound method for the discrimination and classification of Antarctic fishes. In the future, various sampling strategies that cover all geographic sections and depth strata of the Cosmonaut Sea are encouraged to enhance our understanding of local fish communities, within which DNA barcoding can play an important role in either molecular taxonomy or the establishment of a dedicated local reference database for eDNA metabarcoding analyses.
Topics: Animals; DNA Barcoding, Taxonomic; Fishes; Biodiversity; Antarctic Regions; Electron Transport Complex IV; Phylogeny; Oceans and Seas
PubMed: 38927627
DOI: 10.3390/genes15060691 -
Genes May 2024Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the...
Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the feasibility of earlier prenatal diagnosis by celocentesis in four cases of cystic fibrosis and one case of cystic fibrosis and β-thalassemia co-inherited in the same fetus. Celomic fluids were aspired from the celomic cavity between 8 and 9 weeks of gestation and fetal cells were picked up by micromanipulator. Maternal DNA contamination was tested and target regions of fetal DNA containing parental pathogenetic variants of and genes were amplified and sequenced. Four of the five fetuses resulted as being affected by cystic fibrosis and, in all cases, the women decided to interrupt the pregnancy. In the other case, the fetus presented a healthy carrier of cystic fibrosis. The results were confirmed in three cases on placental tissue. In one case, no abortive tissue was obtained. In the last case, the woman refused the prenatal diagnosis to confirm the celocentesis data; the pregnancy is ongoing without complications. This procedure provides prenatal diagnosis of monogenic diseases at least four weeks earlier than traditional procedures, reducing the anxiety of patients and providing the option for medical termination of the affected fetus at 8-10 weeks of gestation, which is less traumatic and safer than surgical termination in the second trimester.
Topics: Humans; Cystic Fibrosis; Female; Pregnancy; Prenatal Diagnosis; Cystic Fibrosis Transmembrane Conductance Regulator; Adult; beta-Thalassemia; Fetus
PubMed: 38927598
DOI: 10.3390/genes15060662 -
Genes May 2024A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors,...
A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. An examination of the tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some neuronal ceroid lipofuscinosis (NCL) diseases. The dog also exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband's DNA revealed a homozygous C to T substitution that altered the intron 3-exon 4 splice site of . Other mutations in cause NCL diseases in humans and animals, including dogs. The CLN6 protein was undetectable with immunolabeling in the tissues of the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the disorder in this dog was classified as an NCL resulting from the absence of the CLN6 protein. Screening the dog's genome for a panel of breed-specific polymorphisms indicated that its ancestry included numerous breeds, with no single breed predominating. This suggests that the disease variant is likely to be present in other mixed-breed dogs and at least some ancestral breeds, although it is likely to be rare since other cases have not been reported to date.
Topics: Neuronal Ceroid-Lipofuscinoses; Animals; Dogs; Male; Dog Diseases; RNA Splice Sites; Membrane Proteins; Mitochondrial Proton-Translocating ATPases; Brain; Mutation
PubMed: 38927597
DOI: 10.3390/genes15060661