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European Journal of Human Genetics :... Nov 2023Embryonic development requires tight control of gene expression levels, activity, and localisation. This control is coordinated by multiple levels of regulation on DNA,... (Review)
Review
Embryonic development requires tight control of gene expression levels, activity, and localisation. This control is coordinated by multiple levels of regulation on DNA, RNA and protein. RNA-binding proteins (RBPs) are recognised as key regulators of post-transcriptional gene regulation, where their binding controls splicing, polyadenylation, nuclear export, mRNA stability, translation rate and decay. In brain development, the ELAVL family of RNA binding proteins undertake essential functions across spatiotemporal windows to help regulate and specify transcriptomic programmes for cell specialisation. Despite their recognised importance in neural tissues, their molecular roles and connections to pathology are less explored. Here we provide an overview of the neuronal ELAVL family, noting commonalities and differences amongst different species, their molecular characteristics, and roles in the cell. We bring together the available molecular genetics evidence to link different ELAVL proteins to phenotypes and disease, in both the brain and beyond, including ELAVL2, which is the least studied ELAVL family member. We find that ELAVL-related pathology shares a common neurological theme, but different ELAVL proteins are more strongly connected to different phenotypes, reflecting their specialised expression across time and space.
Topics: Humans; RNA; RNA-Binding Proteins; RNA Splicing; Brain; Molecular Biology
PubMed: 37697079
DOI: 10.1038/s41431-023-01456-z -
ACS Applied Bio Materials Oct 2023Sensitive, rapid, and portable molecular diagnostics is the future of disease surveillance, containment, and therapy. The recent SARS-CoV-2 pandemic has reminded us of... (Review)
Review
Sensitive, rapid, and portable molecular diagnostics is the future of disease surveillance, containment, and therapy. The recent SARS-CoV-2 pandemic has reminded us of the vulnerability of lives from ever-evolving pathogens. At the same time, it has provided opportunities to bridge the gap by translating basic molecular biology into therapeutic tools. One such molecular biology technique is CRISPR (clustered regularly interspaced short palindromic repeat) which has revolutionized the field of molecular diagnostics at the need of the hour. The use of CRISPR-Cas systems has been widespread in biology research due to the ease of performing genetic manipulations. In 2012, CRISPR-Cas systems were, for the first time, shown to be reprogrammable, i.e., capable of performing sequence-specific gene editing. This discovery catapulted the field of CRISPR-Cas research and opened many unexplored avenues in the field of gene editing, from basic research to therapeutics. One such field that benefitted greatly from this discovery was molecular diagnostics, as using CRISPR-Cas technologies enabled existing diagnostic methods to become more sensitive, accurate, and portable, a necessity in disease control. This Review aims to capture some of the trajectories and advances made in this arena and provides a comprehensive understanding of the methods and their potential use as point-of-care diagnostics.
Topics: Pathology, Molecular; Gene Editing; CRISPR-Cas Systems; Genetic Therapy; Point-of-Care Testing
PubMed: 37788375
DOI: 10.1021/acsabm.3c00439 -
Scientific Reports Nov 2023To investigate the clinical and molecular characteristics and evolution of the Zika virus (ZIKV) in Thailand from March 2020 to March 2023. In all, 751 serum samples...
To investigate the clinical and molecular characteristics and evolution of the Zika virus (ZIKV) in Thailand from March 2020 to March 2023. In all, 751 serum samples from hospitalized patients in Bangkok and the surrounding areas were screened for ZIKV using real-time RT-PCR. Demographic data and clinical variables were evaluated. Phylogenetic and molecular clock analysis determined the genetic relationships among the ZIKV strains, emergence timing, and their molecular characteristics. Among the 90 confirmed ZIKV cases, there were no significant differences in infection prevalence when comparing age groups and sexes. Rash was strongly associated with ZIKV infection. Our ZIKV Thai isolates were categorized into two distinct clades: one was related to strains from Myanmar, Vietnam, Oceania, and various countries in the Americas, and the other was closely related to previously circulating strains in Thailand, one of which shared a close relation to a neurovirulent ZIKV strain from Cambodia. Moreover, ZIKV Thai strains could be further classified into multiple sub-clades, each exhibiting specific mutations suggesting the genetic diversity among the circulating strains of ZIKV in Thailand. Understanding ZIKV epidemiology and genetic diversity is crucial for tracking the virus's evolution and adapting prevention and control strategies.
Topics: Humans; Zika Virus Infection; Zika Virus; Phylogeny; Thailand; Molecular Epidemiology
PubMed: 38030715
DOI: 10.1038/s41598-023-48508-4 -
Cell Reports Nov 2023Human brain size changes dynamically through early development, peaks in adolescence, and varies up to 2-fold among adults. However, the molecular genetic underpinnings...
Human brain size changes dynamically through early development, peaks in adolescence, and varies up to 2-fold among adults. However, the molecular genetic underpinnings of interindividual variation in brain size remain unknown. Here, we leveraged postmortem brain RNA sequencing and measurements of brain weight (BW) in 2,531 individuals across three independent datasets to identify 928 genome-wide significant associations with BW. Genes associated with higher or lower BW showed distinct neurodevelopmental trajectories and spatial patterns that mapped onto functional and cellular axes of brain organization. Expression of BW genes was predictive of interspecies differences in brain size, and bioinformatic annotation revealed enrichment for neurogenesis and cell-cell communication. Genome-wide, transcriptome-wide, and phenome-wide association analyses linked BW gene sets to neuroimaging measurements of brain size and brain-related clinical traits. Cumulatively, these results represent a major step toward delineating the molecular pathways underlying human brain size variation in health and disease.
Topics: Adult; Humans; Organ Size; Transcriptome; Brain; Phenotype; Genome-Wide Association Study; Molecular Biology; Genetic Predisposition to Disease
PubMed: 37963017
DOI: 10.1016/j.celrep.2023.113439 -
Genes Aug 2023Cardiovascular and cerebrovascular diseases are the leading causes of the mortality of humans in the 21st century [...].
Cardiovascular and cerebrovascular diseases are the leading causes of the mortality of humans in the 21st century [...].
Topics: Humans; Cardiovascular System; Cerebrovascular Disorders; Genomics; Metabolic Diseases; Molecular Biology
PubMed: 37628620
DOI: 10.3390/genes14081568 -
International Journal of Molecular... Apr 2024Plants have evolved an intricate immune system to protect themselves from potential pathogens [...].
Plants have evolved an intricate immune system to protect themselves from potential pathogens [...].
Topics: Genomics; Herb-Drug Interactions; Molecular Biology
PubMed: 38612780
DOI: 10.3390/ijms25073970 -
Journal of Experimental Botany Aug 2023Our understanding of plant biology has been revolutionized by modern genetics and biochemistry. However, biochemical genetics can be traced back to the foundation of... (Review)
Review
Our understanding of plant biology has been revolutionized by modern genetics and biochemistry. However, biochemical genetics can be traced back to the foundation of Mendelian genetics; indeed, one of Mendel's milestone discoveries of seven characteristics of pea plants later came to be ascribed to a mutation in a starch branching enzyme. Here, we review both current and historical strategies for the elucidation of plant metabolic pathways and the genes that encode their component enzymes and regulators. We use this historical review to discuss a range of classical genetic phenomena including epistasis, canalization, and heterosis as viewed through the lens of contemporary high-throughput data obtained via the array of approaches currently adopted in multiomics studies.
Topics: Multiomics; Plants; Mutation; Molecular Biology
PubMed: 37170864
DOI: 10.1093/jxb/erad177 -
Pathologie (Heidelberg, Germany) Dec 2023Primary vitreoretinal lymphoma (PVRL) represents a subtype of intraocular lymphomas, which are a subgroup of malignant lymphomas of the eye. PVRL is considered... (Review)
Review
Primary vitreoretinal lymphoma (PVRL) represents a subtype of intraocular lymphomas, which are a subgroup of malignant lymphomas of the eye. PVRL is considered a special form of primary diffuse large cell lymphoma (DLBCL) of the CNS (central nervous system) (PCNSL) and arises primary or secondary to PCNSL. According to the cell of origin (COO) classification of DLBCL, PVRL largely belongs to the activated B‑cell (ABC) type of DLBCL. Based on a recently established genetic-biological classification of DLBCL, PCNSL and thus also PVRL belong to a group of DLBCL of the MYD88/CD79B-mutated (MCD) or cluster 5 subtype, which often shows extranodal manifestations and MYD88 and CD79A mutations as well as CDKN2A deletions.PVRL diagnostics is often complicated as it represents a classic masquerade syndrome. Due to the usually limited material with often large numbers of reactive lymphocytes and/or degenerative changes in the cells, the results of diagnostic tests are difficult to interpret. Classic diagnostic tests include cytology on vitreous aspirates, immunocytochemistry, and clonality analysis.New insights into the spectrum of genetic alterations of vitreoretinal lymphomas (VRL) confirm the close relationship to PCNSL and could significantly improve pathological diagnosis. Next-generation sequencing panel-based diagnostics allow VRL diagnosis confirmation with little DNA in almost 100% of patients in cases with insufficient cytological evidence or lack of clonality detection. PVRL, as well as secondary vitreoretinal lymphomas after PCNSL or extracerebral DLBCL, have high mutation frequencies in characteristically mutated genes in PCNSL or MCD/cluster 5 type DLBCL. Supporting diagnostics, mutation detection can also be performed on cell-free DNA from the vitreous supernatant.
Topics: Humans; Retinal Neoplasms; Myeloid Differentiation Factor 88; Pathology, Molecular; Vitreous Body; Eye Neoplasms; Lymphoma, Large B-Cell, Diffuse; Central Nervous System Neoplasms
PubMed: 37947807
DOI: 10.1007/s00292-023-01251-z -
Virchows Archiv : An International... Feb 2024With the explosion in knowledge about the molecular landscape of lymphoid malignancies and the increasing availability of high throughput techniques, molecular... (Review)
Review
With the explosion in knowledge about the molecular landscape of lymphoid malignancies and the increasing availability of high throughput techniques, molecular diagnostics in hematopathology has moved from isolated marker studies to a more comprehensive approach, integrating results of multiple genes analyzed with a variety of techniques on the DNA and RNA level. Although diagnosis of lymphoma still relies on the careful integration of clinical, morphological, phenotypic, and, if necessary molecular features, and only few entities are defined strictly by genetic features, genetic profiling has contributed profoundly to our current understanding of lymphomas and shaped the two current lymphoma classifications, the International Consensus Classification and the fifth edition of the WHO classification of lymphoid malignancies. In this review, the current state of the art of molecular diagnostics in lymphoproliferations is summarized, including clonality analysis, mutational studies, and gene expression profiling, with a focus on practical applications for diagnosis and prognostication. With consideration for differences in accessibility of high throughput techniques and cost limitations, we tried to distinguish between diagnostically relevant and in part disease-defining molecular features and optional, more extensive genetic profiling, which is usually restricted to clinical studies, patients with relapsed or refractory disease or specific therapeutic decisions. Although molecular diagnostics in lymphomas currently is primarily done for diagnosis and subclassification, prognostic stratification and predictive markers will gain importance in the near future.
Topics: Humans; Pathology, Molecular; Prognosis; Lymphoma; Gene Expression Profiling; Mutation
PubMed: 37747559
DOI: 10.1007/s00428-023-03644-0 -
Journal of the American Chemical Society Feb 2024Aggregate is one of the most extensive existing modes of matters in the world. Besides the research objectives of inanimate systems in physical science, the entities in... (Review)
Review
Aggregate is one of the most extensive existing modes of matters in the world. Besides the research objectives of inanimate systems in physical science, the entities in life science can be regarded as living aggregates, which are far from being thoroughly understood despite the great advances in molecular biology. Molecular biology follows the research philosophy of reductionism, which generally reduces the whole into parts to study. Although reductionism benefits the understanding of molecular behaviors, it encounters limitations when extending to the aggregate level. Holism is another epistemology comparable to reductionism, which studies objectives at the aggregate level, emphasizing the interactions and synergetic/antagonistic effects of a group of composed single entities in determining the characteristics of a whole. As a representative of holism, aggregation-induced emission (AIE) materials have made great achievements in the past two decades in both physical and life science. In particular, the unique properties of AIE materials endow them with in situ and real-time visual methods to investigate the inconsistency between microscopic molecules and macroscopic substances, offering researchers excellent toolkits to study living aggregates. The applications of AIE materials in life science are still in their infancy and worth expanding. In this Perspective, we summarize the research progress of AIE materials in unveiling some phenomena and processes of living systems, aiming to provide a general research approach from the viewpoint of holism. At last, insights into what we can do in the near future are also raised and discussed.
Topics: Philosophy; Molecular Biology
PubMed: 38359354
DOI: 10.1021/jacs.3c09892