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Neuron Sep 2018The impact of molecular dynamics (MD) simulations in molecular biology and drug discovery has expanded dramatically in recent years. These simulations capture the... (Review)
Review
The impact of molecular dynamics (MD) simulations in molecular biology and drug discovery has expanded dramatically in recent years. These simulations capture the behavior of proteins and other biomolecules in full atomic detail and at very fine temporal resolution. Major improvements in simulation speed, accuracy, and accessibility, together with the proliferation of experimental structural data, have increased the appeal of biomolecular simulation to experimentalists-a trend particularly noticeable in, although certainly not limited to, neuroscience. Simulations have proven valuable in deciphering functional mechanisms of proteins and other biomolecules, in uncovering the structural basis for disease, and in the design and optimization of small molecules, peptides, and proteins. Here we describe, in practical terms, the types of information MD simulations can provide and the ways in which they typically motivate further experimental work.
Topics: Computational Biology; Humans; Molecular Biology; Molecular Dynamics Simulation; Peptides; Protein Conformation; Proteins
PubMed: 30236283
DOI: 10.1016/j.neuron.2018.08.011 -
Journal of B.U.ON. : Official Journal... 2021Molecular biology of cancer cell is a domain of medical science that is rapidly growing in our days. Knowing the ways and paths that cancer cells follow is crucial to... (Review)
Review
Molecular biology of cancer cell is a domain of medical science that is rapidly growing in our days. Knowing the ways and paths that cancer cells follow is crucial to the prevention of cancer itself. Central role to these paths, concerning the cell cycle and the process of apoptosis, has the protein p53. The whole mechanism of the cell cycle is activated by the action of various mitogens, such as growth factors, hormones and cytokines. Carcinogenesis involves alterations of genes (proto-oncogenes and tumor suppressor genes), which encode proteins of the signal transduction. Many of the damages that lead to carcinogenesis may be due to the lack of repressive signals for cell division, but also to the absence of the sensitivity of cells to repressive signals. The cell has mechanisms of receiving apoptotic-antitumor signals and mechanisms of execution of these instructions. A percentage of cancers (4-8%) are etiologically linked to germ (stem) cells mutations and occur at an increased frequency in families (hereditary cancers). Substantial progress in understanding the mechanisms of carcinogenesis, filtration and metastasis of cancer has highlighted the key role of specific genes, primarily oncogenes and tumor suppressor genes.
Topics: Humans; Molecular Biology; Neoplasms
PubMed: 34761575
DOI: No ID Found -
Comptes Rendus Biologies 2016The origins of genetics are to be found in Gregor Mendel's memoir on plant hybridization (1865). However, the word 'genetics' was only coined in 1906, to designate the... (Review)
Review
The origins of genetics are to be found in Gregor Mendel's memoir on plant hybridization (1865). However, the word 'genetics' was only coined in 1906, to designate the new science of heredity. Founded upon the Mendelian method for analyzing the products of crosses, this science is distinguished by its explicit purpose of being a general 'science of heredity', and by the introduction of totally new biological concepts (in particular those of gene, genotype, and phenotype). In the 1910s, Mendelian genetics fused with the chromosomal theory of inheritance, giving rise to what is still called 'classical genetics'. Within this framework, the gene is simultaneously a unit of function and transmission, a unit of recombination, and of mutation. Until the early 1950s, these concepts of the gene coincided. But when DNA was found to be the material basis of inheritance, this congruence dissolved. Then began the venture of molecular biology, which has never stopped revealing the complexity of the way in which hereditary material functions.
Topics: Animals; Epigenomics; Genes; Genetics; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Molecular Biology; Plants
PubMed: 27263362
DOI: 10.1016/j.crvi.2016.05.009 -
Biomolecules May 2021Homocysteine is a non-proteinogenic sulfhydryl-containing amino acid derived from methionine and is a homologue of cysteine [...].
Homocysteine is a non-proteinogenic sulfhydryl-containing amino acid derived from methionine and is a homologue of cysteine [...].
Topics: Animals; Biochemistry; Disease; Homocysteine; Humans; Molecular Biology
PubMed: 34063494
DOI: 10.3390/biom11050737 -
Journal For Immunotherapy of Cancer Mar 2020Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient... (Review)
Review
Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
Topics: Consensus; Guidelines as Topic; Humans; Immunogenic Cell Death; Molecular Biology
PubMed: 32209603
DOI: 10.1136/jitc-2019-000337 -
Microbiology Spectrum Feb 2015The use of Cre recombinase to carry out conditional mutagenesis of transgenes and insert DNA cassettes into eukaryotic chromosomes is widespread. In addition to the... (Review)
Review
The use of Cre recombinase to carry out conditional mutagenesis of transgenes and insert DNA cassettes into eukaryotic chromosomes is widespread. In addition to the numerous in vivo and in vitro applications that have been reported since Cre was first shown to function in yeast and mammalian cells nearly 30 years ago, the Cre-loxP system has also played an important role in understanding the mechanism of recombination by the tyrosine recombinase family of site-specific recombinases. The simplicity of this system, requiring only a single recombinase enzyme and short recombination sequences for robust activity in a variety of contexts, has been an important factor in both cases. This review discusses advances in the Cre recombinase field that have occurred over the past 12 years since the publication of Mobile DNA II. The focus is on those recent contributions that have provided new mechanistic insights into the reaction. Also discussed are modifications of Cre and/or the loxP sequence that have led to improvements in genome engineering applications.
Topics: Integrases; Models, Biological; Molecular Biology; Mutagenesis, Insertional; Recombination, Genetic
PubMed: 26104563
DOI: 10.1128/microbiolspec.MDNA3-0014-2014 -
Journal of Hepatology Oct 2021Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify...
BACKGROUND AND AIMS
Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies.
METHODS
We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays.
RESULTS
Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p <0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs. 2% in viral/alcohol-HCC, p = 0.03). Tumour mutational burden was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 vs. 0.94 mutations/megabase; p <0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/TGF-β proliferation subclass tumours (42% vs. 26%, p = 0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of an immunosuppressive cancer field. In 3 murine models of NASH-HCC, key features of human NASH-HCC were preserved.
CONCLUSIONS
NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature.
LAY SUMMARY
The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH) is increasing globally, but its molecular traits are not well characterised. In this study, we uncovered higher rates of ACVR2A mutations (10%) - a potential tumour suppressor - and the presence of a novel mutational signature that characterises NASH-related HCC.
Topics: Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Molecular Biology; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 33992698
DOI: 10.1016/j.jhep.2021.04.049 -
Mathematical Biosciences and... Mar 2020
Topics: Computational Biology; Machine Learning; Molecular Biology
PubMed: 32987499
DOI: 10.3934/mbe.2020156 -
The FEBS Journal Jul 2022In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future...
In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Rudi Beyaert is Full Professor in Molecular Biology at the Department of Biomedical Molecular Biology, Faculty of Sciences, of the University of Ghent (Belgium). He also serves as Vice-Science Director of the Center for Inflammation Research of the VIB in Ghent, where he is heading the Unit of Molecular Signal Transduction in Inflammation. He has served as an Editorial Board Member of The FEBS Journal since 2016.
Topics: Faculty; Humans; Inflammation; Male; Molecular Biology; Signal Transduction
PubMed: 35852037
DOI: 10.1111/febs.16570 -
The Journal of Neuroscience : the... Jan 2020Without question, molecular biology drives modern neuroscience. The past 50 years has been nothing short of revolutionary as key findings have moved the field from... (Review)
Review
Without question, molecular biology drives modern neuroscience. The past 50 years has been nothing short of revolutionary as key findings have moved the field from correlation toward causation. Most obvious are the discoveries and strategies that have been used to build tools for visualizing circuits, measuring activity, and regulating behavior. Less flashy, but arguably as important are the myriad investigations uncovering the actions of single molecules, macromolecular structures, and integrated machines that serve as the basis for constructing cellular and signaling pathways identified in wide-scale gene or RNA studies and for feeding data into informational networks used in systems biology. This review follows the pathways that were opened in neuroscience by major discoveries and set the stage for the next 50 years.
Topics: Animals; CRISPR-Cas Systems; Exocytosis; Gene Expression Regulation; Gene Transfer Techniques; Genes, Reporter; History, 20th Century; History, 21st Century; Humans; In Situ Hybridization; Microscopy; Molecular Biology; Nerve Tissue Proteins; Neurosciences; PDZ Domains; Polymerase Chain Reaction; Protein Engineering; RNA; Recombinant Proteins; Sequence Analysis, DNA
PubMed: 31630114
DOI: 10.1523/JNEUROSCI.0743-19.2019