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Epigenomes Aug 2022Every cell of an organism shares the same genome; even so, each cellular lineage owns a different transcriptome and proteome. The Polycomb group proteins (PcG) are... (Review)
Review
Every cell of an organism shares the same genome; even so, each cellular lineage owns a different transcriptome and proteome. The Polycomb group proteins (PcG) are essential regulators of gene repression patterning during development and homeostasis. However, it is unknown how the repressive complexes, PRC1 and PRC2, identify their targets and elicit new Polycomb domains during cell differentiation. Classical recruitment models consider the pre-existence of repressive histone marks; still, target binding overcomes the absence of both H3K27me3 and H2AK119ub. The CpG islands (CGIs), non-core proteins, and RNA molecules are involved in Polycomb recruitment. Nonetheless, it is unclear how targets are identified depending on the physiological context and developmental stage and which are the leading players stabilizing Polycomb complexes at domain nucleation sites. Here, we examine the features of sites and the accessory elements bridging its recruitment and discuss the first steps of Polycomb domain formation and transcriptional regulation, comprehended by the experimental reconstruction of the repressive domains through time-resolved genomic analyses in mammals.
PubMed: 35997371
DOI: 10.3390/epigenomes6030025 -
Frontiers in Genetics 2022Mosaicism-the existence of genetically distinct populations of cells in a particular organism-is an important cause of genetic disease. Mosaicism can appear as DNA... (Review)
Review
Mosaicism-the existence of genetically distinct populations of cells in a particular organism-is an important cause of genetic disease. Mosaicism can appear as DNA mutations, epigenetic alterations of DNA, and chromosomal abnormalities. Neurodevelopmental or neuropsychiatric diseases, including autism-often arise by mutations that usually not present in either of the parents. mutations might occur as early as in the parental germline, during embryonic, fetal development, and/or post-natally, through ageing and life. Mutation timing could lead to mutation burden of less than heterozygosity to approaching homozygosity. Developmental timing of somatic mutation attainment will affect the mutation load and distribution throughout the body. In this review, we discuss the timing of mutations, spanning from mutations in the germ lineage (all ages), to post-zygotic, embryonic, fetal, and post-natal events, through aging to death. These factors can determine the tissue specific distribution and load of mutations, which can affect disease. The disease threshold burden of somatic mutations of a particular gene in any tissue will be important to define.
PubMed: 36226191
DOI: 10.3389/fgene.2022.983668 -
Frontiers in Molecular Biosciences 2021Nicotinamide adenine dinucleotide (NAD) is an essential metabolite with wide-ranging and significant roles in the cell. Defects in NAD metabolism have been associated... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is an essential metabolite with wide-ranging and significant roles in the cell. Defects in NAD metabolism have been associated with many human disorders; it is therefore an emerging therapeutic target. Moreover, NAD metabolism is perturbed during colonization by a variety of pathogens, either due to the molecular mechanisms employed by these infectious agents or by the host immune response they trigger. Three main biosynthetic pathways, including the and salvage pathways, contribute to the production of NAD with a high degree of conservation from bacteria to humans. biosynthesis, which begins with l-tryptophan in eukaryotes, is also known as the kynurenine pathway. Intermediates of this pathway have various beneficial and deleterious effects on cellular health in different contexts. For example, dysregulation of this pathway is linked to neurotoxicity and oxidative stress. Activation of the pathway is also implicated in various infections and inflammatory signaling. Given the dynamic flexibility and multiple roles of NAD intermediates, it is important to understand the interconnections and cross-regulations of NAD precursors and associated signaling pathways to understand how cells regulate NAD homeostasis in response to various growth conditions. Although regulation of NAD homeostasis remains incompletely understood, studies in the genetically tractable budding yeast may help provide some molecular basis for how NAD homeostasis factors contribute to the maintenance and regulation of cellular function and how they are regulated by various nutritional and stress signals. Here we present a brief overview of recent insights and discoveries made with respect to the relationship between NAD metabolism and selected human disorders and infections, with a particular focus on the pathway. We also discuss how studies in budding yeast may help elucidate the regulation of NAD homeostasis.
PubMed: 34095234
DOI: 10.3389/fmolb.2021.686412 -
World Journal of Gastroenterology May 2023Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors. The small size and concealed...
BACKGROUND
Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors. The small size and concealed position of these tumors make it difficult to distinguish them from nonneoplastic polyps and carcinoma in adenoma (CIA). The invasive depth and metastatic potential determine the operation regimen, which in turn affects the overall survival and distant prognosis. The previous studies have confirmed the malignant features and clinicopathological features of colorectal cancer (CRC).
AIM
To provide assistance for diagnosis and treatment, but the lack of a summary of endoscopic features and assessment of risk factors that differ from the CIA prompted us to conduct this retrospective study.
METHODS
In total, 167 patients with small-sized CRCs diagnosed by endoscopy were reviewed. The patients diagnosed as advanced CRCs and other malignant cancers or chronic diseases that could affect distant outcomes were excluded. After screening, 63 cases were excluded, including 33 and 30 CIA cases. Patient information, including their follow-up information, was obtained from an electronic His-system. The characteristics between two group and risk factors for invasion depth were analyzed with SPSS 25.0 software.
RESULTS
Nearly half of the CRCs were smaller than 1 cm ( = 16, 48.5%) and the majority were located in the distal colon ( = 26, 78.8%). The IIc type was the most common macroscopic type of CRC. In a Pearson analysis, the differential degree, Sano, JNET, and Kudo types, surrounding mucosa, and chicken skin mucosa (CSM) were correlated with the invasion depth ( < 0.001). CSM was a significant risk factor for deep invasion and disturbed judgment of endoscopic ultrasound. A high degree of tumor budding and tumor-infiltrating lymphocytes are accompanied by malignancy. Finally, CRCs have worse outcomes than CIA CRCs.
CONCLUSION
This is the first comprehensive study to analyze the features of CRCs to distinguish them from nonneoplastic polyps. It is also the first study paying attention to CSM invasive depth measurement. This study emphasizes the high metastatic potential of CRCs and highlights the need for more research on this tumor type.
Topics: Humans; Retrospective Studies; Colorectal Neoplasms; Endoscopy; Risk Factors; Adenoma
PubMed: 37274065
DOI: 10.3748/wjg.v29.i18.2836 -
Journal of Neurophysiology Apr 2023De novo motor learning is a form of motor learning characterized by the development of an entirely new and distinct motor controller to accommodate a novel motor demand.... (Review)
Review
De novo motor learning is a form of motor learning characterized by the development of an entirely new and distinct motor controller to accommodate a novel motor demand. Inversely, adaptation is a form of motor learning characterized by rapid, unconscious modifications in a previously established motor controller to accommodate small deviations in task demands. As most of the motor learning involves the adaptation of previously established motor controllers, de novo learning can be challenging to isolate and observe. The recent publication from Haith et al. (Haith AM, Yang CS, Pakpoor J, Kita K. J 128: 982-993, 2022.) details a novel method to investigate de novo learning using a complex bimanual cursor control task. This research is especially important in the context of future brain-machine interface devices that will present users with an entirely novel motor learning demand, requiring de novo learning.
Topics: Brain-Computer Interfaces; Learning; Adaptation, Physiological
PubMed: 36883755
DOI: 10.1152/jn.00496.2022 -
Frontiers in Immunology 2019The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains... (Review)
Review
The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or GN after kidney transplantation, ascertaining potential disparities between "high risk" disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease.
Topics: Glomerulonephritis; Glomerulonephritis, IGA; Glomerulosclerosis, Focal Segmental; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Recurrence; Risk Factors; Transplantation, Homologous
PubMed: 31475005
DOI: 10.3389/fimmu.2019.01944 -
Cell Regeneration (London, England) Jan 2023De novo organ regeneration is the process in which adventitious roots or shoots regenerate from detached or wounded organs. De novo organ regeneration can occur either... (Review)
Review
De novo organ regeneration is the process in which adventitious roots or shoots regenerate from detached or wounded organs. De novo organ regeneration can occur either in natural conditions, e.g. adventitious root regeneration from the wounded sites of detached leaves or stems, or in in-vitro tissue culture, e.g. organ regeneration from callus. In this review, we summarize recent advances in research on the molecular mechanism of de novo organ regeneration, focusing on the role of the WUSCHEL-RELATED HOMEOBOX11 (WOX11) gene in the model plant Arabidopsis thaliana. WOX11 is a direct target of the auxin signaling pathway, and it is expressed in, and regulates the establishment of, the founder cell during de novo root regeneration and callus formation. WOX11 activates the expression of its target genes to initiate root and callus primordia. Therefore, WOX11 links upstream auxin signaling to downstream cell fate transition during regeneration. We also discuss the role of WOX11 in diverse species and its evolution in plants.
PubMed: 36596978
DOI: 10.1186/s13619-022-00140-9 -
Annual Review of Biochemistry Jun 2022Over the past fifteen years, we have unveiled a new mechanism by which cells achieve greater efficiency in de novo purine biosynthesis. This mechanism relies on the... (Review)
Review
Over the past fifteen years, we have unveiled a new mechanism by which cells achieve greater efficiency in de novo purine biosynthesis. This mechanism relies on the compartmentalization of de novo purine biosynthetic enzymes into a dynamic complex called the purinosome. In this review, we highlight our current understanding of the purinosome with emphasis on its biophysical properties and function and on the cellular mechanisms that regulate its assembly. We propose a model for functional purinosomes in which they consist of at least ten enzymes that localize near mitochondria and carry out de novo purine biosynthesis by metabolic channeling. We conclude by discussing challenges and opportunities associated with studying the purinosome and analogous metabolons.
Topics: Animals; Mammals; Mitochondria; Purines
PubMed: 35320684
DOI: 10.1146/annurev-biochem-032620-105728 -
Frontiers in Cell and Developmental... 2022In cycling cells, new centrioles are assembled in the vicinity of pre-existing centrioles. Although this canonical centriole duplication is a tightly regulated process... (Review)
Review
In cycling cells, new centrioles are assembled in the vicinity of pre-existing centrioles. Although this canonical centriole duplication is a tightly regulated process in animal cells, centrioles can also form in the absence of pre-existing centrioles; this process is termed centriole formation. centriole formation is triggered by the removal of all pre-existing centrioles in the cell in various manners. Moreover, overexpression of polo-like kinase 4 (Plk4), a master regulatory kinase for centriole biogenesis, can induce centriole formation in some cell types. Under these conditions, structurally and functionally normal centrioles can be formed . While centriole formation is normally suppressed in cells with intact centrioles, depletion of certain suppressor proteins leads to the ectopic formation of centriole-related protein aggregates in the cytoplasm. It has been shown that centriole formation also occurs naturally in some species. For instance, during the multiciliogenesis of vertebrate epithelial cells, massive centriole amplification occurs to form numerous motile cilia. In this review, we summarize the previous findings on centriole formation, particularly under experimental conditions, and discuss its regulatory mechanisms.
PubMed: 35445021
DOI: 10.3389/fcell.2022.861864 -
Chemical Reviews Jul 2022One of the hallmark advances in our understanding of metalloprotein function is showcased in our ability to design new, non-native, catalytically active protein... (Review)
Review
One of the hallmark advances in our understanding of metalloprotein function is showcased in our ability to design new, non-native, catalytically active protein scaffolds. This review highlights progress and milestone achievements in the field of metalloprotein design focused on reports from the past decade with special emphasis on designs couched within common subfields of bioinorganic study: heme binding proteins, monometal- and dimetal-containing catalytic sites, and metal-containing electron transfer sites. Within each subfield, we highlight several of what we have identified as significant and important contributions to either our understanding of that subfield or metalloprotein design as a discipline. These reports are placed in context both historically and scientifically. General suggestions for future directions that we feel will be important to advance our understanding or accelerate discovery are discussed.
Topics: Binding Sites; Catalysis; Catalytic Domain; Electrons; Metalloproteins; Models, Molecular
PubMed: 35763791
DOI: 10.1021/acs.chemrev.1c01025