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Experimental & Molecular Medicine Apr 2017Histone modifications are key epigenetic regulatory features that have important roles in many cellular events. Lysine methylations mark various sites on the tail and... (Review)
Review
Histone modifications are key epigenetic regulatory features that have important roles in many cellular events. Lysine methylations mark various sites on the tail and globular domains of histones and their levels are precisely balanced by the action of methyltransferases ('writers') and demethylases ('erasers'). In addition, distinct effector proteins ('readers') recognize specific methyl-lysines in a manner that depends on the neighboring amino-acid sequence and methylation state. Misregulation of histone lysine methylation has been implicated in several cancers and developmental defects. Therefore, histone lysine methylation has been considered a potential therapeutic target, and clinical trials of several inhibitors of this process have shown promising results. A more detailed understanding of histone lysine methylation is necessary for elucidating complex biological processes and, ultimately, for developing and improving disease treatments. This review summarizes enzymes responsible for histone lysine methylation and demethylation and how histone lysine methylation contributes to various biological processes.
Topics: Animals; Histone Code; Histone Demethylases; Histone-Lysine N-Methyltransferase; Histones; Humans; Methylation; Protein Processing, Post-Translational
PubMed: 28450737
DOI: 10.1038/emm.2017.11 -
Reproduction (Cambridge, England) Feb 2021Idiopathic or 'unexplained' infertility represents as many as 30% of infertility cases worldwide. Conception, implantation, and term delivery of developmentally healthy... (Review)
Review
Idiopathic or 'unexplained' infertility represents as many as 30% of infertility cases worldwide. Conception, implantation, and term delivery of developmentally healthy infants require chromosomally normal (euploid) eggs and sperm. The crux of euploid egg production is error-free meiosis. Pathologic genetic variants dysregulate meiotic processes that occur during prophase I, meiotic resumption, chromosome segregation, and in cell cycle regulation. This dysregulation can result in chromosomally abnormal (aneuploid) eggs. In turn, egg aneuploidy leads to a broad range of clinical infertility phenotypes, including primary ovarian insufficiency and early menopause, egg fertilization failure and embryonic developmental arrest, or recurrent pregnancy loss. Therefore, maternal genetic variants are emerging as infertility biomarkers, which could allow informed reproductive decision-making. Here, we select and deeply examine human genetic variants that likely cause dysregulation of critical meiotic processes in 14 female infertility-associated genes: SYCP3, SYCE1, TRIP13, PSMC3IP, DMC1, MCM8, MCM9, STAG3, PATL2, TUBB8, CEP120, AURKB, AURKC, andWEE2. We discuss the function of each gene in meiosis, explore genotype-phenotype relationships, and delineate the frequencies of infertility-associated variants.
Topics: ATPases Associated with Diverse Cellular Activities; Aneuploidy; Aurora Kinase C; Cell Cycle Proteins; Chromosome Segregation; Female; Humans; Infertility, Female; Male; Meiosis; Nuclear Proteins; Pregnancy; Spermatozoa; Trans-Activators; Tubulin
PubMed: 33170803
DOI: 10.1530/REP-20-0422 -
Progress in Neurobiology 2013Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using... (Review)
Review
Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7-10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxic-ischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development.
Topics: Animals; Brain; Brain Injuries; Humans; Hypoxia-Ischemia, Brain; Neurogenesis; Oligodendroglia; Rodentia
PubMed: 23583307
DOI: 10.1016/j.pneurobio.2013.04.001 -
Cold Spring Harbor Perspectives in... Sep 2012Wnt proteins comprise a major family of signaling molecules that orchestrate and influence a myriad of cell biological and developmental processes. Although our... (Review)
Review
Wnt proteins comprise a major family of signaling molecules that orchestrate and influence a myriad of cell biological and developmental processes. Although our understanding of the role of Wnt signaling in regulating development and affecting disease, such as cancer, has been ever increasing, the study of the Wnt proteins themselves has been painstaking and slow moving. Despite advances in the biochemical characterization of Wnt proteins, many mysteries remain unsolved. In contrast to other developmental signaling molecules, such as fibroblast growth factors (FGF), transforming growth factors (TGFβ), and Sonic hedgehog (Shh), Wnt proteins have not conformed to many standard methods of protein production, such as bacterial overexpression, and analysis, such as ligand-receptor binding assays. The reasons for their recalcitrant nature are likely a consequence of the complex set of posttranslational modifications involving several highly specialized and poorly characterized processing enzymes. With the recent description of the first Wnt protein structure, the time is ripe to uncover and possibly resolve many of the remaining issues surrounding Wnt proteins and their interactions. Here we describe the process of maturation of Wnt from its initial translation to its eventual release from a cell and interactions in the extracellular environment.
Topics: Alternative Splicing; Animals; Gene Expression Regulation, Developmental; Humans; Protein Processing, Post-Translational; Protein Sorting Signals; Protein Structure, Tertiary; Protein Transport; Signal Transduction; Wnt Proteins
PubMed: 22952392
DOI: 10.1101/cshperspect.a007864 -
Journal of Cell Science Jul 2020Mitochondrial fusion and fission (mitochondrial dynamics) are homeostatic processes that safeguard normal cellular function. This relationship is especially strong in... (Review)
Review
Mitochondrial fusion and fission (mitochondrial dynamics) are homeostatic processes that safeguard normal cellular function. This relationship is especially strong in tissues with constitutively high energy demands, such as brain, heart and skeletal muscle. Less is known about the role of mitochondrial dynamics in developmental systems that involve changes in metabolic function. One such system is spermatogenesis. The first mitochondrial dynamics gene, (), was discovered in 1997 to mediate mitochondrial fusion during spermatogenesis. In mammals, however, the role of mitochondrial fusion during spermatogenesis remained unknown for nearly two decades after discovery of Mammalian spermatogenesis is one of the most complex and lengthy differentiation processes in biology, transforming spermatogonial stem cells into highly specialized sperm cells over a 5-week period. This elaborate differentiation process requires several developmentally regulated mitochondrial and metabolic transitions, making it an attractive model system for studying mitochondrial dynamics We review the emerging role of mitochondrial biology, and especially its dynamics, during the development of the male germ line.
Topics: Animals; Drosophila; Drosophila Proteins; Male; Mitochondria; Mitochondrial Dynamics; Spermatogenesis
PubMed: 32675215
DOI: 10.1242/jcs.235937 -
Journal of Speech, Language, and... Aug 2019Purpose Current approaches to speech production aim to explain adult behavior and so make assumptions that, when taken to their logical conclusion, fail to adequately... (Review)
Review
Purpose Current approaches to speech production aim to explain adult behavior and so make assumptions that, when taken to their logical conclusion, fail to adequately account for development. This failure is problematic if adult behavior can be understood to emerge from the developmental process. This problem motivates the proposal of a developmentally sensitive theory of speech production. The working hypothesis, which structures the theory, is that feedforward representations and processes mature earlier than central feedback control processes in speech production. Method Theoretical assumptions that underpin the 2 major approaches to adult speech production are reviewed. Strengths and weaknesses are evaluated with respect to developmental patterns. A developmental approach is then pursued. The strengths of existing theories are borrowed, and the ideas are resynthesized under the working hypothesis. The speech production process is then reimagined in developmental stages, with each stage building on the previous one. Conclusion The resulting theory proposes that speech production relies on conceptually linked representations that are information-reduced holistic perceptual and motoric forms, constituting the phonological aspect of a system that is acquired with the lexicon. These forms are referred to as exemplars and schemas, respectively. When a particular exemplar and schema are activated with the selection of a particular lexical concept, their forms are used to define unique trajectories through an endogenous perceptual-motor space that guides implementation. This space is not linguistic, reflecting its origin in the prespeech period. Central feedback control over production emerges with failures in communication and the development of a self-concept.
Topics: Adult; Child; Child Language; Human Development; Humans; Models, Theoretical; Phonetics; Speech
PubMed: 31465709
DOI: 10.1044/2019_JSLHR-S-CSMC7-18-0130 -
Frontiers in Nutrition 2019Recently, processed foods received negative images among consumers and experts regarding food-health imbalance. This stresses the importance of the food... (Review)
Review
Recently, processed foods received negative images among consumers and experts regarding food-health imbalance. This stresses the importance of the food processing-nutrition interface and its relevance within the diet-health debates. In this review, we approach the related questions in a 3-fold way. Pointing out the distinguished role food processing has played in the development of the human condition and during its 1.7 million year old history, we show the function of food processing for the general design principles of food products. Secondly, a detailed analysis of consumer related design principles and processing reveals questions remaining from the historical transformation from basic cooking into advanced food technology. As a consequence, we analyze new and emerging technologies in relation to their contributions to food-health impacts. During the last 35 years, new and emerging food technologies have initiated a paradigm shift away from conventional process methodologies to gentler, non-thermal processing. Reducing the existing uncertainties in the assessment of impact of technology like "minimal processing," we propose the use of the newly established ISO standard for natural food ingredients as a "reference point." Finally, we assess the usefulness of recently proposed classification systems, e.g., NOVA classification, based on comprehensive insights of recently published nutritional analysis of those classifications. This paper calls for a radical change and worldwide adaptation of the key research and developmental areas tackling the grand challenges in our food systems.
PubMed: 31294027
DOI: 10.3389/fnut.2019.00085 -
Current Biology : CB Jul 2016Cell death is an inherent process that is required for the proper wiring of the nervous system. Studies over the last four decades have shown that, in a parallel... (Review)
Review
Cell death is an inherent process that is required for the proper wiring of the nervous system. Studies over the last four decades have shown that, in a parallel developmental pathway, axons and dendrites are eliminated without the death of the neuron. This developmentally regulated 'axonal death' results in neuronal remodeling, which is an essential mechanism to sculpt neuronal networks in both vertebrates and invertebrates. Studies across various organisms have demonstrated that a conserved strategy in the formation of adult neuronal circuitry often involves generating too many connections, most of which are later eliminated with high temporal and spatial resolution. Can neuronal remodeling be regarded as developmentally and spatially regulated neurodegeneration? It has been previously speculated that injury-induced degeneration (Wallerian degeneration) shares some molecular features with 'dying back' neurodegenerative diseases. In this opinion piece, we examine the similarities and differences between the mechanisms regulating neuronal remodeling and those being perturbed in dying back neurodegenerative diseases. We focus primarily on amyotrophic lateral sclerosis and peripheral neuropathies and highlight possible shared pathways and mechanisms. While mechanistic data are only just beginning to emerge, and despite the inherent differences between disease-oriented and developmental processes, we believe that some of the similarities between these developmental and disease-initiated degeneration processes warrant closer collaborations and crosstalk between these different fields.
Topics: Amyotrophic Lateral Sclerosis; Animals; Apoptosis; Humans; Invertebrates; Neurodegenerative Diseases; Neurogenesis; Neuronal Plasticity; Peripheral Nervous System Diseases; Vertebrates
PubMed: 27404258
DOI: 10.1016/j.cub.2016.05.025 -
Frontiers in Physiology 2022Cullins (CULs) are a core component of cullin-RING E3 ubiquitin ligases (CRLs), which regulate the degradation, function, and subcellular trafficking of proteins. CULs... (Review)
Review
Cullins (CULs) are a core component of cullin-RING E3 ubiquitin ligases (CRLs), which regulate the degradation, function, and subcellular trafficking of proteins. CULs are post-translationally regulated through neddylation, a process that conjugates the ubiquitin-like modifier protein neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) to target cullins, as well as non-cullin proteins. Counteracting neddylation is the deneddylase, COP9 signalosome (CSN), which removes NEDD8 from target proteins. Recent comparative genomics studies revealed that CRLs and the CSN are highly conserved in Amoebozoa. A well-studied representative of Amoebozoa, the social amoeba , has been used for close to 100 years as a model organism for studying conserved cellular and developmental processes owing to its unique life cycle comprised of unicellular and multicellular phases. The organism is also recognized as an exceptional model system for studying cellular processes impacted by human diseases, including but not limited to, cancer and neurodegeneration. Recent work shows that the neddylation inhibitor, MLN4924 (Pevonedistat), inhibits growth and multicellular development in , which supports previous work that revealed the cullin interactome in and the roles of cullins and the CSN in regulating cellular and developmental processes during the life cycle. Here, we review the roles of cullins, neddylation, and the CSN in to guide future work on using this biomedical model system to further explore the evolutionarily conserved functions of cullins and neddylation.
PubMed: 35586714
DOI: 10.3389/fphys.2022.827435