scholarly journals Methylation of Histone 4's Lysine 20: A critical analysis of the state of the field

2020 ◽  
Author(s):  
Adriana Z. Corvalan ◽  
Hilary A. Coller
Keyword(s):  
Posttranslational Modification ◽  
Current Knowledge ◽  
Dynamic Structure ◽  
Future Research ◽  
Biological Processes ◽  
Histone H4 ◽  
Histone Tails ◽  
Nonhistone Proteins ◽  
Multiple Processes ◽  
Cycle Regulation

Chromatin is a highly dynamic structure whose plasticity is achieved through multiple processes including the posttranslational modification of histone tails. Histone modifications function through the recruitment of nonhistone proteins to chromatin and thus have the potential to influence many fundamental biological processes. Here, we focus on the function and regulation of lysine 20 of histone H4 (H4K20) methylation in multiple biological processes including DNA repair, cell cycle regulation and DNA replication. The purpose of this review is to highlight recent studies that elucidate the functions associated with each of the methylation states of H4K20, their modifying enzymes, and their protein readers. Based on our current knowledge of H4K20 methylation, we critically analyze the data supporting these functions and outline questions for future research.

scholarly journals Posttranslational modification and beyond: interplay between histone deacetylase 6 and heat-shock protein 90

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Ping Liu ◽  
Ji Xiao ◽  
Yiliang Wang ◽  
Xiaowei Song ◽  
Lianzhou Huang ◽  
...  
Keyword(s):  
Protein Stability ◽  
Histone Deacetylase ◽  
Gene Transcription ◽  
Posttranslational Modification ◽  
Current Knowledge ◽  
Heat Shock Protein 90 ◽  
Biological Processes ◽  
Histone Deacetylase 6 ◽  
Post Translational Modification ◽  
Nonhistone Proteins

AbstractPosttranslational modification (PTM) and regulation of protein stability are crucial to various biological processes. Histone deacetylase 6 (HDAC6), a unique histone deacetylase with two functional catalytic domains (DD1 and DD2) and a ZnF-UBP domain (ubiquitin binding domain, BUZ), regulates a number of biological processes, including gene expression, cell motility, immune response, and the degradation of misfolded proteins. In addition to the deacetylation of histones, other nonhistone proteins have been identified as substrates for HDAC6. Hsp90, a molecular chaperone that is a critical modulator of cell signaling, is one of the lysine deacetylase substrates of HDAC6. Intriguingly, as one of the best-characterized regulators of Hsp90 acetylation, HDAC6 is the client protein of Hsp90. In addition to regulating Hsp90 at the post-translational modification level, HDAC6 also regulates Hsp90 at the gene transcription level. HDAC6 mainly regulates the Hsp90-HSF1 complex through the ZnF-UBP domain, thereby promoting the HSF1 entry into the nucleus and activating gene transcription. The mutual interaction between HDAC6 and Hsp90 plays an important role in the regulation of protein stability, cell migration, apoptosis and other functions. Plenty of of studies have indicated that blocking HDAC6/Hsp90 has a vital regulatory role in multifarious diseases, mainly in cancers. Therefore, developing inhibitors or drugs against HDAC6/Hsp90 becomes a promising development direction. Herein, we review the current knowledge on molecular regulatory mechanisms based on the interaction of HDAC6 and Hsp90 and inhibition of HDAC6 and/or Hsp90 in oncogenesis and progression, antiviral and immune-related diseases and other vital biological processes.

scholarly journals Evolution, structure and emerging roles of C1ORF112 in DNA replication, DNA damage responses, and cancer

2021 ◽  
Author(s):  
Jacob Edogbanya ◽  
Daniela Tejada‐Martinez ◽  
Nigel J. Jones ◽  
Amit Jaiswal ◽  
Sarah Bell ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Current Knowledge ◽  
Future Research ◽  
Fanconi Anaemia ◽  
Mammalian Development ◽  
Damage Repair ◽  
Disease Relevance ◽  
Helical Protein ◽  
Cycle Regulation

AbstractThe C1ORF112 gene initially drew attention when it was found to be strongly co‐expressed with several genes previously associated with cancer and implicated in DNA repair and cell cycle regulation, such as RAD51 and the BRCA genes. The molecular functions of C1ORF112 remain poorly understood, yet several studies have uncovered clues as to its potential functions. Here, we review the current knowledge on C1ORF112 biology, its evolutionary history, possible functions, and its potential relevance to cancer. C1ORF112 is conserved throughout eukaryotes, from plants to humans, and is very highly conserved in primates. Protein models suggest that C1ORF112 is an alpha-helical protein. Interestingly, homozygous knockout mice are not viable, suggesting an essential role for C1ORF112 in mammalian development. Gene expression data show that, among human tissues, C1ORF112 is highly expressed in the testes and overexpressed in various cancers when compared to healthy tissues. C1ORF112 has also been shown to have altered levels of expression in some tumours with mutant TP53. Recent screens associate C1ORF112 with DNA replication and reveal possible links to DNA damage repair pathways, including the Fanconi anaemia pathway and homologous recombination. These insights provide important avenues for future research in our efforts to understand the functions and potential disease relevance of C1ORF112.

scholarly journals Biological Characteristics and Roles of Noncoding RNAs in Milk-Derived Extracellular Vesicles

2020 ◽  
Author(s):  
Bin Zeng ◽  
Ting Chen ◽  
Jun-Yi Luo ◽  
Lin Zhang ◽  
Qian-Yun Xi ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Current Data ◽  
Biological Characteristics ◽  
Future Research ◽  
Circular Rnas ◽  
Physiological Effects ◽  
Biological Processes

ABSTRACT Extracellular vesicles (EVs) have diverse roles in the transport of proteins, lipids, and nucleic acids between cells, and they serve as mediators of intercellular communication. Noncoding RNAs (ncRNAs) that are present in EVs, including microRNAs, long noncoding RNAs, and circular RNAs, have been found to participate in complex networks of interactions and regulate a wide variety of genes in animals. Milk is an important source of nutrition for humans and other mammals. Evidence suggests that milk-derived EVs contain abundant ncRNAs, which are stable and can be transported to the offspring and other consumers. Current data suggest a strong link between milk EV ncRNAs and many biological processes, and these ncRNAs have been drawing increasing attention and might play an epigenetic regulatory role in recipients, though further research is still necessary to understand their precise roles. The present review introduces basic information about milk EV ncRNAs, summarizes their expression profiles, biological characteristics, and functions based on current knowledge, and discusses their biological roles, indeterminate issues, and perspectives. Our goal is to provide a deeper understanding of the physiological effects of milk EV ncRNAs on offspring and to provide a reference for future research in this field.

Amruthapala (Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter): A Comprehensive Review on Diversity, Therapeutic Uses, and Valorization of Bioactive Constituents

2019 ◽  
Vol 20 (5) ◽  
pp. 376-389 ◽  
Author(s):  
Sonali Mishra ◽  
Nupur Srivastava ◽  
Velusamy Sundaresan ◽  
Karuna Shanker
Keyword(s):  
Secondary Metabolite ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Critical Discussion ◽  
Future Research ◽  
Bioactive Constituents ◽  
Medicinal Uses ◽  
Comprehensive Review ◽  
Therapeutic Uses ◽  
Decalepis Arayalpathra

Background: Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter is used primarily for nutrition besides its therapeutic values. Traditional preparations/formulations from its tuber are used as a vitalizer and blood purifier drink. The folklore medicinal uses cover inflammation, cough, wound healing, antipyretic, and digestive system management. A comprehensive review of the current understanding of the plant is required due to emerging concerns over its safety and efficacy. Objective: The systematic collection of the authentic information from different sources with the critical discussion is summarised in order to address various issues related to botanical identity, therapeutic medicine, nutritional usage, phytochemical, and pharmacological potentials of the D. arayalpathra. Current use of traditional systems of medicine can be used to expand future research opportunities. Materials and Methods: Available scripted information was collected manually, from peered review research papers and international databases viz. Science Direct, Google Scholar, SciFinder, Scopus, etc. The unpublished resources which were not available in database were collected through the classical books of ‘Ayurveda’ and ‘Siddha’ published in regional languages. The information from books, Ph.D. and MSc dissertations, conference papers and government reports were also collected. We thoroughly screened the scripted information of classical books, titles, abstracts, reports, and full-texts of the journals to establish the reliability of the content. Results: Tuber bearing vanilla like signature flavor is due to the presence of 2-hydroxy-4-methoxybenzaldehyde (HMB). Among five other species, Decalepis arayalpathra (DA) has come under the ‘critically endangered’ category, due to over-exploitation for traditional, therapeutic and cool drink use. The experimental studies proved that it possesses gastro-protective, anti-tumor, and antiinflammatory activities. Some efforts were also made to develop better therapeutics by logical modifications in 2-Hydroxy-4-methoxy-benzaldehyde, which is a major secondary metabolite of D. arayalpathra. ‘Amruthapala’ offers the enormous opportunity to develop herbal drink with health benefits like gastro-protective, anti-oxidant and anti-inflammatory actions. Results: The plant has the potential to generate the investigational new lead (IND) based on its major secondary metabolite i.e. 2-Hydroxy-4-methoxy-benzaldehyde. The present mini-review summarizes the current knowledge on Decalepis arayalpathra, covering its phytochemical diversity, biological potentials, strategies for its conservation, and intellectual property rights (IPR) status. Chemical Compounds: 2-hydroxy-4-methoxybenzaldehyde (Pubchem CID: 69600), α-amyrin acetate (Pubchem CID: 293754), Magnificol (Pubchem CID: 44575983), β-sitosterol (Pubchem CID: 222284), 3-hydroxy-p-anisaldehyde (Pubchem CID: 12127), Naringenin (Pubchem CID: 932), Kaempferol (Pubchem CID: 5280863), Aromadendrin (Pubchem CID: 122850), 3-methoxy-1,2-cyclopentanedione (Pubchem CID: 61209), p-anisaldehyde (Pubchem CID: 31244), Menthyl acetate (Pubchem CID: 27867), Benzaldehyde (Pubchem CID: 240), p-cymene (Pubchem CID: 7463), Salicylaldehyde (Pubchem CID: 6998), 10-epi-γ-eudesmol (Pubchem CID: 6430754), α -amyrin (Pubchem CID: 225688), 3-hydroxy-4-methoxy benzaldehyde (Pubchem CID: 12127).

Molecular pathways of Interferon–Stimulated Gene 15: Implications in cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Angeles C. Tecalco–Cruz
Keyword(s):  
Posttranslational Modification ◽  
Human Interferon ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Small Protein ◽  
Target Proteins ◽  
Central Elements ◽  
Cancer Types ◽  
Interferon Stimulated Gene 15

Abstract:: Human interferon–stimulated gene 15 (ISG15) is a 15–kDa ubiquitin–like protein that can be detected as either free ISG15 or covalently associated with its target proteins through a process termed ISGylation. Interestingly, extracellular free ISG15 has been proposed as a cytokine–like protein, whereas ISGylation is a posttranslational modification. ISG15 is a small protein with implications in some biological processes and pathologies that include cancer. This review highlights the findings of both free ISG15 and protein ISGylation involved in several molecular pathways, emerging as central elements in some cancer types.

Disparities in Health Between Black and White Americans: Current Knowledge and Directions for Future Research

2018 ◽  
pp. 456-478
Author(s):  
Thomas E. Fuller-Rowell ◽  
David S. Curtis ◽  
Adrienne M. Duke
Keyword(s):  
Health Disparities ◽  
Current Knowledge ◽  
Public Investment ◽  
The United States ◽  
Future Research ◽  
Sociocultural Factors ◽  
White Americans ◽  
Biological Mechanisms ◽  
Black And White ◽  
Racial Ethnic

Conceptual frameworks for racial/ethnic health disparities are abundant, but many have received insufficient empirical attention. As a result, there are substantial gaps in scientific knowledge and a range of untested hypotheses. Particularly lacking is specificity in behavioral and biological mechanisms for such disparities and their underlying social determinants. Alongside lack of political will and public investment, insufficient clarity in mechanisms has stymied efforts to address racial health disparities. Capitalizing on emergent findings from the Midlife in the United States (MIDUS) study and other longitudinal studies of aging, this chapter evaluates research on health disparities between black and white US adults. Attention is given to candidate behavioral and biological mechanisms as precursors to group differences in morbidity and mortality and to environmental and sociocultural factors that may underlie these mechanisms. Future research topics are discussed, emphasizing those that offer promise with respect to illuminating practical solutions to racial/ethnic health disparities.

scholarly journals Protocol for a systematic review on the experience of informal caregivers for people with a moderate to advanced dementia within a domestic home setting

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Charles James ◽  
Catherine Walshe ◽  
Katherine Froggatt
Keyword(s):  
Systematic Review ◽  
Negative Impact ◽  
Current Knowledge ◽  
Informal Caregivers ◽  
Informal Caregiving ◽  
Bibliographic Databases ◽  
Future Research ◽  
Advanced Dementia ◽  
Home Setting ◽  
Search Terms

Abstract Background The knowledge about the experience of informal caregivers who provide care to people with moderate to advanced dementia in a domestic home setting is limited. A consequence of long hours of caregiving in addition to dealing with normal challenges of daily living is their experience of a poor quality of life. Some of their experiences may be described in terms of a feeling of powerlessness to make changes during care provision. This feeling may also suggest an experience of moral distress. The aim of this systematic review is to synthesise qualitative evidence relating to these experiences. Methods This review adopts a narrative synthesis approach. A search will be conducted for studies written in the English language in the bibliographic databases MEDLINE Complete, CINAHL, EMBASE, PsycINFO, Web of Science and Academic Search Complete covering periods from 1984 to present. Included studies will be qualitative or mixed-methods designs. The search terms will be related to dementia and caregivers, and the process will be focused on dementia at the moderate to the advanced stages within the domestic home setting. Reference lists of included papers will also be searched for additional relevant citations. Search terms and strategies will be checked by two independent reviewers. The identification of abstracts and full texts of studies will be done by the author, while the quality and the risk of bias will also be checked by the two independent reviewers. Discussion Psychological distress is cited as an experience reported within informal caregiving. For the caregiver, it is associated with a negative impact on general health. To date, no synthesis exists on the specific experience of informal caregiving for people with moderate to advanced dementia within the domestic home setting. This review considers that variation of accounts contributes to how the informal caregivers’ general experience is explored in future research. This may enable gaps in current knowledge to be highlighted within the wider context of caregiving in the domestic home setting. Systematic review registration This review is registered with PROSPERO (CRD42020183649).

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals Knowledge Gaps in Understanding the Etiology of Anemia in Indonesian Adolescents

2021 ◽  
Vol 42 (1_suppl) ◽  
pp. S39-S58
Author(s):  
Kesso Gabrielle van Zutphen ◽  
Klaus Kraemer ◽  
Alida Melse-Boonstra
Keyword(s):  
Current Knowledge ◽  
Vitamin A Deficiency ◽  
Public Health Problem ◽  
Population Group ◽  
Future Research ◽  
Folic Acid Deficiency ◽  
Knowledge Gaps ◽  
Local Conditions ◽  
Etiological Factors ◽  
Infection And Inflammation

Background: Anemia is a public health problem among adolescents in Indonesia. Strategies to prevent or treat anemia should be tailored to local conditions, taking into account its specific etiology and prevalence in a given setting and population group. Objective: This review aims to (1) identify and synthesize the current knowledge on the etiology of anemia among adolescents in Indonesia, (2) reveal knowledge gaps in this area, and (3) suggest directions for future research and programmatic work. Methods: We systematically searched PubMed, Web of Science, Scopus, Medline, and WorldCat databases for peer-reviewed journal articles to identify which etiological factors were related to anemia among Indonesian adolescents. Research papers were reviewed and included in the review according to inclusion criteria. Results: Of 13 studies, 8 showed that anemia was associated with iron deficiency; 4 are suggestive of vitamin A deficiency; and 2 of folic acid deficiency. Five studies underscore different etiological determinants for anemia, such as malaria, protein and energy malnutrition, vitamin B2 deficiency, calcium, and vitamin C deficiency. Based on these findings, we developed a framework on knowledge gaps on the etiology of anemia among adolescents in Indonesia, divided in 3 levels of knowledge: (1) significant knowledge gaps, (2) knowledge gaps, and (3) established knowledge. Conclusions: The knowledge gaps around the etiology of anemia among Indonesian adolescents are significant. Our framework emphasizes the need for further research across all etiological factors, namely inadequate nutritional intake and absorption, genetic hemoglobin disorders, infection and inflammation, and menstrual disorders.

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