Role of γ-H2AX in DNA damage response

M.S. University of Hawaii at Manoa 2011.Includes bibliographical references.Little is known about the molecular mechanism of γ-H2AX in DNA damage response in mammalian embryos when compared to the somatic cells. An integrative review of the literature on the molecular mechanism of γ-H2AX in DNA damage response in somatic cells and in mammalian embryos was performed. The objective of the study is to summarize and synthesize the published databased literature over the last 10 years on molecular mechanism of γ-H2AX in mouse pre-implantation embryos and somatic cells using the key words--"γ-H2AX", "DNA damage", "somatic cells", "mouse embryo". An initial medline search was performed using our inclusion and exclusion criteria and then expanded by snowballing. The articles were compiled in the form of a Review Matrix. The knowledge gap was investigated and the conceptual model was formulated to hypothesize the sequence of DNA damage responses occurring during the time of early mouse embryogenesis. Major themes drawn from the studies are-1). Periodic appearance and disappearance of γ-H2AX in early mouse pre-implantation embryos, 2) Development of γ-H2AX foci in the pronuclei without imposing any replicative stress on the mouse embryo, 3) Occurrence of γ-H2AX in the S-phase of somatic cells under replicative stress and normal embryos, 4) Prevalence of prominent γ-H2AX signal in male pronuclei compared to the female pronuclei during mouse embryogenesis. The study will also show scopes of future research to explore the arena in clinical context

The Relationship of 5-Aminolevulinic Acid on Mood and Coping Ability in Prediabetic Middle Aged and Older Adults

In 2010, approximately 79 million Americans had prediabetes and about 50 percent of those individuals were 65 years and older. The most effective diabetes prevention method in prediabetic adults is lifestyle modification. However, despite the benefits of lifestyle change, diabetes prevalence continues to increase. Maintaining a regular exercise routine and a healthy eating plan may be difficult because of the negative emotional barriers (i.e., stress, mood) that a prediabetic individual faces. This is particularly evident in older individuals when you combine that with decreases in mobility and geriatric syndromes. A potential treatment for these emotional barriers is a natural supplement called 5-aminolevulinic acid (5-ALA). In the current study, the group included 154 participants, both men and women, ranging between the ages of 41 to 71 years old. The study design was a double-blind, randomized parallel-group study. The Psychosocial Depressive Symptoms Questionnaire (PDS) and the Perceived Stress Scale (PSS) were used to examine the effect of two doses of 5-ALA (15 mg and 50 mg) on various components of mood (i.e., hopefulness, loneliness, and motivation) and coping ability. Using SAS software, an ordered logistic regression model was used to analyze the association between the dose groups (control, 15 mg, and 50 mg) and the responses to the two questionnaires, the PDS and PSS, used in this study. An integrative literature review, using the PubMed database, searched for studies on the relationship between 5-ALA administration and mood and coping ability. Our literature review resulted in zero published articles. Next, we found that the intake of 5-ALA was significantly associated with improved coping ability (p = 0.004) and improved self-perception of effort spent (p = 0.002). Finally, we found a significant dose-dependent relationship for the association of 5-ALA intake on measures of effort (p = 0.003), loneliness (p = 0.006), and coping ability (p = 0.003). The 50 mg dose was more effective than the 15 mg dose in improving these measures. In conclusion, after 12 weeks of taking 5-ALA, we found significant improvements in self-perception of effort spent, loneliness, and coping ability in prediabetic middle age and older adults. Improved mood and coping ability may allow prediabetic individuals to overcome the emotional obstacles preventing them from maintaining a healthy lifestyle and ultimately, help them to avoid the development of diabetes

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.This article is published as Klionsky, Daniel J., Amal Kamal Abdel-Aziz, Sara Abdelfatah, Mahmoud Abdellatif, Asghar Abdoli, Steffen Abel, Hagai Abeliovich et al. "Guidelines for the use and interpretation of assays for monitoring autophagy." autophagy 17, no. 1 (2021): 1-382. doi:https://doi.org/10.1080/15548627.2020.1797280. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field