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Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.

DNA methylation patterns have profound impacts on genome stability, gene expression and development. The molecular base of DNA methylation patterns has long been focused at single CpG sites level. Here, we construct a kinetic model of DNA methylation with collaborations between CpG sites, from which a correlation function was established based on experimental data. The function consists of three parts that suggest three possible sources of the correlation: movement of enzymes along DNA, collaboration between DNA methylation and nucleosome modification, and global enzyme concentrations within a cell. Moreover, the collaboration strength between DNA methylation and nucleosome modification is universal for mouse early embryo cells. The obtained correlation function provides insightful understanding for the mechanisms of inheritance of DNA methylation patterns.

BioScience Managers banks on growth of anti-infectives market.

Rodin Therapeutics applies insights of epigenetics to neurological disorders.

LBT Innovations finalizes joint venture to drive global production of world-class automated diagnostics technology.

Phylogica expands collaborations with Janssen for peptide-drug conjugates.

Immune Design and Medicago announce license agreement and collaboration to develop novel adjuvanted pandemic influenza vaccines.

Bayat Foundation inaugurates new pediatric critical care facility at Indira Gandhi Hospital in Kabul.

SINGAPORE – NUS Study Uncovers Novel Genetic Alterations Contributing to Development of Leukaemia.

AUSTRALIA – Meat Consumption Contributing to Global Obesity.

AUSTRALIA – Warmer Climate Could Lower Dengue Risk.

UNITED KINGDOM – Treatment Option for Alzheimer’s Disease Possible.

UNITED STATES – Hot News Flash! Menopause, Sleepless Nights Make Women’s Bodies Age Faster.

UNITED STATES – Innovative Technology Improves Detection of Bladder Cancer.

UNITED STATES – Research Shows New Neurons Created Through Exercise Don’t Cause You to Forget Old Memories.

INDIA – Praj to be the First Indian Technology Provider to Launch ‘Green Fund’ for 2G Ethanol Projects.

MALAYSIA – Tunku Laksamana Johor Cancer Foundation Partners Singapore-based Asian American Medical Group to Conduct Feasibility of Establishing Centre of Excellence in Southern Malaysia to Treat Cancer.

TAIWAN – Curcumin Derivatives May Prevent Alzheimer’s Disease by Promoting Amyloid-β Clearance.

The aim of this research proposal was to investigate the effects of tetrahydropalmatine (THP) on gene expression in a post-traumatic stress disorder (PTSD) rodent model. Eighty male Sprague-Dawley rats were randomly assigned to the nonstressed groups or the 3-day restraint shock PTSD rodent model groups. There were four groups within the nonstressed rats (control, THP, midazolam, and midazolam with THP) and four groups within the stressed rats (control, THP, midazolam, and midazolam with THP). After injection the subjects were euthanized and the amygdala and hippocampus were sent for reverse transcriptase-polymerase chain reaction gene expression analysis. Of the genes interrogated, 17 genes in the amygdala and 18 genes in the hippocampus were found to have significant changes in gene expression and regulation. Significant transcriptional fold changes were found in important genes involved in dopamine, serotonin, acetylcholine, and gamma-aminobutyric acid neurotransmitter systems. The results provide quantifiable data demonstrating gene expression changes in PTSD-stressed and nonstressed rats receiving various treatments. These findings contribute important data to the limited molecular details pertaining to the neurobiology of PTSD.

Oogenesis in mammalian females, including humans, is arrested prior to birth. Females, therefore, are born with a limited number of primary oocytes. This is in direct contrast to males in whom spermatogenesis continues during the entire lifespan following puberty. Here, we discuss possible evolutionary advantages that this confers and contrast this with age-related decline in oocyte quality that results in diminished fertility with advancing maternal age. We believe that a better understanding of these processes would be helpful in developing strategies to preserve fertility as maternal age increases, especially in the context of the current demographic shift with more and more women seeking fertility treatment at advanced age.

The team’s initial hypothesis states that the Mereon Matrix’s First Principles constitute a unitive template generally applicable as an information model. For verification of this premise, the knowledge domain of human molecular genetics was used in a study called ATCG. The Matrix’s seven functions and its fractal principle were applied using the latest (at the point of writing, i.e. up to the beginning of the year 2013) original scientific literature as the source of domain information. ATCG was elaborated through all seven functions with each further explored through its level of micro-functions. The Mereon Matrix was extremely useful in modelling as it constantly forced authors to pose specific questions with respect to the topics inherent at different micro-functions. This allowed searching for answers in the literature using an iterative and incremental modelling process. Upon completing the project it was concluded that the Mereon Matrix as a template for modelling human molecular genetics met and exceeded what was anticipated.

Identifying functional elements and predicting mechanistic insight from non-coding DNA and noncoding variation remains a challenge. Advances in genome-scale, high-throughput technology, however, have brought these answers closer within reach than ever, though there is still a need for new computational approaches to analysis and integration. This workshop aims to explore these resources and new computational methods applied to regulatory elements, chromatin interactions, non-protein-coding genes, and other non-coding DNA.

The progress made in genomics technology provides unprecedented opportunity for the research community to accelerate discovering the genetic etiology of autism. A clear trend in the literature from genecentric studies to whole-genome approaches is the best illustration of the incorporation of the state-of-the art techniques in autism research, which has progressed from the era of linkage scans, single gene and genome-wide association studies, and copy number variations to next-generation sequencing of the entire human genome. However, with the exception of studies that identified a few causative genes and a limited number of replicated findings, the rest have mainly contributed to the ever growing list of potential autism candidate genes, awaiting replication. This unexpected outcome has now become an additional challenge in moving forward from gene discoveries to diagnostic tests and treatment options in autism. In this chapter, we highlight findings derived from a few integrative approaches using unconventional models, which have resulted in promising discoveries and provided practical examples of how uncovering genetic causes of autism may be accelerated.

Significant recent progress has been made in deciphering the genetic basis of autism spectrum disorder (ASD), revealing a key role for synaptic gene mutations. However, relevant mechanisms for gene-environment interactions and their contribution to the ASD phenotype remain largely unknown. RNA is emerging as a central substrate for encoding environmental exposures at the molecular level, especially in the nervous system. One effective mechanism for regulating gene function and dosage in response to the changing environment is RNA editing. Recently, we showed that adenosine-to-inosine (A-to-I) RNA editing of synaptic genes is altered in postmortem brains of individuals with ASD, suggesting that this epigenetic mechanism could play a role in ASD. Here we review our current understanding of RNA editing at the molecular level, describe the behavioral phenotypes associated with altered A-to-I editing in animal models, discuss recent discoveries in human A-to-I editing, and speculate about the diagnostic and prognostic potential of A-to-I editing changes in ASD.

Despite many gains in our understanding of genetic aspects of autism, the etiologic basis of autism in most affected individuals is unknown and there is a very incomplete understanding about the downstream biology occurring in the autistic brain. Epigenetics has emerged as a promising field that may explain how some cases of autism arise, both as a result of and independently from monogenic and chromosomal mutations. Here we discuss the emerging evidence of how epigenetic dysregulation may play a role in autism pathophysiology, as well as the challenges and potential strategies in studying possible epigenetic processes in autism.

Previous studies have established that there is a strong genetic component to the development of ASD, but these genetic risks do not account for all of the heritability of the disorder. This raises the prospect that alternative, epigenetic mechanisms may play a role in ASD development. Epigenetic mechanisms facilitate temporal and spatial regulation of gene expression, but are independent of changes to the underlying DNA sequence. Because epigenetic profiles are labile, they represent an intriguing mechanism whereby environmental influences, which are not severe enough to alter the DNA sequence of a cell, may alter gene expression and cellular response and contribute to ASD. In this chapter, we discuss the role of DNA methylation and histone modifications in the development of ASD.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by communication and social impairments, as well as repetitive behaviors. ASDs are highly heritable, but environmental contributions to risk are also likely. To date, only a few specific genes or environmental factors have been definitively characterized. Typically, genetic and environmental research in ASD etiology have been distinct pursuits, rather than carried out in a combined gene-environment context. This chapter offers evidence in support of both genetic and environmental etiology perspectives and suggestions for how to integrate the two fields moving forward, highlighting the potential benefits, and how to navigate particular challenges.

While autism spectrum disorders (ASD) have a strong genetic basis, the apparent increase in prevalence in recent generations has raised concerns about environmental exposures and potential interactions with genetic risk factors. DNA methylation is an epigenetic layer on top of DNA sequence at the interface of genetic and environmental factors known to overlap with metabolism and nutrition. Here we review and discuss the evidence from human studies pointing to complex interactions between genetic factors and in utero environment. We also examine the impact of chemical exposures on DNA methylation in brain as well as overall effect on development and reproduction. Transgenerational effects of chemical exposures on ASD risk are still an open question, but evidence supporting the need to ask such questions are summarized.