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Stress-induced acidification may contribute to formation of unusual structures in C9orf72-repeats

Conclusions In the proper sequence context, i-motif structures can form at pH values found in some cells in vivo. General Significance DNA conformational plasticity exists over broad range of solution conditions.
Source: Biochimica et Biophysica Acta (BBA) General Subjects - Category: Biochemistry Source Type: research

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Abstract BACKGROUND: Expansion of the C9orf72 hexanucleotide repeat (GGGGCC)n•(GGCCCC)n is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both strands of the C9orf72 repeat have been shown to form unusual DNA and RNA structures that are thought to be involved in mutagenesis and/or pathogenesis. We previously showed that the C-rich DNA strands from the C9orf72 repeat can form four-stranded quadruplexes at neutral pH. The cytosine residues become protonated under slightly acidic pH (pH 4.5 - 6.2), facilitating the formation of intercalated i-motif structures. ...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Tags: Biochim Biophys Acta Source Type: research
In conclusion, the present study demonstrated that TIGIT is a prominent negative immune regulator involved in immunosenescence. This novel finding is highly significant, as targeting TIGIT might be an effective strategy to improve the immune response and decrease age-related comorbidities. Delivery of Extracellular Vesicles as a Potential Basis for Therapies https://www.fightaging.org/archives/2018/01/delivery-of-extracellular-vesicles-as-a-potential-basis-for-therapies/ Here I'll point out a readable open access review paper on the potential use of extracellular vesicles as a basis for therapy: harveste...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
When I was in high school applying for colleges, I had two criteria for my potential university: strong academics and football. I knew I wanted the camaraderie of a football game day. My older sister, Beth, attended Marshall University during the Randy Moss/Chad Pennington years, and I was fortunate to attend many Thundering Herd home games during her time there. I chose the University of Tennessee for my undergraduate degree. Saturday game day in the Southeastern Conference with the Vol Navy was even more than I had expected. The power-T and tailgating were even enough to get my parents to make the drive from William...
Source: American Speech-Language-Hearing Association (ASHA) Press Releases - Category: Speech-Language Pathology Authors: Tags: Speech-Language Pathology Cognitive Rehabilitation Language Disorders Traumatic Brain Injury Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Down's syndrome (DS; also known as trisomy 21; T21) is caused by a triplication of all or part of human chromosome 21 (chr21). DS is the most common genetic cause of intellectual disability attributable to a naturally-occurring imbalance in gene dosage. DS incurs huge medical, healthcare, and socioeconomic costs, and there are as yet no effective treatments for this incapacitating human neurogenetic disorder. There is a remarkably wide variability in the 'phenotypic spectrum' associated with DS; the progression of symptoms and the age of DS onset fluctuate, and there is further variability in the biophysi...
Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research
Abstract Cyclin F, encoded by CCNF, is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCF(cyclinF). E3 ubiquitin ligases play a key role in ubiquitin-proteasome mediated protein degradation, an essential component of protein homeostatic mechanisms within the cell. By recognising and regulating the availability of several protein substrates, SCF(cyclinF) plays a role in regulating various cellular processes including replication and repair of DNA and cell cycle checkpoint control. Cyclin F dysfunction has been implicated in various forms of cancer and CCNF mutations were rec...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
Steve and Kristie Matt met 13 years ago and have been married for 12 of those years. “We immediately knew we were the perfect match from the moment we met,” says Kristie. They also both worked in Philadelphia’s bar/restaurant industry for years—many of them side-by-side—with Steve cooking and Kristie tending bar. A little more than two years ago, Steve noticed hoarseness and low volume in his voice. Shortly thereafter, he began to experience weakness in his legs. Steve and Kristie Matt Diagnosed with bulbar-onset amyotrophic lateral sclerosis (ALS) in January 2016, Steve immediately jumpe...
Source: American Speech-Language-Hearing Association (ASHA) Press Releases - Category: Speech-Language Pathology Authors: Tags: Speech-Language Pathology ALS Dysphagia Swallowing Disorders Source Type: blogs
In fruit flies modeled with IBMPFD disease, mitochondria (red circles) are severely disrupted. Treatment of VCP inhibitors in these diseased flies reversed  mitochondrial damage (green circles). FINDINGSUCLA researchers have discovered the molecular basis of, and identified potential treatment for, an incurable disease known as inclusion body myopathy, Paget disease with frontotemporal dementia, or IBMPFD. Using both genetically engineered fruit flies that have the fly equivalent of the disease gene as well as cells from people with IBMPFD, the researchers discovered how mutations carried by those with IBMPFD cau...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Cochrane-wide prioritisation remains an important project, with over 140 priority reviews or updates have been published since it began in January 2015.The December 2016 revision of the Cochrane Priority Reviews List includes new titles from the Cochrane Airways, Anaesthesia, Dementia&Cognitive Improvement, ENT, Epilepsy, Gynaecological, Neuro-oncology and Orphan Cancers, Gynaecology&Fertility, Haematological Malignancies, Heart, Incontinence, Kidney&Transplant, Lung Cancer, Neuromuscular Disease, Oral Health, Skin, Stroke, and Urology Groups.The following titles on the list are open to new authors:Long-acting ...
Source: Cochrane News and Events - Category: Information Technology Authors: Source Type: news
This study aimed to explore the trends of DNR consent and hospice care utilization among noncancer decedents in a tertiary hospital in Taiwan. We analyzed the Death and Hospice Palliative Care Database from the Taipei Veterans General Hospital in Taiwan. The Death and Hospice Palliative Care Database contains information including patient sex, major diagnosis, admission date, date of death, age at death, department at discharge, status of DNR consent, and status of hospice care of patients who died in the Taipei Veterans General Hospital. Data on patients aged 20 years old or more who died of major terminal noncancer disea...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
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