Search results for "pur"
showing 10 items of 5529 documents
Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the Europe…
2020
Background Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in the FDA drug label and a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic…
Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
2017
AbstractThe association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL includin…
Genomic landscape analyses in cervical carcinoma and consequences for treatment.
2020
Where we are on the road to ‘tailor-made’ precision medicine for drug-resistant cervical carcinoma? We explored studies about analyses of viral and human genomes, epigenomes and transcriptomes, DNA mutation analyses, their importance in detecting HPV sequences, mechanisms of drug resistance to established and targeted therapies with small molecule or therapeutic antibodies, to radiosensitivity and to chemoradiotherapy. The value of repurposing of old drugs initially approved for other disease indications and now considered for cervix cancer therapy is also discussed. The microbiome influences drug response and survival too. HPV genomic integration sites were less significant. Nomograms (Lee…
Microbial diversity along a gradient in peatlands treating mining-affected waters.
2018
Peatlands are used for the purification of mining-affected waters in Northern Finland. In Northern climate, microorganisms in treatment peatlands (TPs) are affected by long and cold winters, but studies about those microorganisms are scarce. Thus, the bacterial, archaeal and fungal communities along gradients of mine water influence in two TPs were investigated. The TPs receive waters rich in contaminants, including arsenic (As), sulfate (SO42-) and nitrate (NO3-). Microbial diversity was high in both TPs, and microbial community composition differed between the studied TPs. Bacterial communities were dominated by Proteobacteria, Actinobacteria, Chloroflexi and Acidobacteria, archaeal commu…
Incidence, Diagnosis, and Outcome of Acquired Thrombotic Thrombocytopenic Purpura (aTTP): A Nationwide Survey By the Spanish Apheresis Group
2019
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare disease characterized by a severe deficiency of the enzymatic activity of ADAMTS13 caused by autoantibodies, with an incidence of 3-4 x106inhabitants per year according to the few published data available. Accurate estimates of the incidence of aTTP are important to assess the resources required for current treatments and to anticipate the need to develop new treatments. The aim of this study was to determine the actualincidence of aTTP in Spain, as well as its diagnosis, management, and associated complications. Material and methods:A cross-sectional surveywascarried out among hematologists working in Spanish hospi…
Chimeric proteins tagged with specific 3xHA cassettes may present instability and functional problems
2017
Epitope-tagging of proteins has become a widespread technique for the analysis of protein function, protein interactions and protein localization among others. Tagging of genes by chromosomal integration of PCR amplified cassettes is a widely used and fast method to label proteins in vivo. Different systems have been developed during years in the yeast Saccharomyces cerevisiae. In the present study, we analysed systematically a set of yeast proteins that were fused to different tags. Analysis of the tagged proteins revealed an unexpected general effect on protein level when some specific tagging module was used. This was due in all cases to a destabilization of the proteins and caused a red…
DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
2019
Background Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. Methods We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. Results We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) associated with exposure to maternal smoking in adolesc…
Confirmation of PDZD7 as a Nonsyndromic Hearing Loss Gene.
2016
Objective PDZD7 was identified in 2009 in a family with apparent nonsyndromic sensorineural hearing loss. However, subsequent clinical reports have associated PDZD7 with digenic Usher syndrome, the most common cause of deaf-blindness, or as a modifier of retinal disease. No further reports have validated this gene for nonsyndromic hearing loss, intuitively calling correct genotype-phenotype association into question. This report describes a validating second case for biallelic mutations in PDZD7 causing nonsyndromic mild to severe sensorineural hearing loss. It also provides detailed audiometric and ophthalmologic data excluding Usher syndrome in both the present proband (proband 1) and the…
Allopurinol partially prevents disuse muscle atrophy in mice and humans
2018
AbstractDisuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The pro…
Cell Type-Specific Tandem Affinity Purification of the Mouse Hippocampal CB1 Receptor-Associated Proteome
2016
G protein coupled receptors (GPCRs) exert their effects through multiprotein signaling complexes. The cannabinoid receptor type 1 (CB1) is among the most abundant GPCRs in the mammalian brain and involved in a plethora of physiological functions. We used a combination of viral-mediated cell type-specific expression of a tagged CB1 fusion protein (CB1-SF), tandem affinity purification (TAP) and proteomics on hippocampal mouse tissue to analyze the composition and differences of CB1 protein complexes in glutamatergic neurons and in GABAergic interneurons. Purified proteins underwent tryptic digestion and were identified using deep-coverage data-independent acquisition with ion mobility separa…