Δευτέρα 17 Σεπτεμβρίου 2018

Evolutionarily conserved coding properties favour the neuronal representation of heterospecific signals of a sympatric katydid species

Abstract

To function as a mechanism in premating isolation, the divergent and species-specific calling songs of acoustic insects must be reliably processed by the afferent auditory pathway of receivers. Here, we analysed the responses of interneurons in a katydid species that uses long-lasting acoustic trills and compared these with previously reported data for homologous interneurons of a sympatric species that uses short chirps as acoustic signals. Some interneurons of the trilling species respond exclusively to the heterospecific chirp due to selective, low-frequency tuning and "novelty detection". These properties have been considered as evolutionary adaptations in the sensory system of the chirper, which allow it to detect signals effectively during the simultaneous calling of the sympatric sibling species. We propose that these two mechanisms, shared by the interneurons of both species, did not evolve in the chirper to guarantee its ability to detect the chirp under masking conditions. Instead we suggest that chirpers evolved an additional, 2-kHz component in their song and exploited pre-existing neuronal properties for detecting their song under masking noise. The failure of some interneurons to respond to the conspecific song in trillers does not prevent intraspecific communication, as other interneurons respond to the trill.



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Genomic screening in rare disorders: New mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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Genomic duplication in the 19q13.42 imprinted region identified as a new genetic cause of intrauterine growth restriction

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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PharmGKB summary: oxycodone pathway, pharmacokinetics

No abstract available

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Functional expression of human arylamine N-acetyltransferase NAT1*10 and NAT1*11 alleles: a mini review

The arylamine N-acetyltransferase (NAT) nomenclature committee assigns functional phenotypes for human arylamine N-acetyltransferase 1 (NAT1) alleles in those instances in which the committee determined a consensus has been achieved in the scientific literature. In the most recent nomenclature update, the committee announced that functional phenotypes for NAT1*10 and NAT1*11 alleles were not provided owing to a lack of consensus. Phenotypic inconsistencies observed among various studies for NAT1*10 and NAT1*11 may be owing to variable allelic expression among different tissues, the limitations of the genotyping assays (which mostly relied on techniques not involving direct DNA sequencing), the differences in recombinant protein expression systems used (bacteria, yeast, and mammalian cell lines) and/or the known inherent instability of human NAT1 protein, which requires very careful handling of native and recombinant cell lysates. Three recent studies provide consistent evidence of the mechanistic basis underlying the functional phenotype of NAT1*10 and NAT1*11 as 'increased-activity' alleles. Some NAT1 variants (e.g. NAT1*14, NAT1*17, and NAT1*22) may be designated as 'decreased-activity' alleles and other NAT1 variants (e.g. NAT1*15 and NAT1*19) may be designated as 'no-activity' alleles compared with the NAT1*4 reference allele. We propose that phenotypic designations as 'rapid' and 'slow' acetylator should be discontinued for NAT1 alleles, although these designations remain very appropriate for NAT2 alleles. Correspondence to David W. Hein, PhD, Kosair Charities Clinical and Translational Research Building, Room 303, 505 South Hancock Street, Louisville, KY 40202-1617, USA Tel: +1 502 852 6252; fax: +1 502 852 7868; e-mail: d.hein@louisville.edu Received May 17, 2018 Accepted August 28, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The role of genetic polymorphisms in the thymidylate synthase (TYMS) gene in methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

Objective Methotrexate (MTX) is an important drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). MTX is cytotoxic as it impairs DNA and RNA synthesis by inhibiting the enzymes dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS). The association between genetic variants within the TYMS gene and MTX-induced toxicity has been studied, but results are inconsistent. We determined the role of three previously described variants within the TYMS gene and MTX-induced oral mucositis in a prospective cohort of Dutch children with ALL and performed a meta-analysis of the previous results. Materials and methods We analyzed the presence of a 28-base pair tandem repeat (rs34743033; 2R3R), a single nucleotide polymorphism present within the 28-base pair repeat on the 3R allele (rs2853542; 3RG>C) and a 6-base pair deletion (rs15126436; TTAAAG) within the TYMS gene in germline DNA of 117 pediatric patients with ALL. Oral mucositis was defined as grade≥3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. Data were analyzed for the individual rs34743033 (2R3R) and rs151264360 (6 bp deletion) polymorphisms, whereas rs2853542 (3RG>C) was combined with rs34743033 (2R3R) and analyzed according to predicted expression levels of TYMS: low expression (2R/2R, 2R/3RC and 3RC/3RC), median expression (2R/3RG and 3RC/3RG) and high expression (3RG/3RG). We performed a meta-analysis of the current literature on these polymorphisms in relation to oral mucositis using a fixed effects model. Results The 2R2R genotype (rs34743033) was not significantly associated with developing MTX-induced oral mucositis compared with the 2R3R/3R3R genotypes, which was confirmed in a meta-analysis [odds ratio (OR): 1.17 (0.62–2.19)]. Patients carrying the low-expression TYMS genotype (2R2R, 2R3RC, 3RC3RC) had an increased odds of developing MTX-induced oral mucositis [OR: 2.42 (0.86–6.80)], which did not reach statistical significance. The 6-bp deletion [rs151264360, OR: 0.79 (0.20–3.19)] was not associated with the development of MTX-induced oral mucositis. Conclusion The TYMS 6-bp deletion and 2R3R polymorphism were not associated with MTX-induced oral mucositis. Validation studies in prospective cohorts are necessary to assess the possible role of the low-expression TYMS genotypes in relation to MTX-induced oral mucositis. Correspondence to Sandra G. Heil, PhD, Department of Clinical Chemistry, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands Tel: +31 10 703 2433; fax: +31 10 704 4895; e-mail: s.heil@erasmusmc.nl Received February 5, 2018 Accepted July 25, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Κυριακή 16 Σεπτεμβρίου 2018

Noninvasive neuromodulation techniques for the management of phantom limb pain: a systematic review of randomized controlled trials

Neuromodulation techniques work by modulating pain perception by inducing changes in polarity of the neuronal membrane and thereby cortical excitability. The aim of this review is to evaluate the efficiency and safety of noninvasive neuromodulation techniques for phantom limb pain (PLP). A systematic literature search in the PubMed, Scopus, Web of Science, and Cochrane Library databases was performed to identify studies investigating the effects of noninvasive neuromodulation for PLP. The included journal articles were assessed with Furlan et al.'s method for examining the risk of bias to assess methodologic quality, and evidence was graded using the GRADE approach. The literature search identified 239 studies. Of these 239, four studies fulfilled the inclusion criteria and were included for data extraction. Two of the studies focused on repetitive transcranial magnetic stimulation (rTMS) whereas two other concentrated on transcranial direct current stimulation (tDCS). The present review showed that there is conflicting evidence to support the use of tDCS in short term and moderate evidence to support the use of rTMS in immediate and short term. It is important to recognize that this evidence comes from a very small sample size. No serious adverse effects were reported. Further information from randomized controlled trials with larger sample size investigating immediate and short-term and long-term effects are needed to clarify the best effective stimulation parameters and number of sessions of tDCS and rTMS for PLP. Correspondence to Gulseren Akyuz, MD, Department of Physical Medicine and Rehabilitation and Division of Pain Medicine, Marmara University School of Medicine, Istanbul, Turkey Tel: +90 216 625 4657; fax: +90 216 450 0077; e-mail: gulserena@gmail.com Received July 17, 2018 Accepted August 31, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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