Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair

Cataloged from PDF version of article.Background: Human de novo single-nucleotide variation (SNV) rate is estimated to range between 0.82-1.70×10-8 mutations per base per generation. However, contribution of early postzygotic mutations to the overall human de novo SNV rate is unknown. Methods: We performed deep whole-genome sequencing (more than 30-fold coverage per individual) of the whole-blood-derived DNA samples of a healthy monozygotic twin pair and their parents. We examined the genotypes of each individual simultaneously for each of the SNVs and discovered de novo SNVs regarding the timing of mutagenesis. Putative de novo SNVs were validated using Sanger-based capillary sequencing. Results: We conservatively characterised 23 de novo SNVs shared by the twin pair, 8 de novo SNVs specific to twin I and 1 de novo SNV specific to twin II. Based on the number of de novo SNVs validated by Sanger sequencing and the number of callable bases of each twin, we calculated the overall de novo SNV rate of 1.31×10-8 and 1.01×10-8 for twin I and twin II, respectively. Of these, rates of the early postzygotic de novo SNVs were estimated to be 0.34×10-8 for twin I and 0.04×10-8 for twin II. Conclusions: Early postzygotic mutations constitute a substantial proportion of de novo mutations in humans. Therefore, genome mosaicism resulting from early mitotic events during embryogenesis is common and could substantially contribute to the development of diseases

A Survey of Bayesian Statistical Approaches for Big Data

The modern era is characterised as an era of information or Big Data. This has motivated a huge literature on new methods for extracting information and insights from these data. A natural question is how these approaches differ from those that were available prior to the advent of Big Data. We present a review of published studies that present Bayesian statistical approaches specifically for Big Data and discuss the reported and perceived benefits of these approaches. We conclude by addressing the question of whether focusing only on improving computational algorithms and infrastructure will be enough to face the challenges of Big Data

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Guidelines for postoperative care in gynecologic/oncology surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations - Part II.

This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

Residual effects of static stretching and self-myofascial-release exercises on flexibility and lower body explosive strength in well-trained combat athletes

BACKGROUND: The self-myofascial technique is a new exercise modality that is thought to improve muscular performance and restore soft tissue. However, there are limited empirical data demonstrating the efficacy of this technique on athletic performance. OBJECTIVE: The purpose of this study was to determine the effects of self-myofascial-releasing exercises on the residual characteristics of the sit and reach (S&R) and countermovement jump (CMJ) performance in well-trained combat athletes. METHODS: Sixteen well-trained male combat athletes (age: 23.9 ± 3.6 years, mass: 78.78 ± 10.41 kg, combat experience: 12.87 ± 5.23 years) performed three exercise sessions called "aerobic running (AR)", "aerobic running combined with static stretching (AR + SS)", and "aerobic running combined with self-myofascial release (AR + SMR)" at 48 hour intervals in a randomized crossover design. After each session, the subjects performed the S&R and CMJ tests successively with 30-s of rest between the tests at the 15th second and at the 2nd, 4th, 6th, 8th, 10th, 15th, and 30th minute during the recovery period. RESULTS: ANOVA and the post-hoc LSD (Least Significant Difference) test revealed that the AR + SMR treatment increased the flexibility greater than AR + SS (p = 0.029) at the 45th second. Additionally, the AR + SMR treatment resulted in less of a decrease in CMJ height compared to AR + SS at the 10th minute (p = 0.025). A larger decrease in the CMJ height was found after AR + SS compared to the AR and AR + SMR treatments at the 10th and 15th minute, respectively (p = 0.025 and p = 0.038). These results revealed that SMR had no advantage over AR and SS in terms of enhancing flexibility. A statistically insignificant inhibitory effect of SMR was detected on the CMJ performance. SS appeared to have an inhibitory effect on the CMJ performance for approximately 15 minutes. CONCLUSION: SMR may have a detrimental effect on CMJ performance. Trainers or athletes should consider using the SMR technique before training or competition to prevent possible power decrement. © 2017-IOS Press and the authors. All rights reserved

Comparison of the essential oils of Prangos turcica A. Duran, M. Sagiroglu et H. Duman fruits obtained by different isolation techniques

Baser, K. Husnu Can/0000-0003-2710-0231; Ozek, Temel/0000-0003-4251-8783WOS: 000240698400013The essential oils from fruits of Prangos turcica A. Duran, M. Sagiroglu et H. Duman were obtained by hydrodistillation (HD), microdistillation (MD), micro-steam distilled solid-phase microextraction (MSD-SPME) techniques and then analyzed by GC and GC/MS methods. The oils showed similar composition with some quantitative differences. The main components of the oils were found to be alpha-humulene, germacrene D, naphthalene, terpinolene, p-cymene, gamma-elemene and bornyl acetate

SIMULTANEOUS SELF-SUSTAINED ACTUATION AND PARALLEL READOUT WITH MEMS CANTILEVER SENSOR ARRAY

Parallel readout of a microcantilever array using single magnetic actuator and a single photo detector for concurrent detection is reported. The system includes MEMS cantilever array designed for different resonance frequencies, optical elements for laser beam shaping and focusing, one detector and feedback electronics, and single broadband actuator for parallel excitation. The cantilevers are made using a simple one-mask fabrication process with embedded amplitude gratings at the tips. A line shaped laser beam is used to illuminate the cantilevers. A single readout photodiode is placed at the first order diffraction beam location on the Fourier plane. The amplified photodiode signal is fed back into the magnetic actuation using a preamplifier and a broadband current amplifier. In this paper, we report for the first time parallel monitoring of the thermal resonance peaks of inherently frequency-multiplexed MEMS cantilevers. We demonstrated simultaneous self-sustained oscillations of seven cantilevers by using a single actuator and detector in air environment. The method is suitable for low-cost multiplexed portable biosensors

Manipulating the permeation of charged compounds through the MscL nanovalve

MscL is a bacterial mechanosensor that serves as a biological emergency release valve, releasing cytoplasmic solutes to the environment on osmotic downshock. Previous studies have recognized that this channel has properties that make it ideal for use as a triggered nanovalve for vesicular-based targeted drug-release devices. One can even change the modality of the sensor. Briefly, the introduction of charges into the MscL pore lumen gates the channel in the absence of membrane tension; thus, by inserting compounds that acquire a charge on exposure to an alternative stimulus, such as light or pH, into the pore of the channel, controllable nanoswitches that detect these alternative modalities have been engineered. However, a charge in the pore lumen could not only encourage actuation of the nanopore but also have a significant influence on the permeation of large charged compounds, which would thus have important implications for the efficiency of drug-release devices. In this study, we used in vivo and electrophysiological approaches to demonstrate that the introduction of a charge into pore lumen of MscL does indeed influence the permeation of charged molecules. These effects were more drastic for larger compounds and, surprisingly, were related to the orientation of the MscL channel in the membrane.—Yang, L-M, Blount, P. Manipulating the permeation of charged compounds through the MscL nanovalve