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

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

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

THE INVESTIGATION OF THE STRENGTH REDUCTION FACTOR IN PREDICTING THE SHEAR STRENGTH

Design codes propose to restrict the nominal probability of failure within specific target structural reliability levels using a load factor and a strength reduction factor. In the current ACI318 Code, the strength reduction factor varies from 0.65 to 0.90, and the value considered in predicting the shear strength equals to 0.75. In this study, the change in the strength reduction factor in predicting the shear strength according to ACI318 has been investigated for different coefficients of variation of concrete compressive strength by using the first-order second moment approach, and the strength reduction factor is proposed for the target values of failure probability

The Presence of Donor-Specific Antibodies in Renal Transplantation

Determining the presence of anti-HLA antibodies before transplantation is an important factor to prevent loss of function among renal transplantations. In addition, recent studies have shown that not only the pretransplantation existence of anti-HLA antibody but also posttransplantation donor-specific antibodies (DSA) and non-donor-specific antibodies are significantly associated with allograft rejection or loss of graft function. This study presented DSA among patients after renal transplantation together with graft function and survival

The investigation of the strength reduction factor in predicting the shear strength

Design codes propose to restrict the nominal probability of failure within specific target structural reliability levels using a load factor and a strength reduction factor. In the current ACI318 Code, the strength reduction factor varies from 0.65 to 0.90, and the value considered in predicting the shear strength equals to 0.75. In this study, the change in the strength reduction factor in predicting the shear strength according to ACI318 has been investigated for different coefficients of variation of concrete compressive strength by using the first-order second moment approach, and the strength reduction factor is proposed for the target values of failure probability

Clinical and Histopathological Findings of Chordomas: a Case Report

Chordomas are rare malignant tumors that develop from the residual of embryonic notochord. These tumors may be seen along the spine and have a local aggressive progression. Skull base chordomas often originate from the clivus as localization. These tumors are usually found to be overgrown when they are diagnosed. They are locally invasive and rarely develop distant metastasis. These chordomas cannot usually be completely removed due to their localization. Because these tumors are advanced at the time of diagnosis and are adjacent to important structures, they are among the tumors with high rates of mortality and morbidity. Surgery and/or radiotherapy is administered for the treatment

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

A Sensory Valve in Liposomal Drug Delivery Systems

A mechano-gated membrane channel protein is used as a controllable, nonselective, large, aqueous pore in sterically stabilized liposomal drug delivery systems. The channel protein is engineered first to sense the light and/or the pH under iso-osmotic conditions, and then to convert these signals into conformational changes ultimately leading to pore formation in the drug loaded liposomes. This system offers not only the target specific drug delivery but also control over the timing of the delivery.