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Abstract Recent research into structural variants (SVs) has established their importance to medicine and molecular biology, elucidating their role in various diseases, regulation of gene expression, ethnic diversity, and large-scale chromosome evolution—giving rise to the differences within populations and among species. Nevertheless, characterizing SVs and determining the optimal approach for a given experimental design remains a computational and scientific challenge. Multiple approaches have emerged to target various SV classes, zygosities, and size ranges. Here, we review these approaches with respect to their ability to infer SVs across the full spectrum of large, complex variations and present computational methods for each approach.

Objective: Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients. Design and methods: Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specific radioimmunoassay in plasma samples collected during an oral glucose tolerance test. Results: 26RFa and GPR103 are present all along the gut but are more abundant in the stomach and duodenum. In the stomach, the peptide and its receptor are highly expressed in the gastric glands, whereas in the duodenum, ileum and colon they are present in the enterocytes and the goblet cells. In the pancreatic islets, the 26RFa/ GPR103 system is mostly present in the β cells. During an oral glucose tolerance test, plasma 26RFa profile is different between obese patients and healthy volunteers, and we found strong positive correlations between 26RFa blood level s and the BMI, and with various parameters of insulin secretion and insulin resistance.

Heteropagus twins are an extremely rare condition and the term describes asymmetrical conjoined twins in which one twin (“autosite”) has a mostly intact body and the other twin (“parasite”) remains anatomically incomplete but is attached to and nourished by the other one. Autosites may show severe malformations themselves that are not associated with the twins’ fusion. Beyond the challenge of surgical separation further complex reconstructions may be necessary. In this case series we want to demonstrate that despite complex anatomic features, good functional (e.g. gastrointestinal, genitourinary and motoric) and aesthetic results can be achieved.

The putative effectiveness of working memory (WM) training at enhancing cognitive and academic skills is still ardently debated. Several researchers have claimed that WM training fosters not only skills such as visuospatial WM and short-term memory (STM), but also abilities outside the domain of WM, such as fluid intelligence and mathematics. Other researchers, while acknowledging the positive effect of WM training on WM-related cognitive skills, are much more pessimistic about the ability of WM training to improve other cognitive and academic skills. In other words, the idea that far-transfer--that is, the generalization of a set of skills across two domains only loosely related to each other--may take place in WM training is still controversial. In this meta-analysis, the authors focused on the effects of WM training on cognitive and academic skills (e.g., fluid intelligence, attention/inhibition, mathematics, and literacy) in typically developing (TD) children (aged 3 to 16). Whereas WM training exerted a significant effect on cognitive skills related to WM training (g-bar = 0.46), little evidence was found regarding far-transfer effects (g-bar = 0.12). Moreover, the size of the effects was inversely related to the quality of the design (i.e., random allocation to the groups and presence of an active control group). Results suggest that WM training is ineffective at enhancing TD children's cognitive or academic skills and that, when positive effects are observed, they are modest at best. Thus, in line with other types of training, far-transfer rarely occurs and its effects are minimal.

Purpose: Laparoscopic ureteroureterostomy (LUU) has been proposed as an alternative to common sheath ureteral reimplantation (CSUR) in children with symptomatic duplex kidneys. However, data is limited for LUU in the pediatric population. The aim of this study was to analyze our experience with LUU and to compare the results with those after CSUR to assess whether a less invasive surgical approach could be a valid alternative.Patients and methods: The data of all children with duplex kidneys who underwent either LUU or CSUR at our center from 2006 to 2018 were reviewed retrospectively. After parental counseling, the option of LUU was provided as an alternative to CSUR for unilateral procedures and in the absence of vesicoureteral reflux to the receiving ureter. Baseline characteristics, indication for surgery, hospitalization and operative times, and intraoperative, post-operative, and late complications were analyzed. Preoperative and 1-year post-operative sonographies were reviewed by a pediatric radiologist. Increasing renal pelvic diameter (Δ >5 mm) was regarded as a sign of ureteral obstruction.Results: Forty children were included in this study, with 16 children receiving LUU and 24 children receiving CSUR. The children had a mean age of 2.7 years (7 months−9.8 years) and were followed up in our outpatient clinic for an average of 3.9 years (3 months−10.6 years) after surgery. The median hospital stay was 2 days shorter after LUU. Initially, a considerably longer time was needed for LUU, but after more experience was gained, similar operative times were observed for both procedures. Complications were encountered in both groups. After LUU, two patients developed anastomotic leakage: one was managed conservatively, and one required temporary nephrostomy. In the CSUR group, one patient developed vesicoureteral obstruction during follow-up and required reoperation with LUU. The occurrence of post-operative urinary tract infections was similar in both groups. No complications related to the ureteral stump after LUU arose.Conclusion: LUU is a safe and efficacious treatment option for children with duplex kidney anomalies and can be used as an alternative to CSUR. All children receiving LUU showed a non-obstructive, patent anastomosis and no signs for stenotic compromise of the receiving ureter.

Protein synthesis from mRNA is an energy-intensive and tightly controlled cellular process. Translation elongation is a well-coordinated, multifactorial step in translation that undergoes dynamic regulation owing to cellular state and environmental determinants. Recent studies involving genome-wide approaches have uncovered some crucial aspects of translation elongation including the mRNA itself and the nascent polypeptide chain. Additionally, these studies have fuelled quantitative and mathematical modelling of translation elongation. In this review, we provide a comprehensive overview of the key determinants of translation elongation. We discuss consequences of ribosome stalling or collision, and how the cells regulate translation in case of such events. Next, we review theoretical approaches and widely used mathematical models that have become an essential ingredient to interpret complex molecular datasets and study translation dynamics quantitatively. Finally, we review recent advances in live-cell reporter and related analysis techniques, to monitor the translation dynamics of single cells and single-mRNA molecules in real time.

The glucose-sensing Mondo pathway regulates expression of metabolic genes in mammals. Here, we characterized its function in the zebrafish and revealed an unexpected role of this pathway in vertebrate embryonic development. We showed that knockdown of mondoa impaired the early morphogenetic movement of epiboly in zebrafish embryos and caused microtubule defects. Expression of genes in the terpenoid backbone and sterol biosynthesis pathways upstream of pregnenolone synthesis was coordinately downregulated in these embryos, including the most downregulated gene nsdhl. Loss of Nsdhl function likewise impaired epiboly, similar to MondoA loss of function. Both epiboly and microtubule defects were partially restored by pregnenolone treatment. Maternal-zygotic mutants of mondoa showed perturbed epiboly with low penetrance and compensatory changes in the expression of terpenoid/sterol/steroid metabolism genes. Collectively, our results show a novel role for MondoA in the regulation of early vertebrate development, connecting glucose, cholesterol and steroid hormone metabolism with early embryonic cell movements.

We consider the problem of the numerical computation of its economic capital by an insurance or a bank, in the form of a value-at-risk or expected shortfall of its loss over a given time horizon. This loss includes the appreciation of the mark-to-model of the liabilities of the firm, which we account for by nested Monte Carlo à la Gordy and Juneja [17] or by regression à la Broadie, Du, and Moallemi [10]. Using a stochastic approximation point of view on value-at-risk and expected shortfall, we establish the convergence of the resulting economic capital simulation schemes, under mild assumptions that only bear on the theoretical limiting problem at hand, as opposed to assumptions on the approximating problems in [17] and [10]. Our economic capital estimates can then be made conditional in a Markov framework and integrated in an outer Monte Carlo simulation to yield the risk margin of the firm, corresponding to a market value margin (MVM) in insurance or to a capital valuation adjustment (KVA) in banking parlance. This is illustrated numerically by a KVA case study implemented on GPUs.

Microfossil records from ice archives allow vegetation, fire and land-use activity reconstructions on broad spatial scales. Samples typically contain low microfossil concentrations. Therefore, large ice volumes are often needed for palynology. Hence, it is crucial to extract maximum microfossil numbers through appropriate physical-chemical treatments. We compare six methods covering the main water reduction procedures: evaporation, filtration and centrifugation with snow samples. Adding a known number of Lycopodium marker spores prior to sample treatment and a second marker (Eucalyptus) after laboratory processing allows a quantitative microfossil loss assessment during pollen extraction. We applied the best-performing method (average loss of 22%) to high-alpine firn cores from Colle Gnifetti glacier for validation with a natural archive containing extremely low microfossil concentrations. We conclude that samples processed with different microfossil extraction protocols may give different results for pollen concentrations, percentages and ratios between different pollen types, especially if vesiculate conifer pollen is an important pollen assemblage component. We recommend a new evaporation-based method which delivers the smallest and least variable losses among the tested approaches. Since microfossil losses are inevitable during laboratory procedure, adding markers prior to sample processing is mandatory to achieve reliable microfossil concentration and influx estimates.

Abstract Background Holobionts have a digestive microbiota with catabolic abilities allowing the degradation of complex dietary compounds for the host. In terrestrial herbivores, the digestive microbiota is known to degrade complex polysaccharides from land plants while in marine herbivores, the digestive microbiota is poorly characterized. Most of the latter are generalists and consume red, green, and brown macroalgae, three distinct lineages characterized by a specific composition in complex polysaccharides, which represent half of their biomass. Subsequently, each macroalga features a specific epiphytic microbiota, and the digestive microbiota of marine herbivores is expected to vary with a monospecific algal diet. We investigated the effect of four monospecific diets (Palmaria palmata, Ulva lactuca, Saccharina latissima, Laminaria digitata) on the composition and specificity of the digestive microbiota of a generalist marine herbivore, the abalone, farmed in a temperate coastal area over a year. The microbiota from the abalone digestive gland was sampled every 2 months and explored using metabarcoding. Results Diversity and multivariate analyses showed that patterns of the microbiota were significantly linked to seasonal variations of contextual parameters but not directly to a specific algal diet. Three core genera: Psychrilyobacter, Mycoplasma, and Vibrio constantly dominated the microbiota in the abalone digestive gland. Additionally, a less abundant and diet-specific core microbiota featured genera representing aerobic primary degraders of algal polysaccharides. Conclusions This study highlights the establishment of a persistent core microbiota in the digestive gland of the abalone since its juvenile state and the presence of a less abundant and diet-specific core community. While composed of different microbial taxa compared to terrestrial herbivores, the digestive gland constitutes a particular niche in the abalone holobiont, where bacteria (i) may cooperate to degrade algal polysaccharides to products assimilable by the host or (ii) may have acquired these functions through gene transfer from the aerobic algal microbiota.