Genotyping errors in a calibrated DNA register: implications for identification of individuals

<p>Abstract</p> <p>Background</p> <p>The use of DNA methods for the identification and management of natural resources is gaining importance. In the future, it is likely that DNA registers will play an increasing role in this development. Microsatellite markers have been the primary tool in ecological, medical and forensic genetics for the past two decades. However, these markers are characterized by genotyping errors, and display challenges with calibration between laboratories and genotyping platforms. The Norwegian minke whale DNA register (NMDR) contains individual genetic profiles at ten microsatellite loci for 6737 individuals captured in the period 1997-2008. These analyses have been conducted in four separate laboratories for nearly a decade, and offer a unique opportunity to examine genotyping errors and their consequences in an individual based DNA register. We re-genotyped 240 samples, and, for the first time, applied a mixed regression model to look at potentially confounding effects on genotyping errors.</p> <p>Results</p> <p>The average genotyping error rate for the whole dataset was 0.013 per locus and 0.008 per allele. Errors were, however, not evenly distributed. A decreasing trend across time was apparent, along with a strong within-sample correlation, suggesting that error rates heavily depend on sample quality. In addition, some loci were more error prone than others. False allele size constituted 18 of 31 observed errors, and the remaining errors were ten false homozygotes (i.e., the <it>true </it>genotype was a heterozygote) and three false heterozygotes (i.e., the <it>true </it>genotype was a homozygote).</p> <p>Conclusions</p> <p>To our knowledge, this study represents the first investigation of genotyping error rates in a wildlife DNA register, and the first application of mixed models to examine multiple effects of different factors influencing the genotyping quality. It was demonstrated that DNA registers accumulating data over time have the ability to maintain calibration and genotyping consistency, despite analyses being conducted on different genotyping platforms and in different laboratories. Although errors were detected, it is demonstrated that if the re-genotyping of individual samples is possible, these will have a minimal effect on the database's primary purpose, i.e., to perform individual identification.</p

Identity, Resilience and Power in Self-Determination Conflicts

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Wavelet Screening identifies regions highly enriched for differentially methylated loci for orofacial clefts

DNA methylation is the most widely studied epigenetic mark in humans and plays an essential role in normal biological processes as well as in disease development. More focus has recently been placed on understanding functional aspects of methylation, prompting the development of methods to investigate the relationship between heterogeneity in methylation patterns and disease risk. However, most of these methods are limited in that they use simplified models that may rely on arbitrarily chosen parameters, they can only detect differentially methylated regions (DMRs) one at a time, or they are computationally intensive. To address these shortcomings, we present a wavelet-based method called ‘Wavelet Screening’ (WS) that can perform an epigenome-wide association study (EWAS) of thousands of individuals on a single CPU in only a matter of hours. By detecting multiple DMRs located near each other, WS identifies more complex patterns that can differentiate between different methylation profiles. We performed an extensive set of simulations to demonstrate the robustness and high power of WS, before applying it to a previously published EWAS dataset of orofacial clefts (OFCs). WS identified 82 associated regions containing several known genes and loci for OFCs, while other findings are novel and warrant replication in other OFCs cohorts.publishedVersio

The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation

Current published protocols for targeted differentiation of human stem cells toward pancreatic β-cells fail to deliver sufficiently mature cells with functional properties comparable to human islet β-cells. We aimed to assess whether Wnt-modulation could promote the final protocol stages of β-cell maturation, building our hypothesis on our previous findings of Wnt activation in immature hiPSC-derived stage 7 (S7) cells compared to adult human islets and with recent data reporting a link between Wnt/PCP and in vitro β-cell maturation. In this study, we stimulated canonical and non-canonical Wnt signaling in hiPSC-derived S7 cells using syntetic proteins including WNT3A, WNT4, WNT5A and WNT5B, and we inhibited endogenous Wnt signaling with the Tankyrase inhibitor G007-LK (TKi). Whereas neither canonical nor non-canonical Wnt stimulation alone was able to mature hiPSC-derived S7 cells, WNT-inhibition with TKi increased the fraction of monohormonal cells and global proteomics of TKi-treated S7 cells showed a proteomic signature more similar to adult human islets, suggesting that inhibition of endogenous Wnt contributes toward final β-cell maturation

Life expectancy gains from dietary modifications: a comparative modeling study in 7 countries

Background: Eating healthier is associated with a range of favorable health outcomes. Our previous model estimated the impact of dietary changes on life expectancy gains but did not consider height, weight, or physical activity. Objectives: We aimed to estimate the increase in life expectancy resulting from the transition from typical national dietary patterns to longevity-optimizing dietary changes, more feasible dietary modifications, and optimized vegan dietary changes in China, France, Germany, Iran, Norway, the United Kingdom, and the United States. Methods: Our modeling study used data from meta-analyses presenting dose-response relationships between intake of 15 food groups and mortality. Background mortality data were from the Global Burden of Disease Study. We used national food intake data and adjusted for height, weight, and physical activity level. Results: For 40-y-olds, estimated life expectancy gains ranged from 6.2 y (with uncertainty interval [UI]: 5.7, 7.5 y) for Chinese females to 9.7 y (UI: 8.1, 11.3 y) for United States males following sustained changes from typical country-specific dietary patterns to longevity-optimized dietary changes, and from 5.2 y (UI: 4.0, 6.5 y) for Chinese females to 8.7 y (UI: 7.1, 10.3 y) for United States males following changes to optimized vegan dietary changes. Conclusions: A sustained change from country-specific typical dietary pattern patterns to longevity-optimized dietary changes, more feasible dietary changes, or optimized vegan dietary changes are all projected to result in substantial life expectancy gains across ages and countries. These changes included more whole grains, legumes, and nuts and less red/processed meats and sugars and sugar-sweetened beverages. The largest gains from dietary changes would be in the United States

Arachnoid cysts do not contain cerebrospinal fluid: A comparative chemical analysis of arachnoid cyst fluid and cerebrospinal fluid in adults

<p>Abstract</p> <p>Background</p> <p>Arachnoid cyst (AC) fluid has not previously been compared with cerebrospinal fluid (CSF) from the same patient. ACs are commonly referred to as containing "CSF-like fluid". The objective of this study was to characterize AC fluid by clinical chemistry and to compare AC fluid to CSF drawn from the same patient. Such comparative analysis can shed further light on the mechanisms for filling and sustaining of ACs.</p> <p>Methods</p> <p>Cyst fluid from 15 adult patients with unilateral temporal AC (9 female, 6 male, age 22-77y) was compared with CSF from the same patients by clinical chemical analysis.</p> <p>Results</p> <p>AC fluid and CSF had the same osmolarity. There were no significant differences in the concentrations of sodium, potassium, chloride, calcium, magnesium or glucose. We found significant elevated concentration of phosphate in AC fluid (0.39 versus 0.35 mmol/L in CSF; <it>p </it>= 0.02), and significantly reduced concentrations of total protein (0.30 versus 0.41 g/L; <it>p </it>= 0.004), of ferritin (7.8 versus 25.5 ug/L; <it>p </it>= 0.001) and of lactate dehydrogenase (17.9 versus 35.6 U/L; <it>p </it>= 0.002) in AC fluid relative to CSF.</p> <p>Conclusions</p> <p>AC fluid is not identical to CSF. The differential composition of AC fluid relative to CSF supports secretion or active transport as the mechanism underlying cyst filling. Oncotic pressure gradients or slit-valves as mechanisms for generating fluid in temporal ACs are not supported by these results.</p

Production of charged pions, kaons and protons at large transverse momenta in pp and Pb-Pb collisions at sNN\sqrt{s_{NN}} = 2.76 TeV

Transverse momentum spectra of $\pi^{\pm}, K^{\pm}$ and $p(\bar{p})$ up to $p_T$ = 20 GeV/c at mid-rapidity, |y| $\le$ 0.8, in pp and Pb-Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV have been measured using the ALICE detector at the LHC. At intermediate $p_T$ (2-8 GeV/c) an enhancement of the proton-to-proton ratio, (p + \bar{p})/(\pi^+ + \pi^-\(), with respect to pp collisions is observed and the ratio reaches 0.80 in central Pb-Pb collisions. The measurement of the nuclear modification factors for \(\pi^{\pm}, K^{\pm} and $p(\bar{p})$ indicates that within the systematic and statistical uncertainties they are the same at high $p_T$ (> 10 GeV/c), suggesting that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.publishedVersio

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

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Time Course of Cerebrovascular Reactivity in Patients Treated for Unruptured Intracranial Aneurysms: A One-Year Transcranial Doppler and Acetazolamide Follow-Up Study

Background. Cerebrovascular reactivity (CVR) is often impaired in the early phase after aneurysmal subarachnoid hemorrhage. There is, however, little knowledge about the time course of CVR in patients treated for unruptured intracranial aneurysms (UIA). Methods. CVR, assessed by transcranial Doppler and acetazolamide test, was examined within the first postoperative week after treatment for UIA and reexamined one year later. Results. Of 37 patients initially assessed, 34 were reexamined after one year. Bilaterally, baseline and acetazolamide-induced blood flow velocities were higher in the postoperative week compared with one year later (p<0.001). CVR on the ipsilateral side of treatment was lower in the initial examination compared with follow-up (58.9% versus 66.1%, p=0.04). There was no difference in CVR over time on the contralateral side (63.4% versus 65.0%, p=0.65). When mean values of right and left sides were considered there was no difference in CVR between exams. Larger aneurysm size was associated with increased change in CVR (p=0.04), and treatment with clipping was associated with 13.8%-point increased change in CVR compared with coiling (p=0.03). Conclusion. Patients with UIA may have a temporary reduction in CVR on the ipsilateral side after aneurysm treatment. The change in CVR appears more pronounced for larger-sized aneurysms and in patients treated with clipping. We recommend that ipsilateral and contralateral CVR should be assessed separately, as mean values can conceal side-differences