Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, abeta, and alzheimer's disease.

Background: The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD). Methodology/Principal findings: We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8), fold-increase = 2.12,); the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003). Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2)-C (p = 0.006) and HepG2 (p = 0.02) cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879), we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011) and total measured plasma Abeta levels (b = -0.130, p = 0.009). Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03), and the eleven IDE haplotypes (global p = 0.02) also showed significant association. Conclusions: Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Ass40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs) strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Data from: Ovary development and cold tolerance of the invasive pest Drosophila suzukii (Matsumura) in the central plains of Kansas, United States

Environmental challenges presented by temperature variation can be overcome through phenotypic plasticity in small invasive ectotherms. We tested the effect of thermal exposure to 21, 18, and 11°C throughout the whole life cycle of individuals, thermal exposure of adults reared at 25°C to 15 and 11°C for a 21-d period, and long (14:10 hr) and short (10:14 hr) photoperiod on ovary size and development in Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) cultured from a recently established population in Topeka, Kansas (United States). Examination of the response to temperature and photoperiod variation in this central plains population provides insight into the role of phenotypic plasticity in a climate that is warmer than regions in North America where D. suzukii was initially established. We found both low temperature and short photoperiod resulted in reduced ovary size and level of development. In particular, reduced ovary development was observed following exposure to 15°C, indicating that ovary development in females from the central plains population is more sensitive to lower temperature compared with populations examined from the northern United States and southern Canada. We also provide evidence that D. suzukii reared at 25°C are capable of short-term hardening when exposed to −6°C following 4°C acclimation, contrary to previous reports indicating flies reared at warm temperatures do not rapidly-cold harden. Our study highlights the central role of phenotypic plasticity in response to winter-like laboratory conditions and provides an important geographic comparison to previously published assessments of ovary development and short-term hardening survival response for D. suzukii collected in cooler climates

Ovary and Cold Tolerance D. suzukii Data

A spreadsheet containing ovary dimensional sizes and stages of development for D. suzukii samples in different rearing/temperature conditions

Xander: employing a novel method for efficient gene-targeted metagenomic assembly

BackgroundMetagenomics can provide important insight into microbial communities. However, assembling metagenomic datasets has proven to be computationally challenging. Current methods often assemble only fragmented partial genes.ResultsWe present a novel method for targeting assembly of specific protein-coding genes. This method combines a de Bruijn graph, as used in standard assembly approaches, and a protein profile hidden Markov model (HMM) for the gene of interest, as used in standard annotation approaches. These are used to create a novel combined weighted assembly graph. Xander performs both assembly and annotation concomitantly using information incorporated in this graph. We demonstrate the utility of this approach by assembling contigs for one phylogenetic marker gene and for two functional marker genes, first on Human Microbiome Project (HMP)-defined community Illumina data and then on 21 rhizosphere soil metagenomic datasets from three different crops totaling over 800 Gbp of unassembled data. We compared our method to a recently published bulk metagenome assembly method and a recently published gene-targeted assembler and found our method produced more, longer, and higher quality gene sequences.ConclusionXander combines gene assignment with the rapid assembly of full-length or near full-length functional genes from metagenomic data without requiring bulk assembly or post-processing to find genes of interest. HMMs used for assembly can be tailored to the targeted genes, allowing flexibility to improve annotation over generic annotation pipelines. This method is implemented as open source software and is available at https://github.com/rdpstaff/Xander_assembler

Glycogen depletion can increase the specificity of mucin detection in airway tissues

Objective: Mucin is an important parameter for detection and assessment in studies of airway disease including asthma and cystic fibrosis. Histochemical techniques are often used to evaluate mucin in tissues sections. Periodic acid Schiff (PAS) is a common technique to detect neutral mucins in tissue, but this technique also detects other tissue components including cellular glycogen. We tested whether depletion of glycogen, a common cellular constituent, could impact the detection of mucin in the surface epithelium of the trachea. Results: Normal tissues stained by PAS had significantly more staining than serial sections of glycogen-depleted tissue with PAS staining (i.e. dPAS technique) based on both quantitative analysis and semiquantitative scores. Most of the excess stain by the PAS technique was detected in ciliated cells adjacent to goblet cells. We also compared normal tissues using the Alcian blue technique, which does not have reported glycogen staining, with the dPAS technique. These groups had similar amounts of staining consistent with a high degree of mucin specificity. Our results suggest that when using PAS techniques to stain airways, the dPAS approach is preferred as it enhances the specificity for airway mucin.This article is published as Meyerholz, David K., Amanda P. Beck, J. Adam Goeken, Mariah R. Leidinger, Georgina K. Ofori-Amanfo, Hannah C. Brown, Thomas R. Businga, David A. Stoltz, Leah R. Reznikov, and Heather A. Flaherty. "Glycogen depletion can increase the specificity of mucin detection in airway tissues." BMC Research Notes 11 (2018): 1-5. DOI: 10.1186/s13104-018-3855-y. Copyright 2018 The Author(s). Attribution 4.0 International (CC BY 4.0). Posted with permission

Glycogen depletion can increase the specificity of mucin detection in airway tissues

Abstract Objective Mucin is an important parameter for detection and assessment in studies of airway disease including asthma and cystic fibrosis. Histochemical techniques are often used to evaluate mucin in tissues sections. Periodic acid Schiff (PAS) is a common technique to detect neutral mucins in tissue, but this technique also detects other tissue components including cellular glycogen. We tested whether depletion of glycogen, a common cellular constituent, could impact the detection of mucin in the surface epithelium of the trachea. Results Normal tissues stained by PAS had significantly more staining than serial sections of glycogen-depleted tissue with PAS staining (i.e. dPAS technique) based on both quantitative analysis and semiquantitative scores. Most of the excess stain by the PAS technique was detected in ciliated cells adjacent to goblet cells. We also compared normal tissues using the Alcian blue technique, which does not have reported glycogen staining, with the dPAS technique. These groups had similar amounts of staining consistent with a high degree of mucin specificity. Our results suggest that when using PAS techniques to stain airways, the dPAS approach is preferred as it enhances the specificity for airway mucin

Earnings and Occupational Attainment: Immigrants and the Native Born

This paper examines the determinants of occupational attainment and the impact of occupation on earnings. Results for both the native born and foreign born are presented, and these provide insights as to the earnings penalties associated with the less-than-perfect international transferability of human capital skills. It shows that around 50 percent of the earnings gains associated with years of schooling derives from inter-occupational mobility. When occupation is held constant, there is a large increase in the effect on earnings of pre-immigration labor market experience for the foreign born, but little change in either the payoff to labor market experience for the native born, or in the premium for post-arrival labor market experience for the foreign born. The estimates of the models of occupational attainment show that years of schooling, and, among the foreign born, proficiency in English, are the key factors determining access to high-paying occupations. Labor market experience has little effect on occupational outcomes among the native born. However, evaluated at 10 years, foreign labor market experience has a modest negative impact on current occupational status. Examination of this negative effect using quantile regression shows that it is concentrated among those in high status jobs