effects Effects of School-Wide Positive Behavioral Interventions and Supports on Child Behavior Problems By pediatrics.aappublications.org Published On :: 2012-10-15T00:08:11-07:00 School-Wide Positive Behavioral Interventions and Supports (SWPBIS) is a widely used universal prevention strategy currently implemented in >16 000 schools across the United States. Previous research has shown positive effects on school climate and school-level discipline problems.This study reports multilevel results on data from a 4-year randomized controlled effectiveness trial of SWPBIS in 37 elementary schools. Results indicate significant impacts on children’s aggressive behavior problems, concentration problems, office discipline referrals, emotion regulation, and prosocial behavior. (Read the full article) Full Article
effects Effects of Glutamine on Brain Development in Very Preterm Children at School Age By pediatrics.aappublications.org Published On :: 2012-10-15T00:08:08-07:00 Brain maturation processes of very premature children are adversely affected by serious neonatal infections. Differences in brain development persist into childhood and adolescence, and underpin widespread neurocognitive and behavioral deficits in very preterm children.We present evidence for long-term beneficial effects of early nutritional intervention with glutamine in very preterm infants on brain development at 8 years of age, mediated by a decrease in the number of serious neonatal infections. (Read the full article) Full Article
effects Effects of Iron Supplementation of LBW Infants on Cognition and Behavior at 3 Years By pediatrics.aappublications.org Published On :: 2012-12-10T00:07:55-08:00 Low birth weight (LBW) infants (<2500 g) are at risk for cognitive and behavioral problems later in life. During infancy, they are also at risk for iron deficiency, which has been associated with impaired neurodevelopment in other high-risk groups.Iron supplementation during the first 6 months of life to LBW infants reduces the risk of behavioral problems at 3.5 years. Mild iron deficiency in infancy may be an important, preventable contributor to behavioral problems in children born with LBW. (Read the full article) Full Article
effects Neuropsychological Effects of Konzo: A Neuromotor Disease Associated With Poorly Processed Cassava By pediatrics.aappublications.org Published On :: 2013-03-25T01:07:31-07:00 Konzo is an irreversible sudden-onset upper-motor neuron disorder affecting children dependent on bitter cassava for food. The neuroepidemiology of konzo is well characterized. Children subsisting on poorly processed bitter cassava without adequate dietary sulfur-based amino acids are especially at risk.We found a pervasive subclinical neurocognitive effect in children with konzo. This study provides the first evidence we are aware of that a motor proficiency examination can effectively characterize konzo severity. (Read the full article) Full Article
effects Plate Size and Children's Appetite: Effects of Larger Dishware on Self-Served Portions and Intake By pediatrics.aappublications.org Published On :: 2013-04-08T00:06:51-07:00 Research has shown that dishware size influences self-served portion sizes and meal intake in adults. In children, larger bowls led children to request more food, but whether larger dishware affects children’s self-served portions or intake at meals is not known.We assessed the effect of increasing dishware size on self-served portions and intake in young children. Larger plates and bowls resulted in larger self-served portions, and indirectly promoted greater intake, emphasizing the importance of age-appropriate dishware. (Read the full article) Full Article
effects The Effects of Music Therapy on Vital Signs, Feeding, and Sleep in Premature Infants By pediatrics.aappublications.org Published On :: 2013-04-15T00:06:43-07:00 Recorded music, parent voices, and sung lullabies have been shown to increase oxygen saturation, nonnutritive sucking, and weight gain in premature infants.Parent-preferred melodies and entrained live rhythm and breath sounds can enhance quiet alert and sleep states, suck response, and oxygen saturation in premature infants and significantly reduce fear and anxiety perception in parents. (Read the full article) Full Article
effects Effects of Reduced Juice Allowances in Food Packages for the Women, Infants, and Children Program By pediatrics.aappublications.org Published On :: 2013-04-29T00:06:30-07:00 Juice consumption among 2- to 5-year-old children exceeds dietary recommendations. In 2007, the US Department of Agriculture revised the composition and quantities of prescribed foods in WIC food packages to align them with dietary guidelines. Juice allowances were reduced by approximately half.WIC participants purchased about a quarter less juice volume after implementation of the revised WIC packages. Large reductions in WIC-provided juice were only partly compensated for by extra juice purchases with non-WIC funds. Little compensation occurred for other beverages. (Read the full article) Full Article
effects Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial By pediatrics.aappublications.org Published On :: 2013-11-18T00:06:44-08:00 Late-onset sepsis is a frequent complication of prematurity, contributing to morbidity and mortality. Although evidence is accumulating that administration of probiotics to very preterm infants reduces necrotizing enterocolitis (NEC) and all-cause mortality, the effect on late-onset sepsis is less clear.The probiotic combination Bifidobacterium infantis, Streptococcus thermophilus, and Bifidobacterium lactis reduced NEC in very preterm infants, but not mortality or late-onset sepsis. Probiotics may be of greatest global value in neonatal settings with high rates of NEC. (Read the full article) Full Article
effects Acute and Chronic Effects of Sleep Duration on Blood Pressure By pediatrics.aappublications.org Published On :: 2013-12-16T00:07:06-08:00 Inconsistent results have been reported on the association between sleep duration and blood pressure (BP) in children, likely as a result of inadequate adjustment for confounders and the use of different time frames in assessing sleep duration.Short sleep duration and poor sleep quality are associated with higher BP in normal-weight adolescents. One night of adequate sleep may partially ameliorate the risk of high BP but cannot completely reverse the effect of chronic sleep insufficiency. (Read the full article) Full Article
effects Immunologic Effects of Hydroxyurea in Sickle Cell Anemia By pediatrics.aappublications.org Published On :: 2014-09-01T00:06:19-07:00 Hydroxyurea is a treatment option for young patients with sickle cell disease (SCD). Establishing the safety of hydroxyurea is of paramount importance. The effect of hydroxyurea on immune function and immunizations in SCD has not been studied previously.Children with SCD receiving hydroxyurea have lower lymphocyte, CD4, and memory T-cell counts compared with those receiving placebo, but still in the range for healthy children. Despite slower response to measles vaccine, measles, mumps, and rubella and pneumococcal vaccines are effective. (Read the full article) Full Article
effects Effects of the FITKids Randomized Controlled Trial on Executive Control and Brain Function By pediatrics.aappublications.org Published On :: 2014-09-29T00:06:48-07:00 Physical activity programs have been shown to have positive implications for children’s cognitive performance and brain structure and function. However, additional randomized controlled trials are needed to determine whether daily physical activity influences executive control and its neural underpinnings.The randomized controlled trial, designed to meet daily physical activity recommendations, used behavioral and electrophysiological measures of brain function to demonstrate enhanced attentional inhibition and cognitive flexibility among prepubertal children. (Read the full article) Full Article
effects Academic Effects of Concussion in Children and Adolescents By pediatrics.aappublications.org Published On :: 2015-05-11T00:05:24-07:00 Concussion produces a range of symptoms that may impede academic functioning. The need for empirical validation exists, despite growing consensus on the importance of a guided return-to-school process for students recovering from concussion.This study provides initial evidence of a concussion’s adverse effects on academic learning and performance across all grades, including heightened levels of school-related concern and amplified postinjury academic difficulties experienced by symptomatic students relative to their recovered peers. (Read the full article) Full Article
effects Effects of Physician-Based Preventive Oral Health Services on Dental Caries By pediatrics.aappublications.org Published On :: 2015-06-29T00:07:57-07:00 The US Preventive Services Task Force recommends primary care clinicians apply fluoride varnish to the teeth of all young children, but no studies have examined the effect of comprehensive preventive oral health services on children’s clinical oral health status.Comprehensive preventive oral health services delivered by primary care clinicians can help improve the oral health of Medicaid-enrolled children, but more work is needed to link medical and dental offices to ensure the continuity of dental care for these children. (Read the full article) Full Article
effects Effects of Genotype and Sleep on Temperament By pediatrics.aappublications.org Published On :: 2015-09-14T00:07:39-07:00 Sleep disturbances in infants associate with individual differences in temperament. However, little is known about interindividual differences and potential moderating factors, such as genotype.The results suggest that the cumulative effect of total sleep duration during the first 3 years of life on temperament is moderated by child 5-HTTLPR genotype following a differential susceptibility model. (Read the full article) Full Article
effects Long-term Effects of Pediatric Burns on the Circulatory System By pediatrics.aappublications.org Published On :: 2015-10-12T00:07:18-07:00 Systemic responses occur after burn injury that lead to widespread changes to the body, including the heart. Elevated levels of catecholamines and stress hormones have been found up to 3 years after severe burns. Little is known about the longer-term effects.Children with burns had 1.3 times as many admissions and 2.3 times the number of days in hospital for circulatory diseases compared with uninjured children. Children with minor burns had an increased risk of incident admissions for circulatory diseases. (Read the full article) Full Article
effects Penn State Smeal panel explores pandemic's effects on sustainability, business By news.psu.edu Published On :: Fri, 01 May 2020 13:15 -0400 The Penn State Smeal College of Business Center for the Business of Sustainability recently hosted the first in a series of virtual fireside discussions titled “The Impact of Coronavirus on Sustainability and Social Impact,” to explore how recent momentum in sustainability efforts has been altered. Full Article
effects The Side Effects of Education: Research and Practice By feedproxy.google.com Published On :: Wed, 12 Sep 2018 00:00:00 +0000 If researchers hope to identify programs that will prepare students for the future, then they cannot continue to measure innovation based on the ideas from the past. Full Article Research
effects Microsoft Adds CRT Effects to Windows Terminal By www.pcmag.com Published On :: Now we're typing with scan lines! Full Article
effects Plasma medicine research highlights antibacterial effects and potential uses By news.psu.edu Published On :: Wed, 06 May 2020 09:22 -0400 Researchers in Penn State’s College of Engineering, College of Agricultural Sciences and College of Medicine say direct LTP treatment and plasma-activated media are effective treatments against bacteria found in liquid cultures and have devised a way to create plasma directly in liquids. Full Article
effects Unreal Engine 425 released by Epic Games Brings PS5 and Xbox Series X support and Niagara visual effects system By feedproxy.google.com Published On :: 2020-05-05T20:35:20+05:30 Full Article Gaming
effects Unreal Engine 425 released by Epic Games Brings PS5 and Xbox Series X support and Niagara visual effects system By feedproxy.google.com Published On :: 2020-05-05T20:35:20+05:30 Full Article Gaming
effects Visakhapatnam gas leak: AIIMS director says long-term health effects due to styrene vapour exposure small By www.financialexpress.com Published On :: 2020-05-07T19:21:00+05:30 Guleria said inhalation and ingestion of styrene can cause effect the skin and the eyes. Full Article Health Lifestyle
effects Copenhagen city plans to resist the effects of climatic changes in fu By www.visareporter.com Published On :: Sat, 26 Oct 2013 00:00:00 GMT The threat for global warming is increasing in this world with each passing day. It is not a distant future when the effects of the global warming will hit hard the lives of the human. However, seeing the future threat Denmark has braced itself with… Full Article
effects Study shows toxic effects on human cells of dioxins in recycled toys By chemicalwatch.com Published On :: Thu, 07 May 2020 13:22:00 GMT 'New type of analysis' deployed to determine plastics' toxicity Full Article
effects Google Duo update delivers AR effects, ‘family mode’ and a whole lot more By phandroid.com Published On :: Fri, 08 May 2020 19:49:50 +0000 Google has already rolled out a few updates to Duo since the COVID-19 pandemic hit. Since video chat is more important than ever, Google is making Duo a priority, bring its video chat up to parity with its biggest competitors.This latest update packs in new AR effects which always make video calls a bit more ... Full Article Android Apps Duo Google Duo video calling video calling apps video chat
effects Effects of Increased Solar and Wind Energy on Hydro Plant Operation By feedproxy.google.com Published On :: 2014-12-19T20:30:00Z In many countries, needs to reduce greenhouse gas emissions have led to increased installation of intermittent renewables such as wind and solar. Full Article Solar Hydropower
effects Effects of Increased Solar and Wind Energy on Hydro Plant Operation By feedproxy.google.com Published On :: 2014-12-19T20:30:00Z In many countries, needs to reduce greenhouse gas emissions have led to increased installation of intermittent renewables such as wind and solar. Full Article Solar Hydropower
effects Can Technology Offset the Effects of Population Aging on Economic Growth? New Report from the Asian Development Bank By feedproxy.google.com Published On :: Fri, 27 Mar 2020 02:59:47 +0000 By East-West Center HONOLULU (March 27, 2020)—Population aging is affecting countries all across Asia. This ongoing demographic transition will leave many of the region’s economies increasingly dependent on an aging, and eventually a shrinking, workforce. Economists disagree, however, on whether population aging will necessarily lead to a slowdown in economic growth. This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more. Full Article
effects U.N. Releases Report on Socio-economic Effects of Coronavirus By www.ipsnews.net Published On :: Fri, 03 Apr 2020 12:23:18 +0000 As the number of coronavirus cases continues to grow, concerns are simultaneously growing about the current and long-term effects this will have on certain demographics — specifically, women, the youth, migrant workers, and many employees around the world. This week, the United Nations launched a report “Shared Responsibility, Global Solidarity: Responding to the socio-economic impacts […] The post U.N. Releases Report on Socio-economic Effects of Coronavirus appeared first on Inter Press Service. Full Article Editors' Choice Education Featured Gender Global Headlines Health Human Rights Humanitarian Emergencies IPS UN: Inside the Glasshouse Population Poverty & SDGs TerraViva United Nations Coronavirus COVID-19 International Organization for Migration (IOM) World Health Organisation (WHO)
effects The Effects of Privatization and Corporate Governance of SOEs in Transition Economy: The Case of Kazakhstan By feedproxy.google.com Published On :: 2020-04-24 00:00:00 Privatization has different effects depending on the types of owners to whom it gives control in corporate governance. Full Article
effects The Effects of Privatization and Corporate Governance of SOEs in Transition Economy: The Case of Kazakhstan By www.adb.org Published On :: 2020-04-24 00:00:00 Privatization has different effects depending on the types of owners to whom it gives control in corporate governance. Full Article
effects How I went from selling MDMA to researching the science of its effects By www.newscientist.com Published On :: Thu, 27 Feb 2020 13:27:44 +0000 Christopher Medina-Kirchner used to be a drug dealer. Now he is a researcher looking at their effects, and says society's views on drugs and addiction need updating Full Article
effects 2-Minute Walk Every Hour May Help Offset Effects of Sitting By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: 2-Minute Walk Every Hour May Help Offset Effects of SittingCategory: Health NewsCreated: 4/30/2015 12:00:00 AMLast Editorial Review: 5/1/2015 12:00:00 AM Full Article
effects Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Omega-3 Fish Oil Supplements Might Boost Antidepressants' EffectsCategory: Health NewsCreated: 4/26/2016 12:00:00 AMLast Editorial Review: 4/27/2016 12:00:00 AM Full Article
effects Recommended Diuretic Drug Tied to Harmful Side Effects By www.medicinenet.com Published On :: Wed, 19 Feb 2020 00:00:00 PDT Title: Recommended Diuretic Drug Tied to Harmful Side EffectsCategory: Health NewsCreated: 2/18/2020 12:00:00 AMLast Editorial Review: 2/19/2020 12:00:00 AM Full Article
effects Birth Control Options (Types and Side Effects) By www.medicinenet.com Published On :: Fri, 10 Apr 2020 00:00:00 PDT Title: Birth Control Options (Types and Side Effects)Category: Diseases and ConditionsCreated: 9/13/1999 12:00:00 AMLast Editorial Review: 4/10/2020 12:00:00 AM Full Article
effects Lasix Side Effects, Warnings, and Drug Interactions By www.medicinenet.com Published On :: Wed, 4 Mar 2020 00:00:00 PDT Title: Lasix Side Effects, Warnings, and Drug InteractionsCategory: MedicationsCreated: 3/4/2020 12:00:00 AMLast Editorial Review: 3/4/2020 12:00:00 AM Full Article
effects Birth Control Pills (List of Oral Contraceptives and Side Effects) By www.medicinenet.com Published On :: Thu, 30 Jan 2020 00:00:00 PDT Title: Birth Control Pills (List of Oral Contraceptives and Side Effects)Category: MedicationsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 1/30/2020 12:00:00 AM Full Article
effects Allergy Med Singulair to Get 'Black Box' Warning Over Psych Side Effects: FDA By www.medicinenet.com Published On :: Thu, 5 Mar 2020 00:00:00 PDT Title: Allergy Med Singulair to Get 'Black Box' Warning Over Psych Side Effects: FDACategory: Health NewsCreated: 3/4/2020 12:00:00 AMLast Editorial Review: 3/5/2020 12:00:00 AM Full Article
effects The Additive Effects of Cell Phone Use and Dental Hygiene Practice on Finger Muscle Strength: A Pilot Study By jdh.adha.org Published On :: 2020-04-30T12:39:03-07:00 Purpose: The purpose of this study was to determine strength of muscles involved with instrumentation (scaling) by dental hygienists and the additive effects of cellular (mobile) phone usage, as indicated by measurements of muscular force generation.Methods: A convenience sample of licensed dental hygienists currently in clinical practice (n=16) and an equal number of individuals not currently using devices/tools repetitively for work (n=16), agreed to participate in this pilot study. All participants completed a modified cell phone usage questionnaire to determine their use pattern and frequency. Upon completion of the questionnaire, participants' force production in six muscle groups was measured using a hand-held dynamometer. Descriptive statistics were used to analyze the data.Results: A total of 16 licensed dental hygienists (n=16) and 16 participants with no history of using tools/devices repetitively for work (n=16), comprised the experimental and control groups, repectively. The control group generated greater muscle force than the experimental group for the abductor pollicis longus (p=0.045). Significant differences were identified when comparing the low mobile phone users in the experimental group to the control group for the flexor pollicis brevis (p=0.031), abductor pollicis longus (p=0.031), and flexor digitorum (p=0.006), with the control group demonstrating higher muscle force. Years in clinical practice and mobile phone use was shown to have a significant effect on muscular force generation for the flexor pollicis brevis (F=3.645, df=3, p=0.020) and flexor digitorum (F=3.560, df=3, p=0.022); subjects who practiced dental hygiene the longest produced the least amount of muscle force.Conclusion: Results from this pilot study indicate there are no significant additive effects of cell phone use and dental hygiene practice on finger muscles used for instrumentation. However, results indicate that dental hygiene practice demonstrated significant effects on muscular strength as compared to individuals who do not use tools/devices repetitively for work. The small sample size may have impacted results and the study should be repeated with a larger sample. Full Article
effects Latent Toxoplasmosis Effects on Rodents and Humans: How Much is Real and How Much is Media Hype? By mbio.asm.org Published On :: 2020-03-17T01:30:14-07:00 ABSTRACT Toxoplasma gondii is a ubiquitous, intracellular protozoan parasite with a broad range of intermediate hosts, including humans and rodents. In many hosts, T. gondii establishes a latent long-term infection by converting from its rapidly dividing or lytic form to its slowly replicating and encysting form. In humans and rodents, the major organ for encystment is the central nervous system (CNS), which has led many to investigate how this persistent CNS infection might influence rodent and human behavior and, more recently, neurodegenerative diseases. Given the interest in this topic, here we seek to take a global approach to the data for and against the effects of latent T. gondii on behavior and neurodegeneration and the proposed mechanisms that might underlie behavior modifications. Full Article
effects Early and Often: The Need for Comprehensive Discussion of Treatment-Induced Cancer Late Effects By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 Full Article
effects Parental Considerations Regarding Cure and Late Effects for Children With Cancer By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 BACKGROUND: More than 80% of children with cancer become long-term survivors, yet most survivors experience late effects of treatment. Little is known about how parents and physicians consider late-effects risks against a potential survival benefit when making treatment decisions. METHODS: We used a discrete choice experiment to assess the importance of late effects on treatment decision-making and acceptable trade-offs between late-effects risks and survival benefit. We surveyed 95 parents of children with cancer and 41 physicians at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center to assess preferences for 5 late effects of treatment: neurocognitive impairment, infertility, cardiac toxicity, second malignancies, and impaired growth and development. RESULTS: Each late effect had a statistically significant association with treatment choice, as did survival benefit (P < .001). Avoidance of severe cognitive impairment was the most important treatment consideration to parents and physicians. Parents also valued cure and decreased risk of second malignancies; physician decision-making was driven by avoidance of second malignancies and infertility. Both parents and physicians accepted a high risk of infertility (parents, a 137% increased risk; physicians, an 80% increased risk) in exchange for a 10% greater chance of cure. CONCLUSIONS: Avoidance of severe neurocognitive impairment was the predominant driver of parent and physician treatment preferences, even over an increased chance of cure. This highlights the importance of exploring parental late-effects priorities when discussing treatment options. Full Article
effects Dominance Effects and Functional Enrichments Improve Prediction of Agronomic Traits in Hybrid Maize [Genomic Prediction] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Single-cross hybrids have been critical to the improvement of maize (Zea mays L.), but the characterization of their genetic architectures remains challenging. Previous studies of hybrid maize have shown the contribution of within-locus complementation effects (dominance) and their differential importance across functional classes of loci. However, they have generally considered panels of limited genetic diversity, and have shown little benefit from genomic prediction based on dominance or functional enrichments. This study investigates the relevance of dominance and functional classes of variants in genomic models for agronomic traits in diverse populations of hybrid maize. We based our analyses on a diverse panel of inbred lines crossed with two testers representative of the major heterotic groups in the U.S. (1106 hybrids), as well as a collection of 24 biparental populations crossed with a single tester (1640 hybrids). We investigated three agronomic traits: days to silking (DTS), plant height (PH), and grain yield (GY). Our results point to the presence of dominance for all traits, but also among-locus complementation (epistasis) for DTS and genotype-by-environment interactions for GY. Consistently, dominance improved genomic prediction for PH only. In addition, we assessed enrichment of genetic effects in classes defined by genic regions (gene annotation), structural features (recombination rate and chromatin openness), and evolutionary features (minor allele frequency and evolutionary constraint). We found support for enrichment in genic regions and subsequent improvement of genomic prediction for all traits. Our results suggest that dominance and gene annotations improve genomic prediction across diverse populations in hybrid maize. Full Article
effects Space is the Place: Effects of Continuous Spatial Structure on Analysis of Population Genetic Data [Population and Evolutionary Genetics] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Real geography is continuous, but standard models in population genetics are based on discrete, well-mixed populations. As a result, many methods of analyzing genetic data assume that samples are a random draw from a well-mixed population, but are applied to clustered samples from populations that are structured clinally over space. Here, we use simulations of populations living in continuous geography to study the impacts of dispersal and sampling strategy on population genetic summary statistics, demographic inference, and genome-wide association studies (GWAS). We find that most common summary statistics have distributions that differ substantially from those seen in well-mixed populations, especially when Wright’s neighborhood size is < 100 and sampling is spatially clustered. "Stepping-stone" models reproduce some of these effects, but discretizing the landscape introduces artifacts that in some cases are exacerbated at higher resolutions. The combination of low dispersal and clustered sampling causes demographic inference from the site frequency spectrum to infer more turbulent demographic histories, but averaged results across multiple simulations revealed surprisingly little systematic bias. We also show that the combination of spatially autocorrelated environments and limited dispersal causes GWAS to identify spurious signals of genetic association with purely environmentally determined phenotypes, and that this bias is only partially corrected by regressing out principal components of ancestry. Last, we discuss the relevance of our simulation results for inference from genetic variation in real organisms. Full Article
effects Fast Algorithms for Conducting Large-Scale GWAS of Age-at-Onset Traits Using Cox Mixed-Effects Models [Statistical Genetics and Genomics] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Age-at-onset is one of the critical traits in cohort studies of age-related diseases. Large-scale genome-wide association studies (GWAS) of age-at-onset traits can provide more insights into genetic effects on disease progression and transitions between stages. Moreover, proportional hazards (or Cox) regression models can achieve higher statistical power in a cohort study than a case-control trait using logistic regression. Although mixed-effects models are widely used in GWAS to correct for sample dependence, application of Cox mixed-effects models (CMEMs) to large-scale GWAS is so far hindered by intractable computational cost. In this work, we propose COXMEG, an efficient R package for conducting GWAS of age-at-onset traits using CMEMs. COXMEG introduces fast estimation algorithms for general sparse relatedness matrices including, but not limited to, block-diagonal pedigree-based matrices. COXMEG also introduces a fast and powerful score test for dense relatedness matrices, accounting for both population stratification and family structure. In addition, COXMEG generalizes existing algorithms to support positive semidefinite relatedness matrices, which are common in twin and family studies. Our simulation studies suggest that COXMEG, depending on the structure of the relatedness matrix, is orders of magnitude computationally more efficient than coxme and coxph with frailty for GWAS. We found that using sparse approximation of relatedness matrices yielded highly comparable results in controlling false-positive rate and retaining statistical power for an ethnically homogeneous family-based sample. By applying COXMEG to a study of Alzheimer’s disease (AD) with a Late-Onset Alzheimer’s Disease Family Study from the National Institute on Aging sample comprising 3456 non-Hispanic whites and 287 African Americans, we identified the APOE 4 variant with strong statistical power (P = 1e–101), far more significant than that reported in a previous study using a transformed variable and a marginal Cox model. Furthermore, we identified novel SNP rs36051450 (P = 2e–9) near GRAMD1B, the minor allele of which significantly reduced the hazards of AD in both genders. These results demonstrated that COXMEG greatly facilitates the application of CMEMs in GWAS of age-at-onset traits. Full Article
effects The effects of elevated temperature and PCO2 on the energetics and haemolymph pH homeostasis of juveniles of the European lobster, Homarus gammarus [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-04-16T04:02:51-07:00 Daniel P. Small, Piero Calosi, Samuel P. S. Rastrick, Lucy M. Turner, Stephen Widdicombe, and John I. Spicer Regulation of extracellular acid–base balance, while maintaining energy metabolism, is recognised as an important aspect when defining an organism's sensitivity to environmental changes. This study investigated the haemolymph buffering capacity and energy metabolism (oxygen consumption, haemolymph [l-lactate] and [protein]) in early benthic juveniles (carapace length <40 mm) of the European lobster, Homarus gammarus, exposed to elevated temperature and PCO2. At 13°C, H. gammarus juveniles were able to fully compensate for acid–base disturbances caused by the exposure to elevated seawater PCO2 at levels associated with ocean acidification and carbon dioxide capture and storage (CCS) leakage scenarios, via haemolymph [HCO3–] regulation. However, metabolic rate remained constant and food consumption decreased under elevated PCO2, indicating reduced energy availability. Juveniles at 17°C showed no ability to actively compensate haemolymph pH, resulting in decreased haemolymph pH particularly under CCS conditions. Early benthic juvenile lobsters at 17°C were not able to increase energy intake to offset increased energy demand and therefore appear to be unable to respond to acid–base disturbances due to increased PCO2 at elevated temperature. Analysis of haemolymph metabolites suggests that, even under control conditions, juveniles were energetically limited. They exhibited high haemolymph [l-lactate], indicating recourse to anaerobic metabolism. Low haemolymph [protein] was linked to minimal non-bicarbonate buffering and reduced oxygen transport capacity. We discuss these results in the context of potential impacts of ongoing ocean change and CCS leakage scenarios on the development of juvenile H. gammarus and future lobster populations and stocks. Full Article
effects Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-Inhibitors By jasn.asnjournals.org Published On :: 2020-04-30T10:00:29-07:00 Growing evidence indicates that oxidative and endoplasmic reticular stress, which trigger changes in ion channels and inflammatory pathways that may undermine cellular homeostasis and survival, are critical determinants of injury in the diabetic kidney. Cells are normally able to mitigate these cellular stresses by maintaining high levels of autophagy, an intracellular lysosome-dependent degradative pathway that clears the cytoplasm of dysfunctional organelles. However, the capacity for autophagy in both podocytes and renal tubular cells is markedly impaired in type 2 diabetes, and this deficiency contributes importantly to the intensity of renal injury. The primary drivers of autophagy in states of nutrient and oxygen deprivation—sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), and hypoxia-inducible factors (HIF-1α and HIF-2α)—can exert renoprotective effects by promoting autophagic flux and by exerting direct effects on sodium transport and inflammasome activation. Type 2 diabetes is characterized by marked suppression of SIRT1 and AMPK, leading to a diminution in autophagic flux in glomerular podocytes and renal tubules and markedly increasing their susceptibility to renal injury. Importantly, because insulin acts to depress autophagic flux, these derangements in nutrient deprivation signaling are not ameliorated by antihyperglycemic drugs that enhance insulin secretion or signaling. Metformin is an established AMPK agonist that can promote autophagy, but its effects on the course of CKD have been demonstrated only in the experimental setting. In contrast, the effects of sodium-glucose cotransporter–2 (SGLT2) inhibitors may be related primarily to enhanced SIRT1 and HIF-2α signaling; this can explain the effects of SGLT2 inhibitors to promote ketonemia and erythrocytosis and potentially underlies their actions to increase autophagy and mute inflammation in the diabetic kidney. These distinctions may contribute importantly to the consistent benefit of SGLT2 inhibitors to slow the deterioration in glomerular function and reduce the risk of ESKD in large-scale randomized clinical trials of patients with type 2 diabetes. Full Article
effects Interaction of the Brain-Selective Sulfotransferase SULT4A1 with Other Cytosolic Sulfotransferases: Effects on Protein Expression and Function [Articles] By dmd.aspetjournals.org Published On :: 2020-04-09T08:02:00-07:00 Sulfotransferase (SULT) 4A1 is a brain-selective sulfotransferase-like protein that has recently been shown to be essential for normal neuronal development in mice. In the present study, SULT4A1 was found to colocalize with SULT1A1/3 in human brain neurons. Using immunoprecipitation, SULT4A1 was shown to interact with both SULT1A1 and SULT1A3 when expressed in human cells. Mutation of the conserved dimerization motif located in the C terminus of the sulfotransferases prevented this interaction. Both ectopically expressed and endogenous SULT4A1 decreased SULT1A1/3 protein levels in neuronal cells, and this was also prevented by mutation of the dimerization motif. During differentiation of neuronal SH-SY5Y cells, there was a loss in SULT1A1/3 protein but an increase in SULT4A1 protein. This resulted in an increase in the toxicity of dopamine, a substrate for SULT1A3. Inhibition of SULT4A1 using small interference RNA abrogated the loss in SULT1A1/3 and reversed dopamine toxicity. These results show a reciprocal relationship between SULT4A1 and the other sulfotransferases, suggesting that it may act as a chaperone to control the expression of SULT1A1/3 in neuronal cells. SIGNIFICANCE STATEMENT The catalytically inactive sulfotransferase (SULT) 4A1 may regulate the function of other SULTs by interacting with them via a conserved dimerization motif. In neuron-like cells, SULT4A1 is able to modulate dopamine toxicity by interacting with SULT1A3, potentially decreasing the metabolism of dopamine. Full Article
effects Effects of deficiency in the RLBP1-encoded visual cycle protein CRALBP on visual dysfunction in humans and mice [Cell Biology] By www.jbc.org Published On :: 2020-05-08T03:41:14-07:00 Mutations in retinaldehyde-binding protein 1 (RLBP1), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11-cis-retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal. CRALBP also maintains the 11-cis configuration and protects against unwanted retinaldehyde activity. Studying a sibling pair that is compound heterozygous for mutations in RLBP1/CRALBP, here we expand the phenotype of affected individuals, elucidate a previously unreported phenotype in RLBP1/CRALBP carriers, and demonstrate consistencies between the affected individuals and Rlbp1/Cralbp−/− mice. In the RLBP1/CRALBP-affected individuals, nonrecordable rod-specific electroretinogram traces were recovered after prolonged dark adaptation. In ultrawide-field fundus images, we observed radially arranged puncta typical of RLBP1/CRALBP-associated disease. Spectral domain-optical coherence tomography (SD-OCT) revealed hyperreflective aberrations within photoreceptor-associated bands. In short-wavelength fundus autofluorescence (SW-AF) images, speckled hyperautofluorescence and mottling indicated macular involvement. In both the affected individuals and their asymptomatic carrier parents, reduced SW-AF intensities, measured as quantitative fundus autofluorescence (qAF), indicated chronic impairment in 11-cis-retinal availability and provided information on mutation severity. Hypertransmission of the SD-OCT signal into the choroid together with decreased near-infrared autofluorescence (NIR-AF) provided evidence for retinal pigment epithelial cell (RPE) involvement. In Rlbp1/Cralbp−/− mice, reduced 11-cis-retinal levels, qAF and NIR-AF intensities, and photoreceptor loss were consistent with the clinical presentation of the affected siblings. These findings indicate that RLBP1 mutations are associated with progressive disease involving RPE atrophy and photoreceptor cell degeneration. In asymptomatic carriers, qAF disclosed previously undetected visual cycle deficiency. Full Article