Bone as an ion exchange system: evidence for a link between mechanotransduction and metabolic needs.

PubMed

Rubinacci, A; Covini, M; Bisogni, C; Villa, I; Galli, M; Palumbo, C; Ferretti, M; Muglia, M A; Marotti, G

2002-04-01

To detect whether the mutual interaction occurring between the osteocytes-bone lining cells system (OBLCS) and the bone extracellular fluid (BECF) is affected by load through a modification of the BECF-extracellular fluid (ECF; systemic extracellular fluid) gradient, mice metatarsal bones immersed in ECF were subjected ex vivo to a 2-min cyclic axial load of different amplitudes and frequencies. The electric (ionic) currents at the bone surface were measured by a vibrating probe after having exposed BECF to ECF through a transcortical hole. The application of different loads and different frequencies increased the ionic current in a dose-dependent manner. The postload current density subsequently decayed following an exponential pattern. Postload increment's amplitude and decay were dependent on bone viability. Dummy and static loads did not induce current density modifications. Because BECF is perturbed by loading, it is conceivable that OBLCS tends to restore BECF preload conditions by controlling ion fluxes at the bone-plasma interface to fulfill metabolic needs. Because the electric current reflects the integrated activity of OBLCS, its evaluation in transgenic mice engineered to possess genetic lesions in channels or matrix constituents could be helpful in the characterization of the mechanical and metabolic functions of bone.

Using single-step genomic best linear unbiased predictor to enhance the mitigation of seasonal losses due to heat stress in pigs.

PubMed

Fragomeni, B O; Lourenco, D A L; Tsuruta, S; Bradford, H L; Gray, K A; Huang, Y; Misztal, I

2016-12-01

The purposes of this study were to analyze the impact of seasonal losses due to heat stress in pigs from different breeds raised in different environments and to evaluate the accuracy improvement from adding genomic information to genetic evaluations. Data were available for 2 different swine populations: purebred Duroc animals raised in Texas and North Carolina and commercial crosses of Duroc and F females (Landrace × Large White) raised in Missouri and North Carolina; pedigrees provided links for animals from different states. Pedigree information was available for 553,442 animals, of which 8,232 pure breeds were genotyped. Traits were BW at 170 d for purebred animals and HCW for crossbred animals. Analyses were done with an animal model as either single- or 2-trait models using phenotypes measured in different states as separate traits. Additionally, reaction norm models were fitted for 1 or 2 traits using heat load index as a covariable. Heat load was calculated as temperature-humidity index greater than 70 and was averaged over 30 d prior to data collection. Variance components were estimated with average information REML, and EBV and genomic EBV (GEBV) with BLUP or single-step genomic BLUP (ssGBLUP). Validation was assessed for 146 genotyped sires with progeny in the last generation. Accuracy was calculated as a correlation between EBV and GEBV using reduced data (all animals, except the last generation) and using complete data. Heritability estimates for purebred animals were similar across states (varying from 0.23 to 0.26), and reaction norm models did not show evidence of a heat stress effect. Genetic correlations between states for heat loads were always strong (>0.91). For crossbred animals, no differences in heritability were found in single- or 2-trait analysis (from 0.17 to 0.18), and genetic correlations between states were moderate (0.43). In the reaction norm for crossbreeds, heritabilities ranged from 0.15 to 0.30 and genetic correlations between heat loads were as weak as 0.36, with heat load ranging from 0 to 12. Accuracies with ssGBLUP were, on average, 25% greater than with BLUP. Accuracies were greater in 2-trait reaction norm models and at extreme heat load values. Impacts of seasonality are evident only for crossbred animals. Genomic information can help producers mitigate heat stress in swine by identifying superior sires that are more resistant to heat stress.

Strain gage selection in loads equations using a genetic algorithm

NASA Technical Reports Server (NTRS)

1994-01-01

Traditionally, structural loads are measured using strain gages. A loads calibration test must be done before loads can be accurately measured. In one measurement method, a series of point loads is applied to the structure, and loads equations are derived via the least squares curve fitting algorithm using the strain gage responses to the applied point loads. However, many research structures are highly instrumented with strain gages, and the number and selection of gages used in a loads equation can be problematic. This paper presents an improved technique using a genetic algorithm to choose the strain gages used in the loads equations. Also presented are a comparison of the genetic algorithm performance with the current T-value technique and a variant known as the Best Step-down technique. Examples are shown using aerospace vehicle wings of high and low aspect ratio. In addition, a significant limitation in the current methods is revealed. The genetic algorithm arrived at a comparable or superior set of gages with significantly less human effort, and could be applied in instances when the current methods could not.

Heritabilities of Directional Asymmetry in the Fore- and Hindlimbs of Rabbit Fetuses

PubMed Central

Breno, Matteo; Bots, Jessica; Van Dongen, Stefan

2013-01-01

Directional asymmetry (DA), where at the population level symmetry differs from zero, has been reported in a wide range of traits and taxa, even for traits in which symmetry is expected to be the target of selection such as limbs or wings. In invertebrates, DA has been suggested to be non-adaptive. In vertebrates, there has been a wealth of research linking morphological asymmetry to behavioural lateralisation. On the other hand, the prenatal expression of DA and evidences for quantitative genetic variation for asymmetry may suggest it is not solely induced by differences in mechanic loading between sides. We estimate quantitative genetic variation of fetal limb asymmetry in a large dataset of rabbits. Our results showed a low but highly significant level of DA that is partially under genetic control for all traits, with forelimbs displaying higher levels of asymmetry. Genetic correlations were positive within limbs, but negative across bones of fore and hind limbs. Environmental correlations were positive for all, but smaller across fore and hind limbs. We discuss our results in light of the existence and maintenance of DA in locomotory traits. PMID:24130770

Optimization of laminated stacking sequence for buckling load maximization by genetic algorithm

NASA Technical Reports Server (NTRS)

Le Riche, Rodolphe; Haftka, Raphael T.

1992-01-01

The use of a genetic algorithm to optimize the stacking sequence of a composite laminate for buckling load maximization is studied. Various genetic parameters including the population size, the probability of mutation, and the probability of crossover are optimized by numerical experiments. A new genetic operator - permutation - is proposed and shown to be effective in reducing the cost of the genetic search. Results are obtained for a graphite-epoxy plate, first when only the buckling load is considered, and then when constraints on ply contiguity and strain failure are added. The influence on the genetic search of the penalty parameter enforcing the contiguity constraint is studied. The advantage of the genetic algorithm in producing several near-optimal designs is discussed.

Cell type-selective disease-association of genes under high regulatory load.

PubMed

Galhardo, Mafalda; Berninger, Philipp; Nguyen, Thanh-Phuong; Sauter, Thomas; Sinkkonen, Lasse

2015-10-15

We previously showed that disease-linked metabolic genes are often under combinatorial regulation. Using the genome-wide ChIP-Seq binding profiles for 93 transcription factors in nine different cell lines, we show that genes under high regulatory load are significantly enriched for disease-association across cell types. We find that transcription factor load correlates with the enhancer load of the genes and thereby allows the identification of genes under high regulatory load by epigenomic mapping of active enhancers. Identification of the high enhancer load genes across 139 samples from 96 different cell and tissue types reveals a consistent enrichment for disease-associated genes in a cell type-selective manner. The underlying genes are not limited to super-enhancer genes and show several types of disease-association evidence beyond genetic variation (such as biomarkers). Interestingly, the high regulatory load genes are involved in more KEGG pathways than expected by chance, exhibit increased betweenness centrality in the interaction network of liver disease genes, and carry longer 3' UTRs with more microRNA (miRNA) binding sites than genes on average, suggesting a role as hubs integrating signals within regulatory networks. In summary, epigenetic mapping of active enhancers presents a promising and unbiased approach for identification of novel disease genes in a cell type-selective manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The dopamine-related polymorphisms BDNF, COMT, DRD2, DRD3, and DRD4 are not linked with changes in CSF dopamine levels and frequency of HIV infection.

PubMed

Horn, Anne; Scheller, C; du Plessis, S; Burger, R; Arendt, G; Joska, J; Sopper, S; Maschke, C M; Obermann, M; Husstedt, I W; Hain, J; Riederer, P; Koutsilieri, E

2017-04-01

We showed previously that higher levels in CSF dopamine in HIV patients are associated with the presence of the dopamine transporter (DAT) 10/10-repeat allele which was also detected more frequently in HIV-infected individuals compared to uninfected subjects. In the current study, we investigated further whether other genetic dopamine (DA)-related polymorphisms may be related with changes in CSF DA levels and frequency of HIV infection in HIV-infected subjects. Specifically, we studied genetic polymorphisms of brain-derived neurotrophic factor, catechol-O-methyltransferase, and dopamine receptors DRD2, DRD3, and DRD4 genetic polymorphisms in uninfected and HIV-infected people in two different ethnical groups, a German cohort (Caucasian, 72 individuals with HIV infection and 22 individuals without HIV infection) and a South African cohort (Xhosan, 54 individuals with HIV infection and 19 individuals without HIV infection). We correlated the polymorphisms with CSF DA levels, HIV dementia score, CD4 + T cell counts, and HIV viral load. None of the investigated DA-related polymorphisms was associated with altered CSF DA levels, CD4 + T cell count, viral load, and HIV dementia score. The respective allele frequencies were equally distributed between HIV-infected patients and controls. Our findings do not show any influence of the studied genetic polymorphisms on CSF DA levels and HIV infection. This is in contrast to what we found previously for the DAT 3'UTR VNTR and highlights the specific role of the DAT VNTR in HIV infection and disease.

Variability of individual genetic load: consequences for the detection of inbreeding depression.

PubMed

Restoux, Gwendal; Huot de Longchamp, Priscille; Fady, Bruno; Klein, Etienne K

2012-03-01

Inbreeding depression is a key factor affecting the persistence of natural populations, particularly when they are fragmented. In species with mixed mating systems, inbreeding depression can be estimated at the population level by regressing the average progeny fitness by the selfing rate of their mothers. We applied this method using simulated populations to investigate how population genetic parameters can affect the detection power of inbreeding depression. We simulated individual selfing rates and genetic loads from which we computed fitness values. The regression method yielded high statistical power, inbreeding depression being detected as significant (5 % level) in 92 % of the simulations. High individual variation in selfing rate and high mean genetic load led to better detection of inbreeding depression while high among-individual variation in genetic load made it more difficult to detect inbreeding depression. For a constant sampling effort, increasing the number of progenies while decreasing the number of individuals per progeny enhanced the detection power of inbreeding depression. We discuss the implication of among-mother variability of genetic load and selfing rate on inbreeding depression studies.

Impact of Child Sex Abuse on Adult Psychopathology: A Genetically and Epigenetically Informed Investigation

PubMed Central

Beach, Steven R. H.; Brody, Gene H.; Lei, Man Kit; Gibbons, Frederick X.; Gerrard, Meg; Simons, Ronald L.; Cutrona, Carolyn E.; Philibert, Robert A.

2013-01-01

Genetic, environmental, and epigenetic influences and their transactions were examined in a sample of 155 women from the Iowa Adoptee sample (IAS) who had been removed from their biological parents shortly after birth, and assessed when participants were an average of 41.10 years old. We observed an interactive effect of child sex abuse (CSA) and biological parent psychopathology (i.e., genetic load) on substance abuse as well as a main effect of CSA on substance abuse in adulthood. We also observed main effects of CSA and genetic load on depression and on antisocial characteristics. As predicted, CSA, but not genetic load or later substance abuse, was associated with epigenetic change. In addition, the interaction between genetic load and CSA predicted epigenetic change, indicating a potential genetic basis for differential impact of CSA on epigenetic change. Finally, epigenetic change partially mediated the effect of CSA on antisocial characteristics. The results suggest the relevance of genetic and epigenetic processes for future theorizing regarding marital and family precursors of several forms of adult psychopathology. Implications for preventive intervention are discussed. PMID:23421829

Nature Versus Nurture: Does Proteostasis Imbalance Underlie the Genetic, Environmental, and Age-Related Risk Factors for Alzheimer's Disease?

PubMed

Kikis, Elise A

2017-08-22

Aging is a risk factor for a number of "age-related diseases", including Alzheimer's disease (AD). AD affects more than a third of all people over the age of 85, and is the leading cause of dementia worldwide. Symptoms include forgetfulness, memory loss, and cognitive decline, ultimately resulting in the need for full-time care. While there is no cure for AD, pharmacological approaches to alleviate symptoms and target underlying causes of the disease have been developed, albeit with limited success. This review presents the age-related, genetic, and environmental risk factors for AD and proposes a hypothesis for the mechanistic link between genetics and the environment. In short, much is known about the genetics of early-onset familial AD (EO-FAD) and the central role played by the Aβ peptide and protein misfolding, but late-onset AD (LOAD) is not thought to have direct genetic causes. Nonetheless, genetic risk factors such as isoforms of the protein ApoE have been identified. Additional findings suggest that air pollution caused by the combustion of fossil fuels may be an important environmental risk factor for AD. A hypothesis suggesting that poor air quality might act by disrupting protein folding homeostasis (proteostasis) is presented.

DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders.

PubMed

Ryan, Niamh M; Lihm, Jayon; Kramer, Melissa; McCarthy, Shane; Morris, Stewart W; Arnau-Soler, Aleix; Davies, Gail; Duff, Barbara; Ghiban, Elena; Hayward, Caroline; Deary, Ian J; Blackwood, Douglas H R; Lawrie, Stephen M; McIntosh, Andrew M; Evans, Kathryn L; Porteous, David J; McCombie, W Richard; Thomson, Pippa A

2018-06-07

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes.

Genetic evaluations for growth heat tolerance in Angus cattle.

PubMed

Bradford, H L; Fragomeni, B O; Bertrand, J K; Lourenco, D A L; Misztal, I

2016-10-01

The objectives were to assess the impact of heat stress and to develop a model for genetic evaluation of growth heat tolerance in Angus cattle. The American Angus Association provided weaning weight (WW) and yearling weight (YW) data, and records from the Upper South region were used because of the hot climatic conditions. Heat stress was characterized by a weaning (yearling) heat load function defined as the mean temperature-humidity index (THI) units greater than 75 (70) for 30 (150) d prior to the weigh date. Therefore, a weaning (yearling) heat load of 5 units corresponded to 80 (75) for the corresponding period prior to the weigh date. For all analyses, 82,669 WW and 69,040 YW were used with 3 ancestral generations in the pedigree. Univariate models were a proxy for the Angus growth evaluation, and reaction norms using 2 B-splines for heat load were fit separately for weaning and yearling heat loads. For both models, random effects included direct genetic, maternal genetic, maternal permanent environment (WW only), and residual. Fixed effects included a linear age covariate, age-of-dam class (WW only), and contemporary group for both models and fixed regressions on the B-splines in the reaction norm. Direct genetic correlations for WW were strong for modest heat load differences but decreased to less than 0.50 for large differences. Reranking of proven sires occurred for only WW direct effects for the reaction norms with extreme heat load differences. Conversely, YW results indicated little effect of heat stress on genetic merit. Therefore, weaning heat tolerance was a better candidate for developing selection tools. Maternal heritabilities were consistent across heat loads, and maternal genetic correlations were greater than 0.90 for nearly all heat load combinations. No evidence existed for a genotype × environment interaction for the maternal component of growth. Overall, some evidence exists for phenotypic plasticity for the direct genetic effects of WW, but traditional national cattle evaluations are likely adequately ranking sires for nonextreme environmental conditions.

Association Studies of 22 Candidate SNPs with Late-Onset Alzheimer's Disease

PubMed Central

Figgins, Jessica A.; Minster, Ryan L.; Demirci, F. Yesim; DeKosky, Steven T.; Kamboh, M. Ilyas

2009-01-01

Alzheimer's disease (AD) is a complex and multifactorial disease with the possible involvement of several genes. With the exception of the APOE gene as a susceptibility marker, no other genes have been shown consistently to be associated with late-onset AD (LOAD). A recent genome-wide association study of 17,343 gene-based putative functional single nucleotide polymorphisms (SNPs) found 19 significant variants, including 3 linked to APOE, showing association with LOAD (Hum Mol Genet 2007; 16:865–873). We have set out to replicate the 16 new significant associations in a large case-control cohort of American Whites. Additionally, we examined six variants present in positional and/or biological candidate genes for AD. We genotyped the 22 SNPs in up to 1,009 Caucasian Americans with LOAD and up to 1,010 age-matched healthy Caucasian Americans, using 5′ nuclease assays. We did not observe a statistically significant association between the SNPs and the risk of AD, either individually or stratified by APOE. Our data suggest that the association of the studied variants with LOAD risk, if it exists, is not statistically significant in our sample. PMID:18780302

Internet traffic load balancing using dynamic hashing with flow volume

NASA Astrophysics Data System (ADS)

Jo, Ju-Yeon; Kim, Yoohwan; Chao, H. Jonathan; Merat, Francis L.

2002-07-01

Sending IP packets over multiple parallel links is in extensive use in today's Internet and its use is growing due to its scalability, reliability and cost-effectiveness. To maximize the efficiency of parallel links, load balancing is necessary among the links, but it may cause the problem of packet reordering. Since packet reordering impairs TCP performance, it is important to reduce the amount of reordering. Hashing offers a simple solution to keep the packet order by sending a flow over a unique link, but static hashing does not guarantee an even distribution of the traffic amount among the links, which could lead to packet loss under heavy load. Dynamic hashing offers some degree of load balancing but suffers from load fluctuations and excessive packet reordering. To overcome these shortcomings, we have enhanced the dynamic hashing algorithm to utilize the flow volume information in order to reassign only the appropriate flows. This new method, called dynamic hashing with flow volume (DHFV), eliminates unnecessary flow reassignments of small flows and achieves load balancing very quickly without load fluctuation by accurately predicting the amount of transferred load between the links. In this paper we provide the general framework of DHFV and address the challenges in implementing DHFV. We then introduce two algorithms of DHFV with different flow selection strategies and show their performances through simulation.

Effects of methamphetamine abuse and serotonin transporter gene variants on aggression and emotion-processing neurocircuitry

PubMed Central

Payer, D E; Nurmi, E L; Wilson, S A; McCracken, J T; London, E D

2012-01-01

Individuals who abuse methamphetamine (MA) exhibit heightened aggression, but the neurobiological underpinnings are poorly understood. As variability in the serotonin transporter (SERT) gene can influence aggression, this study assessed possible contributions of this gene to MA-related aggression. In all, 53 MA-dependent and 47 control participants provided self-reports of aggression, and underwent functional magnetic resonance imaging while viewing pictures of faces. Participants were genotyped at two functional polymorphic loci in the SERT gene: the SERT-linked polymorphic region (SERT-LPR) and the intron 2 variable number tandem repeat polymorphism (STin2 VNTR); participants were then classified as having high or low risk for aggression according to individual SERT risk allele combinations. Comparison of SERT risk allele loads between groups showed no difference between MA-dependent and control participants. Comparison of self-report scores showed greater aggression in MA-dependent than control participants, and in high genetic risk than low-risk participants. Signal change in the amygdala was lower in high genetic risk than low-risk participants, but showed no main effect of MA abuse; however, signal change correlated negatively with MA use measures. Whole-brain differences in activation were observed between MA-dependent and control groups in the occipital and prefrontal cortex, and between genetic high- and low-risk groups in the occipital, fusiform, supramarginal and prefrontal cortex, with effects overlapping in a small region in the right ventrolateral prefrontal cortex. The findings suggest that the investigated SERT risk allele loads are comparable between MA-dependent and healthy individuals, and that MA and genetic risk influence aggression independently, with minimal overlap in associated neural substrates. PMID:22832817

A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder.

PubMed

Dezhina, Zalina; Ranlund, Siri; Kyriakopoulos, Marinos; Williams, Steve C R; Dima, Danai

2018-05-10

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks.

Protein microspheres for controlled drug delivery and related analysis of biopolymers

NASA Astrophysics Data System (ADS)

Kirk, James Forrest

Rheumatoid arthritis (RA) is a systemic disorder which manifests itself most notably in the synovial joints. In recent years, methotrexate (MTX), a foliate antagonist, has been used with some success for treatment of RA. MTX has a maximum cumulative dose beyond which it becomes dangerous to administer due primarily to liver toxicity. This unfortunate side effect has prompted research into means of delivering MTX to the synovial joint in hopes of making more efficient use of the drug. Both MTX and its sodium salt (Na-MTX) were loaded into microspheres (MS) composed of bovine serum albumin (BSA) stabilized by cross linking with dialdehydes or ferric ion. MS were prepared with two levels of drug loading at two different levels of cross linking. MTX loading densities as high as 46.8% w/w were achieved in the aldehyde cross linking system and as high as 46.3% w/w were achieved with ferric ion cross linking. Using Na-MTX, the values were 37.2% w/w and 31.7% w/w respectively. Both MTX and Na-MTX were elutable from the MS into phosphate buffered saline at 37sp°C. MTX elution from aldehyde cross linked microspheres was load dependent with ca. 60% eluted by 9 hours at low loading and ca. 60% eluted by 24 hours at high loading. In the ferric ion cross link system, the elution was independent of loading with 50% elution occurring between 20 and 48 hours. Na-MTX elution was independent of drug loading or cross link system with 50% elution occurring in less than two hours in all cases. Other investigations included the loading of mitoxantrone (NOV) and of enzyme. NOV was loaded onto BSA microspheres to a concentration of 19.3% w/w and was used successfully in the treatment of murine ovarian tumors. Acid phosphatase was successfully loaded onto and into BSA microspheres. This enzyme retained its initial activity up to four months on post-loaded spheres. The enzyme also remained active inside the microsphere as demonstrated by a substrate cleavage assay.

Biomechanical Comparison of Standard and Linked Single-Row Rotator Cuff Repairs in a Human Cadaver Model.

PubMed

Meisel, Adam F; Henninger, Heath B; Barber, F Alan; Getelman, Mark H

2017-05-01

The purpose of this study was to evaluate the time zero cyclic and failure loading properties of a linked single-row rotator cuff repair compared with a standard simple suture single-row repair using triple-loaded suture anchors. Eighteen human cadaveric shoulders from 9 matched pairs were dissected, and full-thickness supraspinatus tears were created. The tendon cross-sectional area was recorded. In each pair, one side was repaired with a linked single-row construct and the other with a simple suture single-row construct, both using 2 triple-loaded suture anchors. After preloading, specimens were cycled to 1 MPa of effective stress at 1 Hz for 500 cycles, and gap formation was recorded with a digital video system. Samples were then loaded to failure, and modes of failure were recorded. There was no statistical difference in peak gap formation between the control and linked constructs (3.6 ± 0.9 mm and 3.6 ± 1.2 mm, respectively; P = .697). Both constructs averaged below a 5-mm cyclic failure threshold. There was no statistical difference in ultimate load to failure between the control and linked repair (511.1 ± 139.0 N and 561.2 ± 131.8 N, respectively; P = .164), and both groups reached failure at loads similar to previous studies. Constructs failed predominantly via tissue tearing parallel to the medial suture line. The linked repair performed similarly to the simple single-row repair. Both constructs demonstrated high ultimate load to failure and good resistance to gap formation with cyclic loading, validating the time zero strength of both constructs in a human cadaveric model. The linked repair provided equivalent resistance to gap formation and failure loads compared with simple suture single-row repairs with triple-loaded suture anchors. This suggests that the linked repair is a simplified rip-stop configuration using the existing suture that may perform similarly to current rotator cuff repair techniques. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Lipid-induced mitochondrial stress and insulin action in muscle

PubMed Central

Muoio, Deborah M.; Neufer, P. Darrell

2012-01-01

Summary The interplay between mitochondrial energetics, lipid balance and muscle insulin sensitivity has remained a topic of intense interest and debate for decades. One popular view suggests that increased oxidative capacity benefits metabolic wellness; based on the premise that it is healthier to burn fat than glucose. Attempts to test this hypothesis using genetically-modified mouse models have produced contradictory results; and instead link muscle insulin resistance to excessive fat oxidation, acylcarnitine production and increased mitochondrial H2O2 emitting potential. Here, we consider emerging evidence that insulin action in muscle is driven principally by mitochondrial load and redox signaling rather than oxidative capacity. PMID:22560212

Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease.

PubMed

Kanatsu, Kunihiko; Tomita, Taisuke

2017-01-01

Alzheimer disease (AD) is a neurodegenerative disease characterized by the extensive deposition of senile plaques and neurofibrillary tangles. Until recently, only the APOE gene had been known as a genetic risk factor for late-onset AD (LOAD), which accounts for more than 95% of all AD cases. However, in addition to this well-established genetic risk factor, genome-wide association studies have identified several single nucleotide polymorphisms as genetic risk factors of LOAD, such as PICALM and BIN1 . In addition, whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, including TREM2 . We review the recent findings related to the molecular mechanisms by which these genetic risk factors contribute to AD, and our perspectives regarding the etiology of AD for the development of therapeutic agents.

Genotype × Herbivore Effect on Leaf Litter Decomposition in Betula Pendula Saplings: Ecological and Evolutionary Consequences and the Role of Secondary Metabolites

PubMed Central

Silfver, Tarja; Paaso, Ulla; Rasehorn, Mira; Rousi, Matti; Mikola, Juha

2015-01-01

Plant genetic variation and herbivores can both influence ecosystem functioning by affecting the quantity and quality of leaf litter. Few studies have, however, investigated the effects of herbivore load on litter decomposition at plant genotype level. We reduced insect herbivory using an insecticide on one half of field-grown Betula Pendula saplings of 17 genotypes, representing random intrapopulation genetic variation, and allowed insects to naturally colonize the other half. We hypothesized that due to induced herbivore defence, saplings under natural herbivory produce litter of higher concentrations of secondary metabolites (terpenes and soluble phenolics) and have slower litter decomposition rate than saplings under reduced herbivory. We found that leaf damage was 89 and 53% lower in the insecticide treated saplings in the summer and autumn surveys, respectively, which led to 73% higher litter production. Litter decomposition rate was also affected by herbivore load, but the effect varied from positive to negative among genotypes and added up to an insignificant net effect at the population level. In contrast to our hypothesis, concentrations of terpenes and soluble phenolics were higher under reduced than natural herbivory. Those genotypes, whose leaves were most injured by herbivores, produced litter of lowest mass loss, but unlike we expected, the concentrations of terpenes and soluble phenolics were not linked to either leaf damage or litter decomposition. Our results show that (1) the genetic and herbivore effects on B. pendula litter decomposition are not mediated through variation in terpene or soluble phenolic concentrations and suggest that (2) the presumably higher insect herbivore pressure in the future warmer climate will not, at the ecological time scale, affect the mean decomposition rate in genetically diverse B. pendula populations. However, (3) due to the significant genetic variation in the response of decomposition to herbivory, evolutionary changes in mean decomposition rate are possible. PMID:25622034

Nuclear fuel management optimization using genetic algorithms

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeChaine, M.D.; Feltus, M.A.

1995-07-01

The code independent genetic algorithm reactor optimization (CIGARO) system has been developed to optimize nuclear reactor loading patterns. It uses genetic algorithms (GAs) and a code-independent interface, so any reactor physics code (e.g., CASMO-3/SIMULATE-3) can be used to evaluate the loading patterns. The system is compared to other GA-based loading pattern optimizers. Tests were carried out to maximize the beginning of cycle k{sub eff} for a pressurized water reactor core loading with a penalty function to limit power peaking. The CIGARO system performed well, increasing the k{sub eff} after lowering the peak power. Tests of a prototype parallel evaluation methodmore » showed the potential for a significant speedup.« less

Evaluation of performance and maximum length of continuous decks in bridges : part 2.

DOT National Transportation Integrated Search

2012-08-01

Field experimental measurements and analytical studies showed that the link-slab reinforcement : experiences almost no axial load due to thermal and gravity loading. One of the fundamental : reasons for the low loads in the link-slab reinforcement is...

Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families.

PubMed

Barral, Sandra; Vardarajan, Badri N; Reyes-Dumeyer, Dolly; Faber, Kelley M; Bird, Thomas D; Tsuang, Debby; Bennett, David A; Rosenberg, Roger; Boeve, Bradley F; Graff-Radford, Neill R; Goate, Alison M; Farlow, Martin; Lantigua, Rafael; Medrano, Martin Z; Wang, Xinbing; Kamboh, M Ilyas; Barmada, Mahmud Muhiedine; Schaid, Daniel J; Foroud, Tatiana M; Weamer, Elise A; Ottman, Ruth; Sweet, Robert A; Mayeux, Richard

2015-11-01

Psychotic symptoms are frequent in late-onset Alzheimer's disease (LOAD) patients. Although the risk for psychosis in LOAD is genetically mediated, no genes have been identified. To identify loci potentially containing genetic variants associated with risk of psychosis in LOAD, a total of 263 families from the National Institute of Aging-LOAD cohort were classified into psychotic (LOAD+P, n = 215) and nonpsychotic (LOAD-P, n = 48) families based on the presence/absence of psychosis during the course of LOAD. The LOAD+P families yielded strong evidence of linkage on chromosome 19q13 (two-point [2-pt] ​logarithm of odds [LOD] = 3.8, rs2285513 and multipoint LOD = 2.7, rs541169). Joint linkage and association in 19q13 region detected strong association with rs2945988 (p = 8.7 × 10(-7)). Linkage results for the LOAD-P families yielded nonsignificant 19q13 LOD scores. Several 19q13 single-nucleotide polymorphisms generalized the association of LOAD+P in a Caribbean Hispanic (CH) cohort, and the strongest signal was rs10410711 (pmeta = 5.1 × 10(-5)). A variant located 24 kb upstream of rs10410711 and rs10421862 was strongly associated with LOAD+P (pmeta = 1.0 × 10(-5)) in a meta-analysis of the CH cohort and an additional non-Hispanic Caucasian dataset. Identified variants rs2945988 and rs10421862 affect brain gene expression levels. Our results suggest that genetic variants in genes on 19q13, some of which are involved in brain development and neurodegeneration, may influence the susceptibility to psychosis in LOAD patients. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Exploring links among imitation, mental development, and temperament

PubMed Central

Fenstermacher, Susan K.; Saudino, Kimberly J.

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children’s imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique. PMID:27840593

Exploring links among imitation, mental development, and temperament.

PubMed

Fenstermacher, Susan K; Saudino, Kimberly J

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children's imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique.

Embryonic genetic load in coastal Douglas-fir, Pseudotsuga menziesii var. menziesii.

Treesearch

Frank C. Sorensen

1969-01-01

Genetic load has been estimated for a number of outcrossing organisms, for example, Drosophila (Malogolowkin-Cohen et al. 1964), Tribolium (Levene et al. 1965), and man (Morton, Crow, and Muller 1956). However, little informaiton about load of deleterious genes in higher plants has been published. The purpose of this article is to provide some data on plants by...

Drug Loading and Release Behavior Depending on the Induced Porosity of Chitosan/Cellulose Multilayer Nanofilms.

PubMed

Park, Sohyeon; Choi, Daheui; Jeong, Hyejoong; Heo, Jiwoong; Hong, Jinkee

2017-10-02

The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

EFFECTIVENESS OF SELECTION IN REDUCING THE GENETIC LOAD IN POPULATIONS OF PEROMYSCUS POLIONOTUS DURING GENERATIONS OF INBREEDING.

PubMed

Lacy, Robert C; Ballou, Jonathan D

1998-06-01

It has been hypothesized that natural selection reduces the "genetic load" of deleterious alleles from populations that inbreed during bottlenecks, thereby ameliorating impacts of future inbreeding. We tested the efficiency with which natural selection purges deleterious alleles from three subspecies of Peromyscus polionotus during 10 generations of laboratory inbreeding by monitoring pairing success, litter size, viability, and growth in 3604 litters produced from 3058 pairs. In P. p. subgriseus, there was no reduction across generations in inbreeding depression in any of the fitness components. Strongly deleterious recessive alleles may have been removed previously during episodes of local inbreeding in the wild, and the residual genetic load in this population was not further reduced by selection in the lab. In P. p. rhoadsi, four of seven fitness components did show a reduction of the genetic load with continued inbreeding. The average reduction in the genetic load was as expected if inbreeding depression in this population is caused by highly deleterious recessive alleles that are efficiently removed by selection. For P. p. leucocephalus a population that experiences periodic bottlenecks in the wild, the effect of further inbreeding in the laboratory was to exacerbate rather than reduce the genetic load. Recessive deleterious alleles may have been removed from this population during repeated bottlenecks in the wild; the population may be close to a threshold level of heterozygosity below which fitness declines rapidly. Thus, the effects of selection on inbreeding depression varied substantially among populations, perhaps due to different histories of inbreeding and selection. © 1998 The Society for the Study of Evolution.

Niosome-loaded cold-set whey protein hydrogels.

PubMed

Abaee, Arash; Madadlou, Ashkan

2016-04-01

The α-tocopherol-carrying niosomes with mean diameter of 5.7 μm were fabricated and charged into a transglutaminase-cross-linked whey protein solution that was subsequently gelled with glucono delta-lactone. Encapsulation efficiency of α-tocopherol within niosomes was ≈80% and encapsulation did not influence the radical scavenging activity of α-tocopherol. Fourier transform infrared (FTIR) spectroscopy suggested formation of ε-(γ-glutamyl) lysine cross-linkages by transglutaminase and that enzymatic cross-linking increased proteins hydrophobicity. FTIR also proposed hydrogen bonding between niosomes and proteins. Dynamic rheometry indicated that transglutaminase cross-linking and niosomes charging of the protein solution enhanced the gelation process. However, charging the cross-linked protein solution with niosomal suspension resulted in lower elastic modulus (G') of the subsequently formed gel compared with both non-cross-linked niosome-loaded and cross-linked niosome-free counterparts. Electron microscopy indicated a discontinuous network for the niosome-loaded cross-linked sample. Niosome loading into the protein gel matrix increased its swelling extent in the enzyme-free simulated gastric fluid. Copyright © 2015 Elsevier Ltd. All rights reserved.

Caste load and the evolution of reproductive skew.

PubMed

Holman, Luke

2014-01-01

Reproductive skew theory seeks to explain how reproduction is divided among group members in animal societies. Existing theory is framed almost entirely in terms of selection, though nonadaptive processes must also play some role in the evolution of reproductive skew. Here I propose that a genetic correlation between helper fecundity and breeder fecundity may frequently constrain the evolution of reproductive skew. This constraint is part of a wider phenomenon that I term "caste load," which is defined as the decline in mean fitness caused by caste-specific selection pressures, that is, differential selection on breeding and nonbreeding individuals. I elaborate the caste load hypothesis using quantitative and population genetic arguments and individual-based simulations. Although selection can sometimes erode genetic correlations and resolve caste load, this may be constrained when mutations have similar pleiotropic effects on breeder and helper traits. I document evidence for caste load, identify putative genomic adaptations to it, and suggest future research directions. The models highlight the value of considering adaptation within the boundaries imposed by genetic architecture and incidentally reaffirm that monogamy promotes the evolutionary transition to eusociality.

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus.

PubMed

Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Blanco, Francisco J; Suarez, Ana; Santos, Maria Jose; Papasteriades, Chryssa; Carreira, Patricia; Pullmann, Rudolf; Ordi-Ros, Josep; Marchini, Maurizio; Skopouli, Fotini N; Bijl, Marc; Barrizone, Nadia; Sebastiani, Gian Domenico; Migliaresi, Sergio; Witte, Torsten; Lauwerys, Bernard R; Kovacs, Attila; Ruzickova, Sarka; Gomez-Reino, Juan J; Gonzalez, Antonio

2014-06-19

We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)). Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(-16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(-7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

PubMed Central

2014-01-01

Introduction We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. Methods Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRSs). Results Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRSs. GRSs were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10−16) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10−7), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. Conclusion Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women. PMID:24946689

Dealing with the genetic load in bacterial synthetic biology circuits: convergences with the Ohm's law

PubMed Central

Carbonell-Ballestero, M.; Garcia-Ramallo, E.; Montañez, R.; Rodriguez-Caso, C.; Macía, J.

2016-01-01

Synthetic biology seeks to envision living cells as a matter of engineering. However, increasing evidence suggests that the genetic load imposed by the incorporation of synthetic devices in a living organism introduces a sort of unpredictability in the design process. As a result, individual part characterization is not enough to predict the behavior of designed circuits and thus, a costly trial-error process is eventually required. In this work, we provide a new theoretical framework for the predictive treatment of the genetic load. We mathematically and experimentally demonstrate that dependences among genes follow a quantitatively predictable behavior. Our theory predicts the observed reduction of the expression of a given synthetic gene when an extra genetic load is introduced in the circuit. The theory also explains that such dependence qualitatively differs when the extra load is added either by transcriptional or translational modifications. We finally show that the limitation of the cellular resources for gene expression leads to a mathematical formulation that converges to an expression analogous to the Ohm's law for electric circuits. Similitudes and divergences with this law are outlined. Our work provides a suitable framework with predictive character for the design process of complex genetic devices in synthetic biology. PMID:26656950

Site-specific selfish genes as tools for the control and genetic engineering of natural populations.

PubMed

Burt, Austin

2003-05-07

Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.

[Analysis of genetico-demographic structure of rural populations living near the Semipalatinsk nuclear test site].

PubMed

Sviatova, G S; Berezina, G M; Abil'dinova, G Zh

2001-12-01

Rural populations neighboring the Semipalatinsk nuclear test site were used as a model to develop and test an integrated population-genetic approach to analysis of the medical genetic situation and environmental conditions in the areas studied. The contributions of individual factors of population dynamics into the formation of the genetic load were also assessed. The informative values of some genetic markers were estimated. Based on these estimates, a mathematical model was constructed that makes it possible to calculate numerical scores for analysis of the genetic loads in populations differing in environmental exposure.

The Effect of an Extreme and Prolonged Population Bottleneck on Patterns of Deleterious Variation: Insights from the Greenlandic Inuit.

PubMed

Pedersen, Casper-Emil T; Lohmueller, Kirk E; Grarup, Niels; Bjerregaard, Peter; Hansen, Torben; Siegismund, Hans R; Moltke, Ida; Albrechtsen, Anders

2017-02-01

The genetic consequences of population bottlenecks on patterns of deleterious genetic variation in human populations are of tremendous interest. Based on exome sequencing of 18 Greenlandic Inuit we show that the Inuit have undergone a severe ∼20,000-year-long bottleneck. This has led to a markedly more extreme distribution of allele frequencies than seen for any other human population tested to date, making the Inuit the perfect population for investigating the effect of a bottleneck on patterns of deleterious variation. When comparing proxies for genetic load that assume an additive effect of deleterious alleles, the Inuit show, at most, a slight increase in load compared to European, East Asian, and African populations. Specifically, we observe <4% increase in the number of derived deleterious alleles in the Inuit. In contrast, proxies for genetic load under a recessive model suggest that the Inuit have a significantly higher load (20% increase or more) compared to other less bottlenecked human populations. Forward simulations under realistic models of demography support our empirical findings, showing up to a 6% increase in the genetic load for the Inuit population across all models of dominance. Further, the Inuit population carries fewer deleterious variants than other human populations, but those that are present tend to be at higher frequency than in other populations. Overall, our results show how recent demographic history has affected patterns of deleterious variants in human populations. Copyright © 2017 by the Genetics Society of America.

Genetics Home Reference: cystic fibrosis

MedlinePlus

... Foundation) Genetic Testing (1 link) Genetic Testing Registry: Cystic fibrosis Other Diagnosis and Management Resources (5 links) American Society for Reproductive Medicine: Male Infertility Baby's First Test GeneReview: Cystic Fibrosis and Congenital Absence of the Vas Deferens Genomics ...

Genetic effects on bone mass and turnover-relevance to black/white differences.

PubMed

Parfitt, A M

1997-08-01

The mass of a bone is given by its volume and its apparent density--mass per unit external volume. Most measurements of so-called density are of mass incompletely normalized by some index of bone size. Genes control about 60% to 75% of the variance of peak bone mass/density and a much smaller proportion of the variance in rate of loss. Genetic influence on bone mass/density are mediated in large part by body size, bone size, and muscle mass. Most of the fifty-fold increase in bone mass from birth to maturity is due to bone growth, which is linked to muscle growth and bodily growth. Three-D apparent bone density in the vertebrae increases about 15% during the pubertal growth spurt. The genetic potential for bone accumulation can be frustrated by insufficient calcium intake, disruption of the calendar of puberty and inadequate physical activity. The growing skeleton is much more responsive than the mature skeleton to the osteotrophic effect of exercise, which is mediated by the detection of deviations from a target value for strain, and orchestration of cellular responses that restore the target value, processes collectively termed the mechanostat. Production of metaphyseal cancellous bone and growth in length are both linked to endochondral ossification, which is driven by growth plate cartilage cell proliferation. Production of diaphyseal cortical bone and growth in width are both linked to periosteal apposition, which is driven by osteoblast precursor proliferation. During adolescence trabeculae and cortices become thicker by net endosteal apposition, which increases apparent density. Two lines of evidence support a genetic basis for black/white differences in bone mass. First, the magnitude (10% to 40%) is incommensurate with known nongenetic factors. Second, the difference is already evident in the fetus and increases progressively during growth, especially in adolescence; the difference in peak bone mass persists throughout life. The genetic determination of bone mass is mediated by two classes of gene. The first regulates growth of the body, including muscles and bones, under the control of a master gene or set of genes whose products function as the sizostat. The second regulates the increase in apparent bone density in response to load bearing, under the control of a master gene or set of genes whose products function as the mechanostat.

Optimal Wastewater Loading under Conflicting Goals and Technology Limitations in a Riverine System.

PubMed

Rafiee, Mojtaba; Lyon, Steve W; Zahraie, Banafsheh; Destouni, Georgia; Jaafarzadeh, Nemat

2017-03-01

  This paper investigates a novel simulation-optimization (S-O) framework for identifying optimal treatment levels and treatment processes for multiple wastewater dischargers to rivers. A commonly used water quality simulation model, Qual2K, was linked to a Genetic Algorithm optimization model for exploration of relevant fuzzy objective-function formulations for addressing imprecision and conflicting goals of pollution control agencies and various dischargers. Results showed a dynamic flow dependence of optimal wastewater loading with good convergence to near global optimum. Explicit considerations of real-world technological limitations, which were developed here in a new S-O framework, led to better compromise solutions between conflicting goals than those identified within traditional S-O frameworks. The newly developed framework, in addition to being more technologically realistic, is also less complicated and converges on solutions more rapidly than traditional frameworks. This technique marks a significant step forward for development of holistic, riverscape-based approaches that balance the conflicting needs of the stakeholders.

Disulfide cross-linked polyurethane micelles as a reduction-triggered drug delivery system for cancer therapy.

PubMed

Yu, Shuangjiang; Ding, Jianxun; He, Chaoliang; Cao, Yue; Xu, Weiguo; Chen, Xuesi

2014-05-01

Nanoscale carriers that stably load drugs in blood circulation and release the payloads in desirable sites in response to a specific trigger are of great interest for smart drug delivery systems. For this purpose, a novel type of disulfide core cross-linked micelles, which are facilely fabricated by cross-linking of poly(ethylene glycol)/polyurethane block copolymers containing cyclic disulfide moieties via a thiol-disulfide exchange reaction, are developed. A broad-spectrum anti-cancer drug, doxorubicin (DOX), is loaded into the micelles as a model drug. The drug release from the core cross-linked polyurethane micelles (CCL-PUMs) loaded with DOX is suppressed in normal phosphate buffer saline (PBS), whereas it is markedly accelerated with addition of an intracellular reducing agent, glutathione (GSH). Notably, although DOX-loaded CCL-PUMs display lower cytotoxicity in vitro compared to either free DOX or DOX-loaded uncross-linked polyurethane micelles, the drug-loaded CCL-PUMs show the highest anti-tumor efficacy with reduced toxicity in vivo. Since enhanced anti-tumor efficacy and reduced toxic side effects are key aspects of efficient cancer therapy, the novel reduction-responsive CCL-PUMs may hold great potential as a bio-triggered drug delivery system for cancer therapy. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads and its replication in cell culture.

PubMed

Lin, Ying-Ju; Chen, Chia-Yen; Jeang, Kuan-Teh; Liu, Xiang; Wang, Jen-Hsien; Hung, Chien-Hui; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Lin, Cheng-Wen; Ho, Mao-Wang; Chien, Wen-Kuei; Chen, Jin-Hua; Ho, Tsung-Jung; Tsai, Fuu-Jen

2014-01-01

The human immunodeficiency virus (HIV-1) exploits host proteins to complete its life cycle. Genome-wide siRNA approaches suggested that host proteins affect HIV-1 replication. However, the results barely overlapped. RING finger protein 39 (RNF39) has been identified from genome-wide association studies. However, its function during HIV-1 replication remains unclear. We investigated the relationship between common RNF39 genetic variants and HIV-1 viral loads. The effect of RNF39 protein knockdown or overexpression on HIV-1 replication was then investigated in different cell lines. Two genetic variants were associated with HIV-1 viral loads. Patients with the ht1-GG/GG haplotype presented lower RNF39 expression levels and lower HIV-1 viral load. RNF39 knockdown inhibited HIV-1 expression. RNF39 protein may be involved in HIV-1 replication as observed in genetic studies on patients with HIV-1 and in in vitro cell cultures.

Lipid-induced mitochondrial stress and insulin action in muscle.

PubMed

Muoio, Deborah M; Neufer, P Darrell

2012-05-02

The interplay between mitochondrial energetics, lipid balance, and muscle insulin sensitivity has remained a topic of intense interest and debate for decades. One popular view suggests that increased oxidative capacity benefits metabolic wellness, based on the premise that it is healthier to burn fat than glucose. Attempts to test this hypothesis using genetically modified mouse models have produced contradictory results and instead link muscle insulin resistance to excessive fat oxidation, acylcarnitine production, and increased mitochondrial H(2)O(2)-emitting potential. Here, we consider emerging evidence that insulin action in muscle is driven principally by mitochondrial load and redox signaling rather than oxidative capacity. Copyright © 2012 Elsevier Inc. All rights reserved.

Cross-linked collagen sponges loaded with plant polyphenols with inhibitory activity towards chronic wound enzymes.

PubMed

Antonio, Francesko; Guillem, Rocasalbas; Sonia, Touriño; Clara, Mattu; Piergiorgio, Gentile; Valeria, Chiono; Gianluca, Ciardelli; Tzanov, Tzanko

2011-10-01

Collagen sponges loaded with polyphenols from Hamamelis virginiana were investigated as active materials for chronic wound dressings, evaluating in vitro the inhibition of two major enzymes that impair the wound healing process - myeloperoxidase (MPO) and collagenase. Prior to polyphenols loading, collagen was cross-linked with genipin to improve its biostability. The effect of genipin cross-linking and polyphenol concentration in the development of mechanically and enzymatically stable sponges was studied. The tensile strength of the cross-linked collagen increased with the increase of the cross-linking degree, coupled to decrease in the elongation and the swelling capacity of the sponges. The stability of the sponges to collagenase digestion reached maximum when 1 mM genipin was used. However, the biostability decreased more than 10-fold after loading the sponges with polyphenols (0.5 mg/mL), nevertheless, this effect was partially overcome using higher concentration of polyphenols (1 and 2 mg/mL) to inhibit collagenase. Moreover, the polyphenols released from the sponges were sufficient for complete inhibition of MPO activity. No considerable cytotoxicity of the genipin cross-linked collagen loaded with polyphenols was observed evaluating the NIH 3T3 fibroblasts viability. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simple measurement-based admission control for DiffServ access networks

NASA Astrophysics Data System (ADS)

Lakkakorpi, Jani

2002-07-01

In order to provide good Quality of Service (QoS) in a Differentiated Services (DiffServ) network, a dynamic admission control scheme is definitely needed as an alternative to overprovisioning. In this paper, we present a simple measurement-based admission control (MBAC) mechanism for DiffServ-based access networks. Instead of using active measurements only or doing purely static bookkeeping with parameter-based admission control (PBAC), the admission control decisions are based on bandwidth reservations and periodically measured & exponentially averaged link loads. If any link load on the path between two endpoints is over the applicable threshold, access is denied. Link loads are periodically sent to Bandwidth Broker (BB) of the routing domain, which makes the admission control decisions. The information needed in calculating the link loads is retrieved from the router statistics. The proposed admission control mechanism is verified through simulations. Our results prove that it is possible to achieve very high bottleneck link utilization levels and still maintain good QoS.

A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics.

PubMed

Lu, Qiongshi; Li, Boyang; Ou, Derek; Erlendsdottir, Margret; Powles, Ryan L; Jiang, Tony; Hu, Yiming; Chang, David; Jin, Chentian; Dai, Wei; He, Qidu; Liu, Zefeng; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

2017-12-07

Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses, we demonstrate that our method provides accurate covariance estimates, thereby enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD's correlation with cognitive traits and hints at an autoimmune component for ALS. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Correlation of genetic risk and messenger RNA expression in a Th17/IL23 pathway analysis in inflammatory bowel disease.

PubMed

Fransen, Karin; van Sommeren, Suzanne; Westra, Harm-Jan; Veenstra, Monique; Lamberts, Letitia E; Modderman, Rutger; Dijkstra, Gerard; Fu, Jingyuan; Wijmenga, Cisca; Franke, Lude; Weersma, Rinse K; van Diemen, Cleo C

2014-05-01

The Th17/IL23 pathway has both genetically and biologically been implicated in the pathogenesis of the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. So far, it is unknown whether and how associated risk variants affect expression of the genes encoding for Th17/IL23 pathway proteins. Ten IBD-associated SNPs residing near Th17/IL23 genes were used to construct a genetic risk model in 753 Dutch IBD cases and 1045 controls. In an independent cohort of 40 Crohn's disease, 40 ulcerative colitis, and 40 controls, the genetic risk load and presence of IBD were correlated to quantitative PCR-generated messenger RNA (mRNA) expression of 9 representative Th17/IL23 genes in both unstimulated and PMA/CaLo stimulated peripheral blood mononuclear cells. In 1240 individuals with various immunological diseases with whole genome genotype and mRNA-expression data, we also assessed correlation between genetic risk load and differential mRNA expression and sought for SNPs affecting expression of all currently known Th17/IL23 pathway genes (cis-expression quantitative trait locus). The presence of IBD, but not the genetic risk load, was correlated to differential mRNA expression for IL6 in unstimulated peripheral blood mononuclear cells and to IL23A and RORC in response to stimulation. The cis-expression quantitative trait locus analysis showed little evidence for correlation between genetic risk load and mRNA expression of Th17/IL23 genes, because we identified for only 2 of 22 Th17/IL23 genes a cis-expression quantitative trait locus single nucleotide polymorphism that is also associated to IBD (STAT3 and CCR6). Our results suggest that only the presence of IBD and not the genetic risk load alters mRNA expression levels of IBD-associated Th17/IL23 genes.

Externalizing problems, attention regulation, and household chaos: a longitudinal behavioral genetic study.

PubMed

Wang, Zhe; Deater-Deckard, Kirby; Petrill, Stephen A; Thompson, Lee A

2012-08-01

Previous research documented a robust link between difficulties in self-regulation and development of externalizing problems (i.e., aggression and delinquency). In this study, we examined the longitudinal additive and interactive genetic and environmental covariation underlying this well-established link using a twin design. The sample included 131 pairs of monozygotic twins and 173 pairs of same-sex dizygotic twins who participated in three waves of annual assessment. Mothers and fathers provided reports of externalizing problems. Teacher report and observer rating were used to assess twin's attention regulation. The etiology underlying the link between externalizing problems and attention regulation shifted from a common genetic mechanism to a common environmental mechanism in the transition across middle childhood. Household chaos moderated the genetic variance of and covariance between externalizing problems and attention regulation. The genetic influence on individual differences in both externalizing problems and attention regulation was stronger in more chaotic households. However, higher levels of household chaos attenuated the genetic link between externalizing problems and attention regulation.

Externalizing problems, attention regulation, and household chaos: A longitudinal behavioral genetic study

PubMed Central

Wang, Zhe; Deater-Deckard, Kirby; Petrill, Stephen A.; Thompson, Lee A.

2015-01-01

Previous research has documented a robust link between difficulties in self-regulation and development of externalizing problems (i.e., aggression and delinquency). In the current study, we examined the longitudinal additive and interactive genetic and environmental covariation underlying this well-established link using a twin design. The sample included 131 pairs of monozygotic twins and 173 pairs of same-sex dizygotic twins who participated in three waves of annual assessment. Mothers and fathers provided reports of externalizing problems. Teacher report and observer rating were used to assess twin’s attention regulation. The etiology underlying the link between externalizing problems and attention regulation shifted from a common genetic mechanism to a common environmental mechanism in the transition across middle childhood. Household chaos moderated the genetic variance of and covariance between externalizing problems and attention regulation. The genetic influence on individual differences in both externalizing problems and attention regulation was stronger in more chaotic household. However, higher levels of household chaos attenuated the genetic link between externalizing problems and attention regulation. PMID:22781853

Genetics Home Reference: X-linked dystonia-parkinsonism

MedlinePlus

... X-linked dystonia-parkinsonism syndrome (XDP): clinical and molecular genetic analysis. Brain Pathol. 1992 Oct;2(4):287-95. Review. Citation on PubMed Kaji R, Goto S, Tamiya G, Ando S, Makino S, Lee LV. Molecular dissection and anatomical basis of dystonia: X-linked ...

Neurocognitive functioning in parents of schizophrenia patients: Attentional and executive performance vary with genetic loading.

PubMed

Schulze-Rauschenbach, Svenja; Lennertz, Leonhard; Ruhrmann, Stephan; Petrovsky, Nadine; Ettinger, Ulrich; Pukrop, Ralf; Dreher, Jan; Klosterkötter, Joachim; Maier, Wolfgang; Wagner, Michael

2015-12-30

Neuropsychological deficits are candidate endophenotypes of schizophrenia which can assist to explain the neurocognitive impact of genetic risk variants. The identification of endophenotypes is often based on the familiality of these phenotypes. Several studies demonstrate neuropsychological deficits in unaffected biological relatives of schizophrenia patients without differentiating between genetic and non-genetic factors underlying these deficits. We assessed N=129 unaffected biological parents of schizophrenia patients, N=28 schizophrenia patients (paranoid subtype), and N=143 controls without a family history of schizophrenia with an extensive neuropsychological test battery. Direct comparison of N=22 parents with an ancestral history of schizophrenia (more likely carriers, MLC) and N=17 of their spouses without such a history (less likely carriers, LLC) allowed the separation of genetic and non-genetic aspects in cognition. Overall, parents showed significant deficits in neuropsychological tasks from all cognitive domains with medium effect sizes. Direct comparisons of MLC- and LLC-parents showed that attentional and executive tasks were most strongly affected by genetic loading. To conclude, unaffected parents of schizophrenia patients showed modest yet significant impairments in attention, memory, and executive functioning. In particular, attentional and executive impairments varied most strongly with genetic loading for schizophrenia, prioritising these dysfunctions for genotype-endophenotype analyses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.

PubMed

Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin; Black, Kathleen; Fernandez, Maria Victoria; Budde, John; Ibanez, Laura; Deming, Yuetiva; Kapoor, Manav; Tosto, Giuseppe; Mayeux, Richard P; Holtzman, David M; Fagan, Anne M; Morris, John C; Bateman, Randall J; Goate, Alison M; Harari, Oscar

2018-02-01

To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD). Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk. We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR] = 2.27; P = 1.29 × 10 -7 ) was observed in sEOAD, followed by fLOAD (OR = 1.75; P = 1.12 × 10 -7 ) and sLOAD (OR = 1.40; P = 1.21 × 10 -3 ). The PRS was associated with cerebrospinal fluid ptau 181 -Aβ 42 on eADAD (P = 4.36 × 10 -2 ). Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Heterozygosity-fitness correlations among wild populations of European tree frog (Hyla arborea) detect fixation load.

PubMed

Luquet, E; David, P; Lena, J-P; Joly, P; Konecny, L; Dufresnes, C; Perrin, N; Plenet, S

2011-05-01

Quantifying the impacts of inbreeding and genetic drift on fitness traits in fragmented populations is becoming a major goal in conservation biology. Such impacts occur at different levels and involve different sets of loci. Genetic drift randomly fixes slightly deleterious alleles leading to different fixation load among populations. By contrast, inbreeding depression arises from highly deleterious alleles in segregation within a population and creates variation among individuals. A popular approach is to measure correlations between molecular variation and phenotypic performances. This approach has been mainly used at the individual level to detect inbreeding depression within populations and sometimes at the population level but without consideration about the genetic processes measured. For the first time, we used in this study a molecular approach considering both the interpopulation and intrapopulation level to discriminate the relative importance of inbreeding depression vs. fixation load in isolated and non-fragmented populations of European tree frog (Hyla arborea), complemented with interpopulational crosses. We demonstrated that the positive correlations observed between genetic heterozygosity and larval performances on merged data were mainly caused by co-variations in genetic diversity and fixation load among populations rather than by inbreeding depression and segregating deleterious alleles within populations. Such a method is highly relevant in a conservation perspective because, depending on how populations lose fitness (inbreeding vs. fixation load), specific management actions may be designed to improve the persistence of populations. © 2011 Blackwell Publishing Ltd.

Guided Exploration of Genomic Risk for Gray Matter Abnormalities in Schizophrenia Using Parallel Independent Component Analysis with Reference

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Pearlson, Godfrey D.; Perrone-Bizzozero, Nora; Sui, Jing; Turner, Jessica A.; Bustillo, Juan R; Ehrlich, Stefan; Sponheim, Scott R.; Cañive, José M.; Ho, Beng-Choon; Liu, Jingyu

2013-01-01

One application of imaging genomics is to explore genetic variants associated with brain structure and function, presenting a new means of mapping genetic influences on mental disorders. While there is growing interest in performing genome-wide searches for determinants, it remains challenging to identify genetic factors of small effect size, especially in limited sample sizes. In an attempt to address this issue, we propose to take advantage of a priori knowledge, specifically to extend parallel independent component analysis (pICA) to incorporate a reference (pICA-R), aiming to better reveal relationships between hidden factors of a particular attribute. The new approach was first evaluated on simulated data for its performance under different configurations of effect size and dimensionality. Then pICA-R was applied to a 300-participant (140 schizophrenia (SZ) patients versus 160 healthy controls) dataset consisting of structural magnetic resonance imaging (sMRI) and single nucleotide polymorphism (SNP) data. Guided by a reference SNP set derived from ANK3, a gene implicated by the Psychiatric Genomic Consortium SZ study, pICA-R identified one pair of SNP and sMRI components with a significant loading correlation of 0.27 (p = 1.64×10−6). The sMRI component showed a significant group difference in loading parameters between patients and controls (p = 1.33×10−15), indicating SZ-related reduction in gray matter concentration in prefrontal and temporal regions. The linked SNP component also showed a group difference (p = 0.04) and was predominantly contributed to by 1,030 SNPs. The effect of these top contributing SNPs was verified using association test results of the Psychiatric Genomic Consortium SZ study, where the 1,030 SNPs exhibited significant SZ enrichment compared to the whole genome. In addition, pathway analyses indicated the genetic component majorly relating to neurotransmitter and nervous system signaling pathways. Given the simulation and experiment results, pICA-R may prove a promising multivariate approach for use in imaging genomics to discover reliable genetic risk factors under a scenario of relatively high dimensionality and small effect size. PMID:23727316

Dynamics of fluidic devices with applications to rotor pitch links

NASA Astrophysics Data System (ADS)

Scarborough, Lloyd H., III

Coupling a Fluidic Flexible Matrix Composite (F2MC) to an air-pressurized fluid port produces a fundamentally new class of tunable vibration isolator. This fluidlastic device provides significant vibration reduction at an isolation frequency that can be tuned over a broad frequency range. The material properties and geometry of the F2MC element, as well as the port inertance, determine the isolation frequency. A unique feature of this device is that the port inertance depends on pressure so the isolation frequency can be adjusted by changing the air pressure. For constant port inertance, the isolation frequency is largely independent of the isolated mass so the device is robust to changes in load. A nonlinear model is developed to predict isolator length and port inertance. The model is linearized and the frequency response calculated. Experiments agree with theory, demonstrating a tunable isolation range from 9 Hz to 36 Hz and transmitted force reductions of up to 60 dB at the isolation frequency. Replacing rigid pitch links on rotorcraft with coupled fluidic devices has the potential to reduce the aerodynamic blade loads transmitted through the pitch links to the swashplate. Analytical models of two fluidic devices coupled with three different fluidic circuits are derived. These passive fluidlastic systems are tuned, by varying the fluid inertances and capacitances of each fluidic circuit, to reduce the transmitted pitch-link loads. The different circuit designs result in transmitted pitch link loads reduction at up to three main rotor harmonics. The simulation results show loads reduction at the targeted out-of-phase and in-phase harmonics of up to 88% and 93%, respectively. Experimental validation of two of the fluidic circuits demonstrates loads reduction of up to 89% at the out-of-phase isolation frequencies and up to 81% at the in-phase isolation frequencies. Replacing rigid pitch links on rotorcraft with fluidic pitch links changes the blade torsional impedance. At low frequency, the pitch link must have high impedance to pass through the pilot's collective and cyclic commands to control the aircraft. At higher frequencies, however, the pitch-link impedance can be tuned to change the blade pitching response to higher harmonic loads. Active blade control to produce higher harmonic pitch motions has been shown to reduce hub loads and increase rotor efficiency. This work investigates whether fluidic pitch links can passively provide these benefits. An analytical model of a fluidic pitch link is derived and incorporated into a rotor aeroelastic simulation for a rotor similar to that of the UH-60. Eighty-one simulations with varied fluidic pitch link parameters demonstrate that their impedance can be tailored to reduce rotor power and all six hub forces and moments. While no impedance was found that simultaneously reduced all components, the results include cases with reductions in the lateral 4/rev hub force of up to 91% and 4/rev hub pitching moment of up to 67%, and main rotor power of up to 5%.

Heuristic approaches for energy-efficient shared restoration in WDM networks

NASA Astrophysics Data System (ADS)

Alilou, Shahab

In recent years, there has been ongoing research on the design of energy-efficient Wavelength Division Multiplexing (WDM) networks. The explosive growth of Internet traffic has led to increased power consumption of network components. Network survivability has also been a relevant research topic, as it plays a crucial role in assuring continuity of service with no disruption, regardless of network component failure. Network survivability mechanisms tend to utilize considerable resources such as spare capacity in order to protect and restore information. This thesis investigates techniques for reducing energy demand and enhancing energy efficiency in the context of network survivability. We propose two novel heuristic energy-efficient shared protection approaches for WDM networks. These approaches intend to save energy by setting on sleep mode devices that are not being used while providing shared backup paths to satisfy network survivability. The first approach exploits properties of a math series in order to assign weight to the network links. It aims at reducing power consumption at the network indirectly by aggregating traffic on a set of nodes and links with high traffic load level. Routing traffic on links and nodes that are already under utilization makes it possible for the links and nodes with no load to be set on sleep mode. The second approach is intended to dynamically route traffic through nodes and links with high traffic load level. Similar to the first approach, this approach computes a pair of paths for every newly arrived demand. It computes these paths for every new demand by comparing the power consumption of nodes and links in the network before the demand arrives with their potential power consumption if they are chosen along the paths of this demand. Simulations of two different networks were used to compare the total network power consumption obtained using the proposed techniques against a standard shared-path restoration scheme. Shared-path restoration is a network survivability method in which a link-disjoint backup path and wavelength is reserved at the time of call setup for a working path. However, in order to reduce spare capacity consumption, this reserved backup path and wavelength may be shared with other backup paths. Pool Sharing Scheme (PSS) is employed to implement shared-path restoration scheme [1]. In an optical network, the failure of a single link leads to the failure of all the lightpaths that pass through that particular link. PSS ensures that the amount of backup bandwidth required on a link to restore the failed connections will not be more than the total amount of reserved backup bandwidth on that link. Simulation results indicate that the proposed approaches lead to up to 35% power savings in WDM networks when traffic load is low. However, power saving decreases to 14% at high traffic load level. Furthermore, in terms of the total capacity consumption for working paths, PSS outperforms the two proposed approaches, as expected. In terms of total capacity consumption all the approaches behave similarly. In general, at low traffic load level, the two proposed approaches behave similar to PSS in terms of average link load, and the ratio of block demands. Nevertheless, at high traffic load, the proposed approaches result in higher ratio of blocked demands than PSS. They also lead to higher average link load than PSS for the equal number of generated demands.

Polymer Micelles with Cross-Linked Polyanion Core for Delivery of a Cationic Drug Doxorubicin

PubMed Central

Kim, Jong Oh; Kabanov, Alexander V.; Bronich, Tatiana K.

2009-01-01

Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w %) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX. PMID:19386272

Genetics Home Reference: malignant hyperthermia

MedlinePlus

... Genetic and Rare Diseases Information Center (2 links) King Denborough syndrome Malignant hyperthermia Educational Resources (4 links) ... 19 [updated 2013 Jan 31]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean ...

Genetics Home Reference: primary carnitine deficiency

MedlinePlus

... 1 link) NIH Office of Dietary Supplements: Carnitine Educational Resources (5 links) Disease InfoSearch: Renal carnitine transport defect Orphanet: Systemic primary carnitine deficiency Screening, Technology, and Research in Genetics The Linus Pauling Institute: ...

Genetics Home Reference: Hirschsprung disease

MedlinePlus

... MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How ... Patient Support and Advocacy Resources (4 links) Bowel Group for Kids International Foundation for Functional Gastrointestinal Disorders ...

Erythropoietic Protoporphyria (EPP) or Protoporphyria

MedlinePlus

... protoporphyrin can differentiate X-linked protoporphyria from EPP. Molecular genetic testing can confirm a diagnosis of X-linked ... systematically and comprehensively plan an affected child’s treatment. Genetic ... expression and characterization of erythroid-specific 5-aminolevulinate ...

A survey on investigating the need for intelligent power-aware load balanced routing protocols for handling critical links in MANETs.

PubMed

Sivakumar, B; Bhalaji, N; Sivakumar, D

2014-01-01

In mobile ad hoc networks connectivity is always an issue of concern. Due to dynamism in the behavior of mobile nodes, efficiency shall be achieved only with the assumption of good network infrastructure. Presence of critical links results in deterioration which should be detected in advance to retain the prevailing communication setup. This paper discusses a short survey on the specialized algorithms and protocols related to energy efficient load balancing for critical link detection in the recent literature. This paper also suggests a machine learning based hybrid power-aware approach for handling critical nodes via load balancing.

A Survey on Investigating the Need for Intelligent Power-Aware Load Balanced Routing Protocols for Handling Critical Links in MANETs

PubMed Central

Sivakumar, B.; Bhalaji, N.; Sivakumar, D.

2014-01-01

In mobile ad hoc networks connectivity is always an issue of concern. Due to dynamism in the behavior of mobile nodes, efficiency shall be achieved only with the assumption of good network infrastructure. Presence of critical links results in deterioration which should be detected in advance to retain the prevailing communication setup. This paper discusses a short survey on the specialized algorithms and protocols related to energy efficient load balancing for critical link detection in the recent literature. This paper also suggests a machine learning based hybrid power-aware approach for handling critical nodes via load balancing. PMID:24790546

Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

PubMed Central

Zhao, Hui; Huang, Xiu-Feng; Zheng, Zhi-Li; Deng, Wen-Li; Lei, Xin-Lan; Xing, Dong-Jun; Ye, Liang; Xu, Su-Zhong; Chen, Jie; Zhang, Fang; Yu, Xin-Ping; Jin, Zi-Bing

2016-01-01

Objectives Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. Design Prospective analysis. Patients Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. Setting All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. Results Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. Conclusions The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. PMID:27036142

Missing Links in Genes to Traits: Toward Teaching for an Integrated Framework of Genetics

ERIC Educational Resources Information Center

Pavlova, Iglika V.; Kreher, Scott A.

2013-01-01

Genetics, one of the most influential fields, underlies all of biology and produces discoveries that are in the news daily. However, many students leave introductory biology and genetics courses lacking a coherent framework of knowledge to use in their daily lives. We identify substantial "missing links" in the teaching of foundational…

Linking movement behavior and fine-scale genetic structure to model landscape connectivity for bobcats (Lynx rufus)

Treesearch

Dawn M. Reding; Samuel A. Cushman; Todd E. Gosselink; William R. Clark

2013-01-01

Spatial heterogeneity can constrain the movement of individuals and consequently genes across a landscape, influencing demographic and genetic processes. In this study, we linked information on landscape composition, movement behavior, and genetic differentiation to gain a mechanistic understanding of how spatial heterogeneity may influence movement and gene flow of...

Genetic profile for five common variants associated with age-related macular degeneration in densely affected families: a novel analytic approach

PubMed Central

Sobrin, Lucia; Maller, Julian B; Neale, Benjamin M; Reynolds, Robyn C; Fagerness, Jesen A; Daly, Mark J; Seddon, Johanna M

2010-01-01

About 40% of the genetic variance of age-related macular degeneration (AMD) can be explained by a common variation at five common single-nucleotide polymorphisms (SNPs). We evaluated the degree to which these known variants explain the clustering of AMD in a group of densely affected families. We sought to determine whether the actual number of risk alleles at the five variants in densely affected families matched the expected number. Using data from 322 families with AMD, we used a simulation strategy to generate comparison groups of families and determined whether their genetic profile at the known AMD risk loci differed from the observed genetic profile, given the density of disease observed. Overall, the genotypic loads for the five SNPs in the families did not deviate significantly from the genotypic loads predicted by the simulation. However, for a subset of densely affected families, the mean genotypic load in the families was significantly lower than the expected load determined from the simulation. Given that these densely affected families may harbor rare, more penetrant variants for AMD, linkage analyses and resequencing targeting these families may be an effective approach to finding additional implicated genes. PMID:19844262

Targeted intracellular delivery of proteins with spatial and temporal control.

PubMed

Morales, Demosthenes P; Braun, Gary B; Pallaoro, Alessia; Chen, Renwei; Huang, Xiao; Zasadzinski, Joseph A; Reich, Norbert O

2015-02-02

While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.

Genetics Home Reference: 3-beta-hydroxysteroid dehydrogenase deficiency

MedlinePlus

... Topic: Adrenal Gland Disorders Health Topic: Assisted Reproductive Technology Health Topic: Infertility Genetic and Rare Diseases Information Center (1 link) 3-beta-hydroxysteroid dehydrogenase deficiency Educational Resources (6 links) Boston Children's Hospital: Congenital Adrenal ...

Genetics Home Reference: GM3 synthase deficiency

MedlinePlus

... GM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first ... Testing (1 link) Genetic Testing Registry: Amish infantile epilepsy syndrome Other Diagnosis and Management Resources (2 links) ...

Performance and Loads Correlation of a UH-60A Slowed Rotor at High Advance Ratios

NASA Technical Reports Server (NTRS)

Kottapalli, Sesi B.

2012-01-01

Measured data from the slowed rotor part of the 2010 UH-60A Airloads Rotor test in the NASA Ames 40- by 80- Foot Wind Tunnel are compared with CAMRAD II calculations. The emphasis in this initial study is to correlate overall trends. This analytical effort considers advance ratios from 0.3 to 1.0, with the rotor rotational speed at 40%NR. The rotor performance parameters considered are the thrust coefficient, power coefficient, L/DE, torque, and H-force. The blade loads considered are the half peak-to-peak, mid-span and outboard torsion, flatwise, and chordwise moments, and the pitch link load. For advance ratios . 0.7, the overall trends for the performance and loads (excluding the pitch link load) could be captured, but with substantial overprediction or underprediction. The correlation gradually deteriorates as the advance ratio is increased and for advance ratios . 0.8 there is no correlation. The pitch link load correlation is not good. There is considerable scope for improvement in the prediction of the blade loads. Considering the modeling complexity associated with the unconventional operating condition under consideration, the current predictive ability to capture overall trends is encouraging.

Chewed out: an experimental link between food material properties and repetitive loading of the masticatory apparatus in mammals

PubMed Central

Scott, Jeremiah E.; McAbee, Kevin R.; Veit, Anna J.; Fling, Annika L.

2015-01-01

Using a model organism (rabbits) that resembles a number of mammalian herbivores in key aspects of its chewing behaviors, we examined how variation in dietary mechanical properties affects food breakdown during mastication. Such data have implications for understanding phenotypic variation in the mammalian feeding apparatus, particularly with respect to linking jaw form to diet-induced repetitive loading. Results indicate that chewing frequency (chews/s) is independent of food properties, whereas chewing investment (chews/g) and chewing duration(s), which are proportional to repetitive loading of the jaws, are positively related to food stiffness and toughness. In comparisons of displacement-limited and stress-limited fragmentation indices, which respectively characterize the intraoral breakdown of tough and stiff foods, increases in chewing investment and duration are linked solely to stiffness. This suggests that stiffer foods engender higher peak loads and increased cyclical loading. Our findings challenge conventional wisdom by demonstrating that toughness does not, by itself, underlie increases in cyclical loading and loading duration. Instead, tough foods may be associated with such jaw-loading patterns because they must be processed in greater volumes owing to their lower nutritive quality and for longer periods of time to increase oral exposure to salivary chemicals. PMID:26557436

The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

PubMed Central

Whalley, H C; Papmeyer, M; Sprooten, E; Romaniuk, L; Blackwood, D H; Glahn, D C; Hall, J; Lawrie, S M; Sussmann, Je; McIntosh, A M

2012-01-01

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD. PMID:22760554

Transcriptomics Profiling of Alzheimer’s Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs

PubMed Central

Magistri, Marco; Velmeshev, Dmitry; Makhmutova, Madina; Faghihi, Mohammad Ali

2015-01-01

Abstract The underlying genetic variations of late-onset Alzheimer’s disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD pathological process. Transcriptome profiling using deep sequencing technology offers insight into common altered pathways regardless of underpinning genetic or epigenetic factors and thus represents an ideal tool to investigate molecular mechanisms related to the pathophysiology of LOAD. We performed directional RNA sequencing on high quality RNA samples extracted from hippocampi of LOAD and age-matched controls. We further validated our data using qRT-PCR on a larger set of postmortem brain tissues, confirming downregulation of the gene encoding substance P (TAC1) and upregulation of the gene encoding the plasminogen activator inhibitor-1 (SERPINE1). Pathway analysis indicates dysregulation in neural communication, cerebral vasculature, and amyloid-β clearance. Beside protein coding genes, we identified several annotated and non-annotated long noncoding RNAs that are differentially expressed in LOAD brain tissues, three of them are activity-dependent regulated and one is induced by Aβ1 - 42 exposure of human neural cells. Our data provide a comprehensive list of transcriptomics alterations in LOAD hippocampi and warrant holistic approach including both coding and non-coding RNAs in functional studies aimed to understand the pathophysiology of LOAD. PMID:26402107

Genetics Home Reference: Pompe disease

MedlinePlus

... Genetic Testing (2 links) Genetic Testing Registry: Glycogen storage disease type II, infantile Genetic Testing Registry: Glycogen storage disease, type II Other Diagnosis and Management Resources ( ...

Architecture of the wood-wide web: Rhizopogon spp. genets link multiple Douglas-fir cohorts.

PubMed

Beiler, Kevin J; Durall, Daniel M; Simard, Suzanne W; Maxwell, Sheri A; Kretzer, Annette M

2010-01-01

*The role of mycorrhizal networks in forest dynamics is poorly understood because of the elusiveness of their spatial structure. We mapped the belowground distribution of the fungi Rhizopogon vesiculosus and Rhizopogon vinicolor and interior Douglas-fir trees (Pseudotsuga menziesii var. glauca) to determine the architecture of a mycorrhizal network in a multi-aged old-growth forest. *Rhizopogon spp. mycorrhizas were collected within a 30 x 30 m plot. Trees and fungal genets were identified using multi-locus microsatellite DNA analysis. Tree genotypes from mycorrhizas were matched to reference trees aboveground. Two trees were considered linked if they shared the same fungal genet(s). *The two Rhizopogon species each formed 13-14 genets, each colonizing up to 19 trees in the plot. Rhizopogon vesiculosus genets were larger, occurred at greater depths, and linked more trees than genets of R. vinicolor. Multiple tree cohorts were linked, with young saplings established within the mycorrhizal network of Douglas-fir veterans. A strong positive relationship was found between tree size and connectivity, resulting in a scale-free network architecture with small-world properties. *This mycorrhizal network architecture suggests an efficient and robust network, where large trees play a foundational role in facilitating conspecific regeneration and stabilizing the ecosystem.

Sex-linked dominant

MedlinePlus

Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

Grocery Store Genetics: A PCR-Based Genetics Lab that Links Genotype to Phenotype

ERIC Educational Resources Information Center

Briju, Betsy J.; Wyatt, Sarah E.

2015-01-01

Instructors often present Mendelian genetics and molecular biology separately. As a result, students often fail to connect the two topics in a tangible manner. We have adopted a simple experiment to help link these two important topics in a basic biology course, using red and white onions bought from a local grocery store. A lack of red coloration…

Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease.

PubMed

Ashbrook, David G; Williams, Robert W; Lu, Lu; Stein, Jason L; Hibar, Derrek P; Nichols, Thomas E; Medland, Sarah E; Thompson, Paul M; Hager, Reinmar

2014-10-03

Variation in hippocampal volume has been linked to significant differences in memory, behavior, and cognition among individuals. To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. In addition, mapping studies in mouse model systems have identified genetic variants for brain structure variation with great power. A key challenge is to understand how genetically based differences in brain structure lead to the propensity to develop specific neurological disorders. We combine the largest human GWAS of brain structure with the largest mammalian model system, the BXD recombinant inbred mouse population, to identify novel genetic targets influencing brain structure variation that are linked to increased risk for neurological disorders. We first use a novel cross-species, comparative analysis using mouse and human genetic data to identify a candidate gene, MGST3, associated with adult hippocampus size in both systems. We then establish the coregulation and function of this gene in a comprehensive systems-analysis. We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's.

Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens

PubMed Central

Stathopoulos, Stavros; Neafsey, Daniel E.; Lawniczak, Mara K. N.; Muskavitch, Marc A. T.; Christophides, George K.

2014-01-01

Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component. PMID:24603764

Genetics Home Reference: congenital bilateral absence of the vas deferens

MedlinePlus

... Pathway of sperm (image) Health Topic: Assisted Reproductive Technology Health Topic: Male Infertility Genetic and Rare Diseases Information Center (1 link) Congenital bilateral absence of the vas deferens Educational Resources (3 links) American Society for Reproductive Medicine: ...

Dynamically Tuned Blade Pitch Links for Vibration Reduction

NASA Technical Reports Server (NTRS)

Milgram, Judah; Chopra, Inderjit; Kottapalli, Sesi

1994-01-01

A passive vibration reduction device in which the conventional main rotor blade pitch link is replaced by a spring/damper element is investigated using a comprehensive rotorcraft analysis code. A case study is conducted for a modern articulated helicopter main rotor. Correlation of vibratory pitch link loads with wind tunnel test data is satisfactory for lower harmonics. Inclusion of unsteady aerodynamics had little effect on the correlation. In the absence of pushrod damping, reduction in pushrod stiffness from the baseline value had an adverse effect on vibratory hub loads in forward flight. However, pushrod damping in combination with reduced pushrod stiffness resulted in modest improvements in fixed and rotating system hub loads.

Genetics Home Reference: Paget disease of bone

MedlinePlus

... genetic cause of classic Paget disease of bone , accounting for 10 to 50 percent of cases that ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (6 links) Genetic Testing Registry: ...

Nonsyndromic autosomal recessive deafness is linked to the DFNB1 locus in a large inbred Bedouin family from Israel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, D.A.; Sheffield, V.C.; Stone, E.M.

1995-10-01

Nonsyndromic deafness accounts for {approximately}70% of all genetically determined deafness. Several types of nonsyndromic deafness, with a variety of inheritance patterns, have been genetically linked, including dominant, recessive and X-linked forms. Two of these forms - DFNA3, a dominant form causing moderate to severe hearing loss, predominantly in the high frequencies, and DFNB1, a recessive form causing profound, prelingual, neurosensory deafness affecting all frequencies - have been linked to the same pericentromeric region of chromosome 13. This finding is equally compatible with (1) the existence two closely linked deafness genes, (2) different mutations within a single deafness gene, and (3)more » a single mutation in a single gene that behaves differently in different genetic backgrounds. 12 refs., 2 figs., 1 tab.« less

Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

PubMed

Kendler, Kenneth S; Myers, John; Prescott, Carol A

2007-11-01

Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence appear to be specific to those substances.

Hip ontogenesis: how evolution, genes, and load history shape hip morphotype and cartilotype.

PubMed

Hogervorst, Tom; Eilander, Wouter; Fikkers, Joost T; Meulenbelt, Ingrid

2012-12-01

Developmental hip disorders (DHDs), eg, developmental dysplasia of the hip, slipped capitis femoris epiphysis, and femoroacetabular impingement, can be considered morphology variants of the normal hip. The femoroacetabular morphology of DHD is believed to induce osteoarthritis (OA) through local cumulative mechanical overload acting on genetically controlled patterning systems and subsequent damage of joint structures. However, it is unclear why hip morphology differs between individuals with seemingly comparable load histories and why certain hips with DHD progress to symptomatic OA whereas others do not. We asked (1) which mechanical factors influence growth and development of the proximal femur; and (2) which genes or genetic mechanisms are associated with hip ontogenesis. We performed a systematic literature review of mechanical and genetic factors of hip ontogeny. We focused on three fields that in recent years have advanced our knowledge of adult hip morphology: imaging, evolution, and genetics. WHERE ARE WE NOW?: Mechanical factors can be understood in view of human evolutionary peculiarities and may summate to load histories conducive to DHD. Genetic factors most likely act through multiple genes, each with modest effect sizes. Single genes that explain a DHD are therefore unlikely to be found. Apparently, the interplay between genes and load history not only determines hip morphotype, but also joint cartilage robustness ("cartilotype") and resistance to symptomatic OA. WHERE DO WE NEED TO GO?: We need therapies that can improve both morphotype and cartilotype. HOW DO WE GET THERE?: Better phenotyping, improving classification systems of hip morphology, and comparative population studies can be done with existing methods. Quantifying load histories likely requires new tools, but proof of principle of modifying morphotype in treatment of DDH and of cartilotype with exercise is available.

Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.

PubMed

Mascarenhas, Roshan; Pietrzak, Maciej; Smith, Ryan M; Webb, Amy; Wang, Danxin; Papp, Audrey C; Pinsonneault, Julia K; Seweryn, Michal; Rempala, Grzegorz; Sadee, Wolfgang

2015-01-01

mRNA translation into proteins is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs), and genetic variants remains poorly understood. mRNA levels on polysomes have been shown to correlate well with expressed protein levels, pointing to polysomal loading as a critical factor. To study regulation and genetic factors of protein translation we measured levels and allelic ratios of mRNAs and ncRNAs (including microRNAs) in lymphoblast cell lines (LCL) and in polysomal fractions. We first used targeted assays to measure polysomal loading of mRNA alleles, confirming reported genetic effects on translation of OPRM1 and NAT1, and detecting no effect of rs1045642 (3435C>T) in ABCB1 (MDR1) on polysomal loading while supporting previous results showing increased mRNA turnover of the 3435T allele. Use of high-throughput sequencing of complete transcript profiles (RNA-Seq) in three LCLs revealed significant differences in polysomal loading of individual RNA classes and isoforms. Correlated polysomal distribution between protein-coding and non-coding RNAs suggests interactions between them. Allele-selective polysome recruitment revealed strong genetic influence for multiple RNAs, attributable either to differential expression of RNA isoforms or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Genes identified by different allelic RNA ratios between cytosol and polysomes were enriched with published expression quantitative trait loci (eQTLs) affecting RNA functions, and associations with clinical phenotypes. Polysomal RNA-Seq combined with allelic ratio analysis provides a powerful approach to study polysomal RNA recruitment and regulatory variants affecting protein translation.

Laterality and mental disorders in the postgenomic age--A closer look at schizophrenia and language lateralization.

PubMed

Ocklenburg, Sebastian; Güntürkün, Onur; Hugdahl, Kenneth; Hirnstein, Marco

2015-12-01

Most people are right-handed and show left-hemispheric language lateralization, but a minority exhibits left-handedness and right-hemispheric language lateralization. This atypical laterality pattern is observed significantly more often in schizophrenia patients than in the general population, which led several authors to conclude that there is a genetic link between laterality and schizophrenia. It has even been suggested that a failure in the lateralization process, orchestrated by genes, could be the primary cause of schizophrenia. However, the molecular genetic evidence for a link between laterality and schizophrenia is weak. Recent genetic evidence indicates that schizophrenia is not a single disorder but a group of heritable disorders caused by different genotypic networks leading to distinct clinical symptoms. To uncover the link between schizophrenia and laterality we therefore suggest a paradigm shift where genetics are not mapped on schizophrenia as a whole but on discrete schizophrenia symptoms. In addition, we provide a critical evaluation of current theories on the genetic link between schizophrenia and brain asymmetry. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preliminary C3 Loading Analysis for Future High-Altitude Unmanned Aircraft in the NAS

NASA Technical Reports Server (NTRS)

Ho, Yan-Shek; Gheorghisor, Izabela; Box, Frank

2006-01-01

This document provides a preliminary assessment and summary of the command, control, and communications (C(sup 3)) loading requirements of a generic future high-altitude, long-endurance unmanned aircraft (UA) operating at in the National Airspace System. Two principal types of C(sup 3) traffic are considered in our analysis: communications links providing air traffic services (ATS) to the UA and its human pilot, and the command and control data links enabling the pilot to operate the UA remotely. we have quantified the loading requirements of both types of traffic for two different assumed levels of UA autonomy. Our results indicate that the potential use of UA-borne relays for the ATS links, and the degree of autonomy exercised by the UA during the departure and arrival phases of its flight, will be among the key drivers of C(sup 3) loading and bandwidth requirements.

Genetics Home Reference: popliteal pterygium syndrome

MedlinePlus

... Additional Information & Resources MedlinePlus (1 link) Health Topic: Cleft Lip and Palate Genetic and Rare Diseases Information Center (1 link) ... InfoSearch: Popliteal pterygium syndrome March of Dimes: Cleft Lip and Cleft Palate Orphanet: Popliteal pterygium syndrome Patient Support and Advocacy ...

Simultaneous optimization of the cavity heat load and trip rates in linacs using a genetic algorithm

DOE PAGES

Terzić, Balša; Hofler, Alicia S.; Reeves, Cody J.; ...

2014-10-15

In this paper, a genetic algorithm-based optimization is used to simultaneously minimize two competing objectives guiding the operation of the Jefferson Lab's Continuous Electron Beam Accelerator Facility linacs: cavity heat load and radio frequency cavity trip rates. The results represent a significant improvement to the standard linac energy management tool and thereby could lead to a more efficient Continuous Electron Beam Accelerator Facility configuration. This study also serves as a proof of principle of how a genetic algorithm can be used for optimizing other linac-based machines.

FARVATX: FAmily-based Rare Variant Association Test for X-linked genes

PubMed Central

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H.; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-01-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease (COPD). Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. PMID:27325607

FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

PubMed

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-09-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. © 2016 WILEY PERIODICALS, INC.

Peripherally cross-linking the shell of core-shell polymer micelles decreases premature release of physically loaded combretastatin A4 in whole blood and increases its mean residence time and subsequent potency against primary murine breast tumors after IV administration.

PubMed

Wakaskar, Rajesh R; Bathena, Sai Praneeth R; Tallapaka, Shailendra B; Ambardekar, Vishakha V; Gautam, Nagsen; Thakare, Rhishikesh; Simet, Samantha M; Curran, Stephen M; Singh, Rakesh K; Dong, Yuxiang; Vetro, Joseph A

2015-03-01

Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors. Individual Pluronic F127 polymer micelles (F127 PM) peripherally cross-linked with ethylenediamine at 76% of total PEO blocks (X-F127 PM) were physically loaded with combretastatin A4 (CA4) by the solid dispersion method and compared to CA4 physically loaded in uncross-linked F127 PM, CA4 in DMSO in vitro, or water-soluble CA4 phosphate (CA4P) in vivo. X-F127 PM had similar CA4 loading and aqueous solubility as F127 PM up to 10 mg CA4 / mL at 22.9 wt% and did not aggregate in PBS or 90% (v/v) human serum at 37°C for at least 24 h. In contrast, X-F127 PM decreased the unbound fraction of CA4 in whole blood (fu) and increased the mean plasma residence time and subsequent potency of CA4 against the vascular function and growth of primary murine 4T1 breast tumors over CA4 in F127 PM and water-soluble CA4P after IV administration. Given that decreasing the fu is an indication of decreased drug release, peripherally cross-linking the shell of core-shell polymer micelles may be a simple approach to decrease premature release of physically loaded hydrophobic drug in the blood and increase subsequent potency in solid tumors.

Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System

DTIC Science & Technology

2007-02-01

cavity has begun forming above the third pha- lange’s joint . By 21 days postdissection, the cells have re- differentiated, the nail has begun reforming...involved in digit tip regeneration, bone size, skeletal repair and anabolic response to mechanical loading . The molecular genetic approaches have...small number of replicates. Biomechanical Properties: The breaking load for femurs from 14104 and control mice was measured by three-point

Scope for more genetic testing in learning disability. Case report of an inherited duplication on the X-chromosome.

PubMed

Robertshaw, B A; MacPherson, J

2006-08-01

There have been major advances in the past few years in our understanding of the X-linked learning disabilities. The most common of these is the fragile-X syndrome, but the number of other gene defects that are now recognised to be linked with learning disability is increasing year on year. We describe one family displaying a family displaying a rare X-linked abnormality. Repeat genetic testing was requested for a family member with mild learning disability when, following chromosomal analysis for her brother, it became known that he had a genetic defect. The genetic defect 46, Xdup(X) (p22.13 p22.31) was identified. To our knowledge this is the first time this precise configuration has been demonstrated. We conclude that genetic testing for individuals with learning disability is worthwhile, even when there may be only a low index of suspicion.

The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease.

PubMed

Tosto, Giuseppe; Bird, Thomas D; Bennett, David A; Boeve, Bradley F; Brickman, Adam M; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M; Farlow, Martin; Goate, Alison M; Graff-Radford, Neill R; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A; Mayeux, Richard

2016-10-01

The contribution of cardiovascular disease (CV) and cerebrovascular disease to the risk for late-onset Alzheimer disease (LOAD) has been long debated. Investigations have shown that antecedent CV risk factors increase the risk for LOAD, although other investigations have failed to validate this association. To study the contribution of CV risk factors (type 2 diabetes, hypertension, and heart disease) and the history of stroke to LOAD in a data set of large families multiply affected by LOAD. The National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (hereinafter referred to as NIA-LOAD study) is a longitudinal study of families with multiple members affected with LOAD. A multiethnic community-based longitudinal study (Washington Heights-Inwood Columbia Aging Project [WHICAP]) was used to replicate findings. The 6553 participants in the NIA-LOAD study were recruited from 23 US Alzheimer disease centers with ongoing data collection since 2003; the 5972 WHICAP participants were recruited at Columbia University with ongoing data collection since 1992. Data analysis was performed from 2003 to 2015. Generalized mixed logistic regression models tested the association of CV risk factors (primary association) with LOAD. History of stroke was used for the secondary association. A secondary model adjusted for the presence of an apolipoprotein E (APOE) ε4 allele. A genetic risk score, based on common variants associated with LOAD, was used to account for LOAD genetic risk beyond the APOE ε4 effect. Mediation analyses evaluated stroke as a mediating factor between the primary association and LOAD. A total of 6553 NIA-LOAD participants were included in the analyses (4044 women [61.7%]; 2509 men [38.3%]; mean [SD] age, 77.0 [9] years), with 5972 individuals from the WHICAP study included in the replication sample (4072 women [68.2%]; 1900 men [31.8%]; mean [SD] age, 76.5 [7.0] years). Hypertension was associated with decreased LOAD risk (odds ratio [OR], 0.63; 95% CI, 0.55-0.72); type 2 diabetes and heart disease were not. History of stroke conferred greater than 2-fold increased risk for LOAD (OR, 2.23; 95% CI, 1.75-2.83). Adjustment for APOE ε4 did not alter results. The genetic risk score was associated with LOAD (OR, 2.85; 95% CI, 2.05-3.97) but did not change the independent association of LOAD with hypertension or stroke. In the WHICAP sample, hypertension was not associated with LOAD (OR, 0.99; 95% CI, 0.88-1.11), whereas history of stroke increased the risk for LOAD (OR, 1.96; 95% CI, 1.56-2.46). The effect of hypertension on LOAD risk was also mediated by stroke in the NIA-LOAD and the WHICAP samples. In familial and sporadic LOAD, a history of stroke was significantly associated with increased disease risk and mediated the association between selected CV risk factors and LOAD, which appears to be independent of the LOAD-related genetic background.

The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease

PubMed Central

Tosto, Giuseppe; Bird, Thomas D.; Bennett, David A.; Boeve, Bradley F.; Brickman, Adam M.; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M.; Farlow, Martin; Goate, Alison M.; Graff-Radford, Neill R.; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J.; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A.; Mayeux, Richard

2016-01-01

Importance The contribution of cardiovascular disease (CV) and cerebrovascular disease to the risk for late-onset Alzheimer disease (LOAD) has been long debated. Investigations have shown that antecedent CV risk factors increase the risk for LOAD, although other investigations have failed to validate this association. Objective To study the contribution of CV risk factors (type 2 diabetes, hypertension, and heart disease) and the history of stroke to LOAD in a data set of large families multiply affected by LOAD. Design, Setting, and Participants The National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (hereinafter referred to as NIA-LOAD study) is a longitudinal study of families with multiple members affected with LOAD. A multiethnic community-based longitudinal study (Washington Heights–Inwood Columbia Aging Project [WHICAP]) was used to replicate findings. The 6553 participants in the NIA-LOAD study were recruited from 23 US Alzheimer disease centers with ongoing data collection since 2003; the 5972 WHICAP participants were recruited at Columbia University with ongoing data collection since 1992. Data analysis was performed from 2003 to 2015. Main Outcomes and Measures Generalized mixed logistic regression models tested the association of CV risk factors (primary association) with LOAD. History of stroke was used for the secondary association. A secondary model adjusted for the presence of an apolipoprotein E (APOE) ε4 allele. A genetic risk score, based on common variants associated with LOAD, was used to account for LOAD genetic risk beyond the APOE ε4 effect. Mediation analyses evaluated stroke as a mediating factor between the primary association and LOAD. Results A total of 6553 NIA-LOAD participants were included in the analyses (4044 women [61.7%]; 2509 men [38.3%]; mean [SD] age, 77.0 [9] years), with 5972 individuals from the WHICAP study included in the replication sample (4072 women [68.2%]; 1900 men [31.8%]; mean [SD] age, 76.5 [7.0] years). Hypertension was associated with decreased LOAD risk (odds ratio [OR], 0.63; 95% CI, 0.55-0.72); type 2 diabetes and heart disease were not. History of stroke conferred greater than 2-fold increased risk for LOAD (OR, 2.23; 95% CI, 1.75-2.83). Adjustment for APOE ε4 did not alter results. The genetic risk score was associated with LOAD (OR, 2.85; 95% CI, 2.05-3.97) but did not change the independent association of LOAD with hypertension or stroke. In the WHICAP sample, hypertension was not associated with LOAD (OR, 0.99; 95% CI, 0.88-1.11), whereas history of stroke increased the risk for LOAD (OR, 1.96; 95% CI, 1.56-2.46). The effect of hypertension on LOAD risk was also mediated by stroke in the NIA-LOAD and the WHICAP samples. Conclusions and Relevance In familial and sporadic LOAD, a history of stroke was significantly associated with increased disease risk and mediated the association between selected CV risk factors and LOAD, which appears to be independent of the LOAD-related genetic background. PMID:27533593

Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe.

PubMed

Blanquart, François; Wymant, Chris; Cornelissen, Marion; Gall, Astrid; Bakker, Margreet; Bezemer, Daniela; Hall, Matthew; Hillebregt, Mariska; Ong, Swee Hoe; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Fransen, Katrien; Gourlay, Annabelle J; Grabowski, M Kate; Gunsenheimer-Bartmeyer, Barbara; Günthard, Huldrych F; Kivelä, Pia; Kouyos, Roger; Laeyendecker, Oliver; Liitsola, Kirsi; Meyer, Laurence; Porter, Kholoud; Ristola, Matti; van Sighem, Ard; Vanham, Guido; Berkhout, Ben; Kellam, Paul; Reiss, Peter; Fraser, Christophe

2017-06-01

HIV-1 set-point viral load-the approximately stable value of viraemia in the first years of chronic infection-is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%-43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical "Brownian motion" model and another model ("Ornstein-Uhlenbeck") that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%-43%) is consistent with other studies based on regression of viral load in donor-recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.

Teaching Genetics in Secondary Classrooms: a Linguistic Analysis of Teachers' Talk About Proteins

NASA Astrophysics Data System (ADS)

Thörne, Karin; Gericke, Niklas

2014-02-01

This study investigates Swedish biology teachers' inclusion of proteins when teaching genetics in grade nine (students 15-16 years old). For some years, there has been a call to give attention to proteins when teaching genetics as a means of linking the concepts `gene' and `trait'. Students are known to have problems with this relation because the concepts belong to different organizational levels. However, we know little about how the topic is taught and therefore this case study focuses on how teachers talk about proteins while teaching genetics and if they use proteins as a link between the micro and macro level. Four teachers were recorded during entire genetics teaching sequences, 45 lessons in total. The teachers' verbal communication was then analyzed using thematic pattern analysis, which is based in systemic functional linguistics. The linguistic analysis of teachers' talk in action revealed great variations in both the extent to which they used proteins in explanations of genetics and the ways they included proteins in linking genes and traits. Two of the teachers used protein as a link between gene and trait, while two did not. Three of the four teachers included instruction about protein synthesis. The common message from all teachers was that proteins are built, but none of the teachers talked about genes as exclusively encoding proteins. Our results suggest that students' common lack of understanding of proteins as an intermediate link between gene and trait could be explained by limitations in the way the subject is taught.

Development of Groundwater Management Model for Sustainable Groundwater Use in the Agricultural Region

NASA Astrophysics Data System (ADS)

Park, D.; Bae, G.; Lee, K.

2010-12-01

In many agricultural regions, high dependence of irrigation on groundwater has brought about serious concerns about unplanned groundwater developments and over-pumping. Various agricultural activities including fertilization and livestock husbandry usually result in groundwater contamination in those regions. Field works in Icheon, Korea showed that in this region the rice farming still requires a significant amount of water and continuous construction of greenhouse can make the contamination from the fertilization more serious. In this study, a groundwater management model based on the simulation-optimization methodology is developed to achieve sufficient groundwater supply and groundwater quality conservation together on regional-scale. This model can obtain the on-ground contaminant loading mass by integrating an analytical model for 1-D solute transport in unsaturated zone with 3-D groundwater flow and solute transport model, HydroGeosphere. The outputs of the 1-D unsaturated transport model, concentrations of the contaminant leaching on water table, work as contaminant sources in the 3-D solute transport model in saturated zone. This integrated simulation model is linked to genetic algorithm that searches the global optimum for the sustainable groundwater use. And, in order for the design on the contaminant sources to be more effective, it also links the backward transport model useful for evaluating the contamination from contaminant sources to each pumping well. The first objective of the management in this study is to obtain the optimal pumping rates that not only can supply sufficient amount of the groundwater but protect the groundwater from the excessive drawdown and contamination. The second objective is to control the periodic loading of the contaminant by suggesting the allowable contaminant loading mass. For this multi-objective groundwater management, the objective function to maximize both pumping rates and allowable contaminant loading mass and at the same time to satisfy the constraints for contaminant concentration and drawdown are assigned in the optimization model. The proposed methodology can be useful to provide the groundwater management options for sustainable groundwater use in the agricultural regions.

Latest Research: Genetic Links

MedlinePlus

... additional genetic risk factors. The network will also explore the relationship between a genetic disease and its ... surgery involves inserting a hollow needle into the space between the eye's retinal layers and transferring genetic ...

LOADING AND UNLOADING DEVICE

DOEpatents

Treshow, M.

1960-08-16

A device for loading and unloading fuel rods into and from a reactor tank through an access hole includes parallel links carrying a gripper. These links enable the gripper to go through the access hole and then to be moved laterally from the axis of the access hole to the various locations of the fuel rods in the reactor tank.

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

PubMed Central

Weygandt, Martin; Meyer-Arndt, Lil; Behrens, Janina Ruth; Wakonig, Katharina; Bellmann-Strobl, Judith; Ritter, Kerstin; Scheel, Michael; Brandt, Alexander U.; Labadie, Christian; Hetzer, Stefan; Gold, Stefan M.; Paul, Friedemann; Haynes, John-Dylan

2016-01-01

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone. PMID:27821732

Is there a causal link between knee loading and knee osteoarthritis progression? A systematic review and meta-analysis of cohort studies and randomised trials

PubMed Central

Henriksen, Marius; Creaby, Mark W; Lund, Hans; Juhl, Carsten; Christensen, Robin

2014-01-01

Objective We performed a systematic review, meta-analysis and assessed the evidence supporting a causal link between knee joint loading during walking and structural knee osteoarthritis (OA) progression. Design Systematic review, meta-analysis and application of Bradford Hill's considerations on causation. Data sources We searched MEDLINE, Scopus, AMED, CINAHL and SportsDiscus for prospective cohort studies and randomised controlled trials (RCTs) from 1950 through October 2013. Study eligibility criteria We selected cohort studies and RCTs in which estimates of knee joint loading during walking were used to predict structural knee OA progression assessed by X-ray or MRI. Data analyses Meta-analysis was performed to estimate the combined OR for structural disease progression with higher baseline loading. The likelihood of a causal link between knee joint loading and OA progression was assessed from cohort studies using the Bradford Hill guidelines to derive a 0–4 causation score based on four criteria and examined for confirmation in RCTs. Results Of the 1078 potentially eligible articles, 5 prospective cohort studies were included. The studies included a total of 452 patients relating joint loading to disease progression over 12–72 months. There were very serious limitations associated with the methodological quality of the included studies. The combined OR for disease progression was 1.90 (95% CI 0.85 to 4.25; I2=77%) for each one-unit increment in baseline knee loading. The combined causation score was 0, indicating no causal association between knee loading and knee OA progression. No RCTs were found to confirm or refute the findings from the cohort studies. Conclusions There is very limited and low-quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA. Trial registration number CRD42012003253 PMID:25031196

Is there a causal link between knee loading and knee osteoarthritis progression? A systematic review and meta-analysis of cohort studies and randomised trials.

PubMed

Henriksen, Marius; Creaby, Mark W; Lund, Hans; Juhl, Carsten; Christensen, Robin

2014-07-15

We performed a systematic review, meta-analysis and assessed the evidence supporting a causal link between knee joint loading during walking and structural knee osteoarthritis (OA) progression. Systematic review, meta-analysis and application of Bradford Hill's considerations on causation. We searched MEDLINE, Scopus, AMED, CINAHL and SportsDiscus for prospective cohort studies and randomised controlled trials (RCTs) from 1950 through October 2013. We selected cohort studies and RCTs in which estimates of knee joint loading during walking were used to predict structural knee OA progression assessed by X-ray or MRI. Meta-analysis was performed to estimate the combined OR for structural disease progression with higher baseline loading. The likelihood of a causal link between knee joint loading and OA progression was assessed from cohort studies using the Bradford Hill guidelines to derive a 0-4 causation score based on four criteria and examined for confirmation in RCTs. Of the 1078 potentially eligible articles, 5 prospective cohort studies were included. The studies included a total of 452 patients relating joint loading to disease progression over 12-72 months. There were very serious limitations associated with the methodological quality of the included studies. The combined OR for disease progression was 1.90 (95% CI 0.85 to 4.25; I(2)=77%) for each one-unit increment in baseline knee loading. The combined causation score was 0, indicating no causal association between knee loading and knee OA progression. No RCTs were found to confirm or refute the findings from the cohort studies. There is very limited and low-quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA. CRD42012003253. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genetics Home Reference: myasthenia gravis

MedlinePlus

... ventilation assistance. This respiratory failure, called a myasthenic crisis, may be triggered by stresses such as infections ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (2 links) Genetic Testing Registry: ...

Genetics Home Reference: hereditary angioedema

MedlinePlus

... 000 people. Type I is the most common, accounting for 85 percent of cases. Type II occurs ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (3 links) Genetic Testing Registry: ...

Genetics Home Reference: multiminicore disease

MedlinePlus

... are less common than the classic form, together accounting for about 25 percent of all cases. The ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (5 links) Genetic Testing Registry: ...

Human genetic studies in areas of high natural radiation. VIII. Genetic load not related to radiation.

PubMed Central

Freire-Maia, A; Krieger, H

1975-01-01

The genetic load disclosed by inbreeding has been analyzed in a multiple regression model for a population involving several localities in the state of Espírito Santo, Brazil. The inbreeding load has been estimated for number of pregnancies, abortions, stillbirths, children born alive, anomalies in general, sex ratio, infant mortality, post-infant mortality, and sterility and infertility of the couple. There was no evidence of either maternal or paternal inbreeding effects on the variables analyzed. The effect of inbreeding of the zygote was significant only for anomalies in general (B = 2.29 +/- 0.45) and infant mortality (B = 3.19 +/- 1.39). The latter result must be accepted with caution because of the many environmental causes affecting infant mortality. The B/A ratio suggested a predominantly mutational load for anomalies in general (B/A = 25), but with respect to infant mortality (B/A = 6), the ratio is regarded as an underestimate because of the environmental contribution to A and therefore not supportive of the segregational interpretation. PMID:803018

Rapid Y degeneration and dosage compensation in plant sex chromosomes

PubMed Central

Papadopulos, Alexander S. T.; Chester, Michael; Ridout, Kate; Filatov, Dmitry A.

2015-01-01

The nonrecombining regions of animal Y chromosomes are known to undergo genetic degeneration, but previous work has failed to reveal large-scale gene degeneration on plant Y chromosomes. Here, we uncover rapid and extensive degeneration of Y-linked genes in a plant species, Silene latifolia, that evolved sex chromosomes de novo in the last 10 million years. Previous transcriptome-based studies of this species missed unexpressed, degenerate Y-linked genes. To identify sex-linked genes, regardless of their expression, we sequenced male and female genomes of S. latifolia and integrated the genomic contigs with a high-density genetic map. This revealed that 45% of Y-linked genes are not expressed, and 23% are interrupted by premature stop codons. This contrasts with X-linked genes, in which only 1.3% of genes contained stop codons and 4.3% of genes were not expressed in males. Loss of functional Y-linked genes is partly compensated for by gene-specific up-regulation of X-linked genes. Our results demonstrate that the rate of genetic degeneration of Y-linked genes in S. latifolia is as fast as in animals, and that the evolutionary trajectories of sex chromosomes are similar in the two kingdoms. PMID:26438872

Genetics Home Reference: Alexander disease

MedlinePlus

... the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of Alexander disease ... Degenerative Nerve Diseases Health Topic: Leukodystrophies Genetic and Rare Diseases Information Center (1 link) Alexander disease Additional NIH ...

Genetics Home Reference: Gillespie syndrome

MedlinePlus

... the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of Gillespie syndrome ... Developmental Disabilities Health Topic: Eye Diseases Genetic and Rare Diseases Information Center (1 link) Gillespie syndrome Educational Resources ( ...

Genetics Home Reference: combined pituitary hormone deficiency

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... the most common known cause of this disorder, accounting for an estimated 12 to 55 percent of ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (7 links) Genetic Testing Registry: ...

Genetics Home Reference: familial isolated pituitary adenoma

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... 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (1 link) Genetic Testing Registry: ...

Researchers uncover cause of genetic anomaly linked to cancer | Center for Cancer Research

Cancer.gov

In a new study in Nature, Shiv Grewal’s team has identified a process that drives a genetic anomaly linked to cancer and other diseases. This work could open new avenues for treatment of cancer and other human diseases. Learn more...

A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat.

PubMed

Xu, Rong; Wang, QuanQiu; Li, Li

2015-01-01

Dietary intakes of red meat and fat are established risk factors for both colorectal cancer (CRC) and cardiovascular disease (CVDs). Recent studies have shown a mechanistic link between TMAO, an intestinal microbial metabolite of red meat and fat, and risk of CVDs. Data linking TMAO directly to CRC is, however, lacking. Here, we present an unbiased data-driven network-based systems approach to uncover a potential genetic relationship between TMAO and CRC. We constructed two different epigenetic interaction networks (EINs) using chemical-gene, disease-gene and protein-protein interaction data from multiple large-scale data resources. We developed a network-based ranking algorithm to ascertain TMAO-related diseases from EINs. We systematically analyzed disease categories among TMAO-related diseases at different ranking cutoffs. We then determined which genetic pathways were associated with both TMAO and CRC. We show that CVDs and their major risk factors were ranked highly among TMAO-related diseases, confirming the newly discovered mechanistic link between CVDs and TMAO, and thus validating our algorithms. CRC was ranked highly among TMAO-related disease retrieved from both EINs (top 0.02%, #1 out of 4,372 diseases retrieved based on Mendelian genetics and top 10.9% among 882 diseases based on genome-wide association genetics), providing strong supporting evidence for our hypothesis that TMAO is genetically related to CRC. We have also identified putative genetic pathways that may link TMAO to CRC, which warrants further investigation. Through systematic disease enrichment analysis, we also demonstrated that TMAO is related to metabolic syndromes and cancers in general. Our genome-wide analysis demonstrates that systems approaches to studying the epigenetic interactions among diet, microbiome metabolisms, and disease genetics hold promise for understanding disease pathogenesis. Our results show that TMAO is genetically associated with CRC. This study suggests that TMAO may be an important intermediate marker linking dietary meat and fat and gut microbiota metabolism to risk of CRC, underscoring opportunities for the development of new gut microbiome-dependent diagnostic tests and therapeutics for CRC.

Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease.

PubMed

Kurowska, Zuzanna; Jewett, Michael; Brattås, Per Ludvik; Jimenez-Ferrer, Itzia; Kenéz, Xuyian; Björklund, Tomas; Nordström, Ulrika; Brundin, Patrik; Swanberg, Maria

2016-08-23

Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease-like damage in rodent disease models and considered in clinical association studies in PD.

Communication strategies for enhancing understanding of the behavioral implications of genetic and biomarker tests for disease risk: the role of coherence.

PubMed

Cameron, Linda D; Marteau, Theresa M; Brown, Paul M; Klein, William M P; Sherman, Kerry A

2012-06-01

Individuals frequently have difficulty understanding how behavior can reduce genetically-conferred risk for diseases such as colon cancer. With increasing opportunities to purchase genetic tests, communication strategies are needed for presenting information in ways that optimize comprehension and adaptive behavior. Using the Common-Sense Model, we tested the efficacy of a strategy for providing information about the relationships (links) among the physiological processes underlying disease risk and protective action on understanding, protective action motivations, and willingness to purchase tests. We tested the generalizability of the strategy's effects across varying risk levels, for genetic tests versus tests of a non-genetic biomarker, and when using graphic and numeric risk formats. In an internet-based experiment, 749 adults from four countries responded to messages about a hypothetical test for colon cancer risk. Messages varied by Risk-Action Link Information (provision or no provision of information describing how a low-fat diet reduces risk given positive results, indicating presence of a gene fault), Risk Increment (20%, 50%, or 80% risk given positive results), Risk Format (numeric or graphic presentation of risk increments), and Test Type (genetic or enzyme). Providing risk-action link information enhanced beliefs of coherence (understanding how a low-fat diet reduces risk) and response efficacy (low-fat diets effectively reduce risk) and lowered appraisals of anticipated risk of colon cancer given positive results. These effects held across risk increments, risk formats, and test types. For genetic tests, provision of risk-action link information reduced the amount individuals were willing to pay for testing. Brief messages explaining how action can reduce genetic and biomarker-detected risks can promote beliefs motivating protective action. By enhancing understanding of behavioral control, they may reduce the perceived value of genetic risk information.

Insights to Genetic Characterization Tools for Epidemiological Tracking of Francisella tularensis in Sweden

PubMed Central

Wahab, Tara; Birdsell, Dawn N.; Hjertqvist, Marika; Mitchell, Cedar L.; Wagner, David M.; Keim, Paul S.; Hedenström, Ingela; Löfdahl, Sven

2014-01-01

Tularaemia, caused by the bacterium Francisella tularensis, is endemic in Sweden and is poorly understood. The aim of this study was to evaluate the effectiveness of three different genetic typing systems to link a genetic type to the source and place of tularemia infection in Sweden. Canonical single nucleotide polymorphisms (canSNPs), MLVA including five variable number of tandem repeat loci and PmeI-PFGE were tested on 127 F. tularensis positive specimens collected from Swedish case-patients. All three typing methods identified two major genetic groups with near-perfect agreement. Higher genetic resolution was obtained with canSNP and MLVA compared to PFGE; F. tularensis samples were first assigned into ten phylogroups based on canSNPs followed by 33 unique MLVA types. Phylogroups were geographically analysed to reveal complex phylogeographic patterns in Sweden. The extensive phylogenetic diversity found within individual counties posed a challenge to linking specific genetic types with specific geographic locations. Despite this, a single phylogroup (B.22), defined by a SNP marker specific to a lone Swedish sequenced strain, did link genetic type with a likely geographic place. This result suggests that SNP markers, highly specific to a particular reference genome, may be found most frequently among samples recovered from the same location where the reference genome originated. This insight compels us to consider whole-genome sequencing (WGS) as the appropriate tool for effectively linking specific genetic type to geography. Comparing the WGS of an unknown sample to WGS databases of archived Swedish strains maximizes the likelihood of revealing those rare geographically informative SNPs. PMID:25401326

Genetic Testing for Deafness--GJB2 and SLC26A4 as Causes of Deafness.

ERIC Educational Resources Information Center

Smith, Richard J. H.; Robin, Nathaniel H.

2002-01-01

This article introduces the concept of genetic testing for deafness. Two genes that make appreciable contributions to the autosomal recessive non-syndromic deafness (ARNSD) genetic load are reviewed, GJB2 and SLC26A4. In addition, the unique aspects of genetic counseling for deafness and recurrence chance estimates are explained. (Contains…

Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease

PubMed Central

Brandt-Rauf, Sherry I.; Raveis, Victoria H.; Drummond, Nathan F.; Conte, Jill A.; Rothman, Sheila M.

2006-01-01

We explored the advantages and disadvantages of using ethnic categories in genetic research. With the discovery that certain breast cancer gene mutations appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews as genetically unique, a legacy of Tay–Sachs disease research and a particular reading of history, shaped this new approach even as methodological imprecision and new genetic and historical research challenged it. Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy. PMID:17018815

Efficiency optimization of class-D biomedical inductive wireless power transfer systems by means of frequency adjustment.

PubMed

Schormans, Matthew; Valente, Virgilio; Demosthenous, Andreas

2015-01-01

Inductive powering for implanted medical devices is a commonly employed technique, that allows for implants to avoid more dangerous methods such as the use of transcutaneous wires or implanted batteries. However, wireless powering in this way also comes with a number of difficulties and conflicting requirements, which are often met by using designs based on compromise. In particular, one aspect common to most inductive power links is that they are driven with a fixed frequency, which may not be optimal depending on factors such as coupling and load. In this paper, a method is proposed in which an inductive power link is driven by a frequency that is maintained at an optimum value f(opt), to ensure that the link is in resonance. In order to maintain this resonance, a phase tracking technique is employed at the primary side of the link; this allows for compensation of changes in coil separation and load. The technique is shown to provide significant improvements in maintained secondary voltage and efficiency for a range of loads when the link is overcoupled.

Genetics Home Reference: megalencephaly-capillary malformation syndrome

MedlinePlus

... the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of MCAP is ... Brain Malformations Health Topic: Vascular Diseases Genetic and Rare Diseases Information Center (1 link) Megalencephaly-capillary malformation syndrome ...

Genetics Home Reference: Boucher-Neuhäuser syndrome

MedlinePlus

... the cerebellum ). Affected individuals have an unsteady walking style (gait) and frequent falls. Another key feature of ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (1 link) Genetic Testing Registry: ...

Methotrexate loaded alginate microparticles and effect of Ca2+ post-crosslinking: An in vitro physicochemical and biological evaluation.

PubMed

Dhanka, Mukesh; Shetty, Chaitra; Srivastava, Rohit

2018-04-15

Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca 2+ . The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11μm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

Consequences of population topology for studying gene flow using link-based landscape genetic methods.

PubMed

van Strien, Maarten J

2017-07-01

Many landscape genetic studies aim to determine the effect of landscape on gene flow between populations. These studies frequently employ link-based methods that relate pairwise measures of historical gene flow to measures of the landscape and the geographical distance between populations. However, apart from landscape and distance, there is a third important factor that can influence historical gene flow, that is, population topology (i.e., the arrangement of populations throughout a landscape). As the population topology is determined in part by the landscape configuration, I argue that it should play a more prominent role in landscape genetics. Making use of existing literature and theoretical examples, I discuss how population topology can influence results in landscape genetic studies and how it can be taken into account to improve the accuracy of these results. In support of my arguments, I have performed a literature review of landscape genetic studies published during the first half of 2015 as well as several computer simulations of gene flow between populations. First, I argue why one should carefully consider which population pairs should be included in link-based analyses. Second, I discuss several ways in which the population topology can be incorporated in response and explanatory variables. Third, I outline why it is important to sample populations in such a way that a good representation of the population topology is obtained. Fourth, I discuss how statistical testing for link-based approaches could be influenced by the population topology. I conclude the article with six recommendations geared toward better incorporating population topology in link-based landscape genetic studies.

Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

PubMed

McNally, Elizabeth M; Puckelwartz, Megan J

2015-01-01

With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

Software defined network architecture based research on load balancing strategy

NASA Astrophysics Data System (ADS)

You, Xiaoqian; Wu, Yang

2018-05-01

As a new type network architecture, software defined network has the key idea of separating the control place of the network from the transmission plane, to manage and control the network in a concentrated way; in addition, the network interface is opened on the control layer and the data layer, so as to achieve programmable control of the network. Considering that only the single shortest route is taken into the calculation of traditional network data flow transmission, and congestion and resource consumption caused by excessive load of link circuits are ignored, a link circuit load based flow media business QoS gurantee system is proposed in this article to divide the flow in the network into ordinary data flow and QoS flow. In this way, it supervises the link circuit load with the controller so as to calculate reasonable route rapidly and issue the flow table to the exchanger, to finish rapid data transmission. In addition, it establishes a simulation platform to acquire optimized result through simulation experiment.

Genetics Home Reference: X-linked dilated cardiomyopathy

MedlinePlus

... Twitter Home Health Conditions X-linked dilated cardiomyopathy X-linked dilated cardiomyopathy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked dilated cardiomyopathy is a form of heart ...

Genetics Home Reference: X-linked thrombocytopenia

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked thrombocytopenia X-linked thrombocytopenia Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description X-linked thrombocytopenia is a bleeding disorder that primarily ...

Genetics Home Reference: X-linked myotubular myopathy

MedlinePlus

... Twitter Home Health Conditions X-linked myotubular myopathy X-linked myotubular myopathy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked myotubular myopathy is a condition that primarily ...

Genetics Home Reference: X-linked sideroblastic anemia

MedlinePlus

... Twitter Home Health Conditions X-linked sideroblastic anemia X-linked sideroblastic anemia Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked sideroblastic anemia is an inherited disorder that ...

The influence of exogenous cross-linking and compressive creep loading on intradiscal pressure.

PubMed

Chuang, Shih-Youeng; Lin, Leou-Chyr; Hedman, Thomas P

2010-10-01

This study involves a biomechanical evaluation of a prospective injectable treatment for degenerative discs. The high osmolarity of the non-degenerated nucleus pulposus attracts water contributing to the hydrostatic behavior of the tissue. This intradiscal pressure is known to drop as fluid is exuded from the matrix due to compressive loading. The objective of this study was to compare the changes in intradiscal pressure in control and genipin cross-linked intervertebral discs. Thirty bovine lumbar motion segments were randomly divided into a phosphate-buffered saline control group and a 0.33% genipin group and soaked at room temperature for 2 days. A needle pressure sensor was held in the center of the disc while short-term and static creep compressive loads were applied. The control group demonstrated a 25% higher average intradiscal pressure compared to genipin-treated discs under 750 N compressive load (p=0.029). Depressurization during static compressive creep was 56% higher in the control than in the genipin group (p=0.014). These results suggest cross-linking induced changes in the poroelastic properties of the involved tissues affected the mechanics of compressive load support in the disc with lower levels of nucleus pressure, a corresponding decrease in the elastic expansion of the annulus, and an increased axial compressive loading of the inner and outer annulus tissues. It is possible that concurrent changes in hydraulic permeability and proteoglycan retention known to be associated with genipin cross-linking were also contributors to poroelastic changes. Reduction of peak pressures and moderation of pressure fluctuations could be beneficial relative to discogenic pain.

Power electronic interface circuits for batteries and ultracapacitors in electric vehicles and battery storage systems

DOEpatents

King, Robert Dean; DeDoncker, Rik Wivina Anna Adelson

1998-01-01

A method and apparatus for load leveling of a battery in an electrical power system includes a power regulator coupled to transfer power between a load and a DC link, a battery coupled to the DC link through a first DC-to-DC converter and an auxiliary passive energy storage device coupled to the DC link through a second DC-to-DC converter. The battery is coupled to the passive energy storage device through a unidirectional conducting device whereby the battery can supply power to the DC link through each of the first and second converters when battery voltage exceeds voltage on the passive storage device. When the load comprises a motor capable of operating in a regenerative mode, the converters are adapted for transferring power to the battery and passive storage device. In this form, resistance can be coupled in circuit with the second DC-to-DC converter to dissipate excess regenerative power.

Power electronic interface circuits for batteries and ultracapacitors in electric vehicles and battery storage systems

DOEpatents

King, R.D.; DeDoncker, R.W.A.A.

1998-01-20

A method and apparatus for load leveling of a battery in an electrical power system includes a power regulator coupled to transfer power between a load and a DC link, a battery coupled to the DC link through a first DC-to-DC converter and an auxiliary passive energy storage device coupled to the DC link through a second DC-to-DC converter. The battery is coupled to the passive energy storage device through a unidirectional conducting device whereby the battery can supply power to the DC link through each of the first and second converters when battery voltage exceeds voltage on the passive storage device. When the load comprises a motor capable of operating in a regenerative mode, the converters are adapted for transferring power to the battery and passive storage device. In this form, resistance can be coupled in circuit with the second DC-to-DC converter to dissipate excess regenerative power. 8 figs.

Living long and ageing well: is epigenomics the missing link between nature and nurture?

PubMed

Rea, Irene Maeve; Dellet, Margaret; Mills, Ken I

2016-02-01

Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50% of the variability in human lifespan with another 25% explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

Genetics Home Reference: X-linked severe combined immunodeficiency

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked SCID X-linked severe combined immunodeficiency Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked severe combined immunodeficiency (SCID) is an inherited ...

Genetics Home Reference: X-linked adrenal hypoplasia congenita

MedlinePlus

... Home Health Conditions X-linked adrenal hypoplasia congenita X-linked adrenal hypoplasia congenita Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked adrenal hypoplasia congenita is a disorder that ...

Genetics Home Reference: X-linked congenital stationary night blindness

MedlinePlus

... Health Conditions X-linked congenital stationary night blindness X-linked congenital stationary night blindness Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked congenital stationary night blindness is a disorder ...

Genetics Home Reference: X-linked lissencephaly with abnormal genitalia

MedlinePlus

... Health Conditions X-linked lissencephaly with abnormal genitalia X-linked lissencephaly with abnormal genitalia Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked lissencephaly with abnormal genitalia (XLAG) is a ...

Genetics Home Reference: X-linked sideroblastic anemia and ataxia

MedlinePlus

... Health Conditions X-linked sideroblastic anemia and ataxia X-linked sideroblastic anemia and ataxia Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked sideroblastic anemia and ataxia is a rare ...

Genetics Home Reference: X-linked chondrodysplasia punctata 1

MedlinePlus

... Home Health Conditions X-linked chondrodysplasia punctata 1 X-linked chondrodysplasia punctata 1 Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked chondrodysplasia punctata 1 is a disorder of ...

Genetics Home Reference: X-linked intellectual disability, Siderius type

MedlinePlus

... Health Conditions X-linked intellectual disability, Siderius type X-linked intellectual disability, Siderius type Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked intellectual disability, Siderius type is a condition ...

Genetics Home Reference: Leber hereditary optic neuropathy

MedlinePlus

... What is the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of LHON in ... Nerve Disorders Health Topic: Vision Impairment and Blindness Genetic and Rare Diseases Information Center (1 link) Leber hereditary optic neuropathy ...

Packing Boxes into Multiple Containers Using Genetic Algorithm

NASA Astrophysics Data System (ADS)

Menghani, Deepak; Guha, Anirban

2016-07-01

Container loading problems have been studied extensively in the literature and various analytical, heuristic and metaheuristic methods have been proposed. This paper presents two different variants of a genetic algorithm framework for the three-dimensional container loading problem for optimally loading boxes into multiple containers with constraints. The algorithms are designed so that it is easy to incorporate various constraints found in real life problems. The algorithms are tested on data of standard test cases from literature and are found to compare well with the benchmark algorithms in terms of utilization of containers. This, along with the ability to easily incorporate a wide range of practical constraints, makes them attractive for implementation in real life scenarios.

Load Balancing in Multi Cloud Computing Environment with Genetic Algorithm

NASA Astrophysics Data System (ADS)

Vhansure, Fularani; Deshmukh, Apurva; Sumathy, S.

2017-11-01

Cloud is a pool of resources that is available on pay per use model. It provides services to the user which is increasing rapidly. Load balancing is an issue because it cannot handle so many requests at a time. It is also known as NP complete problem. In traditional system the functions consist of various parameter values to maximise it in order to achieve best optimal individualsolutions. Challenge is when there are many parameters of solutionsin the system space. Another challenge is to optimize the function which is much more complex. In this paper, various techniques to handle load balancing virtually (VM) as well as physically (nodes) using genetic algorithm is discussed.

Hypothetical link between infertility and genetically modified food.

PubMed

Gao, Mingxia; Li, Bin; Yuan, Wenzhen; Zhao, Lihui; Zhang, Xuehong

2014-01-01

It is speculated that genetically modified food (GMF)/genetically modified organism (GMO) is responsible for infertility development. The risk linked with a wide use of GMFs/GMOs offers the basic elements for social criticism. However, to date, it has not been justified whether the bad effects are directly resulted from products of genetic modifications or trans-genesis process. Extensive experience with the risk assessment of whole foods has been applied recently on the safety and nutritional testing of GMFs/GMOs. Investigations have tested the safety of GMFs including sub-acute, chronic, reproductive, multi-generation and carcinogenicity studies. We extrapolated the potential risks associated with GMFs/GMOs on reproduction, and analyzed the multi-aspect linked between infertility and GMFs/GMOs. It could be conjectured that GMFs/GMOs could be potential hazard on reproduction, linking to the development of infertility through influencing the endocrine metabolism, endometriosis. However, little evidence shows the impaction on embryo or reproductive related tumor due to the limited literatures, and needs further research. The article presents some related patents on GMFs/GMOs, and some methods for tracking GMOs.

The genetic basis of individual differences in reward processing and the link to addictive behavior and social cognition.

PubMed

Yacubian, J; Büchel, C

2009-11-24

Dopaminergic neurotransmission is widely recognized to be critical to the neurobiology of reward, motivation and addiction. Interestingly, social interactions and related behavior also activate the same neuronal system. Consequently, genetic variations of dopamine neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. This review focuses on advances made to date in an effort to link genetic individual variations and reward processing as a possible basis for addictive behaviors.

Understanding the science-learning environment: A genetically sensitive approach.

PubMed

Haworth, Claire M A; Davis, Oliver S P; Hanscombe, Ken B; Kovas, Yulia; Dale, Philip S; Plomin, Robert

2013-02-01

Previous studies have shown that environmental influences on school science performance increase in importance from primary to secondary school. Here we assess for the first time the relationship between the science-learning environment and science performance using a genetically sensitive approach to investigate the aetiology of this link. 3000 pairs of 14-year-old twins from the UK Twins Early Development Study reported on their experiences of the science-learning environment and were assessed for their performance in science using a web-based test of scientific enquiry. Multivariate twin analyses were used to investigate the genetic and environmental links between environment and outcome. The most surprising result was that the science-learning environment was almost as heritable (43%) as performance on the science test (50%), and showed negligible shared environmental influence (3%). Genetic links explained most (56%) of the association between learning environment and science outcome, indicating gene-environment correlation.

Sex-dependent selection differentially shapes genetic variation on and off the guppy Y chromosome.

PubMed

Postma, Erik; Spyrou, Nicolle; Rollins, Lee Ann; Brooks, Robert C

2011-08-01

Because selection is often sex-dependent, alleles can have positive effects on fitness in one sex and negative effects in the other, resulting in intralocus sexual conflict. Evolutionary theory predicts that intralocus sexual conflict can drive the evolution of sex limitation, sex-linkage, and sex chromosome differentiation. However, evidence that sex-dependent selection results in sex-linkage is limited. Here, we formally partition the contribution of Y-linked and non-Y-linked quantitative genetic variation in coloration, tail, and body size of male guppies (Poecilia reticulata)-traits previously implicated as sexually antagonistic. We show that these traits are strongly genetically correlated, both on and off the Y chromosome, but that these correlations differ in sign and magnitude between both parts of the genome. As predicted, variation in attractiveness was found to be associated with the Y-linked, rather than with the non-Y-linked component of genetic variation in male ornamentation. These findings show how the evolution of Y-linkage may be able to resolve sexual conflict. More generally, they provide unique insight into how sex-specific selection has the potential to differentially shape the genetic architecture of fitness traits across different parts of the genome. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

PubMed Central

Good, Jeffrey M.; Dean, Matthew D.; Nachman, Michael W.

2008-01-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome. PMID:18689897

A complex genetic basis to X-linked hybrid male sterility between two species of house mice.

PubMed

Good, Jeffrey M; Dean, Matthew D; Nachman, Michael W

2008-08-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents.

PubMed

Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V; Bronich, Tatiana K

2010-04-12

Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross-linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs.

Genetics Home Reference: alpha thalassemia X-linked intellectual disability syndrome

MedlinePlus

... thalassemia X-linked intellectual disability syndrome Alpha thalassemia X-linked intellectual disability syndrome Printable PDF Open All ... view the expand/collapse boxes. Description Alpha thalassemia X-linked intellectual disability syndrome is an inherited disorder ...

Increased sediment loads cause non-linear decreases in seagrass suitable habitat extent

PubMed Central

Atkinson, Scott; Klein, Carissa Joy; Weber, Tony; Possingham, Hugh P.

2017-01-01

Land-based activities, including deforestation, agriculture, and urbanisation, cause increased erosion, reduced inland and coastal water quality, and subsequent loss or degradation of downstream coastal marine ecosystems. Quantitative approaches to link sediment loads from catchments to metrics of downstream marine ecosystem state are required to calculate the cost effectiveness of taking conservation actions on land to benefits accrued in the ocean. Here we quantify the relationship between sediment loads derived from landscapes to habitat suitability of seagrass meadows in Moreton Bay, Queensland, Australia. We use the following approach: (1) a catchment hydrological model generates sediment loads; (2) a statistical model links sediment loads to water clarity at monthly time-steps; (3) a species distribution model (SDM) factors in water clarity, bathymetry, wave height, and substrate suitability to predict seagrass habitat suitability at monthly time-steps; and (4) a statistical model quantifies the effect of sediment loads on area of seagrass suitable habitat in a given year. The relationship between sediment loads and seagrass suitable habitat is non-linear: large increases in sediment have a disproportionately large negative impact on availability of seagrass suitable habitat. Varying the temporal scale of analysis (monthly vs. yearly), or varying the threshold value used to delineate predicted seagrass presence vs. absence, both affect the magnitude, but not the overall shape, of the relationship between sediment loads and seagrass suitable habitat area. Quantifying the link between sediment produced from catchments and extent of downstream marine ecosystems allows assessment of the relative costs and benefits of taking conservation actions on land or in the ocean, respectively, to marine ecosystems. PMID:29125843

Plant Sex Chromosomes.

PubMed

Charlesworth, Deborah

2016-04-29

Although individuals in most flowering plant species, and in many haploid plants, have both sex functions, dioecious species-in which individuals have either male or female functions only-are scattered across many taxonomic groups, and many species have genetic sex determination. Among these, some have visibly heteromorphic sex chromosomes, and molecular genetic studies are starting to uncover sex-linked markers in others, showing that they too have fully sex-linked regions that are either too small or are located in chromosomes that are too small to be cytologically detectable from lack of pairing, lack of visible crossovers, or accumulation of heterochromatin. Detailed study is revealing that, like animal sex chromosomes, plant sex-linked regions show evidence for accumulation of repetitive sequences and genetic degeneration. Estimating when recombination stopped confirms the view that many plants have young sex-linked regions, making plants of great interest for studying the timescale of these changes.

The genetic links between the big five personality traits and general interest domains.

PubMed

Kandler, Christian; Bleidorn, Wiebke; Riemann, Rainer; Angleitner, Alois; Spinath, Frank M

2011-12-01

This is the first genetically informative study in which multiple informants were used to quantify the genetic and environmental sources of individual differences in general interests as well as the phenotypic and genetic links between general interests and Big Five personality traits. Self-reports and two peer ratings from 844 individuals, including 225 monozygotic and 113 dizygotic complete twin pairs, were collected. Multiple-rater scores (composites) revealed that the averaged levels of genetic and environmental effects on seven broad interest domains were similar to those on personality traits. Multivariate analyses showed that about 35% of the genetic and 9% of the environmental variance in interests were explained by personality domains, in particular by Openness. The findings suggest that interests cannot easily be considered as a byproduct of the interactions between personality genotypes and the environmental influences but rather as an internal regulation of behavior with an own genetic basis.

Evidence of a genetic link between endometriosis and ovarian cancer.

PubMed

Lee, Alice W; Templeman, Claire; Stram, Douglas A; Beesley, Jonathan; Tyrer, Jonathan; Berchuck, Andrew; Pharoah, Paul P; Chenevix-Trench, Georgia; Pearce, Celeste Leigh

2016-01-01

To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. Pooled genetic analysis. University hospital. Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. None. Endometriosis-associated genetic variation and ovarian cancer. There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions. Copyright © 2016. Published by Elsevier Inc.

Polygenic loading for major depression is associated with specific medical comorbidity

PubMed Central

McCoy, T H; Castro, V M; Snapper, L; Hart, K; Januzzi, J L; Huffman, J C; Perlis, R H

2017-01-01

Major depressive disorder frequently co-occurs with medical disorders, raising the possibility of shared genetic liability. Recent identification of 15 novel genetic loci associated with depression allows direct investigation of this question. In cohorts of individuals participating in biobanks at two academic medical centers, we calculated polygenic loading for risk loci reported to be associated with depression. We then examined the association between such loading and 50 groups of clinical diagnoses, or topics, drawn from these patients' electronic health records, determined using a novel application of latent Dirichilet allocation. Three topics showed experiment-wide association with the depression liability score; these included diagnostic groups representing greater prevalence of mood and anxiety disorders, greater prevalence of cardiac ischemia, and a decreased prevalence of heart failure. The latter two associations persisted even among individuals with no mood disorder diagnosis. This application of a novel method for grouping related diagnoses in biobanks indicate shared genetic risk for depression and cardiac disease, with a pattern suggesting greater ischemic risk and diminished heart failure risk. PMID:28926002

High genetic load in an old isolated butterfly population.

PubMed

Mattila, Anniina L K; Duplouy, Anne; Kirjokangas, Malla; Lehtonen, Rainer; Rastas, Pasi; Hanski, Ilkka

2012-09-11

We investigated inbreeding depression and genetic load in a small (N(e) ∼ 100) population of the Glanville fritillary butterfly (Melitaea cinxia), which has been completely isolated on a small island [Pikku Tytärsaari (PT)] in the Baltic Sea for at least 75 y. As a reference, we studied conspecific populations from the well-studied metapopulation in the Åland Islands (ÅL), 400 km away. A large population in Saaremaa, Estonia, was used as a reference for estimating genetic diversity and N(e). We investigated 58 traits related to behavior, development, morphology, reproductive performance, and metabolism. The PT population exhibited high genetic load (L = 1 - W(PT)/W(ÅL)) in a range of fitness-related traits including adult weight (L = 0.12), flight metabolic rate (L = 0.53), egg viability (L = 0.37), and lifetime production of eggs in an outdoor population cage (L = 0.70). These results imply extensive fixation of deleterious recessive mutations, supported by greatly reduced diversity in microsatellite markers and immediate recovery (heterosis) of egg viability and flight metabolic rate in crosses with other populations. There was no significant inbreeding depression in most traits due to one generation of full-sib mating. Resting metabolic rate was significantly elevated in PT males, which may be related to their short lifespan (L = 0.25). The demographic history and the effective size of the PT population place it in the part of the parameter space in which models predict mutation accumulation. This population exemplifies the increasingly common situation in fragmented landscapes, in which small and completely isolated populations are vulnerable to extinction due to high genetic load.

75 FR 3150 - Airworthiness Directives; The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... fractured front spar assembly for strut No. 3, which resulted in the loss of the strut upper link load path... of a fractured front spar assembly for strut No. 3, which resulted in the loss of the strut upper... loss of the strut upper link load path and consequent fracture of the diagonal brace, which could...

Research on millisecond load recovery strategy in the late period of UHVDC fault dispose

NASA Astrophysics Data System (ADS)

Qiu, Chenguang; Qian, Tiantian; Cheng, Jinmin; Wang, Ke

2018-06-01

When UHVDC has a fault, it needs to quickly cut off the load so that the entire system can keep balance. In the late period of fault dispose, it needs to recover the load step by step. The recovery strategy of millisecond load is studied in this paper. Aimed at the maximum recovery load in one step, combined with grid security constraints, the recovery model of millisecond load is built, and then solved by Genetic Algorithms. The simulation example is established to verify the effectiveness of proposed method.

Genetics Home Reference: surfactant dysfunction

MedlinePlus

... Infant ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (4 links) SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 1 SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 2 ...

Genetics Home Reference: prostate cancer

MedlinePlus

... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

Genetics Home Reference: 3q29 microduplication syndrome

MedlinePlus

... 3q29 Related Information How are genetic conditions and genes named? Additional Information & Resources MedlinePlus (3 links) Encyclopedia: Microcephaly Encyclopedia: Obesity Health Topic: Developmental Disabilities Genetic and Rare Diseases ...

Monogenic Mouse Models of Autism Spectrum Disorders: Common Mechanisms and Missing Links

PubMed Central

Hulbert, Samuel W.; Jiang, Yong-hui

2016-01-01

Autism Spectrum Disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral analysis with circuit-level analysis in genetically modified models with strong construct validity. PMID:26733386

An imaging genetics approach to understanding social influence

PubMed Central

Falk, Emily B.; Way, Baldwin M.; Jasinska, Agnes J.

2012-01-01

Normative social influences shape nearly every aspect of our lives, yet the biological processes mediating the impact of these social influences on behavior remain incompletely understood. In this Hypothesis, we outline a theoretical framework and an integrative research approach to the study of social influences on the brain and genetic moderators of such effects. First, we review neuroimaging evidence linking social influence and conformity to the brain's reward system. We next review neuroimaging evidence linking social punishment (exclusion) to brain systems involved in the experience of pain, as well as evidence linking exclusion to conformity. We suggest that genetic variants that increase sensitivity to social cues may predispose individuals to be more sensitive to either social rewards or punishments (or potentially both), which in turn increases conformity and susceptibility to normative social influences more broadly. To this end, we review evidence for genetic moderators of neurochemical responses in the brain, and suggest ways in which genes and pharmacology may modulate sensitivity to social influences. We conclude by proposing an integrative imaging genetics approach to the study of brain mediators and genetic modulators of a variety of social influences on human attitudes, beliefs, and actions. PMID:22701416

Genetics Home Reference: X-linked hyper IgM syndrome

MedlinePlus

... Home Health Conditions X-linked hyper IgM syndrome X-linked hyper IgM syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked hyper IgM syndrome is a condition that ...

Sex-linked and autosomal microsatellites provide new insights into island populations of the tammar wallaby.

PubMed

MacDonald, A J; Fitzsimmons, N N; Chambers, B; Renfree, M B; Sarre, S D

2014-03-01

The emerging availability of microsatellite markers from mammalian sex chromosomes provides opportunities to investigate both male- and female-mediated gene flow in wild populations, identifying patterns not apparent from the analysis of autosomal markers alone. Tammar wallabies (Macropus eugenii), once spread over the southern mainland, have been isolated on several islands off the Western Australian and South Australian coastlines for between 10,000 and 13,000 years. Here, we combine analyses of autosomal, Y-linked and X-linked microsatellite loci to investigate genetic variation in populations of this species on two islands (Kangaroo Island, South Australia and Garden Island, Western Australia). All measures of diversity were higher for the larger Kangaroo Island population, in which genetic variation was lowest at Y-linked markers and highest at autosomal markers (θ=3.291, 1.208 and 0.627 for autosomal, X-linked and Y-linked data, respectively). Greater relatedness among females than males provides evidence for male-biased dispersal in this population, while sex-linked markers identified genetic lineages not apparent from autosomal data alone. Overall genetic diversity in the Garden Island population was low, especially on the Y chromosome where most males shared a common haplotype, and we observed high levels of inbreeding and relatedness among individuals. Our findings highlight the utility of this approach for management actions, such as the selection of animals for translocation or captive breeding, and the ecological insights that may be gained by combining analyses of microsatellite markers on sex chromosomes with those derived from autosomes.

Performance and Vibratory Loads Data From a Wind-Tunnel Test of a Model Helicopter Main-Rotor Blade With a Paddle-Type Tip

NASA Technical Reports Server (NTRS)

Yeager, William T., Jr.; Noonan, Kevin W.; Singleton, Jeffrey D.; Wilbur, Matthew L.; Mirick, Paul H.

1997-01-01

An investigation was conducted in the Langley Transonic Dynamics Tunnel to obtain data to permit evaluation of paddle-type tip technology for possible use in future U.S. advanced rotor designs. Data was obtained for both a baseline main-rotor blade and a main-rotor blade with a paddle-type tip. The baseline and paddle-type tip blades were compared with regard to rotor performance, oscillatory pitch-link loads, and 4-per-rev vertical fixed-system loads. Data was obtained in hover and forward flight over a nominal range of advance ratios from 0.15 to 0.425. Results indicate that the paddle-type tip offers no performance improvements in either hover or forward flight. Pitch-link oscillatory loads for the paddle-type tip are higher than for the baseline blade, whereas 4-per-rev vertical fixed-system loads are generally lower.

Quantitative structure-property relationship (QSPR) modeling of drug-loaded polymeric micelles via genetic function approximation.

PubMed

Wu, Wensheng; Zhang, Canyang; Lin, Wenjing; Chen, Quan; Guo, Xindong; Qian, Yu; Zhang, Lijuan

2015-01-01

Self-assembled nano-micelles of amphiphilic polymers represent a novel anticancer drug delivery system. However, their full clinical utilization remains challenging because the quantitative structure-property relationship (QSPR) between the polymer structure and the efficacy of micelles as a drug carrier is poorly understood. Here, we developed a series of QSPR models to account for the drug loading capacity of polymeric micelles using the genetic function approximation (GFA) algorithm. These models were further evaluated by internal and external validation and a Y-randomization test in terms of stability and generalization, yielding an optimization model that is applicable to an expanded materials regime. As confirmed by experimental data, the relationship between microstructure and drug loading capacity can be well-simulated, suggesting that our models are readily applicable to the quantitative evaluation of the drug-loading capacity of polymeric micelles. Our work may offer a pathway to the design of formulation experiments.

Quantitative Structure-Property Relationship (QSPR) Modeling of Drug-Loaded Polymeric Micelles via Genetic Function Approximation

PubMed Central

Lin, Wenjing; Chen, Quan; Guo, Xindong; Qian, Yu; Zhang, Lijuan

2015-01-01

Self-assembled nano-micelles of amphiphilic polymers represent a novel anticancer drug delivery system. However, their full clinical utilization remains challenging because the quantitative structure-property relationship (QSPR) between the polymer structure and the efficacy of micelles as a drug carrier is poorly understood. Here, we developed a series of QSPR models to account for the drug loading capacity of polymeric micelles using the genetic function approximation (GFA) algorithm. These models were further evaluated by internal and external validation and a Y-randomization test in terms of stability and generalization, yielding an optimization model that is applicable to an expanded materials regime. As confirmed by experimental data, the relationship between microstructure and drug loading capacity can be well-simulated, suggesting that our models are readily applicable to the quantitative evaluation of the drug-loading capacity of polymeric micelles. Our work may offer a pathway to the design of formulation experiments. PMID:25780923

Genetic and Environmental Links between Natural Language Use and Cognitive Ability in Toddlers

ERIC Educational Resources Information Center

Canfield, Caitlin F.; Edelson, Lisa R.; Saudino, Kimberly J.

2017-01-01

Although the phenotypic correlation between language and nonverbal cognitive ability is well-documented, studies examining the etiology of the covariance between these abilities are scant, particularly in very young children. The goal of this study was to address this gap in the literature by examining the genetic and environmental links between…

Allostatic Load Is Linked to Cortical Thickness Changes Depending on Body-Weight Status

PubMed Central

Ottino-González, Jonatan; Jurado, María A.; García-García, Isabel; Segura, Bàrbara; Marqués-Iturria, Idoia; Sender-Palacios, María J.; Tor, Encarnació; Prats-Soteras, Xavier; Caldú, Xavier; Junqué, Carme; Garolera, Maite

2017-01-01

Objective: Overweight (body mass index or BMI ≥ 25 kg/m2) and stress interact with each other in complex ways. Overweight promotes chronic low-inflammation states, while stress is known to mediate caloric intake. Both conditions are linked to several avoidable health problems and to cognitive decline, brain atrophy, and dementia. Since it was proposed as a framework for the onset of mental illness, the allostatic load model has received increasing attention. Although changes in health and cognition related to overweight and stress are well-documented separately, the association between allostatic load and brain integrity has not been addressed in depth, especially among overweight subjects. Method: Thirty-four healthy overweight-to-obese and 29 lean adults underwent blood testing, neuropsychological examination, and magnetic resonance imaging to assess the relationship between cortical thickness and allostatic load, represented as an index of 15 biomarkers (this is, systolic and diastolic arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6, insulin, cortisol, fibrinogen, and leptin). Results: Allostatic load indexes showed widespread positive and negative significant correlations (p < 0.01) with cortical thickness values depending on body-weight status. Conclusion: The increase of allostatic load is linked to changes in the gray matter composition of regions monitoring behavior, sensory-reward processing, and general cognitive function. PMID:29375342

Genetics Home Reference: Woodhouse-Sakati syndrome

MedlinePlus

... low amounts of hormones that direct sexual development (hypogonadism), which typically becomes apparent during adolescence. Without hormone ... Resources Genetic Testing (1 link) Genetic Testing Registry: Hypogonadism, diabetes mellitus, alopecia, mental retardation and electrocardiographic abnormalities ...

[The links between learning load and well-being of high school seniors].

PubMed

Petrauskiene, Ausra; Matuleviciūte, Deimante

2007-01-01

To evaluate the links between learning overload and psychoemotional well-being of 12th grade students. In April 2006, an anonymous survey of 184 high school seniors was conducted in six secondary schools and one gymnasium of Kaunas. The total learning load of students was too high and made up 54.79+/-0.98 hours on average. The learning load of 61.4% of children was too high; girls mentioned this problem two times more often than boys did. Students suffered from psychoemotional problems: about half of them felt stress at school; every fifth fell asleep with difficulties. Students whose total learning load was too high (more than 48 hours per week) felt stress, tiredness, stomach or abdominal, head or back pains, vertigo or weakness significantly more often in comparison with those who had normal learning load. The total learning load of the majority of investigated high school seniors was too high. The psychoemotional well-being of 12th graders was unsatisfactory; girls complained about worse well-being than boys more frequently, they used medicine more frequently in comparison to the students whose learning load was normal.

Bone Strength Estimated by Micro-Finite Element Analysis (µFEA) Is Heritable and Shares Genetic Predisposition With Areal BMD: The Framingham Study.

PubMed

Karasik, David; Demissie, Serkalem; Lu, Darlene; Broe, Kerry E; Boyd, Steven K; Liu, Ching-Ti; Hsu, Yi-Hsiang; Bouxsein, Mary L; Kiel, Douglas P

2017-11-01

Genetic factors contribute to the risk of bone fractures, partly because of effects on bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) estimates bone strength using micro-finite element analysis (µFEA). The goal of this study was to investigate if the bone failure load estimated by HR-pQCT-based µFEA is heritable and to what extent it shares genetic regulation with areal bone mineral density (aBMD). Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n = 1087, mean age 72 years; 57% women). Radial and tibial failure load in compression were estimated by µFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by dual-energy X-ray absorptiometry (DXA). Heritability (h 2 ) of failure load and aBMD and genetic correlations between them was estimated adjusting for covariates (age and sex). Failure load values at the non-weight-bearing ultradistal radius and at the weight-bearing ultradistal tibia were highly correlated (r = 0.906; p < 0.001). Estimates of h 2 adjusted for covariates were 0.522 for the radius and 0.497 for the tibia. Additional adjustment for height did not impact on the h 2 results, but adjustment for aBMD at the UD and FN somewhat decreased h 2 point estimates: 0.222 and 0.380 for radius and tibia, respectively. In bivariate analysis, there was a high phenotypic and genetic correlation between covariate-adjusted failure load at the radius and UD aBMD (ρ P  = 0.826, ρ G  = 0.954, respectively), whereas environmental correlations were lower (ρ E  = 0.696), all highly significant (p < 0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρ P  = 0.577, ρ G  = 0.703, both p < 0.001; ρ E  = 0.432, p < 0.05). These data from adult members of families from a population-based cohort suggest that bone strength of distal extremities estimated by micro-finite element analysis is heritable and shares some genetic composition with areal BMD, regardless of the skeletal site. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Genetics Home Reference: biotin-thiamine-responsive basal ganglia disease

MedlinePlus

... link) Biotin-Thiamine-Responsive Basal Ganglia Disease Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 (BIOTIN- OR THIAMINE-RESPONSIVE TYPE) ...

Genetics Home Reference: isolated sulfite oxidase deficiency

MedlinePlus

... Metabolic Disorders (CLIMB) March of Dimes: Amino Acid Metabolism Disorders The Compassionate Friends GeneReviews (1 link) Isolated Sulfite Oxidase Deficiency ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Macrophyte Community Response to Nitrogen Loading and Thermal Stressors in Rapidly Flushed Mesocosm Systems

EPA Science Inventory

Increased nitrogen loading has been directly linked to the proliferation of planktonic and macroalgal blooms at a global scale with negative impacts on estuarine ecology and human health. Under excessive anthropogenic nutrient loads, seagrass systems can be replaced by either ma...

Genetic Factors Affecting Late-Onset Alzheimer's Disease Susceptibility.

PubMed

Rezazadeh, Maryam; Khorrami, Aziz; Yeghaneh, Tarlan; Talebi, Mahnaz; Kiani, Seyed Jalal; Heshmati, Yaser; Gharesouran, Jalal

2016-03-01

Alzheimer's disease is considered a progressive brain disease in the older population. Late-onset Alzheimer's disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD and 163 healthy control subjects of Azeri Turkish ethnicity were studied. The Chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. A Bonferroni-corrected p value, based on the number of statistical tests, was considered significant. Our results confirmed that chemokine receptor type 2 (CCR2), estrogen receptor 1 (ESR1), toll-like receptor 2 (TLR2), tumor necrosis factor alpha (TNF α), APOE, bridging integrator 1 (BIN1), and phosphatidylinositol-binding clathrin assembly protein (PICALM) are LOAD susceptibility loci in Azeri Turk ancestry populations. Among them, variants of CCR2, ESR1, TNF α, and APOE revealed associations in three different genetic models. After adjusting for APOE, the association (both allelic and genotypic) with CCR2, BIN1, and ESRα (PvuII) was evident only among subjects without the APOE ε4, whereas the association with CCR5, without Bonferroni correction, was significant only among subjects carrying the APOE ε4 allele. This result is an evidence of a synergistic and antagonistic effect of APOE on variant associations with LOAD.

Enhanced method of fast re-routing with load balancing in software-defined networks

NASA Astrophysics Data System (ADS)

Lemeshko, Oleksandr; Yeremenko, Oleksandra

2017-11-01

A two-level method of fast re-routing with load balancing in a software-defined network (SDN) is proposed. The novelty of the method consists, firstly, in the introduction of a two-level hierarchy of calculating the routing variables responsible for the formation of the primary and backup paths, and secondly, in ensuring a balanced load of the communication links of the network, which meets the requirements of the traffic engineering concept. The method provides implementation of link, node, path, and bandwidth protection schemes for fast re-routing in SDN. The separation in accordance with the interaction prediction principle along two hierarchical levels of the calculation functions of the primary (lower level) and backup (upper level) routes allowed to abandon the initial sufficiently large and nonlinear optimization problem by transiting to the iterative solution of linear optimization problems of half the dimension. The analysis of the proposed method confirmed its efficiency and effectiveness in terms of obtaining optimal solutions for ensuring balanced load of communication links and implementing the required network element protection schemes for fast re-routing in SDN.

Validation of a dynamic linked segment model to calculate joint moments in lifting.

PubMed

de Looze, M P; Kingma, I; Bussmann, J B; Toussaint, H M

1992-08-01

A two-dimensional dynamic linked segment model was constructed and applied to a lifting activity. Reactive forces and moments were calculated by an instantaneous approach involving the application of Newtonian mechanics to individual adjacent rigid segments in succession. The analysis started once at the feet and once at a hands/load segment. The model was validated by comparing predicted external forces and moments at the feet or at a hands/load segment to actual values, which were simultaneously measured (ground reaction force at the feet) or assumed to be zero (external moments at feet and hands/load and external forces, beside gravitation, at hands/load). In addition, results of both procedures, in terms of joint moments, including the moment at the intervertebral disc between the fifth lumbar and first sacral vertebra (L5-S1), were compared. A correlation of r = 0.88 between calculated and measured vertical ground reaction forces was found. The calculated external forces and moments at the hands showed only minor deviations from the expected zero level. The moments at L5-S1, calculated starting from feet compared to starting from hands/load, yielded a coefficient of correlation of r = 0.99. However, moments calculated from hands/load were 3.6% (averaged values) and 10.9% (peak values) higher. This difference is assumed to be due mainly to erroneous estimations of the positions of centres of gravity and joint rotation centres. The estimation of the location of L5-S1 rotation axis can affect the results significantly. Despite the numerous studies estimating the load on the low back during lifting on the basis of linked segment models, only a few attempts to validate these models have been made. This study is concerned with the validity of the presented linked segment model. The results support the model's validity. Effects of several sources of error threatening the validity are discussed. Copyright © 1992. Published by Elsevier Ltd.

Molecular mechanics of silk nanostructures under varied mechanical loading.

PubMed

Bratzel, Graham; Buehler, Markus J

2012-06-01

Spider dragline silk is a self-assembling tunable protein composite fiber that rivals many engineering fibers in tensile strength, extensibility, and toughness, making it one of the most versatile biocompatible materials and most inviting for synthetic mimicry. While experimental studies have shown that the peptide sequence and molecular structure of silk have a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies, in particular, under variations of genetic sequences have been reported. In this study, atomistic-level structures of wildtype as well as modified MaSp1 protein from the Nephila clavipes spider dragline silk sequences, obtained using an in silico approach based on replica exchange molecular dynamics and explicit water molecular dynamics, are subjected to simulated nanomechanical testing using different force-control loading conditions including stretch, pull-out, and peel. The authors have explored the effects of the poly-alanine length of the N. clavipes MaSp1 peptide sequence and identify differences in nanomechanical loading conditions on the behavior of a unit cell of 15 strands with 840-990 total residues used to represent a cross-linking β-sheet crystal node in the network within a fibril of the dragline silk thread. The specific loading condition used, representing concepts derived from the protein network connectivity at larger scales, have a significant effect on the mechanical behavior. Our analysis incorporates stretching, pull-out, and peel testing to connect biochemical features to mechanical behavior. The method used in this study could find broad applications in de novo design of silk-like tunable materials for an array of applications. Copyright © 2011 Wiley Periodicals, Inc.

Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson’s Disease

PubMed Central

Kurowska, Zuzanna; Jewett, Michael; Brattås, Per Ludvik; Jimenez-Ferrer, Itzia; Kenéz, Xuyian; Björklund, Tomas; Nordström, Ulrika; Brundin, Patrik; Swanberg, Maria

2016-01-01

Motor symptoms in Parkinson’s disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/− mouse strain. In contrast, C57Bl/6-En1+/− mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/− and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/− 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson’s disease-like damage in rodent disease models and considered in clinical association studies in PD. PMID:27550741

Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal dominant trait.

PubMed

Goji, Katsumi; Ozaki, Kayo; Sadewa, Ahmad H; Nishio, Hisahide; Matsuo, Masafumi

2006-02-01

Familial hypophosphatemic rickets is usually transmitted as an X-linked dominant disorder (XLH), although autosomal dominant forms have also been observed. Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively. The objective of the study was to describe the molecular genetic findings in a family affected by hypophosphatemic rickets with presumed autosomal dominant inheritance. We studied a family in which the father and the elder of his two daughters, but not the second daughter, were affected by hypophosphatemic rickets. The pedigree interpretation of the family suggested that genetic transmission of the disorder occurred as an autosomal dominant trait. Direct nucleotide sequencing of FGF23 and PHEX revealed that the elder daughter was heterozygous for an R567X mutation in PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an X-linked dominant trait. Unexpectedly, the father was heterozygous for this mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the father using DNA from single hair roots revealed that he was a somatic mosaic for the mutation. Haplotype analysis confirmed that the father transmitted the genotypes for 18 markers on the X chromosome equally to his two daughters. The fact that the father transmitted the mutation to only one of his two daughters indicated that he was a germline mosaic for the mutation. Somatic and germline mosaicism for an X-linked dominant mutation in PHEX may mimic autosomal dominant inheritance.

Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16.

PubMed Central

Reeders, S T; Breuning, M H; Corney, G; Jeremiah, S J; Meera Khan, P; Davies, K E; Hopkinson, D A; Pearson, P L; Weatherall, D J

1986-01-01

The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis. Images FIG 1 PMID:3008903

Genetics Home Reference: GRACILE syndrome

MedlinePlus

... University of Utah Eccles Health Sciences Library: Iron Metabolism Patient Support and Advocacy Resources (1 link) Climb: National Information Centre for Metabolic Diseases Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Using multi-trait and random regression models to identify genetic variation in tolerance of pigs to Porcine Reproductive and Respiratory Syndrome virus

USDA-ARS?s Scientific Manuscript database

Background A host can adopt two response strategies to infection: resistance (reduce pathogen load) and tolerance (minimize impact of infection on performance). Both strategies may be under genetic control and could thus be targeted for genetic improvement. Although there is evidence in support of a...

The Relationship between Sexual Selection and Sexual Conflict

PubMed Central

Kokko, Hanna; Jennions, Michael D.

2014-01-01

Evolutionary conflicts of interest arise whenever genetically different individuals interact and their routes to fitness maximization differ. Sexual selection favors traits that increase an individual’s competitiveness to acquire mates and fertilizations. Sexual conflict occurs if an individual of sex A’s relative fitness would increase if it had a “tool” that could alter what an individual of sex B does (including the parental genes transferred), at a cost to B’s fitness. This definition clarifies several issues: Conflict is very common and, although it extends outside traits under sexual selection, sexual selection is a ready source of sexual conflict. Sexual conflict and sexual selection should not be presented as alternative explanations for trait evolution. Conflict is closely linked to the concept of a lag load, which is context-dependent and sex-specific. This makes it possible to ask if one sex can “win.” We expect higher population fitness if females win. PMID:25038050

Assay of Plasma Membrane H+-ATPase in Plant Tissues under Abiotic Stresses.

PubMed

Janicka, Małgorzata; Wdowikowska, Anna; Kłobus, Grażyna

2018-01-01

Plasma membrane (PM) H + -ATPase, which generates the proton gradient across the outer membrane of plant cells, plays a fundamental role in the regulation of many physiological processes fundamental for growth and development of plants. It is involved in the uptake of nutrients from external solutions, their loading into phloem and long-distance transport, stomata aperture and gas exchange, pH homeostasis in cytosol, cell wall loosening, and cell expansion. The crucial role of the enzyme in resistance of plants to abiotic and biotic stress factors has also been well documented. Such great diversity of physiological functions linked to the activity of one enzyme requires a suitable and complex regulation of H + -ATPase. This regulation comprises the transcriptional as well as post-transcriptional levels. Herein, we describe the techniques that can be useful for the analysis of the plasma membrane proton pump modifications at genetic and protein levels under environmental factors.

Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe

PubMed Central

Wymant, Chris; Cornelissen, Marion; Gall, Astrid; Bakker, Margreet; Bezemer, Daniela; Hall, Matthew; Hillebregt, Mariska; Ong, Swee Hoe; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Fransen, Katrien; Gourlay, Annabelle J.; Grabowski, M. Kate; Gunsenheimer-Bartmeyer, Barbara; Günthard, Huldrych F.; Kivelä, Pia; Kouyos, Roger; Laeyendecker, Oliver; Liitsola, Kirsi; Meyer, Laurence; Porter, Kholoud; Ristola, Matti; van Sighem, Ard; Vanham, Guido; Berkhout, Ben; Kellam, Paul; Reiss, Peter; Fraser, Christophe

2017-01-01

HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%–43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical “Brownian motion” model and another model (“Ornstein–Uhlenbeck”) that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%–43%) is consistent with other studies based on regression of viral load in donor–recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation. PMID:28604782

Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet.

PubMed

Agamia, N F; Abdallah, D M; Sorour, O; Mourad, B; Younan, D N

2016-06-01

Acne vulgaris is a multifactorial disorder of the pilosebaceous units. Several studies have reported that insulin-like growth factor (IGF)-1, forkhead box transcription factor (Fox)O1 and mammalian target of rapamycin (mTOR) interactions may be the key to understanding the links between genetic and environmental factors in acne vulgaris. To evaluate the immunohistochemical detection of mTOR and FoxO1 in the skin, and the serum level of IGF-1 in patients with acne vulgaris. This study was carried out on 60 participants, including 40 patients with acne and 20 controls. A diet questionnaire was administered to the patients and controls. Serum levels of IGF-1 were measured using enzyme-linked immunosorbent assay, and skin biopsies were taken from lesions on the backs of the patients and controls. FoxO1 and mTOR expression was detected using immunohistochemistry. A significantly higher serum IGF-1 level was found in the patients with acne than in the controls. The cytoplasmic expression of FoxO1 was found to be significantly greater in the acne group, whereas in the control subjects this expression was likely to be nuclear. Both the cytoplasmic expression and the nuclear expression of mTOR were significantly more intense in the patients with acne than in the controls. Excess consumption of a high-glycaemic-load diet was significantly associated with higher serum levels of IGF-1 and cytoplasmic expression of FoxO1 and mTOR. These results suggest that FoxO1, mTOR, serum IGF-1 and a high-glycaemic-load diet may play a role in acne pathogenesis. © 2016 British Association of Dermatologists.

Genomic variation in the MMP-1 promoter influences estrogen receptor mediated activity in a mechanically activated environment: potential implications for microgravity risk assessment

NASA Astrophysics Data System (ADS)

Thaler, John; Myers, Ken; Lu, Ting; Hart, David

Background: Mechanotransduction, the conversion of mechanical forces (tensile, compression, shear etc.) into cellular signals is a significant response mechanism in bone that contributes to the balance between formation and resorption and helps maintain bone density. In microgravity the lack of mechanical signals can lead to a loss of bone density, however the signaling pathways responsible are not well understood. For women, sex-specific hormones are also important in maintaining bone density since estrogen deficiency is a major factor in the etiology of osteoporosis in postmenopausal women. Estrogen Receptors (ERs) are present in human connective tissue cells such as osteoblasts and may play a role in mechanotransduction responses. The two ER isoforms, alpha (ER-α) and beta (ER-β) differentially regulate expression of matrixmetalloproteinases (MMPs) which degrade extracellular matrix components found in connective tissues. Mechanical stimulation is known to affect the expression of MMP-1, a collagenase involved in the bone resorption process. The MMP-1 promoter region contains a single nucleotide polymorphism of an additional guanine (G) at position -1607 bp which creates a binding site for a member of the Ets family of mammalian transcription factors. The 2G allele is known to be present in 45-70% of healthy populations and has been associated with higher MMP-1 expression. The 2G allele has been linked to higher risk of several types of cancer but a link to osteoporosis or microgravity induced bone loss has not been explored. The purpose of the present study was to conduct a case-study to determine whether small genetic variations can influence cellular and tissue responses to mechanical loading. Specifically we examined the potential of the 1G/2G -1607 MMP-1 promoter SNP to alter the interplay between mechanical shear stress and estrogen receptors in controlling MMP-1 expression. Methods: Rabbit synovial cells (HIG-82) were used as an in vitro model system to examine the potential impact of the 1G/2G SNP on the cellular response to mechanical loading. HIG-82 cells are estrogen receptor (ER) negative and were transiently transfected with SV40 expression vectors for either ER-α or ER-β isoforms. Cells grown on glass slides were also co-transfected with either a 1G or 2G MMP-1 promoter-luciferase construct. Transfected cells were subjected to dynamic shear stress in a Flexcell Streamer Shear Stress Device. The dynamic loading regime was 0.5 Hz, 10 dyn/cm2 shear for 1 minute followed by 14 minutes rest and repeated for 8 hrs. A Promega Dual Luciferase Reporter Assay System was used to assess MMP-1 promoter activity. Results: Shear stress loading increased both 1G and 2G MMP-1 promoter activity compared to unloaded controls, however the 2G promoter had significantly higher rates of expression than the 1G promoter across all loading regimes and ER co-transfections. Transfection with ER-β resulted in higher MMP-1 promoter activity than that in cells expressing ER-α or in ER-neg cells. Conclusions: Specific genomic variations can lead to differences in cellular responses to changes in mechanical loading environments such as are encountered in microgravity environments or earth-based analogs. These genomic differences may predispose individuals to greater risk of bone loss. It is important to understand the combined effects of mechanical loading, genetic variation and sex hormones on bone maintenance so that risks can be identified for microgravity or analog environments, and specific interventions developed to counteract such risk or even exclude some individuals from prolonged space environments due to the extent of the risk.

Regulatory divergence of X-linked genes and hybrid male sterility in mice.

PubMed

Oka, Ayako; Shiroishi, Toshihiko

2014-01-01

Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

Scratch that itch: revisiting links between self-directed behaviour and parasitological, social and environmental factors in a free-ranging primate

PubMed Central

Romano, Valéria; MacIntosh, Andrew J. J.

2016-01-01

Different hypotheses explain variation in the occurrence of self-directed behaviour such as scratching and self-grooming: a parasite hypothesis linked with ectoparasite load, an environmental hypothesis linked with seasonal conditions and a social hypothesis linked with social factors. These hypotheses are not mutually exclusive but are often considered separately. Here, we revisited these hypotheses together in female Japanese macaques (Macaca fuscata fuscata) of Kōjima islet, Japan. We input occurrences of scratching and self-grooming during focal observations in models combining parasitological (lice load), social (dominance rank, social grooming, aggression received and proximity), and environmental (rainfall, temperature and season) variables. Using an information-theory approach, we simultaneously compared the explanatory value of models against each other using variation in Akaike's information criterion and Akaike's weights. We found that evidence for models with lice load, with or without environmental–social parameters, was stronger than that for other models. In these models, scratching was positively associated with lice load and social grooming whereas self-grooming was negatively associated with lice load and positively associated with social grooming, dominance rank and number of female neighbours. This study indicates that the study animals scratch primarily because of an immune/stimulus itch, possibly triggered by ectoparasite bites/movements. It also confirms that self-grooming could act as a displacement activity in the case of social uncertainty. We advocate that biological hypotheses be more broadly considered even when investigating social processes, as one does not exclude the other. PMID:28018646

The population genetics of X-autosome synthetic lethals and steriles.

PubMed

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

PubMed

Novarino, Gaia; Fenstermaker, Ali G; Zaki, Maha S; Hofree, Matan; Silhavy, Jennifer L; Heiberg, Andrew D; Abdellateef, Mostafa; Rosti, Basak; Scott, Eric; Mansour, Lobna; Masri, Amira; Kayserili, Hulya; Al-Aama, Jumana Y; Abdel-Salam, Ghada M H; Karminejad, Ariana; Kara, Majdi; Kara, Bulent; Bozorgmehri, Bita; Ben-Omran, Tawfeg; Mojahedi, Faezeh; El Din Mahmoud, Iman Gamal; Bouslam, Naima; Bouhouche, Ahmed; Benomar, Ali; Hanein, Sylvain; Raymond, Laure; Forlani, Sylvie; Mascaro, Massimo; Selim, Laila; Shehata, Nabil; Al-Allawi, Nasir; Bindu, P S; Azam, Matloob; Gunel, Murat; Caglayan, Ahmet; Bilguvar, Kaya; Tolun, Aslihan; Issa, Mahmoud Y; Schroth, Jana; Spencer, Emily G; Rosti, Rasim O; Akizu, Naiara; Vaux, Keith K; Johansen, Anide; Koh, Alice A; Megahed, Hisham; Durr, Alexandra; Brice, Alexis; Stevanin, Giovanni; Gabriel, Stacy B; Ideker, Trey; Gleeson, Joseph G

2014-01-31

Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.

Study of a Car Body Tilting System Using a Variable Link Mechanism: Fundamental Characteristics of Pendulum Motion and Strategy for Perfect Tilting

NASA Astrophysics Data System (ADS)

Yoshida, Hidehisa; Nagai, Masao

This paper analyzes the fundamental dynamic characteristics of a tilting railway vehicle using a variable link mechanism for compensating both the lateral acceleration experienced by passengers and the wheel load imbalance between the inner and outer rails. The geometric relations between the center of rotation, the center of gravity, and the positions of all four links of the tilting system are analyzed. Then, equations of the pendulum motions of the railway vehicle body with a four-link mechanism are derived. A theoretically discussion is given on the geometrical shapes employed in the link mechanism that can simultaneously provide zero lateral acceleration and zero wheel load fluctuation. Then, the perfect tilting condition, which is the control target of the feedforward tilting control, is derived from the linear equation of tilting motion.

Clinically relevant lessons from Family HealthLink: a cancer and coronary heart disease familial risk assessment tool.

PubMed

Sweet, Kevin; Sturm, Amy C; Rettig, Amy; McElroy, Joseph; Agnese, Doreen

2015-06-01

A descriptive retrospective study was performed using two separate user cohorts to determine the effectiveness of Family HealthLink as a clinical triage tool. Cohort 1 consisted of 2,502 users who accessed the public website. Cohort 2 consisted of 194 new patients in a Comprehensive Breast Center setting. For patient users, we assessed documentation of family history and genetics referral. For all users seen in a genetics clinic, the Family HealthLink assessment was compared with that performed by genetic counselors and genetic testing outcomes. For general public users, the percentage meeting high-risk criteria were: for cancer only, 22.2%; for coronary heart disease only, 24.3%; and for both diseases, 10.4%. These risk stratification percentages were similar for the patient users. For the patient users, there often was documentation of family history of certain cancer types by oncology professionals, but age of onset and coronary heart disease family history were less complete. Of 142 with high-risk assignments seen in a genetics clinic, 130 (91.5%) of these assignments were corroborated. Forty-two underwent genetic testing and 17 (40.5%) had new molecular diagnoses established. A significant percentage of individuals are at high familial risk and may require more intensive screening and referral. Interactive family history triage tools can aid this process.Genet Med 17 6, 493-500.

Near-Field Based Communication and Electrical Systems

NASA Astrophysics Data System (ADS)

Azad, Umar

A near-field power transfer equation for an inductively coupled near-field system is derived based on the equivalent circuit model of the coupled resonant loops. Experimental results show that the proposed near-field coupling equation is trustworthy as it correctly predicts the transferred power versus distance relationship for different values of loaded quality factors at the transmitter and the receiver. Capacity performance of near-field communication (NFC) links is analyzed for noise limited and interference limited scenarios based on information theory. The analytical results provide guidelines for design of inductively coupled antenna systems as the power and capacity budget of the link is carried out. Examples of inductively coupled VLF NFC links are evaluated for different operating scenarios, demonstrating the efficacy and importance of the proposed near-field link budget. However, in a conventional setup of inductively coupled NFC link, the power coupled through and the bandwidth must be traded off. Direct Antenna Modulation (DAM) is a feasible scheme to break this dilemma. With DAM utilized in NFC link, the power and bandwidth product limit in a high Q system can be circumvented because the non-linear/time-varying nature of the operation allows high speed modulations decoupled from the charging and discharging process of the high-Q resonator. In this work, the theory of NFC link with DAM on the transmitter is presented and validated with an experimental setup. Improvement in reception of the high-speed modulation information is observed in the experiment, implying that a superior capacity performance of a NFC link is achieved through DAM versus the traditional scheme. The resonant coupling efficiency is limited by the product of the quality factors Q, of the transmitter and receiver and the coupling coefficient k. We observe that in order to achieve maximum efficiency, the ratio of the load-to-loss impedances at both the source and load should be equal to a prescribed value. This is the same condition that yields simultaneous impedance matching at source and load. The efficiency limit is then calculated for single transmitter and two uncoupled receivers. In that case, optimal efficiency is obtained when the load-to-loss impedance ratio is equal to the same prescribed value for all devices simultaneously. However, this condition does not provide for simultaneous matching at the source and loads, which turns out to be impossible. The analysis is then generalized for a single transmitter and N uncoupled receivers and we find that as the number of receivers increases, the total efficiency limit also increases. Finally, we present the efficiency limits and optimal conditions for a system consisting of single and multiple repeaters between transmitter and receiver, which have been shown previously to relay power to larger distances.

Polygenic risk scores in familial Alzheimer disease

PubMed Central

Tosto, Giuseppe; Bird, Thomas D.; Tsuang, Debby; Bennett, David A.; Boeve, Bradley F.; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M.; Farlow, Martin; Goate, Alison M.; Bertlesen, Sarah; Graff-Radford, Neill R.; Medrano, Martin; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J.; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A.

2017-01-01

Objective: To investigate the association between a genetic risk score (GRS) and familial late-onset Alzheimer disease (LOAD) and its predictive value in families multiply affected by the disease. Methods: Using data from the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease (National Institute on Aging–Late-Onset Alzheimer's Disease Family Study), mixed regression models tested the association of familial LOAD with a GRS based on single nucleotide polymorphisms (SNPs) previously associated with LOAD. We modeled associations using unweighted and weighted scores with estimates derived from the literature. In secondary models, we adjusted subsequent models for presence of the APOE ε4 allele and further tested the interaction between APOE ε4 and the GRS. We constructed a similar GRS in a cohort of Caribbean Hispanic families multiply affected by LOAD by selecting the SNP with the strongest p value within the same regions. Results: In the NIA-LOAD families, the GRS was significantly associated with LOAD (odds ratio [OR] 1.29; 95% confidence interval 1.21–1.37). The results did not change after adjusting for APOE ε4. In Caribbean Hispanic families, the GRS also significantly predicted LOAD (OR 1.73; 1.57–1.93). Higher scores were associated with lower age at onset in both cohorts. Conclusions: High GRS increases the risk of familial LOAD and lowers the age at onset, regardless of ethnic group. PMID:28213371

Polygenic risk scores in familial Alzheimer disease.

PubMed

Tosto, Giuseppe; Bird, Thomas D; Tsuang, Debby; Bennett, David A; Boeve, Bradley F; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M; Farlow, Martin; Goate, Alison M; Bertlesen, Sarah; Graff-Radford, Neill R; Medrano, Martin; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A; Mayeux, Richard

2017-03-21

To investigate the association between a genetic risk score (GRS) and familial late-onset Alzheimer disease (LOAD) and its predictive value in families multiply affected by the disease. Using data from the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease (National Institute on Aging-Late-Onset Alzheimer's Disease Family Study), mixed regression models tested the association of familial LOAD with a GRS based on single nucleotide polymorphisms (SNPs) previously associated with LOAD. We modeled associations using unweighted and weighted scores with estimates derived from the literature. In secondary models, we adjusted subsequent models for presence of the APOE ε4 allele and further tested the interaction between APOE ε4 and the GRS. We constructed a similar GRS in a cohort of Caribbean Hispanic families multiply affected by LOAD by selecting the SNP with the strongest p value within the same regions. In the NIA-LOAD families, the GRS was significantly associated with LOAD (odds ratio [OR] 1.29; 95% confidence interval 1.21-1.37). The results did not change after adjusting for APOE ε4. In Caribbean Hispanic families, the GRS also significantly predicted LOAD (OR 1.73; 1.57-1.93). Higher scores were associated with lower age at onset in both cohorts. High GRS increases the risk of familial LOAD and lowers the age at onset, regardless of ethnic group. © 2017 American Academy of Neurology.

Genetics Home Reference: Arts syndrome

MedlinePlus

... its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in ... Syndrome ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: motion sickness

MedlinePlus

... motion, particularly traveling in a car, bus, train, airplane, or boat. Amusement park rides, skiing, and virtual ... Association ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Short communication: identification of a novel HIV type 1 subtype H/J recombinant in Canada with discordant HIV viral load (RNA) values in three different commercial assays.

PubMed

Kim, John E; Beckthold, Brenda; Chen, Zhaoxia; Mihowich, Jennifer; Malloch, Laurie; Gill, Michael John

2007-11-01

The presence of HIV-1 non-B subtypes is increasing worldwide. This poses challenges to commercial diagnostic and viral load (RNA) monitoring tests that are predominantly based on HIV-1 subtype B strains. Based on phylogenetic analysis of the gag, pol, and env gene regions, we describe the first HIV-1 H/J recombinant in Canada that presented divergent viral load values. DNA sequence analysis of the gag gene region further revealed that genetic diversity between this H/J recombinant and the primers and probes used in the bio-Merieux Nuclisens HIV-1 QT (Nuclisens) and Roche Amplicor Monitor HIV-1, v1.5 (Monitor) viral RNA assays can erroneously lead to undetectable viral load values. This observation appears to be more problematic in the Nuclisens assay. In light of increasing genetic diversity in HIV worldwide we recommend that DNA sequencing of HIV, especially in the gag gene region targeted by primers and probes used in molecular diagnostic and viral load tests, be incorporated into clinical monitoring practices.

Running accuracy analysis of a 3-RRR parallel kinematic machine considering the deformations of the links

NASA Astrophysics Data System (ADS)

Wang, Liping; Jiang, Yao; Li, Tiemin

2014-09-01

Parallel kinematic machines have drawn considerable attention and have been widely used in some special fields. However, high precision is still one of the challenges when they are used for advanced machine tools. One of the main reasons is that the kinematic chains of parallel kinematic machines are composed of elongated links that can easily suffer deformations, especially at high speeds and under heavy loads. A 3-RRR parallel kinematic machine is taken as a study object for investigating its accuracy with the consideration of the deformations of its links during the motion process. Based on the dynamic model constructed by the Newton-Euler method, all the inertia loads and constraint forces of the links are computed and their deformations are derived. Then the kinematic errors of the machine are derived with the consideration of the deformations of the links. Through further derivation, the accuracy of the machine is given in a simple explicit expression, which will be helpful to increase the calculating speed. The accuracy of this machine when following a selected circle path is simulated. The influences of magnitude of the maximum acceleration and external loads on the running accuracy of the machine are investigated. The results show that the external loads will deteriorate the accuracy of the machine tremendously when their direction coincides with the direction of the worst stiffness of the machine. The proposed method provides a solution for predicting the running accuracy of the parallel kinematic machines and can also be used in their design optimization as well as selection of suitable running parameters.

Frequency Splitting Analysis and Compensation Method for Inductive Wireless Powering of Implantable Biosensors.

PubMed

Schormans, Matthew; Valente, Virgilio; Demosthenous, Andreas

2016-08-04

Inductive powering for implanted medical devices, such as implantable biosensors, is a safe and effective technique that allows power to be delivered to implants wirelessly, avoiding the use of transcutaneous wires or implanted batteries. Wireless powering is very sensitive to a number of link parameters, including coil distance, alignment, shape, and load conditions. The optimum drive frequency of an inductive link varies depending on the coil spacing and load. This paper presents an optimum frequency tracking (OFT) method, in which an inductive power link is driven at a frequency that is maintained at an optimum value to ensure that the link is working at resonance, and the output voltage is maximised. The method is shown to provide significant improvements in maintained secondary voltage and system efficiency for a range of loads when the link is overcoupled. The OFT method does not require the use of variable capacitors or inductors. When tested at frequencies around a nominal frequency of 5 MHz, the OFT method provides up to a twofold efficiency improvement compared to a fixed frequency drive. The system can be readily interfaced with passive implants or implantable biosensors, and lends itself to interfacing with designs such as distributed implanted sensor networks, where each implant is operating at a different frequency.

Membrane formation and drug loading effects in high amylose starch tablets studied by NMR imaging.

PubMed

Thérien-Aubin, Héloïse; Zhu, X X; Ravenelle, François; Marchessault, Robert H

2008-04-01

Cross-linked high amylose starch is used as an excipient in the preparation of pharmaceutical tablets for the sustained release of drugs. NMR imaging with contrast enhanced by proton density and by self-diffusion coefficient was used to follow the water uptake and swelling, two critical parameters controlling the drug release of the cross-linked starch tablets containing 10 wt % of ciprofloxacin and of acetaminophen, respectively. The drug-loaded tablets were studied in a H2O/D2O mixture at 37 degrees C in comparison to the tablets without any drug loading. The diffusion of water in the tablets all showed a Fickian behavior, but the kinetics of water uptake was faster in the case of the drug-loaded tablets. The formation of a membrane at the water/tablet interface was observed.

75 FR 43876 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0100 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... aeroplanes, one of the bolts that connect the horizontal stabilizer control unit actuator with the dog-links... single dog-link connection fails, the complete stabilizer load is taken up by the remaining dog-link... the horizontal stabilizer control unit actuator with the dog-links was found broken (one on the nut...

Genetic Variation Linked to Lung Cancer Survival in White Smokers | Center for Cancer Research

Cancer.gov

CCR investigators have discovered evidence that links lung cancer survival with genetic variations (called single nucleotide polymorphisms) in the MBL2 gene, a key player in innate immunity. The variations in the gene, which codes for a protein called the mannose-binding lectin, occur in its promoter region, where the RNA polymerase molecule binds to start transcription, and

The Winding Road to Discovering the Link between Genetic Material and DNA

ERIC Educational Resources Information Center

Cherif, Abour H.; Roze, Maris; Movahedzadeh, Farahnaz

2015-01-01

This is an account of the three-centuries long journey to the discovery of the link between DNA and the transformation principle of heredity beginning with the discovery of the cell in 1665 and leading up to the 1953 discovery of the genetic code and the structure of DNA. This account also illustrates the way science works and how scientists do…

Genetics Home Reference: lipoid proteinosis

MedlinePlus

... Problems National Alliance on Mental Illness Pediatric Dermatology Research Alliance GeneReviews (1 link) Lipoid Proteinosis Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) LIPOID PROTEINOSIS OF URBACH AND WIETHE MedGen (1 link) Lipid proteinosis Sources for This Page Callizo M, Ibáñez- ...

Results from a large-scale epidemiologic look-back investigation of improperly reprocessed endoscopy equipment.

PubMed

Holodniy, Mark; Oda, Gina; Schirmer, Patricia L; Lucero, Cynthia A; Khudyakov, Yury E; Xia, Guoliang; Lin, Yulin; Valdiserri, Ronald; Duncan, William E; Davey, Victoria J; Cross, Gerald M

2012-07-01

To determine whether improper high-level disinfection practices during endoscopy procedures resulted in bloodborne viral infection transmission.  Retrospective cohort study.  Four Veterans Affairs medical centers (VAMCs).  Veterans who underwent colonoscopy and laryngoscopy (ear, nose, and throat [ENT]) procedures from 2003 to 2009.  Patients were identified through electronic health record searches and serotested for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Newly discovered case patients were linked to a potential source with known identical infection, whose procedure occurred no more than 1 day prior to the case patient's procedure. Viral genetic testing was performed for case/proximate pairs to determine relatedness.  Of 10,737 veterans who underwent endoscopy at 4 VAMCs, 9,879 patients agreed to viral testing. Of these, 90 patients were newly diagnosed with 1 or more viral bloodborne pathogens (BBPs). There were no case/proximate pairings found for patients with either HIV or HBV; 24 HCV case/proximate pairings were found, of which 7 case patients and 8 proximate patients had sufficient viral load for further genetic testing. Only 2 of these cases, both of whom underwent laryngoscopy, and their 4 proximates agreed to further testing. None of the 4 remaining proximate patients who underwent colonoscopy agreed to further testing. Mean genetic distance between the 2 case patients and 4 proximate patients ranged from 13.5% to 19.1%.  Our investigation revealed that exposure to improperly reprocessed ENT endoscopes did not result in viral transmission in those patients who had viral genetic analysis performed. Any potential transmission of BBPs from colonoscopy remains unknown.

An Evolving Genetic Architecture Interacts with Hill–Robertson Interference to Determine the Benefit of Sex

PubMed Central

Whitlock, Alexander O. B.; Peck, Kayla M.; Azevedo, Ricardo B. R.; Burch, Christina L.

2016-01-01

Sex is ubiquitous in the natural world, but the nature of its benefits remains controversial. Previous studies have suggested that a major advantage of sex is its ability to eliminate interference between selection on linked mutations, a phenomenon known as Hill–Robertson interference. However, those studies may have missed both important advantages and important disadvantages of sexual reproduction because they did not allow the distributions of mutational effects and interactions (i.e., the genetic architecture) to evolve. Here we investigate how Hill–Robertson interference interacts with an evolving genetic architecture to affect the evolutionary origin and maintenance of sex by simulating evolution in populations of artificial gene networks. We observed a long-term advantage of sex—equilibrium mean fitness of sexual populations exceeded that of asexual populations—that did not depend on population size. We also observed a short-term advantage of sex—sexual modifier mutations readily invaded asexual populations—that increased with population size, as was observed in previous studies. We show that the long- and short-term advantages of sex were both determined by differences between sexual and asexual populations in the evolutionary dynamics of two properties of the genetic architecture: the deleterious mutation rate (Ud) and recombination load (LR). These differences resulted from a combination of selection to minimize LR, which is experienced only by sexuals, and Hill–Robertson interference experienced primarily by asexuals. In contrast to the previous studies, in which Hill–Robertson interference had only a direct impact on the fitness advantages of sex, the impact of Hill–Robertson interference in our simulations was mediated additionally by an indirect impact on the efficiency with which selection acted to reduce Ud. PMID:27098911

Genetics Home Reference: X-linked spondyloepiphyseal dysplasia tarda

MedlinePlus

... Educational Resources (6 links) Cincinnati Children's Hospital: Coxa Vera Disease InfoSearch: Spondyloepiphyseal dysplasia tarda X-linked Johns ... Free article on PubMed Central Savarirayan R, Thompson E, Gécz J. Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400). ...

Genetics Home Reference: immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

MedlinePlus

... Health Conditions IPEX syndrome Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome Printable PDF Open All Close All ... expand/collapse boxes. Description Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome primarily affects males and is ...

Nano and micro mechanical properties of uncross-linked and cross-linked chitosan films

PubMed Central

Aryaei, Ashkan; Jayatissa, Ahalapitiya H.; Jayasuriya, A. Champa

2016-01-01

The aim of this study is to determine the nano and micro mechanical properties for uncross-linked and cross-linked chitosan films. Specifically, we looked at nanoindentation hardness, microhardness, and elastic modulus. It is important to study the nano and microscale mechanical properties of chitosan since chitosan has been widely used for biomedical applications. Using the solvent-cast method, the chitosan films were prepared at room temperature on the cleaned glass plates. The chitosan solution was prepared by dissolving chitosan in acetic acid 1% (v/v). Tripolyphosphate (TPP) was used to create the cross-links between amine groups in chitosan and phosphate groups in TPP. In this study, atomic force microscopy was used to measure the nanoindentation hardness and surface topography of the uncross-linked and cross-linked chitosan films. Elastic modulus was then calculated from the nanoindentation results. The effective elastic modulus was determined by microhardness with some modifications to previous theories. The microhardness of the chitosan films were measured using Vicker’s hardness meter under three different loads. Our results show that the microhardness and elastic modulus for cross-linked chitosan films are higher than the uncross-linked films. However, the cross-linked chitosan films show increased brittleness when compared to uncross-linked films. By increasing the load magnitude, the microhardness increases for both uncross-linked and cross-linked chitosan films. PMID:22100082

Reproductive cloning and a (kind of) genetic fallacy.

PubMed

Levy, Neil; Lotz, Mianna

2005-06-01

Many people now believe that human reproductive cloning--once sufficiently safe and effective--should be permitted on the grounds that it will allow the otherwise infertile to have children that are biologically closely related to them. However, though it is widely believed that the possession of a close genetic link to our children is morally significant and valuable, we argue that such a view is erroneous. Moreover, the claim that the genetic link is valuable is pernicious; it tends to give rise to highly undesirable consequences, and therefore should be combated rather than pandered to. The emphasis on the genetic is unwarranted and unfortunate; rather than giving us moral reason to support reproductive cloning in the case of infertility, the fact that cloning requests are likely to be motivated by the genetic argument gives us reason to oppose its availability.

Genetics Home Reference: macrozoospermia

MedlinePlus

... Encyclopedia: Semen Analysis MedlinePlus Health Topic: Assisted Reproductive Technology General Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and ...

Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer’s disease

PubMed Central

Alfonso, Stephanie I.; Callender, Julia A.; Hooli, Basavaraj; Antal, Corina E.; Mullin, Kristina; Sherman, Mathew A.; Lesné, Sylvain E.; Leitges, Michael; Newton, Alexandra C.; Tanzi, Rudolph E.; Malinow, Roberto

2016-01-01

Alzheimer’s disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA, the gene that encodes protein kinase Cα (PKCα), in five of the families. All three variants linked with LOAD displayed increased catalytic activity relative to wild-type PKCα as assessed in live-cell imaging experiments using a genetically encoded PKC activity reporter. Deleting PRKCA in mice or adding PKC antagonists to mouse hippocampal slices infected with a virus expressing the Aβ precursor CT100 revealed that PKCα was required for the reduced synaptic activity caused by Aβ. In PRKCA−/− neurons expressing CT100, introduction of PKCα, but not PKCα lacking a PDZ interaction moiety, rescued synaptic depression, suggesting that a scaffolding interaction bringing PKCα to the synapse is required for its mediation of the effects of Aβ. Thus, enhanced PKCα activity may contribute to AD, possibly by mediating the actions of Aβ on synapses. In contrast, reduced PKCα activity is implicated in cancer. Hence, these findings reinforce the importance of maintaining a careful balance in the activity of this enzyme. PMID:27165780

Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

PubMed Central

Cloonan, Suzanne M.; Glass, Kimberly; Laucho-Contreras, Maria E.; Bhashyam, Abhiram R.; Cervo, Morgan; Pabón, Maria A.; Konrad, Csaba; Polverino, Francesca; Siempos, Ilias I.; Perez, Elizabeth; Mizumura, Kenji; Ghosh, Manik C.; Parameswaran, Harikrishnan; Williams, Niamh C.; Rooney, Kristen T.; Chen, Zhi-Hua; Goldklang, Monica P.; Yuan, Guo-Cheng; Moore, Stephen C.; Demeo, Dawn L.; Rouault, Tracey A.; D’Armiento, Jeanine M.; Schon, Eric A.; Manfredi, Giovanni; Quackenbush, John; Mahmood, Ashfaq; Silverman, Edwin K.; Owen, Caroline A.; Choi, Augustine M.K.

2015-01-01

Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. PMID:26752519

Nanotemplated polyelectrolyte films as porous biomolecular delivery systems

PubMed Central

Gand, Adeline; Hindié, Mathilde; Chacon, Diane; van Tassel, Paul R; Pauthe, Emmanuel

2014-01-01

Biomaterials capable of delivering controlled quantities of bioactive agents, while maintaining mechanical integrity, are needed for a variety of cell contacting applications. We describe here a nanotemplating strategy toward porous, polyelectrolyte-based thin films capable of controlled biomolecular loading and release. Films are formed via the layer-by-layer assembly of charged polymers and nanoparticles (NP), then chemically cross-linked to increase mechanical rigidity and stability, and finally exposed to tetrahydrofuran to dissolve the NP and create an intra-film porous network. We report here on the loading and release of the growth factor bone morphogenetic protein 2 (BMP-2), and the influence of BMP-2 loaded films on contacting murine C2C12 myoblasts. We observe nanotemplating to enable stable BMP-2 loading throughout the thickness of the film, and find the nanotemplated film to exhibit comparable cell adhesion, and enhanced cell differentiation, compared with a non-porous cross-linked film (where BMP-2 loading is mainly confined to the film surface). PMID:25482416

Nanotemplated polyelectrolyte films as porous biomolecular delivery systems. Application to the growth factor BMP-2.

PubMed

Gand, Adeline; Hindié, Mathilde; Chacon, Diane; Van Tassel, Paul R; Pauthe, Emmanuel

2014-01-01

Biomaterials capable of delivering controlled quantities of bioactive agents, while maintaining mechanical integrity, are needed for a variety of cell contacting applications. We describe here a nanotemplating strategy toward porous, polyelectrolyte-based thin films capable of controlled biomolecular loading and release. Films are formed via the layer-by-layer assembly of charged polymers and nanoparticles (NP), then chemically cross-linked to increase mechanical rigidity and stability, and finally exposed to tetrahydrofuran to dissolve the NP and create an intra-film porous network. We report here on the loading and release of the growth factor bone morphogenetic protein 2 (BMP-2), and the influence of BMP-2 loaded films on contacting murine C2C12 myoblasts. We observe nanotemplating to enable stable BMP-2 loading throughout the thickness of the film, and find the nanotemplated film to exhibit comparable cell adhesion, and enhanced cell differentiation, compared with a non-porous cross-linked film (where BMP-2 loading is mainly confined to the film surface).

Modulating drug loading and release profile of beta-cyclodextrin polymers by means of cross-linked degree.

PubMed

Wang, Qi-fang; Li, San-ming; Zhang, Yu-yang; Zhang, Hong

2011-02-01

The purpose of the present study is to use beta-cyclodextrin polymers (beta-CDP) with different cross-linked degree (CLD) to form inclusion complexes with ibuprofen and examine the effects of structural and compositional factors of beta-CDP on its drug loading and release behaviors. A series of beta-CDP with different CLD were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and 13C NMR spectrum. The beta-CDP was systemically characterized for the relation between the CLD of beta-CDP and the drug loading and release as well. The results of FT-IR and 13C NMR showed that similar peak-shaped vibration of beta-CDP and beta-CD implies that the polymer keeps the original characteristic structure of beta-CD. The CLD of the beta-CDP played a critical role in the drug loading and release, increasing the CLD resulted in reduction of drug loading, but increase in drug release.

Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

MedlinePlus

... condition damages parts of the brain that control reasoning, personality, social skills, speech, and language. Personality changes, ... Clearinghouse: Paget's Disease of Bone: An Endocrine Society Clinical Practice Guideline Genetic Testing (1 link) Genetic Testing ...

Difficulties in Genetics Problem Solving.

ERIC Educational Resources Information Center

Tolman, Richard R.

1982-01-01

Examined problem-solving strategies of 30 high school students as they solved genetics problems. Proposes a new sequence of teaching genetics based on results: meiosis, sex chromosomes, sex determination, sex-linked traits, monohybrid and dihybrid crosses (humans), codominance (humans), and Mendel's pea experiments. (JN)

Generalist Genes: Genetic Links between Brain, Mind, and Education

ERIC Educational Resources Information Center

Plomin, Robert; Kovas, Yulia; Haworth, Claire M. A.

2007-01-01

Genetics contributes importantly to learning abilities and disabilities--not just to reading, the target of most genetic research, but also to mathematics and other academic areas as well. One of the most important recent findings from quantitative genetic research such as twin studies is that the same set of genes is largely responsible for…

Refining and defining riverscape genetics: How rivers influence population genetic structure

Treesearch

Chanté D. Davis; Clinton W. Epps; Rebecca L. Flitcroft; Michael A. Banks

2018-01-01

Traditional analysis in population genetics evaluates differences among groups of individuals and, in some cases, considers the effects of distance or potential barriers to gene flow. Genetic variation of organisms in complex landscapes, seascapes, or riverine systems, however, may be shaped by many forces. Recent research has linked habitat heterogeneity and landscape...

Genetic and environmental sources of individual religiousness: the roles of individual personality traits and perceived environmental religiousness.

PubMed

Kandler, Christian; Riemann, Rainer

2013-07-01

In the current study, we examined the genetic and environmental sources of the links between individual religiousness and individual personality traits, perceived parental religiousness, and perceived peer religiousness. Data from 870 individuals (incl. 394 twin pairs) were analyzed. Variance in individual religiousness was significantly influenced by genetic effects, environmental influences shared by twins reared together, and individual-specific environmental influences. Individual religiousness showed significant associations with age, sex, specific personality traits (e.g., agreeableness, openness to values), and perceived religiousness of important social interaction partners, such as parents, best friends, and spouses. The links to personality traits were relatively small and primarily genetically mediated. The associations between individual religiousness and parental religiousness were substantial and mediated by shared environmental effects. These links significantly decreased across age accompanying a significant decrease of shared environmental influences on individual religiousness. The correlations between individual religiousness and perceived religiousness of spouses and best friends were relatively moderate but increased with age. These associations were mediated by genetic as well as nonshared environmental sources accompanying an increase of nonshared environmental influences on individual religiousness with age. The results suggest that inter-individual differences in religiousness are due to multiple sources.

Coalescence and genetic diversity in sexual populations under selection.

PubMed

Neher, Richard A; Kessinger, Taylor A; Shraiman, Boris I

2013-09-24

In sexual populations, selection operates neither on the whole genome, which is repeatedly taken apart and reassembled by recombination, nor on individual alleles that are tightly linked to the chromosomal neighborhood. The resulting interference between linked alleles reduces the efficiency of selection and distorts patterns of genetic diversity. Inference of evolutionary history from diversity shaped by linked selection requires an understanding of these patterns. Here, we present a simple but powerful scaling analysis identifying the unit of selection as the genomic "linkage block" with a characteristic length, , determined in a self-consistent manner by the condition that the rate of recombination within the block is comparable to the fitness differences between different alleles of the block. We find that an asexual model with the strength of selection tuned to that of the linkage block provides an excellent description of genetic diversity and the site frequency spectra compared with computer simulations. This linkage block approximation is accurate for the entire spectrum of strength of selection and is particularly powerful in scenarios with many weakly selected loci. The latter limit allows us to characterize coalescence, genetic diversity, and the speed of adaptation in the infinitesimal model of quantitative genetics.

Familial ALS

PubMed Central

Boylan, Kevin

2015-01-01

Synopsis Genes linked to ALS susceptibility are being identified at an increasing rate owing to advances in molecular genetic technology. Genetic mechanisms in ALS pathogenesis appear to exert major effects in ~10% of patients, but genetic factors at some level may be important components of disease risk in most ALS patients. Identification of gene variants associated with ALS has informed concepts of the pathogenesis of ALS, aided the identification of therapeutic targets, facilitated research to develop new ALS biomarkers, and supported the establishment of clinical diagnostic tests for ALS-linked genes. Translation of this knowledge to ALS therapy development is ongoing. PMID:26515623

2q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia

PubMed Central

Karayiorgou, Maria; Simon, Tony J.; Gogos, Joseph A.

2010-01-01

Recent studies are beginning to paint a clear and consistent picture of the impairments in psychological and cognitive competencies that are associated with microdeletions in chromosome 22q11.2. These studies have highlighted a strong link between this genetic lesion and schizophrenia. Parallel studies in humans and animal models are starting to uncover the complex genetic and neural substrates altered by the microdeletion. In addition to offering a deeper understanding of the effects of this genetic lesion, these findings may guide analysis of other copy-number variants associated with cognitive dysfunction and psychiatric disorders. PMID:20485365

Medical genetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorde, L.B.; Carey, J.C.; White, R.L.

This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

Sex-linked genomic variation and its relationship to avian plumage dichromatism and sexual selection.

PubMed

Huang, Huateng; Rabosky, Daniel L

2015-09-16

Sexual dichromatism is the tendency for sexes to differ in color pattern and represents a striking form of within-species morphological variation. Conspicuous intersexual differences in avian plumage are generally thought to result from Darwinian sexual selection, to the extent that dichromatism is often treated as a surrogate for the intensity of sexual selection in phylogenetic comparative studies. Intense sexual selection is predicted to leave a footprint on genetic evolution by reducing the relative genetic diversity on sex chromosome to that on the autosomes. In this study, we test the association between plumage dichromatism and sex-linked genetic diversity using eight species pairs with contrasting levels of dichromatism. We estimated Z-linked and autosomal genetic diversity for these non-model avian species using restriction-site associated (RAD) loci that covered ~3 % of the genome. We find that monochromatic birds consistently have reduced sex-linked genomic variation relative to phylogenetically-paired dichromatic species and this pattern is robust to mutational biases. Our results are consistent with several interpretations. If present-day sexual selection is stronger in dichromatic birds, our results suggest that its impact on sex-linked genomic variation is offset by other processes that lead to proportionately lower Z-linked variation in monochromatic species. We discuss possible factors that may contribute to this discrepancy between phenotypes and genomic variation. Conversely, it is possible that present-day sexual selection -- as measured by the variance in male reproductive success -- is stronger in the set of monochromatic taxa we have examined, potentially reflecting the importance of song, behavior and other non-plumage associated traits as targets of sexual selection. This counterintuitive finding suggests that the relationship between genomic variation and sexual selection is complex and highlights the need for a more comprehensive survey of genomic variation in avian taxa that vary markedly in social and genetic mating systems.

Gone with the currents: lack of genetic differentiation at the circum-continental scale in the Antarctic krill Euphausia superba

PubMed Central

2011-01-01

Background Southern Ocean fauna represent a significant amount of global biodiversity, whose origin may be linked to glacial cycles determining local extinction/eradication with ice advance, survival of refugee populations and post-glacial re-colonization. This pattern implies high potential for differentiation in benthic shelf species with limited dispersal, yet consequences for pelagic organisms are less clear. The present study investigates levels of genetic variation and population structure of the Antarctic krill Euphausia superba using mitochondrial DNA and EST-linked microsatellite markers for an unprecedentedly comprehensive sampling of its populations over a circum-Antarctic range. Results MtDNA (ND1) sequences and EST-linked microsatellite markers indicated no clear sign of genetic structure among populations over large geographic scales, despite considerable power to detect differences inferred from forward-time simulations. Based on ND1, few instances of genetic heterogeneity, not significant after correction for multiple tests, were detected between geographic or temporal samples. Neutrality tests and mismatch distribution based on mtDNA sequences revealed strong evidence of past population expansion. Significant positive values of the parameter g (a measure of population growth) were obtained from microsatellite markers using a coalescent-based genealogical method and suggested a recent start (60 000 - 40 000 years ago) for the expansion. Conclusions The results provide evidence of lack of genetic heterogeneity of Antarctic krill at large geographic scales and unequivocal support for recent population expansion. Lack of genetic structuring likely reflects the tight link between krill and circum-Antarctic ocean currents and is consistent with the hypothesis that differentiation processes in Antarctic species are largely influenced by dispersal potential, whereas small-scale spatial and temporal differentiation might be due to local conditions leading to genetic patchiness. The signal of recent population growth suggests differential impact of glacial cycles on pelagic Antarctic species, which experienced population expansion during glaciations with increased available habitat, versus sedentary benthic shelf species. EST-linked microsatellites provide new perspectives to complement the results based on mtDNA and suggest that data-mining of EST libraries will be a useful approach to facilitate use of microsatellites for additional species. PMID:21486439

Weight optimization of large span steel truss structures with genetic algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mojolic, Cristian; Hulea, Radu; Pârv, Bianca Roxana

2015-03-10

The paper presents the weight optimization process of the main steel truss that supports the Slatina Sport Hall roof. The structure was loaded with self-weight, dead loads, live loads, snow, wind and temperature, grouped in eleven load cases. The optimization of the structure was made using genetic algorithms implemented in a Matlab code. A total number of four different cases were taken into consideration when trying to determine the lowest weight of the structure, depending on the types of connections with the concrete structure ( types of supports, bearing modes), and the possibility of the lower truss chord nodes tomore » change their vertical position. A number of restrictions for tension, maximum displacement and buckling were enforced on the elements, and the cross sections are chosen by the program from a user data base. The results in each of the four cases were analyzed in terms of weight, element tension, element section and displacement. The paper presents the optimization process and the conclusions drawn.« less

Safety Harness For Work Under Suspended Load

NASA Technical Reports Server (NTRS)

Sunoo, Su Young

1994-01-01

Safety device protects worker under suspended engine or other heavy load. Mechanically linked with load so if load should fall, worker yanked safely away. Worker wears chest-plate vest with straps crossing eye on back. Lower safety cable connected to eye extends horizontally away from worker to nearby wall, wrapped on pulley and extends upward to motion amplifier or reducer. Safety cables transform any sudden downward motion of overhanging load into rapid sideways motion of worker. Net catches worker, preventing worker from bumping against wall.

Genetics Home Reference: microphthalmia with linear skin defects syndrome

MedlinePlus

... oxidative phosphorylation , by which mitochondria generate adenosine triphosphate (ATP), the cell's main energy source. It also plays ... Syndrome ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: Menkes syndrome

MedlinePlus

... males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In about one-third of cases, Menkes syndrome is caused by new ...

Genetics Home Reference: allergic asthma

MedlinePlus

... links) Health Topic: Allergy Health Topic: Asthma Health Topic: Asthma in Children Additional NIH Resources (1 link) National Heart, Lung, and Blood Institute Educational Resources (12 links) American Academy of Allergy Asthma and Immunology: Allergies Asthma and Allergy Foundation of America: What ...

Missing links: the genetic architecture of flowers [correction of flower] and floral diversification.

PubMed

Soltis, Douglas E; Soltis, Pamela S; Albert, Victor A; Oppenheimer, David G; dePamphilis, Claude W; Ma, Hong; Frohlich, Michael W; Theissen, Günter

2002-01-01

To understand the genetic architecture of floral development, including the origin and subsequent diversification of the flower, data are needed not only for a few model organisms but also for gymnosperms, basal angiosperm lineages and early-diverging eudicots. We must link what is known about derived model plants such as Arabidopsis, snapdragon and maize with other angiosperms. To this end, we suggest a massive evolutionary genomics effort focused on the identification and expression patterns of floral genes and elucidation of their expression patterns in 'missing-link' taxa differing in the arrangement, number and organization of floral parts.

The Complex Contributions of Genetics and Nutrition to Immunity in Drosophila melanogaster

PubMed Central

Unckless, Robert L.; Rottschaefer, Susan M.; Lazzaro, Brian P.

2015-01-01

Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and “nutritional immunology” has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional “immune system” that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment. PMID:25764027

The complex contributions of genetics and nutrition to immunity in Drosophila melanogaster.

PubMed

Unckless, Robert L; Rottschaefer, Susan M; Lazzaro, Brian P

2015-03-01

Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment.

Genetic interactions within inositol-related pathways are associated with longitudinal changes in ventricle size

PubMed Central

Koran, Mary Ellen I.; Hohman, Timothy J.; Meda, Shashwath A.; Thornton-Wells, Tricia A.

2013-01-01

The genetic etiology of late onset Alzheimer disease (LOAD) has proven complex, involving clinical and genetic heterogeneity and gene-gene interactions. Recent genome wide association studies (GWAS) in LOAD have led to the discovery of novel genetic risk factors; however, the investigation of gene-gene interactions has been limited. Conventional genetic studies often use binary disease status as the primary phenotype, but for complex brain-based diseases, neuroimaging data can serve as quantitative endophenotypes that correlate with disease status and closely reflect pathological changes. In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, we tested for association of genetic interactions with longitudinal MRI measurements of the inferior lateral ventricles (ILVs), which have repeatedly shown a relationship to LOAD status and progression. We performed linear regression to evaluate the ability of pathway-derived SNP-SNP pairs to predict the slope of change in volume of the ILVs. After Bonferroni correction, we identified four significant interactions in the right ILV (RILV) corresponding to gene-gene pairs SYNJ2-PI4KA, PARD3-MYH2, PDE3A-ABHD12B and OR2L13-PRKG1 and one significant interaction in the left ILV (LILV) corresponding to SYNJ2-PI4KA. The SNP-SNP interaction corresponding to SYNJ2-PI4KA was identical in the RILV and LILV and was the most significant interaction in each (RILV: p=9.10×10−12; LILV: p=8.20×10−13). Both genes belong to the inositol phosphate signaling pathway which has been previously associated with neurodegeneration in AD and we discuss the possibility that perturbation of this pathway results in a down-regulation of the Akt cell survival pathway and, thereby, decreased neuronal survival, as reflected by increased volume of the ventricles. PMID:24077433

Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract.

PubMed

Zhang, D D; Du, J Z; Topolewski, J; Wang, X M

2016-07-29

Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the X or Y chromosome. Congenital cataract is a symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome. On the other hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract. This could help identify novel approaches for the prevention, early diagnosis, and comprehensive disease treatment.

Simulating and Synthesizing Substructures Using Neural Network and Genetic Algorithms

NASA Technical Reports Server (NTRS)

Liu, Youhua; Kapania, Rakesh K.; VanLandingham, Hugh F.

1997-01-01

The feasibility of simulating and synthesizing substructures by computational neural network models is illustrated by investigating a statically indeterminate beam, using both a 1-D and a 2-D plane stress modelling. The beam can be decomposed into two cantilevers with free-end loads. By training neural networks to simulate the cantilever responses to different loads, the original beam problem can be solved as a match-up between two subsystems under compatible interface conditions. The genetic algorithms are successfully used to solve the match-up problem. Simulated results are found in good agreement with the analytical or FEM solutions.

Genetics Home Reference: oral-facial-digital syndrome

MedlinePlus

... Orofaciodigital syndromes Additional NIH Resources (1 link) National Human Genome Research Institute Educational Resources (13 links) Disease InfoSearch: Orofaciodigital syndromes MalaCards: orofaciodigital ...

Genetics Home Reference: hyperprolinemia

MedlinePlus

... Hyperprolinemia type 1 Orphanet: Hyperprolinemia type 2 Screening, Technology and Research in Genetics Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases National Organization for ...

Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

ClinicalTrials.gov

2018-05-16

Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Disease; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

Diatoms to human uses: linking nitrogen deposition, aquatic eutrophication, and ecosystem services

DOE PAGES

Rhodes, Charles; Bingham, Andrew; Heard, Andrea M.; ...

2017-07-24

Nitrogen (N) loading to aquatic ecosystems can lead to eutrophication, changing the ecosystem within a waterbody, including primary productivity, water clarity, and food web dynamics. Nutrient loading often first affects the primary productivity of aquatic systems through shifts in phytoplankton communities. However, ecologically important changes in phytoplankton are often not relatable to the general public—whose behavior would need to change to alter patterns of nutrient loading. Therefore, we use the STressor–Ecological Production function–final ecosystem Services Framework to develop 154 chains that link changes in biological indicators of aquatic eutrophication (a shift in phytoplankton community) to final ecosystem services that peoplemore » use or appreciate. We identify 13 ecological production functions (EPF) within three different ecosystems (alpine lakes, lakes, and estuaries) that connect changes in phytoplankton and algae to ecological endpoints that the general public and policy makers can appreciate. Using the Final Ecosystem Goods and Services Classification System, we identify 18 classes of human beneficiaries that potentially will be impacted by a change in one of these endpoints. We further assign strength-of-science scores to each link within the EPFs for the 154 chains according to how well each link is supported by current peer-reviewed literature. By identifying many pathways through which excess N loading in U.S. surface waters can affect ecosystems and ultimately the beneficiaries of ecosystem services, this work intends to draw attention to gaps in empirical ecological literature that constrain understanding of the magnitude of effects that excess N loading can have on human well-being. Here, results highlight the importance of intersections between the natural and social sciences when managers and policy makers evaluate impacts from ecological stressors. A balance between knowledgeable specialists proved key to applying this approach and will continue to remain important.« less

Diatoms to human uses: linking nitrogen deposition, aquatic eutrophication, and ecosystem services

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rhodes, Charles; Bingham, Andrew; Heard, Andrea M.

Nitrogen (N) loading to aquatic ecosystems can lead to eutrophication, changing the ecosystem within a waterbody, including primary productivity, water clarity, and food web dynamics. Nutrient loading often first affects the primary productivity of aquatic systems through shifts in phytoplankton communities. However, ecologically important changes in phytoplankton are often not relatable to the general public—whose behavior would need to change to alter patterns of nutrient loading. Therefore, we use the STressor–Ecological Production function–final ecosystem Services Framework to develop 154 chains that link changes in biological indicators of aquatic eutrophication (a shift in phytoplankton community) to final ecosystem services that peoplemore » use or appreciate. We identify 13 ecological production functions (EPF) within three different ecosystems (alpine lakes, lakes, and estuaries) that connect changes in phytoplankton and algae to ecological endpoints that the general public and policy makers can appreciate. Using the Final Ecosystem Goods and Services Classification System, we identify 18 classes of human beneficiaries that potentially will be impacted by a change in one of these endpoints. We further assign strength-of-science scores to each link within the EPFs for the 154 chains according to how well each link is supported by current peer-reviewed literature. By identifying many pathways through which excess N loading in U.S. surface waters can affect ecosystems and ultimately the beneficiaries of ecosystem services, this work intends to draw attention to gaps in empirical ecological literature that constrain understanding of the magnitude of effects that excess N loading can have on human well-being. Here, results highlight the importance of intersections between the natural and social sciences when managers and policy makers evaluate impacts from ecological stressors. A balance between knowledgeable specialists proved key to applying this approach and will continue to remain important.« less

Genetic diversity, inbreeding and cancer.

PubMed

Ujvari, Beata; Klaassen, Marcel; Raven, Nynke; Russell, Tracey; Vittecoq, Marion; Hamede, Rodrigo; Thomas, Frédéric; Madsen, Thomas

2018-03-28

Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer. © 2018 The Author(s).

Genetic diversity, inbreeding and cancer

PubMed Central

Klaassen, Marcel; Raven, Nynke; Russell, Tracey; Vittecoq, Marion; Hamede, Rodrigo; Thomas, Frédéric

2018-01-01

Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer. PMID:29563261

Wind-tunnel evaluation of an advanced main-rotor blade design for a utility-class helicopter

NASA Technical Reports Server (NTRS)

Yeager, William T., Jr.; Mantay, Wayne R.; Wilbur, Matthew L.; Cramer, Robert G., Jr.; Singleton, Jeffrey D.

1987-01-01

An investigation was conducted in the Langley Transonic Dynamics Tunnel to evaluate differences between an existing utility-class main-rotor blade and an advanced-design main-rotor blade. The two rotor blade designs were compared with regard to rotor performance oscillatory pitch-link loads, and 4-per-rev vertical fixed-system loads. Tests were conducted in hover and over a range of simulated full-scale gross weights and density altitude conditions at advance ratios from 0.15 to 0.40. Results indicate that the advanced blade design offers performance improvements over the baseline blade in both hover and forward flight. Pitch-link oscillatory loads for the baseline rotor were more sensitive to the test conditions than those of the advanced rotor. The 4-per-rev vertical fixed-system load produced by the advanced blade was larger than that produced by the baseline blade at all test conditions.

Allostatic load mediates the impact of stress and trauma on physical and mental health in Indigenous Australians.

PubMed

Sarnyai, Zoltán; Berger, Maximus; Jawan, Isabella

2016-02-01

A considerable gap exists in health and social emotional well-being between Indigenous people and non-Indigenous Australians. Recent research in stress neurobiology highlights biological pathways that link early adversity and traumas as well as life stresses to ill health. We argue that the neurobiological stress response and its maladaptive changes, termed allostatic load, provide a useful framework to understand how adversity leads to physical and mental illness in Indigenous people. In this paper we review the biology of allostatic load and make links between stress-induced systemic hormonal, metabolic and immunological changes and physical and mental illnesses. Exposure to chronic stress throughout life results in an increased allostatic load that may contribute to a number of metabolic, cardiovascular and mental disorders that shorten life expectancy in Indigenous Australians. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Expression of chloroperoxidase from Pseudomonas pyrrocinia in tobacco plastids for fungal resistance

USDA-ARS?s Scientific Manuscript database

While genetic improvement of susceptible crop species may enhance resistance to microbial pathogens and facilitate reduced pesticide load, the possibility for transmission of novel genes to wild relatives has hampered acceptance of genetically modified (GM) crops in some markets. Chloroplast transf...

Oral delivery of exenatide via microspheres prepared by cross-linking of alginate and hyaluronate.

PubMed

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications.

Oral Delivery of Exenatide via Microspheres Prepared by Cross-Linking of Alginate and Hyaluronate

PubMed Central

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications. PMID:24465870

A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy

PubMed Central

Riordan, Sean M.; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Gazzin, Silvia; Tiribelli, Claudio; Watchko, Jon F.; Wennberg, Richard P.; Shapiro, Steven M.

2016-01-01

Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60–80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a “load” is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load (PGL) that affects the response to a specific insult has been previously reported as a PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system's response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP) causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin induced neurological disorders (BIND) such as kernicterus and could be the key to understanding ranges of outcome severity in complex diseases. We anticipate that this method could be useful for improving the care of jaundiced newborns through its use as an at-risk screen. Importantly, this method would also be useful in uncovering basic knowledge about this and other polygenetic diseases whose genetic source is difficult to discern through traditional means such as a genome-wide association study. PMID:27587993

Genetics Home Reference: shingles

MedlinePlus

... Aftercare MedlinePlus Encyclopedia: Shingles National Health Service (UK): Post-Herpetic Neuralgia Treatment General Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and ...

Genetics Home Reference: hypermethioninemia

MedlinePlus

... Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency Screening, Technology and Research in Genetics Patient Support and Advocacy Resources (1 link) Children Living with Inherited Metabolic Diseases Scientific Articles on ...

Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

MedlinePlus

... Share: Email Facebook Twitter Home Health Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ... Javascript to view the expand/collapse boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ...

Genetics Home Reference: sitosterolemia

MedlinePlus

... Sitosterolemia ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) SITOSTEROLEMIA Sources for This Page Berge KE. Sitosterolemia: a gateway to new knowledge about cholesterol metabolism. Ann Med. 2003;35(7):502-11. Review. ...

76 FR 63278 - Bayer CropScience LP; Determination of Nonregulated Status for Cotton Genetically Engineered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-12

... for Cotton Genetically Engineered for Insect Resistance and Herbicide Tolerance AGENCY: Animal and... determination that a genetically engineered cotton developed by Bayer CropScience LP, designated as TwinLink TM cotton (events T304-40 and GHB119), which has been genetically engineered to be tolerant to the herbicide...

Relationships between migration rates and landscape resistance assessed using individual-based simulations

Treesearch

E. L. Landguth; S. A. Cushman; M. A. Murphy; G. Luikart

2010-01-01

Linking landscape effects on gene flow to processes such as dispersal and mating is essential to provide a conceptual foundation for landscape genetics. It is particularly important to determine how classical population genetic models relate to recent individual-based landscape genetic models when assessing individual movement and its influence on population genetic...

Predicting individual differences in reading comprehension: a twin study

PubMed Central

Cutting, Laurie; Deater-Deckard, Kirby; DeThorne, Laura S.; Justice, Laura M.; Schatschneider, Chris; Thompson, Lee A.; Petrill, Stephen A.

2010-01-01

We examined the Simple View of reading from a behavioral genetic perspective. Two aspects of word decoding (phonological decoding and word recognition), two aspects of oral language skill (listening comprehension and vocabulary), and reading comprehension were assessed in a twin sample at age 9. Using latent factor models, we found that overlap among phonological decoding, word recognition, listening comprehension, vocabulary, and reading comprehension was primarily due to genetic influences. Shared environmental influences accounted for associations among word recognition, listening comprehension, vocabulary, and reading comprehension. Independent of phonological decoding and word recognition, there was a separate genetic link between listening comprehension, vocabulary, and reading comprehension and a specific shared environmental link between vocabulary and reading comprehension. There were no residual genetic or environmental influences on reading comprehension. The findings provide evidence for a genetic basis to the “Simple View” of reading. PMID:20814768

Genetic basis and biotechnological manipulation of sexual dimorphism and sex determination in fish.

PubMed

Mei, Jie; Gui, Jian-Fang

2015-02-01

Aquaculture has made an enormous contribution to the world food production, especially to the sustainable supply of animal proteins. The utility of diverse reproduction strategies in fish, such as the exploiting use of unisexual gynogenesis, has created a typical case of fish genetic breeding. A number of fish species show substantial sexual dimorphism that is closely linked to multiple economic traits including growth rate and body size, and the efficient development of sex-linked genetic markers and sex control biotechnologies has provided significant approaches to increase the production and value for commercial purposes. Along with the rapid development of genomics and molecular genetic techniques, the genetic basis of sexual dimorphism has been gradually deciphered, and great progress has been made in the mechanisms of fish sex determination and identification of sex-determining genes. This review summarizes the progress to provide some directive and objective thinking for further research in this field.

The power of stories in Pediatrics and Genetics.

PubMed

Opitz, John M; Pavone, Lorenzo; Corsello, Giovanni

2016-04-05

On the occasion of the opening ceremony of the 43rd Sicilian Congress of Pediatrics, linked with Italian Society of Pediatrics SIP, SIN, SIMEUP, SIAIP and SINP, held in Catania in November 2015, the Organizing Committee dedicated a tribute to Professor John Opitz and invited him to give a Masters Lecture for the attendees at the Congress. The theme expounded was "Storytelling in Pediatrics and Genetics: Lessons from Aesop and from Mendel". The contribution of John Opitz to the understanding of pediatric clinical disorders and genetic anomalies has been extremely relevant. The interests of Professor John Opitz are linked not only to genetic disorders but also extend to historical medicine, history of the literature and to human evolution. Due to his exceptional talent, combined with his specific interest and basal knowledge in the genetic and pediatric fields, he is widely credited to be one of the best pediatricians in the world.

Simulating natural selection in landscape genetics

Treesearch

E. L. Landguth; S. A. Cushman; N. Johnson

2012-01-01

Linking landscape effects to key evolutionary processes through individual organism movement and natural selection is essential to provide a foundation for evolutionary landscape genetics. Of particular importance is determining how spatially- explicit, individual-based models differ from classic population genetics and evolutionary ecology models based on ideal...

The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis

PubMed Central

Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H.; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Barberio, Manuela Terranova; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D.; Nestle, Frank O.

2015-01-01

Summary Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analysing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets, and uncovered insights into genetic control for regulatory T cells. This dataset also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. PMID:25772697

The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

PubMed

Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

2015-04-09

Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahlstroem, J.; Swanbeck, G.; Inerot, A.

1994-09-01

Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscoremore » over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.« less

Buckling and weight optimization for non-coupled antisymmetric laminates

NASA Astrophysics Data System (ADS)

Bhatnagar, Aditi

This research work describes the application of genetic algorithms to weight minimization and buckling load maximization of the non-coupled antisymmetric composite laminated plates. Previous studies of composite tailoring were limited to symmetric and balanced laminates. With the availability of many methodologies for composite tailoring, genetic algorithm is preferably used because of its ability to handle discrete design variable and attain multiple near optimum design solutions. A comparative study is made between optimum symmetric-balanced laminate designs and optimum non-coupled antisymmetric laminate designs, both of which are subjected to biaxial in-plane compressive loads. With the implementation of various genetic algorithm operators such as selection, crossover and mutation, critical buckling load factors are obtained for the optimum stacking sequence for both types of laminates. The mechanical properties for non-coupled antisymmetric laminates is independent of all types of coupling effects such as bending-twisting coupling, bending-extension coupling, and shear-extension coupling, thus giving the laminate a non-coupling behavior. This is in contrast to that of symmetric-balanced laminates where finite bending-twisting coupling terms are present. Optimized laminate layups satisfying the constraints of balance, buckling and adjoining were obtained for two types of graphite epoxy rectangular composite laminated plates. The current research augments the laminate thickness minimization designs with both odd and even number of layers, and the optimum buckling load maximization designs by the introduction of non-coupled antisymmetric laminates.

Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis.

PubMed

Lee, Seung-Min; Loguinov, Alexandre; Fleming, Robert E; Vulpe, Christopher D

2015-01-01

Hereditary hemochromatosis is an iron overload disorder most commonly caused by a defect in the HFE gene. While the genetic defect is highly prevalent, the majority of individuals do not develop clinically significant iron overload, suggesting the importance of genetic modifiers. Murine hfe knockout models have demonstrated that strain background has a strong effect on the severity of iron loading. We noted that hepatic iron loading in hfe-/- mice occurs primarily over the first postnatal weeks (loading phase) followed by a timeframe of relatively static iron concentrations (plateau phase). We thus evaluated the effects of background strain and of age on hepatic gene expression in Hfe knockout mice (hfe-/-). Hepatic gene expression profiles were examined using cDNA microarrays in 4- and 8-week-old hfe-/- and wild-type mice on two different genetic backgrounds, C57BL/6J (C57) and AKR/J (AKR). Genes differentially regulated in all hfe-/- mice groups, compared with wild-type mice, including those involved in cell survival, stress and damage responses and lipid metabolism. AKR strain-specific changes in lipid metabolism genes and C57 strain-specific changes in cell adhesion and extracellular matrix protein genes were detected in hfe-/- mice. Mouse strain and age are each significantly associated with hepatic gene expression profiles in hfe-/- mice. These affects may underlie or reflect differences in iron loading in these mice.

Association between the APOE ε4 Allele and Late-Onset Alzheimer's Disease in an Ecuadorian Mestizo Population

PubMed Central

Calero, Cristian; Vinueza, Rodrigo; Correa, Patricio; Carrera-Gonzalez, Andrea; Villegas, Franklin; Moreta, Germania; Paredes, Rosario

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease. It has two main pathological hallmarks: amyloid plaques and neurofibrillary tangles. The APOE ε4 allele has been recognized as the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD) in several populations worldwide, yet the risk varies by region and ethnicity. The aims of this study were to describe APOE allele and genotype frequencies and examine the relationship between the APOE ε4 allele and LOAD risk in an Ecuadorian Mestizo population. We carried out a case-control study comprising 56 individuals clinically diagnosed with probable AD (≥65 years of age) and 58 unrelated healthy control subjects (≥65 years of age). Genotyping was performed using the real-time PCR method. Our data showed that allelic and genotypic frequencies follow the trends observed in most worldwide populations. We also found a high-risk association between APOE ε4 allele carriers and LOAD (OR = 7.286; 95% CI = 2.824–18.799; p < 0.001). Therefore, we concluded that APOE ε4 must be considered an important genetic risk factor for LOAD in the Ecuadorian Mestizo population. Additionally, we suggest that in mixed populations the effects of admixture and ethnic identity should be differentiated when evaluating genetic contributions to Alzheimer's disease risk. PMID:29348964

Optimization and resilience of complex supply-demand networks

NASA Astrophysics Data System (ADS)

Zhang, Si-Ping; Huang, Zi-Gang; Dong, Jia-Qi; Eisenberg, Daniel; Seager, Thomas P.; Lai, Ying-Cheng

2015-06-01

Supply-demand processes take place on a large variety of real-world networked systems ranging from power grids and the internet to social networking and urban systems. In a modern infrastructure, supply-demand systems are constantly expanding, leading to constant increase in load requirement for resources and consequently, to problems such as low efficiency, resource scarcity, and partial system failures. Under certain conditions global catastrophe on the scale of the whole system can occur through the dynamical process of cascading failures. We investigate optimization and resilience of time-varying supply-demand systems by constructing network models of such systems, where resources are transported from the supplier sites to users through various links. Here by optimization we mean minimization of the maximum load on links, and system resilience can be characterized using the cascading failure size of users who fail to connect with suppliers. We consider two representative classes of supply schemes: load driven supply and fix fraction supply. Our findings are: (1) optimized systems are more robust since relatively smaller cascading failures occur when triggered by external perturbation to the links; (2) a large fraction of links can be free of load if resources are directed to transport through the shortest paths; (3) redundant links in the performance of the system can help to reroute the traffic but may undesirably transmit and enlarge the failure size of the system; (4) the patterns of cascading failures depend strongly upon the capacity of links; (5) the specific location of the trigger determines the specific route of cascading failure, but has little effect on the final cascading size; (6) system expansion typically reduces the efficiency; and (7) when the locations of the suppliers are optimized over a long expanding period, fewer suppliers are required. These results hold for heterogeneous networks in general, providing insights into designing optimal and resilient complex supply-demand systems that expand constantly in time.

Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD.

PubMed

Carrasquillo, Minerva M; Khan, Qurat ul Ain; Murray, Melissa E; Krishnan, Siddharth; Aakre, Jeremiah; Pankratz, V Shane; Nguyen, Thuy; Ma, Li; Bisceglio, Gina; Petersen, Ronald C; Younkin, Steven G; Dickson, Dennis W; Boeve, Bradley F; Graff-Radford, Neill R; Ertekin-Taner, Nilüfer

2014-04-22

To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical regions, and with risk of "posterior AD" neuropathology. We assessed 81 participants with PCA diagnosed clinically and 54 with neuropathologic diagnosis of posterior AD vs 2,523 controls for association with 11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies. There was highly significant association with APOE ε4 and increased risk of PCA (p = 0.0003, odds ratio [OR] = 3.17) and posterior AD (p = 1.11 × 10(-17), OR = 6.43). No other locus was significant after corrections for multiple testing, although rs11136000 near CLU (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated nominally significantly with posterior AD, and rs3851179 at the PICALM locus had significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP rs3764650, which was also tested under the recessive model because of Hardy-Weinberg disequilibrium, also had nominally significant association with PCA risk. The direction of association at APOE, CLU, and BIN1 loci was the same for participants with PCA and posterior AD. The effects for all SNPs, except rs3851179, were consistent with those for LOAD risk. We identified a significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk loci for PCA and posterior AD. Our findings suggest that at least some of the genetic risk factors for LOAD are shared with these atypical conditions and provide effect-size estimates for their future genetic studies.

Construction of a general human chromosome jumping library, with application to cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, F.S.; Drumm, M.L.; Cole, J.L.

1987-02-27

In many genetic disorders, the responsible gene and its protein product are unknown. The technique known as reverse genetics, in which chromosomal map positions and genetically linked DNA markers are used to identify and clone such genes, is complicated by the fact that the molecular distances from the closest DNA markers to the gene itself are often too large to traverse by standard cloning techniques. To address this situation, a general human chromosome jumping library was constructed that allows the cloning of DNA sequences approximately 100 kilobases away from any starting point in genomic DNA. As an illustration of itsmore » usefulness, this library was searched for a jumping clone, starting at the met oncogene, which is a marker tightly linked to the cystic fibrosis gene that is located on human chromosome 7. Mapping of the new genomic fragment by pulsed field gel electrophoresis confirmed that it resides on chromosome 7 within 240 kilobases downstream of the met gene. The use of chromosome jumping should be applicable to any genetic locus for which a closely linked DNA marker is available.« less

An invasive social insect overcomes genetic load at the sex locus.

PubMed

Gloag, Rosalyn; Ding, Guiling; Christie, Joshua R; Buchmann, Gabriele; Beekman, Madeleine; Oldroyd, Benjamin P

2016-11-07

Some invasive hymenopteran social insects found new populations with very few reproductive individuals. This is despite the high cost of founder effects for such insects, which generally require heterozygosity at a single locus-the complementary sex determiner, csd-to develop as females. Individuals that are homozygous at csd develop as either infertile or subfertile diploid males or not at all. Furthermore, diploid males replace the female workers that are essential for colony function. Here we document how the Asian honey bee (Apis cerana) overcame the diploid male problem during its invasion of Australia. Natural selection prevented the loss of rare csd alleles due to genetic drift and corrected the skew in allele frequencies caused by founder effects to restore high average heterozygosity. Thus, balancing selection can alleviate the genetic load at csd imposed by severe bottlenecks, and so facilitate invasiveness.

A Multi-Cycle Q-Modulation for Dynamic Optimization of Inductive Links.

PubMed

Lee, Byunghun; Yeon, Pyungwoo; Ghovanloo, Maysam

2016-08-01

This paper presents a new method, called multi-cycle Q-modulation, which can be used in wireless power transmission (WPT) to modulate the quality factor (Q) of the receiver (Rx) coil and dynamically optimize the load impedance to maximize the power transfer efficiency (PTE) in two-coil links. A key advantage of the proposed method is that it can be easily implemented using off-the-shelf components without requiring fast switching at or above the carrier frequency, which is more suitable for integrated circuit design. Moreover, the proposed technique does not need any sophisticated synchronization between the power carrier and Q-modulation switching pulses. The multi-cycle Q-modulation is analyzed theoretically by a lumped circuit model, and verified in simulation and measurement using an off-the-shelf prototype. Automatic resonance tuning (ART) in the Rx, combined with multi-cycle Q-modulation helped maximizing PTE of the inductive link dynamically in the presence of environmental and loading variations, which can otherwise significantly degrade the PTE in multi-coil settings. In the prototype conventional 2-coil link, the proposed method increased the power amplifier (PA) plus inductive link efficiency from 4.8% to 16.5% at ( R L = 1 kΩ, d 23 = 3 cm), and from 23% to 28.2% at ( R L = 100 Ω, d 23 = 3 cm) after 11% change in the resonance capacitance, while delivering 168.1 mW to the load (PDL).

New genetic and morphological evidence suggests a single hoaxer created `Piltdown man'

NASA Astrophysics Data System (ADS)

De Groote, Isabelle; Flink, Linus Girdland; Abbas, Rizwaan; Bello, Silvia M.; Burgia, Lucia; Buck, Laura Tabitha; Dean, Christopher; Freyne, Alison; Higham, Thomas; Jones, Chris G.; Kruszynski, Robert; Lister, Adrian; Parfitt, Simon A.; Skinner, Matthew M.; Shindler, Karolyn; Stringer, Chris B.

2016-08-01

In 1912, palaeontologist Arthur Smith Woodward and amateur antiquarian and solicitor Charles Dawson announced the discovery of a fossil that supposedly provided a link between apes and humans: Eoanthropus dawsoni (Dawson's dawn man). The publication generated huge interest from scientists and the general public. However, `Piltdown man's' initial celebrity has long been overshadowed by its subsequent infamy as one of the most famous scientific frauds in history. Our re-evaluation of the Piltdown fossils using the latest scientific methods (DNA analyses, high-precision measurements, spectroscopy and virtual anthropology) shows that it is highly likely that a single orang-utan specimen and at least two human specimens were used to create the fake fossils. The modus operandi was found consistent throughout the assemblage (specimens are stained brown, loaded with gravel fragments and restored using filling materials), linking all specimens from the Piltdown I and Piltdown II sites to a single forger-Charles Dawson. Whether Dawson acted alone is uncertain, but his hunger for acclaim may have driven him to risk his reputation and misdirect the course of anthropology for decades. The Piltdown hoax stands as a cautionary tale to scientists not to be led by preconceived ideas, but to use scientific integrity and rigour in the face of novel discoveries.

Tricomponent Immunopotentiating System as a Novel Molecular Design Strategy for Malaria Vaccine Development ▿

PubMed Central

Miyata, Takeshi; Harakuni, Tetsuya; Tsuboi, Takafumi; Sattabongkot, Jetsumon; Ikehara, Ayumu; Tachibana, Mayumi; Torii, Motomi; Matsuzaki, Goro; Arakawa, Takeshi

2011-01-01

The creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsically weak immunogenicity of the recombinant antigens. We have developed a novel strategy to increase immune responses by creating genetic fusion proteins to target specific antigen-presenting cells (APCs). The fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric α-helical coiled-coil core, and (iii) an APC-targeting ligand linked to the core via a flexible linker. The vaccine efficacy of the tricomponent complex was evaluated using an ookinete surface protein of Plasmodium vivax, Pvs25, and merozoite surface protein-1 of Plasmodium yoelii. Immunization of mice with the tricomponent complex induced a robust antibody response and conferred substantial levels of P. vivax transmission blockade as evaluated by a membrane feed assay, as well as protection from lethal P. yoelii infection. The observed effect was strongly dependent on the presence of all three components physically integrated as a fusion complex. This system, designated the tricomponent immunopotentiating system (TIPS), onto which any recombinant protein antigens or nonproteinaceous substances could be loaded, may be a promising strategy for devising subunit vaccines or adjuvants against various infectious diseases, including malaria. PMID:21807905

Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation.

PubMed

Hermouet, Sylvie; Bigot-Corbel, Edith; Gardie, Betty

2015-01-01

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.

Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

PubMed Central

Bigot-Corbel, Edith; Gardie, Betty

2015-01-01

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation. PMID:26538820

New genetic and morphological evidence suggests a single hoaxer created 'Piltdown man'.

PubMed

De Groote, Isabelle; Flink, Linus Girdland; Abbas, Rizwaan; Bello, Silvia M; Burgia, Lucia; Buck, Laura Tabitha; Dean, Christopher; Freyne, Alison; Higham, Thomas; Jones, Chris G; Kruszynski, Robert; Lister, Adrian; Parfitt, Simon A; Skinner, Matthew M; Shindler, Karolyn; Stringer, Chris B

2016-08-01

In 1912, palaeontologist Arthur Smith Woodward and amateur antiquarian and solicitor Charles Dawson announced the discovery of a fossil that supposedly provided a link between apes and humans: Eoanthropus dawsoni (Dawson's dawn man). The publication generated huge interest from scientists and the general public. However, 'Piltdown man's' initial celebrity has long been overshadowed by its subsequent infamy as one of the most famous scientific frauds in history. Our re-evaluation of the Piltdown fossils using the latest scientific methods (DNA analyses, high-precision measurements, spectroscopy and virtual anthropology) shows that it is highly likely that a single orang-utan specimen and at least two human specimens were used to create the fake fossils. The modus operandi was found consistent throughout the assemblage (specimens are stained brown, loaded with gravel fragments and restored using filling materials), linking all specimens from the Piltdown I and Piltdown II sites to a single forger-Charles Dawson. Whether Dawson acted alone is uncertain, but his hunger for acclaim may have driven him to risk his reputation and misdirect the course of anthropology for decades. The Piltdown hoax stands as a cautionary tale to scientists not to be led by preconceived ideas, but to use scientific integrity and rigour in the face of novel discoveries.

Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fain, P.R.; Barker, D.F.; Chance, P.F.

1994-02-01

Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

Conservation of Sex-Linked Markers among Conspecific Populations of a Viviparous Skink, Niveoscincus ocellatus, Exhibiting Genetic and Temperature-Dependent Sex Determination

PubMed Central

Burridge, Christopher P; Ezaz, Tariq; Wapstra, Erik

2018-01-01

Abstract Sex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here, we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whereas in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater differentiation of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems can be facilitated by subtle genetic differences. PMID:29659810

Optimization of culture conditions and bench-scale production of L-asparaginase by submerged fermentation of Aspergillus terreus MTCC 1782.

PubMed

Gurunathan, Baskar; Sahadevan, Renganathan

2012-07-01

Optimization of culture conditions for L-asparaginase production by submerged fermentation of Aspergillus terreus MTCC 1782 was studied using a 3-level central composite design of response surface methodology and artificial neural network linked genetic algorithm. The artificial neural network linked genetic algorithm was found to be more efficient than response surface methodology. The experimental L-asparaginase activity of 43.29 IU/ml was obtained at the optimum culture conditions of temperature 35 degrees C, initial pH 6.3, inoculum size 1% (v/v), agitation rate 140 rpm, and incubation time 58.5 h of the artificial neural network linked genetic algorithm, which was close to the predicted activity of 44.38 IU/ml. Characteristics of L-asparaginase production by A. terreus MTCC 1782 were studied in a 3 L bench-scale bioreactor.

Genetics Home Reference: McKusick-Kaufman syndrome

MedlinePlus

... Kaufman syndrome Additional NIH Resources (1 link) National Human Genome Research Institute: Gene Linked to Developmental Syndrome in Old Order Amish Identified by NIH Scientists Educational Resources ( ...

R-loops cause genomic instability in T helper lymphocytes from patients with Wiskott-Aldrich syndrome.

PubMed

Sarkar, Koustav; Han, Seong-Su; Wen, Kuo-Kuang; Ochs, Hans D; Dupré, Loïc; Seidman, Michael M; Vyas, Yatin M

2017-12-15

Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT), and X-linked neutropenia, which are caused by WAS mutations affecting Wiskott-Aldrich syndrome protein (WASp) expression or activity, manifest in immunodeficiency, autoimmunity, genomic instability, and lymphoid and other cancers. WASp supports filamentous actin formation in the cytoplasm and gene transcription in the nucleus. Although the genetic basis for XLT/WAS has been clarified, the relationships between mutant forms of WASp and the diverse features of these disorders remain ill-defined. We sought to define how dysfunctional gene transcription is causally linked to the degree of T H cell deficiency and genomic instability in the XLT/WAS clinical spectrum. In human T H 1- or T H 2-skewing cell culture systems, cotranscriptional R-loops (RNA/DNA duplex and displaced single-stranded DNA) and DNA double-strand breaks (DSBs) were monitored in multiple samples from patients with XLT and WAS and in normal T cells depleted of WASp. WASp deficiency provokes increased R-loops and R-loop-mediated DSBs in T H 1 cells relative to T H 2 cells. Mechanistically, chromatin occupancy of serine 2-unphosphorylated RNA polymerase II is increased, and that of topoisomerase 1, an R-loop preventing factor, is decreased at R-loop-enriched regions of IFNG and TBX21 (T H 1 genes) in T H 1 cells. These aberrations accompany increased unspliced (intron-retained) and decreased spliced mRNA of IFNG and TBX21 but not IL13 (T H 2 gene). Significantly, increased cellular load of R-loops and DSBs, which are normalized on RNaseH1-mediated suppression of ectopic R-loops, inversely correlates with disease severity scores. Transcriptional R-loop imbalance is a novel molecular defect causative in T H 1 immunodeficiency and genomic instability in patients with WAS. The study proposes that cellular R-loop load could be used as a potential biomarker for monitoring symptom severity and prognostic outcome in the XLT-WAS clinical spectrum and could be targeted therapeutically. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Causal Genetic Variation Underlying Metabolome Differences.

PubMed

Swain-Lenz, Devjanee; Nikolskiy, Igor; Cheng, Jiye; Sudarsanam, Priya; Nayler, Darcy; Staller, Max V; Cohen, Barak A

2017-08-01

An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals. We mapped differences in urea cycle metabolites to genetic variation in specific genes known to regulate amino acid biosynthesis. Our functional assays reveal that genetic variation in two genes, AUA1 and ARG81 , cause the differences in the abundance of several urea cycle metabolites. Based on knowledge of the urea cycle, we predicted and then validated a new phenotype: sensitivity to a particular class of amino acid isomers. Our results are a proof-of-concept that untargeted mass spectrometry can reveal links between natural genetic variants and metabolome diversity. The interpretability of our results demonstrates the promise of using genetic variants underlying natural differences in the metabolome to predict novel phenotypes from genotype. Copyright © 2017 by the Genetics Society of America.

Structured parenting of toddlers at high versus low genetic risk: two pathways to child problems.

PubMed

Leve, Leslie D; Harold, Gordon T; Ge, Xiaojia; Neiderhiser, Jenae M; Shaw, Daniel; Scaramella, Laura V; Reiss, David

2009-11-01

Little is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. We used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for psychopathology. The sample included 290 linked sets of adoptive families and birth mothers and 95 linked birth fathers. Genetic risk was assessed via birth mother and birth father psychopathology (anxiety, depression, antisociality, and drug use). Structured parenting was assessed via microsocial coding of adoptive mothers' behavior during a cleanup task. Toddler behavior problems were assessed with the Child Behavior Checklist. Controlling for temperamental risk at 9 months, there was an interaction between birth mother psychopathology and adoptive mothers' parenting on toddler behavior problems at 18 months. The interaction indicated two pathways to child problems: structured parenting was beneficial for toddlers at high genetic risk but was related to behavior problems for toddlers at low genetic risk. This crossover interaction pattern was replicated with birth father psychopathology as the index of genetic risk. The effects of structured parenting on toddler behavior problems varied as a function of genetic risk. Children at genetic risk might benefit from parenting interventions during toddlerhood that enhance structured parenting.

The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

PubMed

Christensen, G B; Knight, S; Camp, N J

2009-11-01

We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

MedlinePlus

... translocase deficiency Orphanet: Carnitine-acylcarnitine translocase deficiency Screening, Technology, and Research in Genetics Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) FOD (Fatty ...

Genetics Home Reference: N-acetylglutamate synthase deficiency

MedlinePlus

... Hyperammonemia due to N-acetylglutamate synthase deficiency Screening, Technology and Research in Genetics Patient Support and Advocacy Resources (4 links) Children Living with Inherited Metabolic Diseases National Organization for ...

Genetic and Environmental Links Between Natural Language Use and Cognitive Ability in Toddlers.

PubMed

Canfield, Caitlin F; Edelson, Lisa R; Saudino, Kimberly J

2017-03-01

Although the phenotypic correlation between language and nonverbal cognitive ability is well-documented, studies examining the etiology of the covariance between these abilities are scant, particularly in very young children. The goal of this study was to address this gap in the literature by examining the genetic and environmental links between language use, assessed through conversational language samples, and nonverbal cognition in a sample of 3-year-old twins (N = 281 pairs). Significant genetic and nonshared environmental influences were found for nonverbal cognitive ability and language measures, including mean length of utterance and number of different words, as well as significant genetic covariance between cognitive ability and both language measures. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

Golden tapetal reflex in male patients with X-linked retinitis pigmentosa. Case report and practical implications.

PubMed

van Osch, L; van Schooneveld, M; Bleekerwagemakers, E M

1990-12-01

The golden tapetal reflex in the ocular fundus is considered pathognomonic of the carrier state in some families with X-linked retinitis pigmentosa (XRP). Reports concerning affected males with this characteristic reflex are scarce. A six-year-old boy with XRP having a tapetal reflex is described. Recently the tapetal reflex has drawn attention in linkage studies. XRP is probably genetically heterogeneous and has at least two genetic forms. The finding of a tapetal reflex in one or more female carriers in a family with XRP may be helpful in differentiating between these two genetic forms.

Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord.

PubMed

Starr, Lisa R; Hammen, Constance

2016-05-01

Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR) and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement-depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. The results have important implications for understanding the romantic involvement-depression link and the behavioral and emotional correlates of the 5-HTTLPR genotype.

Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord

PubMed Central

Starr, Lisa R.; Hammen, Constance

2017-01-01

Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR), and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement-depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. Results have important implications for understanding the romantic involvement-depression link and the behavioral and emotional Correlates of the 5-HTTLPR genotype. PMID:26037034

HLA-linked rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasstedt, S.J.; Clegg, D.O.; Ingles, L.

Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. Inmore » addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically. 79 refs., 9 tabs.« less

Distributed Load Shedding over Directed Communication Networks with Time Delays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Tao; Wu, Di

When generation is insufficient to support all loads under emergencies, effective and efficient load shedding needs to be deployed in order to maintain the supply-demand balance. This paper presents a distributed load shedding algorithm, which makes efficient decision based on the discovered global information. In the global information discovery process, each load only communicates with its neighboring load via directed communication links possibly with arbitrarily large but bounded time varying communication delays. We propose a novel distributed information discovery algorithm based on ratio consensus. Simulation results are used to validate the proposed method.

Health Benefits of Animal Research: The Mouse in Biomedical Research.

ERIC Educational Resources Information Center

Jonas, Albert M.

1984-01-01

Traces the history of using mice for medical research and discusses the benefits of using these animals for studies in bacteriology, virology, genetics (considering X-linked genetic homologies between mice and humans), molecular biology, immunology, hematology, immune response disorders, oncology, radiobiology, pharmacology, behavior genetics,…

Imaging-Genetics Applications in Child Psychiatry

ERIC Educational Resources Information Center

Pine, Daniel S.; Ernst, Monique; Leibenluft, Ellen

2010-01-01

Objective: To place imaging-genetics research in the context of child psychiatry. Method: A conceptual overview is provided, followed by discussion of specific research examples. Results: Imaging-genetics research is described linking brain function to two specific genes, for the serotonin-reuptake-transporter protein and a monoamine oxidase…

Using the Drosophila Melanogaster Genetics Reference Panel to Identify Toxicity Pathways for Toluene

EPA Science Inventory

Mechanistic information is needed to link effects of chemicals at molecular targets in high­ throughput screening assays to adverse outcomes in whole organisms. This study was designed to use the Drosophila Genetic Reference Panel (DGRP), a set of genetically well...

The mean A beta load in the hippocampus correlates with duration and severity of dementia in subgroups of Alzheimer disease.

PubMed

Bartoo, G T; Nochlin, D; Chang, D; Kim, Y; Sumi, S M

1997-05-01

Using image analysis techniques to quantify the percentage area covered by the immunopositive marker for amyloid beta-peptide (A beta), we examined subjects with combinations of either early-onset or late-onset Alzheimer disease (AD) and either familial Alzheimer disease (FAD) or sporadic Alzheimer disease (SAD). We measured the mean and maximum A beta loads, in the hippocampus of each subject. There were no statistically significant differences in the mean A beta load between familial and sporadic AD subjects. Although sample sizes were too small for statistical testing, subjects with the epsilon 4/epsilon 4 allele of the apolipoprotein E (ApoE) gene had higher mean A beta loads than those with the epsilon 3/epsilon 3 or epsilon 3/epsilon 4 alleles. Members of the Volga German families (recently linked to chromosome 1) all had high mean A beta loads, and one of the chromosome 14-linked subjects had the highest mean A beta load while the other had a relatively small load, but the sample was too small for statistical comparisons. The duration of dementia and neuropsychological test scores showed a statistically significant correlation with the mean A beta load in the hippocampus, but not with the maximum A beta load. This difference indicates that the mean A beta load may be a more useful feature than the maximum A beta load as an objective neuropathological measure for cognitive status. This finding may help to improve the established methods for quantitative assessment of the neuropathological changes in AD.

61. The World-Wide Inaccessible Web, Part 2: Internet Routes

ERIC Educational Resources Information Center

Baggaley, Jon; Batpurev, Batchuluun; Klaas, Jim

2007-01-01

In the previous report in this series, Web browser loading times were measured in 12 Asian countries, and were found to be up to four times slower than commonly prescribed as acceptable. Failure of webpages to load at all was frequent. The current follow-up study compares these loading times with the complexity of the Internet routes linking the…

Genetics Home Reference: X-linked creatine deficiency

MedlinePlus

... been identified. The disorder has been estimated to account for between 1 and 2 percent of males with intellectual disability. Related Information What information about a genetic condition can statistics ...

Genetics Home Reference: acute necrotizing encephalopathy type 1

MedlinePlus

... the signs and symptoms of this condition. The health history of the individual, such as nutritional status and number of prior ... (1 link) Genetic Testing Registry: Encephalopathy, acute, infection- ...

A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

ClinicalTrials.gov

2018-06-16

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy

ClinicalTrials.gov

2017-12-11

Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

GENETIC VARIATION IN BABOON CRANIOFACIAL SEXUAL DIMORPHISM

PubMed Central

Willmore, Katherine E.; Roseman, Charles C.; Rogers, Jeffrey; Richtsmeier, Joan T.; Cheverud, James M.

2010-01-01

Sexual dimorphism is a widespread phenomenon and contributes greatly to intraspecies variation. Despite a long history of active research, the genetic basis of dimorphism for complex traits remains unknown. Understanding the sex-specific differences in genetic architecture for cranial traits in a highly dimorphic species could identify possible mechanisms through which selection acts to produce dimorphism. Using distances calculated from three-dimensional landmark data from CT scans of 402 baboon skulls from a known genealogy, we estimated genetic variance parameters in both sexes to determine the presence of gene-by-sex (G × S) interactions and X-linked heritability. We hypothesize that traits exhibiting the greatest degree of sexual dimorphism (facial traits in baboons) will demonstrate either stronger G × S interactions or X-linked effects. We found G × S interactions and X-linked effects for a few measures that span the areas connecting the face to the neurocranium but for no traits restricted to the face. This finding suggests that facial traits will have a limited response to selection for further evolution of dimorphism in this population. We discuss the implications of our results with respect to the origins of cranial sexual dimorphism in this baboon sample, and how the genetic architecture of these traits affects their potential for future evolution. PMID:19210535

Damage evolution analysis of coal samples under cyclic loading based on single-link cluster method

NASA Astrophysics Data System (ADS)

Zhang, Zhibo; Wang, Enyuan; Li, Nan; Li, Xuelong; Wang, Xiaoran; Li, Zhonghui

2018-05-01

In this paper, the acoustic emission (AE) response of coal samples under cyclic loading is measured. The results show that there is good positive relation between AE parameters and stress. The AE signal of coal samples under cyclic loading exhibits an obvious Kaiser Effect. The single-link cluster (SLC) method is applied to analyze the spatial evolution characteristics of AE events and the damage evolution process of coal samples. It is found that a subset scale of the SLC structure becomes smaller and smaller when the number of cyclic loading increases, and there is a negative linear relationship between the subset scale and the degree of damage. The spatial correlation length ξ of an SLC structure is calculated. The results show that ξ fluctuates around a certain value from the second cyclic loading process to the fifth cyclic loading process, but spatial correlation length ξ clearly increases in the sixth loading process. Based on the criterion of microcrack density, the coal sample failure process is the transformation from small-scale damage to large-scale damage, which is the reason for changes in the spatial correlation length. Through a systematic analysis, the SLC method is an effective method to research the damage evolution process of coal samples under cyclic loading, and will provide important reference values for studying coal bursts.

A comparison of superconductor and manganin technology for electronic links used in space mission applications

NASA Technical Reports Server (NTRS)

Caton, R.; Selim, R.; Buoncristiani, A. M.

1992-01-01

The electronic link connecting cryogenically cooled radiation detectors to data acquisition and signal processing electronics at higher temperatures contributes significantly to the total heat load on spacecraft cooling systems that use combined mechanical and cryogenic liquid cooling. Using high transition temperature superconductors for this link has been proposed to increase the lifetime of space missions. Herein, several YBCO (YBa2Cu3O7) superconductor-substrate combinations were examined and total heat loads were compared to manganin wire technology in current use. Using numerical solutions to the heat-flow equations, it is shown that replacing manganin technology with YBCO thick film technology can extend a 7-year mission by up to 1 year.

Discovering Link Communities in Complex Networks by an Integer Programming Model and a Genetic Algorithm

PubMed Central

Li, Zhenping; Zhang, Xiang-Sun; Wang, Rui-Sheng; Liu, Hongwei; Zhang, Shihua

2013-01-01

Identification of communities in complex networks is an important topic and issue in many fields such as sociology, biology, and computer science. Communities are often defined as groups of related nodes or links that correspond to functional subunits in the corresponding complex systems. While most conventional approaches have focused on discovering communities of nodes, some recent studies start partitioning links to find overlapping communities straightforwardly. In this paper, we propose a new quantity function for link community identification in complex networks. Based on this quantity function we formulate the link community partition problem into an integer programming model which allows us to partition a complex network into overlapping communities. We further propose a genetic algorithm for link community detection which can partition a network into overlapping communities without knowing the number of communities. We test our model and algorithm on both artificial networks and real-world networks. The results demonstrate that the model and algorithm are efficient in detecting overlapping community structure in complex networks. PMID:24386268

Genetics Home Reference: lacrimo-auriculo-dento-digital syndrome

MedlinePlus

... Information Center (1 link) Lacrimo-auriculo-dento-digital syndrome Additional NIH Resources (2 links) National Eye Institute: Facts About Dry Eye National Institute of Dental and Craniofacial Research: ...

Genetic Essentialism, Neuroessentialism, and Stigma: Commentary on Dar-Nimrod and Heine (2011)

ERIC Educational Resources Information Center

Haslam, Nick

2011-01-01

Dar-Nimrod and Heine (2011) presented a masterfully broad review of the implications of genetic essentialism for understandings of human diversity. This commentary clarifies the reasons that essentialist thinking has problematic social consequences and links genetic forms of essentialism to those invoking neural essences. The mounting evidence…

Genetics Home Reference: sialuria

MedlinePlus

... inheritance of sialuria, an inborn error of feedback inhibition. Am J Hum Genet. 2001 Jun;68(6): ... Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & Players ...

Genetics Home Reference: homocystinuria

MedlinePlus

... reductase deficiency Orphanet: Homocystinuria without methylmalonic aciduria Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (6 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) CLIMB: ...

Genetics Home Reference: isobutyryl-CoA dehydrogenase deficiency

MedlinePlus

... dehydrogenase deficiency Orphanet: Isobutyryl-CoA dehydrogenase deficiency Screening, Technology and Research in Genetics Patient Support and Advocacy Resources (3 links) Children's Cardiomyopathy Foundation CLIMB (Children Living with Inherited Metabolic ...

Genetics Home Reference: congenital contractural arachnodactyly

MedlinePlus

... 9 Related Information How are genetic conditions and genes named? Additional Information & Resources MedlinePlus (5 links) Encyclopedia: Arachnodactyly Encyclopedia: Contracture Deformity Encyclopedia: Skeletal Limb Abnormalities Health Topic: Connective Tissue Disorders Health ...

Genetics Home Reference: desmosterolosis

MedlinePlus

... dehydrocholesterol reductase, which is involved in the production (synthesis) of cholesterol. Cholesterol is a waxy, fat-like ... 2 links) Health Topic: Cholesterol Health Topic: Lipid Metabolism Disorders Genetic and Rare Diseases Information Center (1 ...

Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy

ClinicalTrials.gov

2018-01-16

Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

Preparation of novel alginate based anion exchanger from Ulva japonica and its application for the removal of trace concentrations of fluoride from water.

PubMed

Paudyal, Hari; Pangeni, Bimala; Inoue, Katsutoshi; Kawakita, Hidetaka; Ohto, Keisuke; Ghimire, Kedar Nath; Alam, Shafiq

2013-11-01

A green seaweed, Ulva japonica, was modified by loading multivalent metal ions such as Zr(IV) and La(III) after CaCl2 cross-linking to produce metal loaded cross-linked seaweed (M-CSW) adsorbents, which were characterized by elemental analysis, functional groups identification, and metal content determination. Maximum sorption potential for fluoride was drastically increased after La(III) and Zr(IV) loading, which were evaluated as 0.58 and 0.95 mmol/g, respectively. Loaded fluoride was quantitatively desorbed by using dilute alkaline solution for its regeneration. Mechanism of fluoride adsorption was inferred in terms of ligand exchange reaction between hydroxyl ion on co-ordination sphere of the loaded metal ions of M-CSW and fluoride ion in aqueous solution. Application of M-CSW for the treatment of actual waste plating solution exhibited successful removal of fluoride to clear the effluent and environmental standards in Japan, suggesting high possibility of its application for the treatment of fluoride rich waste water. Copyright © 2013 Elsevier Ltd. All rights reserved.

Discrimination and anger control as pathways linking socioeconomic disadvantage to allostatic load in midlife.

PubMed

Zilioli, Samuele; Imami, Ledina; Ong, Anthony D; Lumley, Mark A; Gruenewald, Tara

2017-12-01

Recent evidence suggests that experiences of discrimination contribute to socioeconomic status health disparities. The current study examined if the experience and regulation of anger-an expected emotional response to discrimination-serves as an explanatory factor for the previously documented links between socioeconomic disadvantage (SED), discrimination, and allostatic load. Data were drawn from the second wave of the Midlife in the United States (MIDUS) study and included 909 adults who participated in the biomarkers subproject. Results revealed that perceived discrimination was associated with higher levels of allostatic load. Furthermore, we found evidence that perceived discrimination and anger control sequentially explained the relationship between SED and allostatic load, such that greater discrimination was associated with lower levels of anger control, which, in turn accounted for the effects of discrimination on allostatic load. These results remained significant after controlling for negative affect, positive affect, other forms of anger expression, as well as demographic covariates. Our findings suggest that low anger control may be an important psychological pathway through which experiences of discrimination influence health. Copyright © 2017 Elsevier Inc. All rights reserved.

Borderline personality disorder traits and their relationship with dimensions of normative personality: a web-based cohort and twin study

PubMed Central

Kendler, K. S.; Myers, J.; Reichborn-Kjennerud, T.

2011-01-01

Objective To describe the structure of genetic and environmental risk factors for four dimensions of borderline personality disorder (BPD) and to understand the source of resemblance of these dimensions and normal personality. Method A web-based sample (n = 44,112 including 542 twin pairs) completed items from 4 scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire and the Big Five Inventory. Results A one-factor common pathway model best fits the 4 BPD scales producing a highly heritable latent liability (heritability = 60%) and strong loadings on all 4 dimensions. Affective instability had the lowest trait-specific genetic loading, suggesting that it was a core feature of BPD. A complex pattern of genetic and environmental associations was found between the big five personality traits and BPD dimensions. The strongest genetic correlations with the BPD traits were generally seen for neuroticism (positive), followed by conscientiousness and agreeableness, both negative. Conclusion In the general population, these four BPD dimensions reflect one underlying highly heritable factor. The association between normative personality and dimensions of BPD is complex with high degrees of genetic correlation. PMID:21198457

Borderline personality disorder traits and their relationship with dimensions of normative personality: a web-based cohort and twin study.

PubMed

Kendler, K S; Myers, J; Reichborn-Kjennerud, T

2011-05-01

To describe the structure of genetic and environmental risk factors for four dimensions of borderline personality disorder (BPD) and to understand the source of resemblance of these dimensions and normal personality. A web-based sample (n = 44,112 including 542 twin pairs) completed items from 4 scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire and the Big Five Inventory. A one-factor common pathway model best fits the 4 BPD scales producing a highly heritable latent liability (heritability = 60%) and strong loadings on all 4 dimensions. Affective instability had the lowest trait-specific genetic loading, suggesting that it was a core feature of BPD. A complex pattern of genetic and environmental associations was found between the big five personality traits and BPD dimensions. The strongest genetic correlations with the BPD traits were generally seen for neuroticism (positive), followed by conscientiousness and agreeableness, both negative. In the general population, these four BPD dimensions reflect one underlying highly heritable factor. The association between normative personality and dimensions of BPD is complex with high degrees of genetic correlation. © 2010 John Wiley & Sons A/S.

X-linked juvenile retinoschisis in a consanguineous family: phenotypic variability and report of a homozygous female patient.

PubMed

Gliem, Martin; Holz, Frank G; Stöhr, Heidi; Weber, Bernhard H F; Charbel Issa, Peter

2014-12-01

To describe the phenotypic variability in a consanguineous family with genetically confirmed X-linked retinoschisis. Five patients, including one homozygous female, were characterized by clinical examination, optical coherence tomography, fundus autofluorescence, mapping of macular pigment optical density, electroretinography, and DNA testing. The 36-year-old male index patient showed a ring of enhanced autofluorescence and outer retinal atrophy on optical coherence tomography. Electroretinography testing revealed a reduced a/b ratio. His mother presented with a central atrophic retina with markedly reduced autofluorescence signal and a surrounding ring of enhanced autofluorescence. The 40-year-old brother of the index patient and his 2 sons showed characteristic signs for X-linked retinoschisis, including retinal schisis and a reduced a/b ratio. Genetic testing revealed a c.293C>A mutation in the RS1 gene in all affected family members while the mother of the index patient was homozygous for this mutation. X-linked retinoschisis can present with a wide phenotypic variability. Here, detailed family history and genetic testing established the diagnosis of X-linked retinoschisis despite striking differences in phenotypic presentation in affected subjects, homozygosity of one affected female, and seemingly dominant inheritance in three subsequent generations because of multiple consanguinity.

Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

PubMed Central

Mądry, Edyta; Fidler, Ewa; Sobczyńska-Tomaszewska, Agnieszka; Lisowska, Aleksandra; Krzyżanowska, Patrycja; Pogorzelski, Andrzej; Minarowski, Łukasz; Oralewska, Beata; Mojs, Ewa; Sapiejka, Ewa; Marciniak, Ryszard; Sands, Dorota; Korzon-Burakowska, Anna; Kwiecień, Jarosław; Walkowiak, Jarosław

2011-01-01

Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with −13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (P<0.0028) and in patients with at least one mild mutation (P<0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable. PMID:21407263

Genetic architecture and balancing selection: the life and death of differentiated variants.

PubMed

Llaurens, Violaine; Whibley, Annabel; Joron, Mathieu

2017-05-01

Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co-occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems. © 2017 John Wiley & Sons Ltd.

[Hereditary fructose intolerance].

PubMed

Rumping, Lynne; Waterham, Hans R; Kok, Irene; van Hasselt, Peter M; Visser, Gepke

2014-01-01

Hereditary fructose intolerance (HFI) is a rare metabolic disease affecting fructose metabolism. After ingestion of fructose, patients may present with clinical symptoms varying from indefinite gastrointestinal symptoms to life-threatening hypoglycaemia and hepatic failure. A 13-year-old boy was referred to the department of metabolic diseases because of an abnormal fructose loading test. He was known with persistent gastrointestinal symptoms since infancy. His dietary history revealed an avoidance of fruit and sweets. Because malabsorption was suspected, an oral fructose loading test was performed. During this test, he developed severe vagal symptoms which were probably caused by a potentially fatal hypoglycaemia. The diagnosis of HFI was confirmed by genetic analysis. A good dietary history may be of important help in the diagnosis of HFI. On suspicion of HFI, genetic analysis is easy and the first choice in the diagnostic work-up. With timely diagnosis and adequate dietary treatment patients have an excellent prognosis. Fructose loading tests as part of the diagnostics can be dangerous.

Expectations and experiences of gamete donors and donor-conceived adults searching for genetic relatives using DNA linking through a voluntary register.

PubMed

van den Akker, O B A; Crawshaw, M A; Blyth, E D; Frith, L J

2015-01-01

What are the experiences of donor-conceived adults and donors who are searching for a genetic link through the use of a DNA-based voluntary register service? Donor-conceived adults and donors held positive beliefs about their search and although some concerns in relation to finding a genetically linked relative were reported, these were not a barrier to searching. Research with donor-conceived people has consistently identified their interest in learning about-and in some cases making contact with-their donor and other genetic relatives. However, donor-conceived individuals or donors rarely have the opportunity to act on these desires. A questionnaire was administered for online completion using Bristol Online Surveys. The survey was live for 3 months and responses were collected anonymously. The survey was completed by 65 donor-conceived adults, 21 sperm donors and 5 oocyte donors who had registered with a DNA-based voluntary contact register in the UK. The questionnaire included socio-demographic questions, questions specifically developed for the purposes of this study and the standardized Aspects of Identity Questionnaire (AIQ). Motivations for searching for genetic relatives were varied, with the most common reasons being curiosity and passing on information. Overall, participants who were already linked and those awaiting a link were positive about being linked and valued access to a DNA-based register. Collective identity (reflecting self-defining feelings of continuity and uniqueness), as assessed by the AIQ, was significantly lower for donor-conceived adults when compared with the donor groups (P < 0.05), but not significantly different between linked/not linked or length of time since disclosure of donor conception (all Ps > 0.05) for donor-conceived adults. Participants were members of a UK DNA-based registry which is unique. It was therefore not possible to determine how representative participants were of those who did not register for the service, those in other countries or of those who do not seek information exchange or contact. This is the first survey exploring the experiences of donor-conceived adults and donors using a DNA-based voluntary register to seek information about and contact with genetic relatives and the first to measure aspects of identity using standardized measures. Findings provide valuable information about patterns of expectations and experiences of searching through DNA linking, identity and of having contact in the context of donor conception that will inform future research, practice and policy development. No funding was obtained for this study. The authors have no competing interests to declare except for M.C. who was national adviser to UKDL from 2003-2013. Not applicable. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Learning about Huntington's Disease

MedlinePlus

... Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers ... Education Kit Online Genetics Education Resources Smithsonian NHGRI Genome ... Subjects Research Informed Consent for Genomics Research Intellectual ...

Learning about Myotonic Dystrophy

MedlinePlus

... Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers ... Education Kit Online Genetics Education Resources Smithsonian NHGRI Genome ... Subjects Research Informed Consent for Genomics Research Intellectual ...

Genetics Home Reference: prolidase deficiency

MedlinePlus

... mutations as a tool to investigate structure-function relationship. J Hum Genet. 2004;49(9):500-6. ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

Genetics Home Reference: citrullinemia

MedlinePlus

... Type II MalaCards: citrullinemia, classic Orphanet: Citrullinemia Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (5 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) National ...

Genetics Home Reference: methylmalonic acidemia with homocystinuria

MedlinePlus

... Orphanet: Methylmalonic acidemia with homocystinuria, type cblD Screening, Technology, and Research in Genetics (STAR-G) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) Organic ...

Genetics Home Reference: nephronophthisis

MedlinePlus

... which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related ...

46 CFR 160.073-15 - Tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Tests. 160.073-15 Section 160.073-15 Shipping COAST...-15 Tests. (a) The manufacturer shall perform a tensile test on the first three links made from a particular spool of wire. The test must be done by slowly loading the link until it breaks. The link must...

46 CFR 160.073-15 - Tests.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Tests. 160.073-15 Section 160.073-15 Shipping COAST...-15 Tests. (a) The manufacturer shall perform a tensile test on the first three links made from a particular spool of wire. The test must be done by slowly loading the link until it breaks. The link must...

46 CFR 160.073-15 - Tests.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Tests. 160.073-15 Section 160.073-15 Shipping COAST...-15 Tests. (a) The manufacturer shall perform a tensile test on the first three links made from a particular spool of wire. The test must be done by slowly loading the link until it breaks. The link must...

46 CFR 160.073-15 - Tests.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Tests. 160.073-15 Section 160.073-15 Shipping COAST...-15 Tests. (a) The manufacturer shall perform a tensile test on the first three links made from a particular spool of wire. The test must be done by slowly loading the link until it breaks. The link must...

46 CFR 160.073-15 - Tests.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Tests. 160.073-15 Section 160.073-15 Shipping COAST...-15 Tests. (a) The manufacturer shall perform a tensile test on the first three links made from a particular spool of wire. The test must be done by slowly loading the link until it breaks. The link must...

76 FR 423 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0100 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... dog-links was found broken (one on the nut side & one on the head side). In both occasions, the bolt... affected. If a single dog-link connection fails, the complete stabilizer load is taken up by the remaining dog-link connection. * * * To address and correct this unsafe condition EASA [European Aviation Safety...

Load balancing prediction method of cloud storage based on analytic hierarchy process and hybrid hierarchical genetic algorithm.

PubMed

Zhou, Xiuze; Lin, Fan; Yang, Lvqing; Nie, Jing; Tan, Qian; Zeng, Wenhua; Zhang, Nian

2016-01-01

With the continuous expansion of the cloud computing platform scale and rapid growth of users and applications, how to efficiently use system resources to improve the overall performance of cloud computing has become a crucial issue. To address this issue, this paper proposes a method that uses an analytic hierarchy process group decision (AHPGD) to evaluate the load state of server nodes. Training was carried out by using a hybrid hierarchical genetic algorithm (HHGA) for optimizing a radial basis function neural network (RBFNN). The AHPGD makes the aggregative indicator of virtual machines in cloud, and become input parameters of predicted RBFNN. Also, this paper proposes a new dynamic load balancing scheduling algorithm combined with a weighted round-robin algorithm, which uses the predictive periodical load value of nodes based on AHPPGD and RBFNN optimized by HHGA, then calculates the corresponding weight values of nodes and makes constant updates. Meanwhile, it keeps the advantages and avoids the shortcomings of static weighted round-robin algorithm.

Parameter Optimization of Pseudo-Rigid-Body Models of MRI-Actuated Catheters

PubMed Central

Greigarn, Tipakorn; Liu, Taoming; Çavuşoğlu, M. Cenk

2016-01-01

Simulation and control of a system containing compliant mechanisms such as cardiac catheters often incur high computational costs. One way to reduce the costs is to approximate the mechanisms with Pseudo-Rigid-Body Models (PRBMs). A PRBM generally consists of rigid links connected by spring-loaded revolute joints. The lengths of the rigid links and the stiffnesses of the springs are usually chosen to minimize the tip deflection differences between the PRBM and the compliant mechanism. In most applications, only the relationship between end load and tip deflection is considered. This is obviously not applicable for MRI-actuated catheters which is actuated by the coils attached to the body. This paper generalizes PRBM parameter optimization to include loading and reference points along the body. PMID:28261009

Learning about Gaucher Disease

MedlinePlus

... Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers ... at the Medical Genetics Branch of the National Human Genome Research Institute by Dr. Ellen Sidransky. Dr. Sidransky ...

Learning about Charcot-Marie-Tooth Disease

MedlinePlus

... Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers ... Education Kit Online Genetics Education Resources Smithsonian NHGRI Genome ... Subjects Research Informed Consent for Genomics Research Intellectual ...

Genetics Home Reference: Y chromosome infertility

MedlinePlus

... deletions" of the human Y chromosome and their relationship with male infertility. J Genet Genomics. 2008 Apr; ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

Genetics Home Reference: otopalatodigital syndrome type 2

MedlinePlus

... Testing (1 link) Genetic Testing Registry: Oto-palato-digital syndrome, type II Other Diagnosis and Management Resources ( ... syndrome FPO OPD syndrome, type 2 oto-palato-digital syndrome, type II Taybi syndrome Related Information How ...

Genetics Home Reference: otopalatodigital syndrome type 1

MedlinePlus

... Testing (1 link) Genetic Testing Registry: Oto-palato-digital syndrome, type I Other Diagnosis and Management Resources ( ... syndrome FPO OPD syndrome, type 1 oto-palato-digital syndrome, type I Taybi syndrome Related Information How ...

Genetics Home Reference: short/branched chain acyl-CoA dehydrogenase deficiency

MedlinePlus

... PDF) Orphanet: 2-methylbutyryl-CoA dehydrogenase deficiency Screening, Technology, and Research in Genetics Patient Support and Advocacy Resources (2 links) Children Living with Inherited Metabolic Diseases (CLIMB) Organic Acidemia ...

Genetics Home Reference: holocarboxylase synthetase deficiency

MedlinePlus

... holocarboxylase synthetase deficiency Orphanet: Multiple carboxylase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases Organic Acidemia Association ...

Genetics Home Reference: 3-hydroxyacyl-CoA dehydrogenase deficiency

MedlinePlus

... short chain 3-hydroxylacyl-CoA dehydrogenase deficiency Screening, Technology and Research in Genetics (STAR-G) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) FOD (Fatty ...

Genetics Home Reference: beta-ketothiolase deficiency

MedlinePlus

... Beta Ketothiolase Deficiency Orphanet: Beta-ketothiolase deficiency Screening, Technology And Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (2 links) Children Living with Inherited Metabolic Diseases Organic Acidemia Association ...

Genetics Home Reference: short-chain acyl-CoA dehydrogenase deficiency

MedlinePlus

... Orphanet: Short chain acyl-CoA dehydrogenase deficiency Screening, Technology and Research in Genetics Patient Support and Advocacy Resources (5 links) Children Living with Inherited Metabolic Disease (CLIMB) Children's Mitochondrial ...

Genetics Home Reference: isovaleric acidemia

MedlinePlus

... Consortium of Metabolic Programs Orphanet: Isovaleric acidemia Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) CLIMB (Children Living With Inherited Metabolic Diseases) (UK) National Organization ...

Genetics Home Reference: propionic acidemia

MedlinePlus

... Consortium of Metabolic Programs Orphanet: Propionic acidemia Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (6 links) CLIMB (Children Living With Inherited Metabolic Diseases) (UK) National Organization ...

Genetics Home Reference: mitochondrial trifunctional protein deficiency

MedlinePlus

... protein deficiency Orphanet: Mitochondrial trifunctional protein deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) Children Living with Inherited Metabolic Diseases (CLIMB) Children's Mitochondrial ...

Genetics Home Reference: MPV17-related hepatocerebral mitochondrial DNA depletion syndrome

MedlinePlus

... Genetic Testing Registry: Navajo neurohepatopathy Other Diagnosis and Management Resources (2 links) GeneReview: MPV17-Related Hepatocerebral Mitochondrial DNA Maintenance Defect The United Mitochondrial Disease Foundation: Treatments and ...

Genetics Home Reference: Townes-Brocks Syndrome

MedlinePlus

... MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How ... JB, Wu BL, Korf BR. Townes-Brocks syndrome versus expanded spectrum hemifacial microsomia: review of eight patients ...

Genetics Home Reference: Costello syndrome

MedlinePlus

... MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How ... 44. Citation on PubMed Rauen KA. Distinguishing Costello versus cardio-facio-cutaneous syndrome: BRAF mutations in patients ...

Genetics Home Reference: hereditary hypophosphatemic rickets

MedlinePlus

... noticeable of these abnormalities are bowed legs or knock knees (a condition in which the lower legs ... Information & Resources MedlinePlus (4 links) Encyclopedia: Bowlegs Encyclopedia: Knock Knees Encyclopedia: Rickets Health Topic: Rickets Genetic and ...

Genetics Home Reference: spina bifida

MedlinePlus

... PubMed or Free article on PubMed Central Bassuk AG, Kibar Z. Genetic basis of neural tube defects. ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

Genetics Home Reference: anencephaly

MedlinePlus

... PubMed or Free article on PubMed Central Bassuk AG, Kibar Z. Genetic basis of neural tube defects. ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

Genetics Home Reference: histidinemia

MedlinePlus

... condition characterized by elevated blood levels of the amino acid histidine, a building block of most proteins. Histidinemia ... Additional Information & Resources MedlinePlus (2 links) Health Topic: Amino Acid Metabolism Disorders Health Topic: Newborn Screening Genetic and ...

Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants in Parkinson’s Disease

PubMed Central

Helley, Martin P.; Pinnell, Jennifer; Sportelli, Carolina; Tieu, Kim

2017-01-01

Parkinson’s disease (PD) is a devastating neurological movement disorder. Since its first discovery 200 years ago, genetic and environmental factors have been identified to play a role in PD development and progression. Although genetic studies have been the predominant driving force in PD research over the last few decades, currently only a small fraction of PD cases can be directly linked to monogenic mutations. The remaining cases have been attributed to other risk associated genes, environmental exposures and gene–environment interactions, making PD a multifactorial disorder with a complex etiology. However, enormous efforts from global research have yielded significant insights into pathogenic mechanisms and potential therapeutic targets for PD. This review will highlight mitochondrial dysfunction as a common pathway involved in both genetic mutations and environmental toxicants linked to PD. PMID:29204154

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

PubMed

Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

2018-02-19

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Glass is Half Full and Half Empty: A population-representative twin study testing if Optimism and Pessimism are distinct systems

PubMed Central

Bates, Timothy C.

2015-01-01

Optimism and pessimism are associated with important outcomes including health and depression. Yet it is unclear if these apparent polar opposites form a single dimension or reflect two distinct systems. The extent to which personality accounts for differences in optimism/pessimism is also controversial. Here, we addressed these questions in a genetically informative sample of 852 pairs of twins. Distinct genetic influences on optimism and pessimism were found. Significant family-level environment effects also emerged, accounting for much of the negative relationship between optimism and pessimism, as well as a link to neuroticism. A general positive genetics factor exerted significant links among both personality and life-orientation traits. Both optimism bias and pessimism also showed genetic variance distinct from all effects of personality, and from each other. PMID:26561494

Advances in human genetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, H.; Hirschhorn, K.

1993-01-01

This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention,more » to its organ system involvement and molecular biology.« less

Genetic Disorders

MedlinePlus

... from the baby’s father. What determines my baby’s sex? Your baby’s sex is determined by sex chromosomes. ... be a carrier of the disorder. What are sex-linked disorders? Sex-linked disorders are caused by ...

Genetics Home Reference: Lowe syndrome

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. In some cases of Lowe ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetics Home Reference: Danon disease

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. Related Information What does it ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetics Home Reference: frontometaphyseal dysplasia

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. Related Information What does it ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetic Vulnerability Interacts with Parenting and Early Care and Education to Predict Increasing Externalizing Behavior

ERIC Educational Resources Information Center

Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.

2014-01-01

The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental…

A discriminative test among the different theories proposed to explain the origin of the genetic code: the coevolution theory finds additional support.

PubMed

Giulio, Massimo Di

2018-05-19

A discriminative statistical test among the different theories proposed to explain the origin of the genetic code is presented. Gathering the amino acids into polarity and biosynthetic classes that are the first expression of the physicochemical theory of the origin of the genetic code and the second expression of the coevolution theory, these classes are utilized in the Fisher's exact test to establish their significance within the genetic code table. Linking to the rows and columns of the genetic code of probabilities that express the statistical significance of these classes, I have finally been in the condition to be able to calculate a χ value to link to both the physicochemical theory and to the coevolution theory that would express the corroboration level referred to these theories. The comparison between these two χ values showed that the coevolution theory is able to explain - in this strictly empirical analysis - the origin of the genetic code better than that of the physicochemical theory. Copyright © 2018 Elsevier B.V. All rights reserved.

Studies on Monitoring and Tracking Genetic Resources: An Executive Summary

PubMed Central

Garrity, George M.; Thompson, Lorraine M.; Ussery, David W.; Paskin, Norman; Baker, Dwight; Desmeth, Philippe; Schindel, D.E.; Ong, P.S.

2009-01-01

The principles underlying fair and equitable sharing of benefits derived from the utilization of genetic resources are set out in Article 15 of the UN Convention on Biological Diversity, which stipulate that access to genetic resources is subject to the prior informed consent of the country where such resources are located and to mutually agreed terms regarding the sharing of benefits that could be derived from such access. One issue of particular concern for provider countries is how to monitor and track genetic resources once they have left the provider country and enter into use in a variety of forms. This report was commissioned to provide a detailed review of advances in DNA sequencing technologies, as those methods apply to identification of genetic resources, and the use of globally unique persistent identifiers for persistently linking to data and other forms of digital documentation that is linked to individual genetic resources. While the report was written for an audience with a mixture of technical, legal, and policy backgrounds it is relevant to the genomics community as it is an example of downstream application of genomics information. PMID:21304641

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

DOE PAGES

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong; ...

2015-11-09

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

Load beam unit replaceable inserts for dry coal extrusion pumps

DOEpatents

Saunders, Timothy; Brady, John D.

2012-11-13

A track assembly for a particulate material extrusion pump according to an exemplary aspect of the present disclosure includes a link assembly with a roller bearing. An insert mounted to a load beam located such that the roller bearing contacts the insert.

Seeking the Cause of Correlations among Mental Abilities: Large Twin Analysis in a National Testing Program.

ERIC Educational Resources Information Center

Page, Ellis B.; Jarjoura, David

1979-01-01

A computer scan of ACT Assessment records identified 3,427 sets of twins. The Hardy-Weinberg rule was used to estimate the proportion of monozygotic twins in the sample. Matrices of genetic and environmental influences were produced. The heaviest loadings were clearly in the genetic matrix. (SJL)

Complementary sex determination substantially increases extinction proneness of haplodiploid populations.

PubMed

Zayed, Amro; Packer, Laurence

2005-07-26

The role of genetic factors in extinction is firmly established for diploid organisms, but haplodiploids have been considered immune to genetic load impacts because deleterious alleles are readily purged in haploid males. However, we show that single-locus complementary sex determination ancestral to the haplodiploid Hymenoptera (ants, bees, and wasps) imposes a substantial genetic load through homozygosity at the sex locus that results in the production of inviable or sterile diploid males. Using stochastic modeling, we have discovered that diploid male production (DMP) can initiate a rapid and previously uncharacterized extinction vortex. The extinction rate in haplodiploid populations with DMP is an order of magnitude greater than in its absence under realistic but conservative demographic parameter values. Furthermore, DMP alone can elevate the base extinction risk in haplodiploids by over an order of magnitude higher than that caused by inbreeding depression in threatened diploids. Thus, contrary to previous expectations, haplodiploids are more, rather than less, prone to extinction for genetic reasons. Our findings necessitate a fundamental shift in approaches to the conservation and population biology of these ecologically and economically crucial insects.

Genomic atlas of the human plasma proteome.

PubMed

Sun, Benjamin B; Maranville, Joseph C; Peters, James E; Stacey, David; Staley, James R; Blackshaw, James; Burgess, Stephen; Jiang, Tao; Paige, Ellie; Surendran, Praveen; Oliver-Williams, Clare; Kamat, Mihir A; Prins, Bram P; Wilcox, Sheri K; Zimmerman, Erik S; Chi, An; Bansal, Narinder; Spain, Sarah L; Wood, Angela M; Morrell, Nicholas W; Bradley, John R; Janjic, Nebojsa; Roberts, David J; Ouwehand, Willem H; Todd, John A; Soranzo, Nicole; Suhre, Karsten; Paul, Dirk S; Fox, Caroline S; Plenge, Robert M; Danesh, John; Runz, Heiko; Butterworth, Adam S

2018-06-01

Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases. We show that protein quantitative trait loci overlap with gene expression quantitative trait loci, as well as with disease-associated loci, and find evidence that protein biomarkers have causal roles in disease using Mendelian randomization analysis. By linking genetic factors to diseases via specific proteins, our analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development.

Genetics and language: a neurobiological perspective on the missing link (-ing hypotheses).

PubMed

Poeppel, David

2011-12-01

The paper argues that both evolutionary and genetic approaches to studying the biological foundations of speech and language could benefit from fractionating the problem at a finer grain, aiming not to map genetics to "language"-or even subdomains of language such as "phonology" or "syntax"-but rather to link genetic results to component formal operations that underlie processing the comprehension and production of linguistic representations. Neuroanatomic and neurophysiological research suggests that language processing is broken down in space (distributed functional anatomy along concurrent pathways) and time (concurrent processing on multiple time scales). These parallel neuronal pathways and their local circuits form the infrastructure of speech and language and are the actual targets of evolution/genetics. Therefore, investigating the mapping from gene to brain circuit to linguistic phenotype at the level of generic computational operations (subroutines actually executable in these circuits) stands to provide a new perspective on the biological foundations in the healthy and challenged brain.

Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system

PubMed Central

Belbin, Gillian Morven; Odgis, Jacqueline; Sorokin, Elena P; Yee, Muh-Ching; Kohli, Sumita; Glicksberg, Benjamin S; Gignoux, Christopher R; Wojcik, Genevieve L; Van Vleck, Tielman; Jeff, Janina M; Linderman, Michael; Schurmann, Claudia; Ruderfer, Douglas; Cai, Xiaoqiang; Merkelson, Amanda; Justice, Anne E; Young, Kristin L; Graff, Misa; North, Kari E; Peters, Ulrike; James, Regina; Hindorff, Lucia; Kornreich, Ruth; Edelmann, Lisa; Gottesman, Omri; Stahl, Eli EA; Cho, Judy H; Loos, Ruth JF; Bottinger, Erwin P; Nadkarni, Girish N; Abul-Husn, Noura S

2017-01-01

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease. PMID:28895531

Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks

PubMed Central

Ulitsky, Igor; Shamir, Ron

2007-01-01

The biological interpretation of genetic interactions is a major challenge. Recently, Kelley and Ideker proposed a method to analyze together genetic and physical networks, which explains many of the known genetic interactions as linking different pathways in the physical network. Here, we extend this method and devise novel analytic tools for interpreting genetic interactions in a physical context. Applying these tools on a large-scale Saccharomyces cerevisiae data set, our analysis reveals 140 between-pathway models that explain 3765 genetic interactions, roughly doubling those that were previously explained. Model genes tend to have short mRNA half-lives and many phosphorylation sites, suggesting that their stringent regulation is linked to pathway redundancy. We also identify ‘pivot' proteins that have many physical interactions with both pathways in our models, and show that pivots tend to be essential and highly conserved. Our analysis of models and pivots sheds light on the organization of the cellular machinery as well as on the roles of individual proteins. PMID:17437029

Characterization of the Neutralizing Antibody Response in a Case of Genetically Linked HIV Superinfection.

PubMed

Ssemwanga, Deogratius; Doria-Rose, Nicole A; Redd, Andrew D; Shiakolas, Andrea R; Longosz, Andrew F; Nsubuga, Rebecca N; Mayanja, Billy N; Asiki, Gershim; Seeley, Janet; Kamali, Anatoli; Ransier, Amy; Darko, Samuel; Walker, Michael P; Bruno, Daniel; Martens, Craig; Douek, Daniel; Porcella, Stephen F; Quinn, Thomas C; Mascola, John R; Kaleebu, Pontiano

2018-04-23

This report describes the identification of a genetically confirmed linked heterosexual human immunodeficiency virus (HIV) superinfection (HIV-SI) in a woman with chronic HIV infection who acquired a second strain of the virus from her husband. Serum neutralizing antibody (NAb) responses against their homologous and heterologous viruses, including the superinfecting strain, in the woman and her husband were examined before and after onset of HIV-SI. The woman displayed a moderately potent and broad anti-HIV NAb response prior to superinfection but did not possess NAb activity against the superinfecting strain. This case highlights the unique potential of linked HIV-SI studies to examine natural protection from HIV infection.

HDL cholesterol and bone mineral density: Is there a genetic link?

PubMed Central

Ackert-Bicknell, Cheryl L.

2011-01-01

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high-density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases. PMID:21810493

Genetics Home Reference: factor V Leiden thrombophilia

MedlinePlus

... Additional NIH Resources (3 links) National Center for Biotechnology Information: Mutations and Blood Clots National Heart, Lung, and Blood Institute: Deep Vein Thrombosis National Human Genome Research Institute Educational Resources (3 links) Factor V ...

A Trial of Metformin in Individuals With Fragile X Syndrome

ClinicalTrials.gov

2018-06-05

Fragile X Syndrome; Fragile X Mental Retardation Syndrome; Mental Retardation, X Linked; Genetic Diseases, X-Linked; Trinucleotide Repeat Expansion; Fra(X) Syndrome; Intellectual Disability; FXS; Neurobehavioral Manifestations; Sex Chromosome Disorders

Genetics Home Reference: X-linked juvenile retinoschisis

MedlinePlus

... juvenile retinoschisis (XLRS): a review of genotype-phenotype relationships. Semin Ophthalmol. 2013 Sep-Nov;28(5-6): ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

Genetics Home Reference: Snyder-Robinson syndrome

MedlinePlus

... syndromic, snyder-robinson type Merck Manual Home Health Handbook for Patients & Caregivers: Osteoporosis Orphanet: X-linked intellectual ... in X-linked intellectual disability (Snyder-Robinson syndrome). Methods Mol Biol. 2011;720:437-45. doi: 10. ...

Genetics Home Reference: McCune-Albright syndrome

MedlinePlus

... while other cells have the mutated version. This phenomenon is called mosaicism . The severity of this disorder ... 1 link) Eunice Kennedy Shriver National Institute for Child Health and Human Development Educational Resources (3 links) ...

Genetics Home Reference: Wiskott-Aldrich syndrome

MedlinePlus

... other disorders: X-linked thrombocytopenia and severe congenital neutropenia . These conditions have overlapping signs and symptoms and ... Aldrich syndrome , X-linked thrombocytopenia , and severe congenital neutropenia are sometimes collectively referred to as WAS-related ...

Genetics Home Reference: mucopolysaccharidosis type II

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. Related Information What does it ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetics Home Reference: familial dilated cardiomyopathy

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. Related Information What does it ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetics Home Reference: phosphoglycerate kinase deficiency

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. Related Information What does it ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetics Home Reference: Melnick-Needles syndrome

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. Related Information What does it ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetics Home Reference: hypochondroplasia

MedlinePlus

... the elbows, a sway of the lower back ( lordosis ), and bowed legs. These signs are generally less ... Management Resources (2 links) GeneReview: Hypochondroplasia MedlinePlus Encyclopedia: Lordosis General Information from MedlinePlus (5 links) Diagnostic Tests ...

Genetics Home Reference: CDKL5 deficiency disorder

MedlinePlus

... Recurrent mutations in the CDKL5 gene: genotype-phenotype relationships. Am J Med Genet A. 2012 Jul;158A( ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

Genetics Home Reference: glutaric acidemia type I

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... Acidemia I Orphanet: Glutaryl-CoA dehydrogenase deficiency Screening, Technology and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) National Organization ...

Genetics Home Reference: multiple epiphyseal dysplasia

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... MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How ... manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study. BMC Musculoskelet ...

Genetics Home Reference: HIVEP2-related intellectual disability

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... to have difficulty with this activity; their walking style (gait) is often unbalanced and wide-based. Speech ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources General Information from MedlinePlus (5 links) Diagnostic ...

How Are Genetic Conditions Treated or Managed?

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... trials. Find out more about the treatment and management of genetic conditions: Links to information about the ... Where can I find information about diagnosis or management of...?" GeneReviews , a resource from the University of ...

Genetics Home Reference: complement factor I deficiency

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... F, Zelazko M, Marquart H, Muller K, Sjöholm AG, Truedsson L, Villoutreix BO, Blom AM. Genetic, molecular ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

Genetics Home Reference: glycine encephalopathy

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... a molecule called glycine. This molecule is an amino acid , which is a building block of proteins. Glycine ... Additional Information & Resources MedlinePlus (3 links) Health Topic: Amino Acid Metabolism Disorders Health Topic: Genetic Brain Disorders Health ...

Genetics Home Reference: glutamate formiminotransferase deficiency

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... two steps in the breakdown (metabolism) of the amino acid histidine, a building block of most proteins. It ... 4 links) Encyclopedia: Megaloblastic Anemia (image) Health Topic: Amino Acid Metabolism Disorders Health Topic: Genetic Brain Disorders Health ...

Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids

PubMed Central

Shvets, Elena; Bitsikas, Vassilis; Howard, Gillian; Hansen, Carsten Gram; Nichols, Benjamin J.

2015-01-01

Caveolae have long been implicated in endocytosis. Recent data question this link, and in the absence of specific cargoes the potential cellular function of caveolar endocytosis remains unclear. Here we develop new tools, including doubly genome-edited cell lines, to assay the subcellular dynamics of caveolae using tagged proteins expressed at endogenous levels. We find that around 5% of the cellular pool of caveolae is present on dynamic endosomes, and is delivered to endosomes in a clathrin-independent manner. Furthermore, we show that caveolae are indeed likely to bud directly from the plasma membrane. Using a genetically encoded tag for electron microscopy and ratiometric light microscopy, we go on to show that bulk membrane proteins are depleted within caveolae. Although caveolae are likely to account for only a small proportion of total endocytosis, cells lacking caveolae show fundamentally altered patterns of membrane traffic when loaded with excess glycosphingolipid. Altogether, these observations support the hypothesis that caveolar endocytosis is specialized for transport of membrane lipid. PMID:25897946

The relationship between sexual selection and sexual conflict.

PubMed

Kokko, Hanna; Jennions, Michael D

2014-07-18

Evolutionary conflicts of interest arise whenever genetically different individuals interact and their routes to fitness maximization differ. Sexual selection favors traits that increase an individual's competitiveness to acquire mates and fertilizations. Sexual conflict occurs if an individual of sex A's relative fitness would increase if it had a "tool" that could alter what an individual of sex B does (including the parental genes transferred), at a cost to B's fitness. This definition clarifies several issues: Conflict is very common and, although it extends outside traits under sexual selection, sexual selection is a ready source of sexual conflict. Sexual conflict and sexual selection should not be presented as alternative explanations for trait evolution. Conflict is closely linked to the concept of a lag load, which is context-dependent and sex-specific. This makes it possible to ask if one sex can "win." We expect higher population fitness if females win. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Alcohol dependence as a chronic pain disorder

PubMed Central

Egli, Mark; Koob, George F.; Edwards, Scott

2013-01-01

Dysregulation of pain neurocircuitry and neurochemistry has been increasingly recognized as playing a critical role in a diverse spectrum of diseases including migraine, fibromyalgia, depression, and PTSD. Evidence presented here supports the hypothesis that alcohol dependence is among the pathologies arising from aberrant neurobiological substrates of pain. In this review, we explore the possible influence of alcohol analgesia and hyperalgesia in promoting alcohol misuse and dependence. We examine evidence that neuroanatomical sites involved in the negative emotional states of alcohol dependence also play an important role in pain transmission and may be functionally altered under chronic pain conditions. We also consider possible genetic links between pain transmission and alcohol dependence. We propose an allostatic load model in which episodes of alcohol intoxication and withdrawal, traumatic stressors, and injury are each capable of dysregulating an overlapping set of neural substrates to engender sensory and affective pain states that are integral to alcohol dependence and comorbid conditions such as anxiety, depression, and chronic pain. PMID:22975446

Does major depressive disorder in parents predict specific fears and phobias in offspring?

PubMed

Biel, Matthew G; Klein, Rachel G; Mannuzza, Salvatore; Roizen, Erica R; Truong, Nhan L; Roberson-Nay, Roxann; Pine, Daniel S

2008-01-01

Evidence suggests a relationship between parental depression and phobias in offspring as well as links between childhood fears and risk for major depression. This study examines the relationship between major depressive disorder (MDD) and anxiety disorders in parents and specific fears and phobias in offspring. Three hundred and eighteen children of parents with lifetime MDD, anxiety disorder, MDD+anxiety disorder, or neither were psychiatrically assessed via parent interview. Rates of specific phobias in offspring did not differ significantly across parental groups. Specific fears were significantly elevated in offspring of parents with MDD+anxiety disorder relative to the other groups (MDD, anxiety disorder, and controls, which did not differ). We failed to find increased phobias in offspring of parents with MDD without anxiety disorder. Elevated rates of specific fears in offspring of parents with MDD+anxiety disorder may be a function of more severe parental psychopathology, increased genetic loading, or unmeasured environmental influences. (c) 2007 Wiley-Liss, Inc.

A location selection policy of live virtual machine migration for power saving and load balancing.

PubMed

Zhao, Jia; Ding, Yan; Xu, Gaochao; Hu, Liang; Dong, Yushuang; Fu, Xiaodong

2013-01-01

Green cloud data center has become a research hotspot of virtualized cloud computing architecture. And load balancing has also been one of the most important goals in cloud data centers. Since live virtual machine (VM) migration technology is widely used and studied in cloud computing, we have focused on location selection (migration policy) of live VM migration for power saving and load balancing. We propose a novel approach MOGA-LS, which is a heuristic and self-adaptive multiobjective optimization algorithm based on the improved genetic algorithm (GA). This paper has presented the specific design and implementation of MOGA-LS such as the design of the genetic operators, fitness values, and elitism. We have introduced the Pareto dominance theory and the simulated annealing (SA) idea into MOGA-LS and have presented the specific process to get the final solution, and thus, the whole approach achieves a long-term efficient optimization for power saving and load balancing. The experimental results demonstrate that MOGA-LS evidently reduces the total incremental power consumption and better protects the performance of VM migration and achieves the balancing of system load compared with the existing research. It makes the result of live VM migration more high-effective and meaningful.

A Location Selection Policy of Live Virtual Machine Migration for Power Saving and Load Balancing

PubMed Central

Xu, Gaochao; Hu, Liang; Dong, Yushuang; Fu, Xiaodong

2013-01-01

Green cloud data center has become a research hotspot of virtualized cloud computing architecture. And load balancing has also been one of the most important goals in cloud data centers. Since live virtual machine (VM) migration technology is widely used and studied in cloud computing, we have focused on location selection (migration policy) of live VM migration for power saving and load balancing. We propose a novel approach MOGA-LS, which is a heuristic and self-adaptive multiobjective optimization algorithm based on the improved genetic algorithm (GA). This paper has presented the specific design and implementation of MOGA-LS such as the design of the genetic operators, fitness values, and elitism. We have introduced the Pareto dominance theory and the simulated annealing (SA) idea into MOGA-LS and have presented the specific process to get the final solution, and thus, the whole approach achieves a long-term efficient optimization for power saving and load balancing. The experimental results demonstrate that MOGA-LS evidently reduces the total incremental power consumption and better protects the performance of VM migration and achieves the balancing of system load compared with the existing research. It makes the result of live VM migration more high-effective and meaningful. PMID:24348165

Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers.

PubMed

Aidaralieva, Nuripa Jenishbekovna; Kamino, Kouzin; Kimura, Ryo; Yamamoto, Mitsuko; Morihara, Takeshi; Kazui, Hiroaki; Hashimoto, Ryota; Tanaka, Toshihisa; Kudo, Takashi; Kida, Tomoyuki; Okuda, Jun-Ichiro; Uema, Takeshi; Yamagata, Hidehisa; Miki, Tetsuro; Akatsu, Hiroyasu; Kosaka, Kenji; Takeda, Masatoshi

2008-01-01

Alzheimer disease (AD) is characterized by progressive cognitive decline caused by synaptic dysfunction and neurodegeneration in the brain, and late-onset AD (LOAD), genetically classified as a polygenetic disease, is the major form of dementia in the elderly. It has been shown that beta amyloid, deposited in the AD brain, interacts with dynamin 1 and that the dynamin 2 (DNM2) gene homologous to the dynamin 1 gene is encoded at chromosome 19p13.2 where a susceptibility locus has been detected by linkage analysis. To test the genetic association of LOAD with the DNM2 gene, we performed a case-control study of 429 patients with LOAD and 438 sex- and age-matched control subjects in a Japanese population. We found a significant association of LOAD with single nucleotide polymorphism markers of the DNM2 gene, especially in non-carriers of the apolipoprotein E-epsilon4 allele. Even though subjects with the genotype homozygous for the risk allele at rs892086 showed no mutation in exons of the DNM2 gene, expression of DNM2 mRNA in the hippocampus was decreased in the patients compared to non-demented controls. We propose that the DNM2 gene is a novel susceptibility gene for LOAD.

Investigating Environmental Links Between Parent Depression and Child Depressive/Anxiety Symptoms Using an Assisted Conception Design

PubMed Central

Lewis, Gemma; Rice, Frances; Harold, Gordon T.; Collishaw, Stephan; Thapar, Anita

2011-01-01

Objective Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited effects, shared adversity, and child age and gender. Method Eight hundred fifty-two families with a child born by assisted conception provided questionnaire data. Mothers and fathers were genetically related or unrelated to the child depending on conception method. Parental depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Child depression/anxiety symptoms were assessed using the Short Mood and Feelings questionnaire and six items tapping generalized anxiety disorder symptoms. Associations between maternal and child symptoms were examined separately for genetically unrelated and related mother–child pairs, adjusting for three measurements of shared adversity: negative life events, family income, and socioeconomic status. Analyses were then run separately for boys and girls and for children and adolescents, and the role of paternal depression symptoms was also examined. Results Significant associations between parent and child symptoms were found for genetically unrelated mother–child (r = 0.32, p < .001) and father–child (r = 0.17, p < .05) pairs and genetically related mother–child (r = 0.31, p < .001) and father–child (r = 0.23, p < .001) pairs and were not explained by the shared adversity measurements. Environmental links were present for children and adolescents and were stronger for girls. Conclusions The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes. PMID:21515194

A three-way parallel ICA approach to analyze links among genetics, brain structure and brain function.

PubMed

Vergara, Victor M; Ulloa, Alvaro; Calhoun, Vince D; Boutte, David; Chen, Jiayu; Liu, Jingyu

2014-09-01

Multi-modal data analysis techniques, such as the Parallel Independent Component Analysis (pICA), are essential in neuroscience, medical imaging and genetic studies. The pICA algorithm allows the simultaneous decomposition of up to two data modalities achieving better performance than separate ICA decompositions and enabling the discovery of links between modalities. However, advances in data acquisition techniques facilitate the collection of more than two data modalities from each subject. Examples of commonly measured modalities include genetic information, structural magnetic resonance imaging (MRI) and functional MRI. In order to take full advantage of the available data, this work extends the pICA approach to incorporate three modalities in one comprehensive analysis. Simulations demonstrate the three-way pICA performance in identifying pairwise links between modalities and estimating independent components which more closely resemble the true sources than components found by pICA or separate ICA analyses. In addition, the three-way pICA algorithm is applied to real experimental data obtained from a study that investigate genetic effects on alcohol dependence. Considered data modalities include functional MRI (contrast images during alcohol exposure paradigm), gray matter concentration images from structural MRI and genetic single nucleotide polymorphism (SNP). The three-way pICA approach identified links between a SNP component (pointing to brain function and mental disorder associated genes, including BDNF, GRIN2B and NRG1), a functional component related to increased activation in the precuneus area, and a gray matter component comprising part of the default mode network and the caudate. Although such findings need further verification, the simulation and in-vivo results validate the three-way pICA algorithm presented here as a useful tool in biomedical data fusion applications. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular genetic analysis of retinitis pigmentosa in Indonesia using genome-wide homozygosity mapping

PubMed Central

Siemiatkowska, Anna M.; Arimadyo, Kentar; Moruz, Luminita M.; Astuti, Galuh D.N.; de Castro-Miro, Marta; Zonneveld, Marijke N.; Strom, Tim M.; de Wijs, Ilse J.; Hoefsloot, Lies H.; Faradz, Sultana M.H.; Cremers, Frans P.M.; den Hollander, Anneke I.

2011-01-01

Purpose Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous retinal disorder. Despite tremendous knowledge about the genes involved in RP, little is known about the genetic causes of RP in Indonesia. Here, we aim to identify the molecular genetic causes underlying RP in a small cohort of Indonesian patients, using genome-wide homozygosity mapping. Methods DNA samples from affected and healthy individuals from 14 Indonesian families segregating autosomal recessive, X-linked, or isolated RP were collected. Homozygosity mapping was conducted using Illumina 6k or Affymetrix 5.0 single nucleotide polymorphism (SNP) arrays. Known autosomal recessive RP (arRP) genes residing in homozygous regions and X-linked RP genes were sequenced for mutations. Results In ten out of the 14 families, homozygous regions were identified that contained genes known to be involved in the pathogenesis of RP. Sequence analysis of these genes revealed seven novel homozygous mutations in ATP-binding cassette, sub-family A, member 4 (ABCA4), crumbs homolog 1 (CRB1), eyes shut homolog (Drosophila) (EYS), c-mer proto-oncogene tyrosine kinase (MERTK), nuclear receptor subfamily 2, group E, member 3 (NR2E3) and phosphodiesterase 6A, cGMP-specific, rod, alpha (PDE6A), all segregating in the respective families. No mutations were identified in the X-linked genes retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (X-linked recessive; RP2). Conclusions Homozygosity mapping is a powerful tool to identify the genetic defects underlying RP in the Indonesian population. Compared to studies involving patients from other populations, the same genes appear to be implicated in the etiology of recessive RP in Indonesia, although all mutations that were discovered are novel and as such may be unique for this population. PMID:22128245

[Importance of genetics for health inequalities].

PubMed

Mielck, Andreas; Rogowski, W

2007-02-01

In Germany it has rarely been assessed in a systematic way, if and how genetic disposition and genetic testing are linked to health inequality. The paper aims to be a contribution towards closing this gap. In a first step, it is pointed out that the discussion about potential links between genetic causes of social inequalities has concentrated on issues such as body height and intelligence. It is stressed that, of course, social status is mainly determined socially and not genetically. In the second step, medical benefits of genetic testing are discussed. It can be assumed that low status groups are using these tests less often than high status groups, and that they are less capable of interpreting the results. Tests that can have a positive effect on health could thus lead to an increase of health inequalities. However, empirical studies for testing these hypotheses are hardly available. In the third step, the question is raised whether genetic information could lead to social discrimination (e.g. concerning health insurance, life insurance or employer). According to the current empirical literature, to date, this risk is (still) rather small. Thus, it is stressed that more research is needed, and that already today there is some need for intervention (e.g. concerning equal access to genetic testing, better information of low status groups).

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy.

PubMed

Iarossi, Giancarlo; Bertelli, Matteo; Maltese, Paolo Enrico; Gusson, Elena; Marchini, Giorgio; Bruson, Alice; Benedetti, Sabrina; Volpetti, Sabrina; Catena, Gino; Buzzonetti, Luca; Ziccardi, Lucia

2017-01-01

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4 , LRP5 , TSPAN12 , and NDP . Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands ( NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy

PubMed Central

Marchini, Giorgio; Volpetti, Sabrina; Catena, Gino

2017-01-01

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family. PMID:28758032

Synthesis and Characterization of Cleavable Core-Cross-Linked Micelles Based on Amphiphilic Block Copolypeptoids as Smart Drug Carriers.

PubMed

Li, Ang; Zhang, Donghui

2016-03-14

Amphiphilic block copolypeptoids consisting of a hydrophilic poly(N-ethyl glycine) segment and a hydrophobic poly[(N-propargyl glycine)-r-(N-decyl glycine)] random copolymer segment [PNEG-b-P(NPgG-r-NDG), EPgD] have been synthesized by sequential primary amine-initiated ring-opening polymerization (ROP) of the corresponding N-alkyl N-carboxyanhydride monomers. The block copolypeptoids form micelles in water and the micellar core can be cross-linked with a disulfide-containing diazide cross-linker by copper-mediated alkyne-azide cycloaddition (CuAAC) in aqueous solution. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis revealed the formation of spherical micelles with uniform size for both the core-cross-linked micelles (CCLMs) and non-cross-linked micelles (NCLMs) precursors for selective block copolypeptoid polymers. The CCLMs exhibited increased dimensional stability relative to the NCLMs in DMF, a nonselective solvent for the core and corona segments. Micellar dissociation of CCLMs can be induced upon addition of a reducing agent (e.g., dithiothreitol) in dilute aqueous solutions, as verified by a combination of fluorescence spectroscopy, size exclusion chromatography (SEC), and (1)H NMR spectroscopic measurement. Doxorubicin (DOX), an anticancer drug, can be loaded into the hydrophobic core of CCLMs with a maximal 23% drug loading capacity (DLC) and 37% drug loading efficiency (DLE). In vitro DOX release from the CCLMs can be triggered by DTT (10 mM), in contrast to significantly reduced DOX release in the absence of DTT, attesting to the reductively responsive characteristic of the CCLMs. While the CCLMs exhibited minimal cytotoxicity toward HepG2 cancer cells, DOX-loaded CCLMs inhibited the proliferation of the HepG2 cancer cells in a concentration and time dependent manner, suggesting the controlled release of DOX from the DOX-loaded CCLMS in the cellular environment.

Novel Spray Dried Glycerol 2-Phosphate Cross-Linked Chitosan Microparticulate Vaginal Delivery System—Development, Characterization and Cytotoxicity Studies

PubMed Central

Szymańska, Emilia; Szekalska, Marta; Czarnomysy, Robert; Lavrič, Zoran; Srčič, Stane; Miltyk, Wojciech; Winnicka, Katarzyna

2016-01-01

Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human vaginal epithelial cells. The presence of glycerol 2-phosphate influenced drug loading and encapsulation efficacy in chitosan microparticles. By increasing the cross-linking ratio, the microparticles with lower diameter, moisture content and smoother surface were observed. Mucoadhesive studies displayed that all formulations possessed mucoadhesive properties. The in vitro release profile of clotrimazole was found to alter considerably by changing the glycerol 2-phosphate/chitosan ratio. Results from cytotoxicity studies showed occurrence of apoptotic cells in the presence of chitosan and ion cross-linked chitosan microparticles, followed by a loss of membrane potential suggesting that cell death might go through the mitochondrial apoptotic pathway. PMID:27690062

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

PubMed Central

Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa

2013-01-01

Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395

Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis

PubMed Central

Bush, Ronald A.; Wei, Lisa L.; Sieving, Paul A.

2015-01-01

Retinoschisis is an X-linked recessive genetic disease that leads to vision loss in males. X-linked retinoschisis (XLRS) typically affects young males; however, progressive vision loss continues throughout life. Although discovered in 1898 by Haas in two brothers, the underlying biology leading to blindness has become apparent only in the last 15 years with the advancement of human genetic analyses, generation of XLRS animal models, and the development of ocular monitoring methods such as the electroretinogram and optical coherence tomography. It is now recognized that retinoschisis results from cyst formations within the retinal layers that interrupt normal visual neurosignaling and compromise structural integrity. Mutations in the human retinoschisin gene have been correlated with disease severity of the human XLRS phenotype. Introduction of a normal human retinoschisin cDNA into retinoschisin knockout mice restores retinal structure and improves neural function, providing proof-of-concept that gene replacement therapy is a plausible treatment for XLRS. PMID:26101206

Genetics of non syndromic hearing loss.

PubMed

Venkatesh, M D; Moorchung, Nikhil; Puri, Bipin

2015-10-01

Non Syndromic Hearing Loss is an important cause for hearing loss. One in 1000 newborns have some hearing impairment. Over 400 genetic syndromes have been described. Non Syndromic Hearing Loss (NSHL) can be inherited in an Autosomal Dominant, Autosomal Recessive or a Sex Linked fashion. There are several reasons why genetic testing should be done in cases of NSHL, the main reasons being for genetic screening and for planning treatment. This review describes the genes involved in NSHL and the genetic mechanisms involved in the pathogenesis of the disease.

Genetics Home Reference: X-linked lymphoproliferative disease

MedlinePlus

... infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, ... severe susceptibility to EBV infection severe susceptibility to infectious mononucleosis X-linked lymphoproliferative syndrome XLP Related Information How ...

Genetics Home Reference: adenylosuccinate lyase deficiency

MedlinePlus

... its chemical cousin RNA, and molecules such as ATP that serve as energy sources in the cell. ... For People With Intellectual and Developmental Disabilities Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: histiocytosis-lymphadenopathy plus syndrome

MedlinePlus

... its chemical cousin RNA, and molecules such as ATP and GTP, which serve as energy sources in ... Skin Association Histiocytosis Association: Rosai-Dorfman Disease Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: Ohdo syndrome, Maat-Kievit-Brunner type

MedlinePlus

... inheritance is that fathers cannot pass X-linked traits to their sons. Related Information What does it ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

Genetics Home Reference: Manitoba oculotrichoanal syndrome

MedlinePlus

... opening in the wall of the abdomen (an omphalocele ) that allows the abdominal organs to protrude through ... 2 links) GeneReview: Manitoba Oculotrichoanal Syndrome MedlinePlus Encyclopedia: Omphalocele Repair General Information from MedlinePlus (5 links) Diagnostic ...

Learning about Trimethylaminuria

MedlinePlus

... Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers ... ncbi.nlm.nih.gov] An electronic catalog of human genes and genetic ... Center for Biotechnology Information (NCBI). The language on this page about ...

Genetics Home Reference: 3-methylcrotonyl-CoA carboxylase deficiency

MedlinePlus

... Targets Orphanet: 3-methylcrotonyl-CoA carboxylase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) Organic ...

Genetics Home Reference: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

MedlinePlus

... Targets Orphanet: 3-hydroxy-3-methylglutaric aciduria Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) FOD ( ...

Genetics Home Reference: 3q29 microdeletion syndrome

MedlinePlus

... social interaction and communication), anxiety, bipolar disorder , and schizophrenia . Infants with 3q29 microdeletion syndrome often have feeding ... Bipolar Disorder Health Topic: Developmental Disabilities Health Topic: Schizophrenia Genetic and Rare Diseases Information Center (1 link) ...

Genetics Home Reference: PMM2-congenital disorder of glycosylation

MedlinePlus

... vision loss. Females with PMM2 -CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct ... Additional Information & Resources MedlinePlus (3 links) Encyclopedia: Hypogonadotropic Hypogonadism Health Topic: Genetic Brain Disorders Health Topic: Metabolic ...

Diallel analysis for sex-linked and maternal effects.

PubMed

Zhu, J; Weir, B S

1996-01-01

Genetic models including sex-linked and maternal effects as well as autosomal gene effects are described. Monte Carlo simulations were conducted to compare efficiencies of estimation by minimum norm quadratic unbiased estimation (MINQUE) and restricted maximum likelihood (REML) methods. MINQUE(1), which has 1 for all prior values, has a similar efficiency to MINQUE(θ), which requires prior estimates of parameter values. MINQUE(1) has the advantage over REML of unbiased estimation and convenient computation. An adjusted unbiased prediction (AUP) method is developed for predicting random genetic effects. AUP is desirable for its easy computation and unbiasedness of both mean and variance of predictors. The jackknife procedure is appropriate for estimating the sampling variances of estimated variances (or covariances) and of predicted genetic effects. A t-test based on jackknife variances is applicable for detecting significance of variation. Worked examples from mice and silkworm data are given in order to demonstrate variance and covariance estimation and genetic effect prediction.

Investigating Environmental Links between Parent Depression and Child Depressive/Anxiety Symptoms Using an Assisted Conception Design

ERIC Educational Resources Information Center

Lewis, Gemma; Rice, Frances; Harold, Gordon T.; Collishaw, Stephan; Thapar, Anita

2011-01-01

Objective: Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited…

Pronounced differences in genetic structure despite overall ecological similarity for two Ambystoma salamanders in the same landscape

Treesearch

Andrew R. Whiteley; Kevin McGarigal; Michael K. Schwartz

2014-01-01

Studies linking genetic structure in amphibian species with ecological characteristics have focused on large differences in dispersal capabilities. Here, we test whether two species with similar dispersal potential but subtle differences in other ecological characteristics also exhibit strong differences in genetic structure in the same landscape. We examined eight...

The Covariation of Antisocial Behavior and Substance Use in Adolescence: A Behavioral Genetic Perspective

ERIC Educational Resources Information Center

McAdams, Tom; Rowe, Richard; Rijsdijk, Fruhling; Maughan, Barbara; Eley, Thalia C.

2012-01-01

Multivariate genetic studies have revealed genetic correlations between antisocial behavior (ASB) and substance use (SU). However, ASB is heterogeneous, and it remains unclear whether all forms are similarly related to SU. The present study examines links between cannabis use, alcohol consumption, and aggressive and delinquent forms of ASB using a…

Variables Affecting Secondary School Students' Willingness to Eat Genetically Modified Food Crops

ERIC Educational Resources Information Center

Maes, Jasmien; Bourgonjon, Jeroen; Gheysen, Godelieve; Valcke, Martin

2018-01-01

A large-scale cross-sectional study (N = 4002) was set up to determine Flemish secondary school students' willingness to eat genetically modified food (WTE) and to link students' WTE to previously identified key variables from research on the acceptance of genetic modification (GM). These variables include subjective and objective knowledge about…

Satellite control of electric power distribution

NASA Technical Reports Server (NTRS)

Bergen, L.

1981-01-01

An L-band frequencies satellite link providing the medium for direct control of electrical loads at individual customer sites from remote central locations is described. All loads supplied under interruptible-service contracts are likely condidates for such control, and they can be cycled or switched off to reduce system loads. For every kW of load eliminated or deferred to off-peak hours, the power company reduces its need for additional generating capacity. In addition, the satellite could switch meter registers so that their readings automatically reflected the time of consumption. The system would perform load-shedding operations during emergencies, disconnecting large blocks of load according to predetermined priorities. Among the distribution operations conducted by the satellite in real time would be: load reconfiguration, voltage regulation, fault isolation, and capacitor and feeder load control.

Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading.

PubMed

Johnstone, Daniel; Graham, Ross M; Trinder, Debbie; Delima, Roheeth D; Riveros, Carlos; Olynyk, John K; Scott, Rodney J; Moscato, Pablo; Milward, Elizabeth A

2012-04-11

Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe(-/-) mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe(-/-) mouse brain showed numerous significant changes in transcript levels (p<0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Selection methods for resistance to and tolerance of helminths in livestock

PubMed Central

McManus, Concepta; Paim, Tiago do Prado; de Melo, Cristiano Barros; Brasil, Bruno S. A. F.; Paiva, Samuel R.

2014-01-01

Helminthiases are among the most important livestock diseases worldwide, in particular for small ruminants, which are the focus of this review. Resource Allocation Theory implies that high-productivity farm animals proportionate insufficient resources for adequate coping with stressful conditions. Significant differences between breeds and within breeds are seen, as well as genotype vs. environment interactions. With improvement of genetic host resistance to infection, transmission of infection will be impacted. On the other hand, genetic improvement of resilience can lead to a reduction in clinical signs of disease, but not necessarily reduce transmission of infection to other animals. Faecal egg count (FEC) is the main measurement used to evaluate helminthiasis load, despite the fact that the protocols and analytical methods can affect the results, and the FEC data frequently shows aggregative, negative skewed distribution, and a high coefficient of variation. Mass selection where heritability is generally medium to low generally produces slow results and low economic returns. Many studies have been published linking resistance to nematodes in livestock to Quantitative Trait Loci and most studies have concentrated on chromosomes where the major histocompatibility complex region is located. Nevertheless, these complex traits have been seen to be affected by thousands of variants that each has a small effect. More recent studies have shown that genome-wide selection strategies can be useful in selecting animals for improved production and resistance traits in this case. PMID:25350972

Integration of Tidal Prism Model and HSPF for simulating indicator bacteria in coastal watersheds

NASA Astrophysics Data System (ADS)

Sobel, Rose S.; Rifai, Hanadi S.; Petersen, Christina M.

2017-09-01

Coastal water quality is strongly influenced by tidal fluctuations and water chemistry. There is a need for rigorous models that are not computationally or economically prohibitive, but still allow simulation of the hydrodynamics and bacteria sources for coastal, tidally influenced streams and bayous. This paper presents a modeling approach that links a Tidal Prism Model (TPM) implemented in an Excel-based modeling environment with a watershed runoff model (Hydrologic Simulation Program FORTRAN, HSPF) for such watersheds. The TPM is a one-dimensional mass balance approach that accounts for loading from tidal exchange, runoff, point sources and bacteria die-off at an hourly time step resolution. The novel use of equal high-resolution time steps in this study allowed seamless integration of the TPM and HSPF. The linked model was calibrated to flow and E. Coli data (for HSPF), and salinity and enterococci data (for the TPM) for a coastal stream in Texas. Sensitivity analyses showed the TPM to be most influenced by changes in net decay rates followed by tidal and runoff loads, respectively. Management scenarios were evaluated with the developed linked models to assess the impact of runoff load reductions and improved wastewater treatment plant quality and to determine the areas of critical need for such reductions. Achieving water quality standards for bacteria required load reductions that ranged from zero to 90% for the modeled coastal stream.

Linked Hydrologic-Hydrodynamic Model Framework to Forecast Impacts of Rivers on Beach Water Quality

NASA Astrophysics Data System (ADS)

Anderson, E. J.; Fry, L. M.; Kramer, E.; Ritzenthaler, A.

2014-12-01

The goal of NOAA's beach quality forecasting program is to use a multi-faceted approach to aid in detection and prediction of bacteria in recreational waters. In particular, our focus has been on the connection between tributary loads and bacteria concentrations at nearby beaches. While there is a clear link between stormwater runoff and beach water quality, quantifying the contribution of river loadings to nearshore bacterial concentrations is complicated due to multiple processes that drive bacterial concentrations in rivers as well as those processes affecting the fate and transport of bacteria upon exiting the rivers. In order to forecast potential impacts of rivers on beach water quality, we developed a linked hydrologic-hydrodynamic water quality framework that simulates accumulation and washoff of bacteria from the landscape, and then predicts the fate and transport of washed off bacteria from the watershed to the coastal zone. The framework includes a watershed model (IHACRES) to predict fecal indicator bacteria (FIB) loadings to the coastal environment (accumulation, wash-off, die-off) as a function of effective rainfall. These loadings are input into a coastal hydrodynamic model (FVCOM), including a bacteria transport model (Lagrangian particle), to simulate 3D bacteria transport within the coastal environment. This modeling system provides predictive tools to assist local managers in decision-making to reduce human health threats.

Linking trading ratio with TMDL (total maximum daily load) allocation matrix and uncertainty analysis.

PubMed

Zhang, H X

2008-01-01

An innovative approach for total maximum daily load (TMDL) allocation and implementation is the watershed-based pollutant trading. Given the inherent scientific uncertainty for the tradeoffs between point and nonpoint sources, setting of trading ratios can be a contentious issue and was already listed as an obstacle by several pollutant trading programs. One of the fundamental reasons that a trading ratio is often set higher (e.g. greater than 2) is to allow for uncertainty in the level of control needed to attain water quality standards, and to provide a buffer in case traded reductions are less effective than expected. However, most of the available studies did not provide an approach to explicitly address the determination of trading ratio. Uncertainty analysis has rarely been linked to determination of trading ratio.This paper presents a practical methodology in estimating "equivalent trading ratio (ETR)" and links uncertainty analysis with trading ratio determination from TMDL allocation process. Determination of ETR can provide a preliminary evaluation of "tradeoffs" between various combination of point and nonpoint source control strategies on ambient water quality improvement. A greater portion of NPS load reduction in overall TMDL load reduction generally correlates with greater uncertainty and thus requires greater trading ratio. The rigorous quantification of trading ratio will enhance the scientific basis and thus public perception for more informed decision in overall watershed-based pollutant trading program. (c) IWA Publishing 2008.

Effects of Nitrogen Inputs and Watershed Characteristics on Summer Stream Nitrogen Concentrations: A National-Scale Analysis

EPA Science Inventory

Nitrogen (N) inputs to the landscape have been linked previously to N loads exported from watersheds at the national scale; however, stream N concentration is arguably more relevant than N load for drinking water quality, freshwater biological responses and establishment of nutri...

Honeycomb structural composite polymer network of gelatin and functional cellulose ester for controlled release of omeprazole.

PubMed

Zhuang, Chen; Shi, Chengmei; Tao, Furong; Cui, Yuezhi

2017-12-01

The functionalized cellulose ester MCN was firstly synthesized and used to cross-link gelatin by amidation between -NH 2 in gelatin and active ester groups in MCN to form a composite polymer network Gel-MCN, which was confirmed by Van Slyke method, FTIR, XRD and TGA-DTG spectra. The model drug omeprazole was loaded in Gel-MCN composites mainly by electrostatic interaction and hydrogen bonds, which were certified by FTIR, XRD and TGA-DSC. Thermal stability, anti-biodegradability, mechanical property and surface hydrophobicity of the composites with different cross-linking extents and drug loading were systematically investigated. SEM images demonstrated the honeycomb structural cells of cross-linked gelatin networks and this ensured drug entrapment. The drug release mechanism was dominated by a combined effect of diffusion and degradation, and the release rate decreased with cross-linking degree increased. The developed drug delivery system had profound significance in improving pesticide effect and bioavailability of drugs. Copyright © 2017. Published by Elsevier B.V.

A comparison of the wear of cross-linked polyethylene against itself with the wear of ultra-high molecular weight polyethylene against itself.

PubMed

Joyce, T J; Unsworth, A

1996-01-01

Wear tests were carried out on reciprocating pin-on-plate machines which had pins loaded at 10 N and 40 N. The materials tested were irradiated cross-linked polyethylene sliding against itself, irradiated ultra-high molecular weight polyethylene sliding against itself and non-irradiated ultra-high molecular weight polyethylene sliding against itself. After 153.5 km of sliding, the non-irradiated ultra-high molecular weight polyethylene plates and pins showed mean wear factors under 10 N loads, or a nominal contact stress of 0.51 MPa, of 84.0 x 10(-6) mm3/N m for the plates and 81.3 x 10(-6) mm3/N m for the pins. Under 40 N loads, or a nominal contact stress of 2.04 MPa, the non-irradiated ultra-high molecular weight polyethylene pins sheared at 22.3 km. At the last measurement point prior to this failure, 19.1 km, wear factors of 158 x 10(-6) mm3/N m for the plates and 85.0 x 10(-6) mm3/N m for the pins had been measured. After 152.8 km. the irradiated ultra-high molecular weight polyethylene plates and pins showed mean wear factors under 10 N loads of 59.8 x 10(-6) mm3/N m for the plates and 31.1 x 10(-6) mm3/N m for the pins. In contrast, after 150.2 km, a mean wear factor of 0.72 x 10(-6) mm3/N m was found for the irradiated cross-linked polyethylene plates compared with 0.053 x 10(-6) mm3/N m for the irradiated cross-linked polyethylene pins.

Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links.

PubMed

Abolmaali, Samira Sadat; Tamaddon, Ali; Yousefi, Gholamhossein; Javidnia, Katayoun; Dinarvand, Rasoul

2014-01-01

A functional polycation nanonetwork was developed for delivery of water soluble chemotherapeutic agents. The complexes of polyethyleneimine grafted methoxy polyethylene glycol (PEI-g-mPEG) and Zn(2+) were utilized as the micellar template for cross-linking with dithiodipropionic acid, followed by an acidic pH dialysis to remove the metal ion from the micellar template. The synthesis method was optimized according to pH, the molar ratio of Zn(2+), and the cross-link ratio. The atomic force microscopy showed soft, discrete, and uniform nano-networks. They were sensitive to the simulated reductive environment as determined by Ellman's assay. They showed few positive ζ potential and an average hydrodynamic diameter of 162±10 nm, which decreased to 49±11 nm upon dehydration. The ionic character of the nano-networks allowed the achievement of a higher-loading capacity of methotrexate (MTX), approximately 57% weight per weight, depending on the cross-link and the drug feed ratios. The nano-networks actively loaded with MTX presented some suitable properties, such as the hydrodynamic size of 117±16 nm, polydispersity index of 0.22, and a prolonged swelling-controlled release profile over 24 hours that boosted following reductive activation of the nanonetwork biodegradation. Unlike the PEI ionomer, the nano-networks provided an acceptable cytotoxicity profile. The drug-loaded nano-networks exhibited more specific cytotoxicity against human hepatocellular carcinoma cells if compared to free MTX at concentrations above 1 μM. The enhanced antitumor activity in vitro might be attributed to endocytic entry of MTX-loaded nano-networks that was found in the epifluorescence microscopy experiment for the fluorophore-labeled nano-networks.

Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links

PubMed Central

Abolmaali, Samira Sadat; Tamaddon, Ali; Yousefi, Gholamhossein; Javidnia, Katayoun; Dinarvand, Rasoul

2014-01-01

A functional polycation nanonetwork was developed for delivery of water soluble chemotherapeutic agents. The complexes of polyethyleneimine grafted methoxy polyethylene glycol (PEI-g-mPEG) and Zn2+ were utilized as the micellar template for cross-linking with dithiodipropionic acid, followed by an acidic pH dialysis to remove the metal ion from the micellar template. The synthesis method was optimized according to pH, the molar ratio of Zn2+, and the cross-link ratio. The atomic force microscopy showed soft, discrete, and uniform nano-networks. They were sensitive to the simulated reductive environment as determined by Ellman’s assay. They showed few positive ζ potential and an average hydrodynamic diameter of 162±10 nm, which decreased to 49±11 nm upon dehydration. The ionic character of the nano-networks allowed the achievement of a higher-loading capacity of methotrexate (MTX), approximately 57% weight per weight, depending on the cross-link and the drug feed ratios. The nano-networks actively loaded with MTX presented some suitable properties, such as the hydrodynamic size of 117±16 nm, polydispersity index of 0.22, and a prolonged swelling-controlled release profile over 24 hours that boosted following reductive activation of the nanonetwork biodegradation. Unlike the PEI ionomer, the nano-networks provided an acceptable cytotoxicity profile. The drug-loaded nano-networks exhibited more specific cytotoxicity against human hepatocellular carcinoma cells if compared to free MTX at concentrations above 1 μM. The enhanced antitumor activity in vitro might be attributed to endocytic entry of MTX-loaded nano-networks that was found in the epifluorescence microscopy experiment for the fluorophore-labeled nano-networks. PMID:24944513

Genetics Home Reference: RAPADILINO syndrome

MedlinePlus

... 3 links) Health Topic: Bone Diseases Health Topic: Cleft Lip and Palate Health Topic: Hand Injuries and Disorders Genetic and ... Anomaly MalaCards: rapadilino syndrome March of Dimes: Cleft Lip and Cleft Palate Orphanet: RAPADILINO syndrome Patient Support and Advocacy Resources ( ...

Genetics Home Reference: very long-chain acyl-CoA dehydrogenase deficiency

MedlinePlus

... Very long chain acyl-CoA dehydrogenase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) Children's Mitochondrial Disease Network (UK) FOD (Fatty Oxidation Disorders) ...

Genetics Home Reference: long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

MedlinePlus

... Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) Children Living with Inherited Metabolic Diseases (CLIMB) Children's Mitochondrial ...

Genetics Home Reference: atypical hemolytic-uremic syndrome

MedlinePlus

... Kidney Diseases: Kidney Failure: Choosing a Treatment That's Right for You Educational Resources (6 links) Disease InfoSearch: Hemolytic uremic syndrome, atypical MalaCards: genetic atypical hemolytic-uremic syndrome Merck Manual Consumer Version: Overview of Anemia Merck Manual Consumer Version: ...

Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells

ClinicalTrials.gov

2017-01-12

Stem Cell Transplantation; Bone Marrow Transplantation; Peripheral Blood Stem Cell Transplantation; Allogeneic Transplantation; Genetic Diseases; Thalassemia; Pediatrics; Diamond-Blackfan Anemia; Combined Immune Deficiency; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Lymphoproliferative Disease; Metabolic Diseases

Genetics Home Reference: GM2-gangliosidosis, AB variant

MedlinePlus

... link) National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet Educational Resources (3 links) ... Chen B, Rigat B, Curry C, Mahuran DJ. Structure of the GM2A gene: identification of an exon ...

Genetics Home Reference: X-linked cardiac valvular dysplasia

MedlinePlus

... inflammation of the inner lining of the heart (endocarditis), abnormal blood clots, or sudden death. X-linked ... Johns Hopkins Medicine: Mitral Valve Prolapse MedlinePlus Encyclopedia: Endocarditis MedlinePlus Encyclopedia: Mitral Valve Prolapse General Information from ...

Genetics Home Reference: familial osteochondritis dissecans

MedlinePlus

... Familial osteochondritis dissecans Seattle Children's TeensHealth from Nemours: Knee Injuries University of Connecticut Health Center Patient Support and Advocacy Resources (1 link) American College of Rheumatology: Osteoarthritis ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles ...

Genetics Home Reference: congenital insensitivity to pain

MedlinePlus

... insensitivity to pain is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which ... link) National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Information Page Educational Resources (5 links) Disease InfoSearch: ...

Genetics Home Reference: X-linked agammaglobulinemia

MedlinePlus

... Sep;104(3):221-30. Citation on PubMed Smith CIE, Berglöf A. X-Linked Agammaglobulinemia. 2001 Apr ... Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ...

Highly specific detection of genetic modification events using an enzyme-linked probe hybridization chip.

PubMed

Zhang, M Z; Zhang, X F; Chen, X M; Chen, X; Wu, S; Xu, L L

2015-08-10

The enzyme-linked probe hybridization chip utilizes a method based on ligase-hybridizing probe chip technology, with the principle of using thio-primers for protection against enzyme digestion, and using lambda DNA exonuclease to cut multiple PCR products obtained from the sample being tested into single-strand chains for hybridization. The 5'-end amino-labeled probe was fixed onto the aldehyde chip, and hybridized with the single-stranded PCR product, followed by addition of a fluorescent-modified probe that was then enzymatically linked with the adjacent, substrate-bound probe in order to achieve highly specific, parallel, and high-throughput detection. Specificity and sensitivity testing demonstrated that enzyme-linked probe hybridization technology could be applied to the specific detection of eight genetic modification events at the same time, with a sensitivity reaching 0.1% and the achievement of accurate, efficient, and stable results.

Vision-based stress estimation model for steel frame structures with rigid links

NASA Astrophysics Data System (ADS)

Park, Hyo Seon; Park, Jun Su; Oh, Byung Kwan

2017-07-01

This paper presents a stress estimation model for the safety evaluation of steel frame structures with rigid links using a vision-based monitoring system. In this model, the deformed shape of a structure under external loads is estimated via displacements measured by a motion capture system (MCS), which is a non-contact displacement measurement device. During the estimation of the deformed shape, the effective lengths of the rigid link ranges in the frame structure are identified. The radius of the curvature of the structural member to be monitored is calculated using the estimated deformed shape and is employed to estimate stress. Using MCS in the presented model, the safety of a structure can be assessed gauge-freely. In addition, because the stress is directly extracted from the radius of the curvature obtained from the measured deformed shape, information on the loadings and boundary conditions of the structure are not required. Furthermore, the model, which includes the identification of the effective lengths of the rigid links, can consider the influences of the stiffness of the connection and support on the deformation in the stress estimation. To verify the applicability of the presented model, static loading tests for a steel frame specimen were conducted. By comparing the stress estimated by the model with the measured stress, the validity of the model was confirmed.

Influence of a Small Fraction of Individuals with Enhanced Mutations on a Population Genetic Pool

NASA Astrophysics Data System (ADS)

Cebrat, S.; Stauffer, D.

It has been observed that a higher mutation load could be introduced into the genomes of children conceived by assisted reproduction technology (fertilization in-vitro). This generates two effects — slightly higher mutational pressure on the whole genetic pool of population and inhomogeneity of mutation distributions in the genetic pool. Computer simulations of the Penna ageing model suggest that already a small fraction of births with enhanced number of new mutations can negatively influence the whole population.

Genetic Variation Linked to Lung Cancer Survival in White Smokers | Center for Cancer Research

Cancer.gov

CCR investigators have discovered evidence that links lung cancer survival with genetic variations (called single nucleotide polymorphisms) in the MBL2 gene, a key player in innate immunity. The variations in the gene, which codes for a protein called the mannose-binding lectin, occur in its promoter region, where the RNA polymerase molecule binds to start transcription, and in the first exon that is responsible for the correct structure of MBL. The findings appear in the September 19, 2007, issue of the Journal of the National Cancer Institute.

Simultaneous optimization of loading pattern and burnable poison placement for PWRs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alim, F.; Ivanov, K.; Yilmaz, S.

2006-07-01

To solve in-core fuel management optimization problem, GARCO-PSU (Genetic Algorithm Reactor Core Optimization - Pennsylvania State Univ.) is developed. This code is applicable for all types and geometry of PWR core structures with unlimited number of fuel assembly (FA) types in the inventory. For this reason an innovative genetic algorithm is developed with modifying the classical representation of the genotype. In-core fuel management heuristic rules are introduced into GARCO. The core re-load design optimization has two parts, loading pattern (LP) optimization and burnable poison (BP) placement optimization. These parts depend on each other, but it is difficult to solve themore » combined problem due to its large size. Separating the problem into two parts provides a practical way to solve the problem. However, the result of this method does not reflect the real optimal solution. GARCO-PSU achieves to solve LP optimization and BP placement optimization simultaneously in an efficient manner. (authors)« less

Extending the ‘cross-disorder’ relevance of executive functions to dimensional neuropsychiatric traits in youth

PubMed Central

McGrath, Lauren M.; Braaten, Ellen B.; Doty, Nathan D.; Willoughby, Brian L.; Wilson, H. Kent; O’Donnell, Ellen H.; Colvin, Mary K.; Ditmars, Hillary L.; Blais, Jessica E.; Hill, Erin N.; Metzger, Aaron; Perlis, Roy H.; Willcutt, Erik G.; Smoller, Jordan W.; Waldman, Irwin D.; Faraone, Stephen V.; Seidman, Larry J.; Doyle, Alysa E.

2016-01-01

Background Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with ‘cross-disorder’ relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability. Methods Data are from 393 participants, ages 8 to 17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of autism spectrum disorder, bipolar illness and schizophrenia, including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively. Results We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting it related to a general increase in psychopathology symptoms across those dimensions. Conclusions Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relate to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability. PMID:26411927

Load forecast method of electric vehicle charging station using SVR based on GA-PSO

NASA Astrophysics Data System (ADS)

Lu, Kuan; Sun, Wenxue; Ma, Changhui; Yang, Shenquan; Zhu, Zijian; Zhao, Pengfei; Zhao, Xin; Xu, Nan

2017-06-01

This paper presents a Support Vector Regression (SVR) method for electric vehicle (EV) charging station load forecast based on genetic algorithm (GA) and particle swarm optimization (PSO). Fuzzy C-Means (FCM) clustering is used to establish similar day samples. GA is used for global parameter searching and PSO is used for a more accurately local searching. Load forecast is then regressed using SVR. The practical load data of an EV charging station were taken to illustrate the proposed method. The result indicates an obvious improvement in the forecasting accuracy compared with SVRs based on PSO and GA exclusively.

Quantifying functional connectivity: The role of breeding habitat, abundance, and landscape features on range-wide gene flow in sage-grouse

Treesearch

Jeffrey R. Row; Kevin E. Doherty; Todd B. Cross; Michael K. Schwartz; Sara Oyler-McCance; Dave E. Naugle; Steven T. Knick; Bradley C. Fedy

2018-01-01

Functional connectivity, quantified using landscape genetics, can inform conservation through the identification of factors linking genetic structure to landscape mechanisms. We used breeding habitat metrics, landscape attributes and indices of grouse abundance, to compare fit between structural connectivity and genetic differentiation within five long‐established Sage...

Relationship between the IQ of People with Prader-Willi Syndrome and that of Their Siblings: Evidence for Imprinted Gene Effects

ERIC Educational Resources Information Center

Whittington, J.; Holland, A.; Webb, T.

2009-01-01

Background: Genetic disorders occasionally provide the means to uncover potential mechanisms linking gene expression and physical or cognitive characteristics or behaviour. Prader-Willi syndrome (PWS) is one such genetic disorder in which differences between the two main genetic subtypes have been documented (e.g. higher verbal IQ in one vs.…

Teaching Genetics in Secondary Classrooms: A Linguistic Analysis of Teachers' Talk about Proteins

ERIC Educational Resources Information Center

Thörne, Karin; Gericke, Niklas

2014-01-01

This study investigates Swedish biology teachers' inclusion of proteins when teaching genetics in grade nine (students 15-16 years old). For some years, there has been a call to give attention to proteins when teaching genetics as a means of linking the concepts "gene" and "trait". Students are known to have problems with this…

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

PubMed

Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan R I; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant; Eriksson, Johan G; Espeseth, Thomas; Freimer, Nelson A; Giakoumaki, Stella; Giegling, Ina; Gill, Michael; Glahn, David C; Hariri, Ahmad R; Hatzimanolis, Alex; Keller, Matthew C; Knowles, Emma; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; Lencz, Todd; Liewald, David C; London, Edythe; Lundervold, Astri J; Malhotra, Anil K; Melle, Ingrid; Morris, Derek; Need, Anna C; Ollier, William; Palotie, Aarno; Payton, Antony; Pendleton, Neil; Poldrack, Russell A; Räikkönen, Katri; Reinvang, Ivar; Roussos, Panos; Rujescu, Dan; Sabb, Fred W; Scult, Matthew A; Smeland, Olav B; Smyrnis, Nikolaos; Starr, John M; Steen, Vidar M; Stefanis, Nikos C; Straub, Richard E; Sundet, Kjetil; Tiemeier, Henning; Voineskos, Aristotle N; Weinberger, Daniel R; Widen, Elisabeth; Yu, Jin; Abecasis, Goncalo; Andreassen, Ole A; Breen, Gerome; Christiansen, Lene; Debrabant, Birgit; Dick, Danielle M; Heinz, Andreas; Hjerling-Leffler, Jens; Ikram, M Arfan; Kendler, Kenneth S; Martin, Nicholas G; Medland, Sarah E; Pedersen, Nancy L; Plomin, Robert; Polderman, Tinca J C; Ripke, Stephan; van der Sluis, Sophie; Sullivan, Patrick F; Vrieze, Scott I; Wright, Margaret J; Posthuma, Danielle

2018-06-25

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean.

PubMed

Fang, Chao; Ma, Yanming; Wu, Shiwen; Liu, Zhi; Wang, Zheng; Yang, Rui; Hu, Guanghui; Zhou, Zhengkui; Yu, Hong; Zhang, Min; Pan, Yi; Zhou, Guoan; Ren, Haixiang; Du, Weiguang; Yan, Hongrui; Wang, Yanping; Han, Dezhi; Shen, Yanting; Liu, Shulin; Liu, Tengfei; Zhang, Jixiang; Qin, Hao; Yuan, Jia; Yuan, Xiaohui; Kong, Fanjiang; Liu, Baohui; Li, Jiayang; Zhang, Zhiwu; Wang, Guodong; Zhu, Baoge; Tian, Zhixi

2017-08-24

Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both correlations among different traits and genetic interactions among genes that affect a single trait pose a challenge to soybean breeding. To understand the genetic networks underlying phenotypic correlations, we collected 809 soybean accessions worldwide and phenotyped them for two years at three locations for 84 agronomic traits. Genome-wide association studies identified 245 significant genetic loci, among which 95 genetically interacted with other loci. We determined that 14 oil synthesis-related genes are responsible for fatty acid accumulation in soybean and function in line with an additive model. Network analyses demonstrated that 51 traits could be linked through the linkage disequilibrium of 115 associated loci and these links reflect phenotypic correlations. We revealed that 23 loci, including the known Dt1, E2, E1, Ln, Dt2, Fan, and Fap loci, as well as 16 undefined associated loci, have pleiotropic effects on different traits. This study provides insights into the genetic correlation among complex traits and will facilitate future soybean functional studies and breeding through molecular design.

Matching oceanography and genetics at the basin scale. Seascape connectivity of the Mediterranean shore crab in the Adriatic Sea.

PubMed

Schiavina, M; Marino, I A M; Zane, L; Melià, P

2014-11-01

Investigating the interactions between the physical environment and early life history is crucial to understand the mechanisms that shape the genetic structure of marine populations. Here, we assessed the genetic differentiation in a species with larval dispersal, the Mediterranean shore crab (Carcinus aestuarii) in the Adriatic Sea (central Mediterranean), and we investigated the role of oceanic circulation in shaping population structure. To this end, we screened 11 polymorphic microsatellite loci from 431 individuals collected at eight different sites. We found a weak, yet significant, genetic structure into three major clusters: a northern Adriatic group, a central Adriatic group and one group including samples from southern Adriatic and Ionian seas. Genetic analyses were compared, under a seascape genetics approach, with estimates of potential larval connectivity obtained with a coupled physical-biological model that integrates a water circulation model and a description of biological traits affecting dispersal. The cross-validation of the results of the two approaches supported the view that genetic differentiation reflects an oceanographic subdivision of the Adriatic Sea into three subbasins, with circulation patterns allowing the exchange of larvae through permanent connections linking north Adriatic sites and ephemeral connections like those linking the central Adriatic with northern and southern locations. © 2014 John Wiley & Sons Ltd.

Human Genetics and Islam: Scientific and Medical Aspects

PubMed Central

Ghareeb, Bilal A.A.

2011-01-01

Objective: To relate diverse aspects of genetics and its applications to concepts in the Glorious Qur’an and the ḥadīth. Study Design: The author compared passages from the Glorious Qur’an and ḥadīth with modern concepts in genetics, such as recessive inheritance, genetic counseling, genetic variation, cytoplasmic inheritance, sex chromosomes, genetics-environment interactions, gender determination, and the hypothesis of “pairing in the universe.” Conclusions: A fresh understanding of Islamic scripture reveals references to principles of genetics that predate contemporary discoveries. This highlights the need for further exploration of possible links between science and religion. PMID:23610491

"Counseling" in Ophthalmology.

ERIC Educational Resources Information Center

Francois, J.

1976-01-01

The need to counsel patients with genetic ophthalmological problems is stressed in the article. Assessment of autosomal dominance or autosomal recessitivity in an individual is explained and sex-linked heredity is traced. Practical examples of genetic abnormalities, such as pigmentary retinopathy and chorodineremia, are discussed. (PHR)

Genetics Home Reference: 5q minus syndrome

MedlinePlus

... in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes. Ann Hematol. 2014 Jan;93( ... Celebrates Its 15th Anniversary Genetic Information Non-Discrimination Act (GINA) Turns 10 All ... is newborn screening? New Pages Lyme disease ...

Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

MedlinePlus

... area? Other Names for This Condition PDGFRA-associated myeloproliferative neoplasm Related Information How are genetic conditions and genes ... Disorders Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasia, MD Anderson Cancer Center ... ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific ...

Using HexSim to link demography and genetics in animal and plant simulations

EPA Science Inventory

Simulation models are essential for understanding the effects of land management practices and environmental drivers, including landscape change, shape population genetic structure and persistence probabilities. The emerging field of eco-evolutionary modeling is beginning to dev...