Characterizing fuels in treated areas.

Treesearch

Roger D. Ottmar; Clinton S. Wright

2002-01-01

Small-log utilization or thinning operations followed by a fuel treatment such as prescribed fire can be used to change the composition and structure of fuelbeds, thereby mitigating deleterious fire effects and reducing the potential for catastrophic wildfires in some forested landscapes. We are developing a national system, Fuel Characteristic Classification (FCC),...

Once More unto the Breaching Experiment: Reconsidering a Popular Pedagogical Tool

ERIC Educational Resources Information Center

Braswell, Matthew

2014-01-01

Instructors frequently utilize breaching experiments in an attempt to "bring sociology to life." However, an uncritical embrace of breaching experiments obscures the complexity of their possible effects on participants and subjects. These experiments have real potential to inflict deleterious consequences on individuals and groups.…

Students' Instructional Dissent and Relationships with Faculty Members' Burnout, Commitment, Satisfaction, and Efficacy

ERIC Educational Resources Information Center

Frisby, Brandi N.; Goodboy, Alan K.; Buckner, Marjorie M.

2015-01-01

Extending research on instructional dissent beyond student reports, this study examined the potential for students' expressed dissent to have deleterious effects on faculty members. Instructors (N = 113) completed surveys about students' instructional dissent regarding their classes and reported their own burnout, commitment, satisfaction, and…

Programmed Writing as a Therapeutic Intervention: A Review of the Literature.

ERIC Educational Resources Information Center

Bibby, Robert Christopher

Traumatic life events are stressful and when coupled with decreased emotional expression they can have deleterious effects on a person's psychological and physical health. The empirical literature on programmed assignments, specifically Programmed Writing (PW) as a therapeutic intervention, was examined for its potential as a means to facilitate…

Oxaloacetate: a novel neuroprotective for acute ischemic stroke.

PubMed

Campos, Francisco; Sobrino, Tomás; Ramos-Cabrer, Pedro; Castillo, José

2012-02-01

It is well established that glutamate acts as an important mediator of neuronal degeneration during cerebral ischemia. Different kind of glutamate antagonists have been used to reduce the deleterious effects of glutamate. However, their preclinical success failed to translate into practical treatments. Far from the classical use of glutamate antagonists employed so far, the systemic administration of oxaloacetate represents a novel neuroprotective strategy to minimize the deleterious effect of glutamate in the brain tissue after ischemic stroke. The neuroprotective effect of oxaloacetate is based on the capacity of this molecule to reduce the brain and blood glutamate levels as a result of the activation of the blood-resident enzyme glutamate-oxaloacetate transaminase. Here we review the recent experimental and clinical results where it is demonstrated the potential applicability of oxaloacetate as a novel and powerful neuroprotective treatment against ischemic stroke. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Safety of new anti-arrhythmic drugs].

PubMed

Touboul, P

2005-04-01

The majority of new antiarrhythmic drugs are still undergoing clinical trials and are not yet available on the French market. The studies of efficacy are mainly targeted on the treatment of atrial fibrillation. Intravenous ibutilide prolongs the duration of the action potential by stimulating sodium exchange during phase 2 of the action potential. Used for terminating episodes of atrial flutter and fibrillation, ibutilide has been shown to have a low proarrhythmic effect. Dofetilide is a pure I(Kr) current antagonist and is given orally. The molecule prolongs the duration of the atrial and ventricular action potentials. The amplitude of this effect is inversely related to the heart rate. No effect has been observed on the mortality rate in the post-infarct period. Adjusting the dosage with respect to renal function has reduced the occurrence of torsades de pointe from 4.8 to 2.9%. Azimilide is an I(Kr) and I(Ks) current blocker and its efficacy decreases at rapid heart rates. After oral administration, azimilide does not appear to have a deleterious effect in patients with a history of myocardial infarction and left ventricular dysfunction. The risk of torsades de pointe is less than 1%. Cases of neutropaenia have been reported. Dronedarone is an amiodarone analogue without iodine. The molecule prolongs atrial and ventricular action potentials and its efficacy is maintained at high heart rates. This drug had deleterious effects when given to patients with coronary artery disease and left ventricular dysfunction. Gastrointestinal side effects may be observed at high dosage. The great advantages of dronedarone are the absence of thyroid complications and of pro-arrhythmic effects.

Experiments on the role of deleterious mutations as stepping stones in adaptive evolution

PubMed Central

Covert, Arthur W.; Lenski, Richard E.; Wilke, Claus O.; Ofria, Charles

2013-01-01

Many evolutionary studies assume that deleterious mutations necessarily impede adaptive evolution. However, a later mutation that is conditionally beneficial may interact with a deleterious predecessor before it is eliminated, thereby providing access to adaptations that might otherwise be inaccessible. It is unknown whether such sign-epistatic recoveries are inconsequential events or an important factor in evolution, owing to the difficulty of monitoring the effects and fates of all mutations during experiments with biological organisms. Here, we used digital organisms to compare the extent of adaptive evolution in populations when deleterious mutations were disallowed with control populations in which such mutations were allowed. Significantly higher fitness levels were achieved over the long term in the control populations because some of the deleterious mutations served as stepping stones across otherwise impassable fitness valleys. As a consequence, initially deleterious mutations facilitated the evolution of complex, beneficial functions. We also examined the effects of disallowing neutral mutations, of varying the mutation rate, and of sexual recombination. Populations evolving without neutral mutations were able to leverage deleterious and compensatory mutation pairs to overcome, at least partially, the absence of neutral mutations. Substantially raising or lowering the mutation rate reduced or eliminated the long-term benefit of deleterious mutations, but introducing recombination did not. Our work demonstrates that deleterious mutations can play an important role in adaptive evolution under at least some conditions. PMID:23918358

Experiments on the role of deleterious mutations as stepping stones in adaptive evolution.

PubMed

Covert, Arthur W; Lenski, Richard E; Wilke, Claus O; Ofria, Charles

2013-08-20

Many evolutionary studies assume that deleterious mutations necessarily impede adaptive evolution. However, a later mutation that is conditionally beneficial may interact with a deleterious predecessor before it is eliminated, thereby providing access to adaptations that might otherwise be inaccessible. It is unknown whether such sign-epistatic recoveries are inconsequential events or an important factor in evolution, owing to the difficulty of monitoring the effects and fates of all mutations during experiments with biological organisms. Here, we used digital organisms to compare the extent of adaptive evolution in populations when deleterious mutations were disallowed with control populations in which such mutations were allowed. Significantly higher fitness levels were achieved over the long term in the control populations because some of the deleterious mutations served as stepping stones across otherwise impassable fitness valleys. As a consequence, initially deleterious mutations facilitated the evolution of complex, beneficial functions. We also examined the effects of disallowing neutral mutations, of varying the mutation rate, and of sexual recombination. Populations evolving without neutral mutations were able to leverage deleterious and compensatory mutation pairs to overcome, at least partially, the absence of neutral mutations. Substantially raising or lowering the mutation rate reduced or eliminated the long-term benefit of deleterious mutations, but introducing recombination did not. Our work demonstrates that deleterious mutations can play an important role in adaptive evolution under at least some conditions.

4-Hydroxytamoxifen induces slight uncoupling of mitochondrial oxidative phosphorylation system in relation to the deleterious effects of tamoxifen.

PubMed

Cardoso, Carla M P; Moreno, António J M; Almeida, Leonor M; Custódio, José B A

2002-10-15

The use of tamoxifen (TAM) has been questioned on the chemotherapy and chemoprevention of breast cancer due to several estrogen receptor-independent cytotoxic effects. As an alternative, its more active metabolite 4-hydroxytamoxifen (OHTAM) has been proposed with presumed lower side effects. In this work, the potential OHTAM toxicity on rat liver mitochondrial bioenergetics in relation to the multiple deleterious effects of TAM was evaluated. OHTAM, at concentrations lower than those putatively reached in tissues following the administration of TAM, does not induce significant perturbations on the respiratory control ratio (RCR), ADP/O, transmembrane potential (DeltaPsi), phosphorylative capacity and membrane integrity of mitochondria. However, at high concentrations, OHTAM depresses the DeltaPsi, RCR and ADP/O, affecting the phosphorylation efficiency, as also inferred from the DeltaPsi fluctuations and pH changes associated with ADP phosphorylation. Moreover, OHTAM, at concentrations that stimulate the rate of state 4 respiration in parallel to the decrease in the DeltaPsi and phosphorylation rate, causes mitochondrial swelling and stimulates both ATPase and citrate synthase activities. However, the OHTAM-observed effects, at high concentrations, are not significant relatively to the damaging effects promoted by TAM and suggest alterations to mitochondrial functions due to proton leak across the mitochondrial inner membrane.

The Prospective Function of Curcumin Against the Negative Effects of Microgravity

NASA Astrophysics Data System (ADS)

Lewis, A.; Johnson, P.; Jejelowo, O. A.; Sodipe, A.; Shishodia, S.

2010-04-01

Microgravity has several deleterious effects on cells. These cells may exhibit an up-regulation or down-regulation of their gene expression. We are investigating the effects of the phytochemical curcumin on microgravity-induced deleterious effects.

Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone.

PubMed

Kast, Richard E

2009-01-01

Since deleterious effects of m-CPP, the primary catabolic metabolite of trazodone, were last reviewed 2 years ago, research data continue to accrue showing that clinically significant levels of m-CPP (a) are generated in patients using trazodone for sleep and (b) are present 24 h a day and (c) have potentially serious ill effects. This commentary argues that the documented potential for harm and multiple risks of m-CPP outweigh potential benefits of trazodone, given the development and marketing of many safer alternatives since trazodone's introduction in the 1980s.

Stigma and Attitudes towards Antenatal Depression and Antidepressant Use during Pregnancy in Healthcare Students

ERIC Educational Resources Information Center

Gawley, Laura; Einarson, Adrienne; Bowen, Angela

2011-01-01

Depression in pregnancy or antenatal depression (AD) occurs in approximately one in five women, with potentially deleterious effects to the mother and fetus. People are encouraged to get treatment for depression; however, pregnant women can experience stigma when they reach out for help with depression. Research indicates that healthcare…

A Meta-Analysis of Parent-Involved Treatment for Child Sexual Abuse

ERIC Educational Resources Information Center

Corcoran, Jacqueline; Pillai, Vijayan

2008-01-01

Sexual abuse in children not only occurs with alarming frequency, it also potentially leads to deleterious consequences for victims. Previous narrative reviews have touted the benefits of including the nonoffending caregiver in child sexual treatment. Objective: A meta-analysis is conducted to determine the effects of parent-involved treatment in…

Podcasting in Education: Are Students as Ready and Eager as We Think They Are?

ERIC Educational Resources Information Center

Walls, Stephen M.; Kucsera, John V.; Walker, Joshua D.; Acee, Taylor W.; McVaugh, Nate K.; Robinson, Daniel H.

2010-01-01

Instructors in higher education are disseminating instructional content via podcasting, as many rally behind the technology's potential benefits. Others have expressed concern about the risks of deleterious effects that might accompany the adoption of podcasting, such as lower class attendance. Yet, relatively few studies have investigated…

Deep sequencing of the mitochondrial genome reveals common heteroplasmic sites in NADH dehydrogenase genes.

PubMed

Liu, Chunyu; Fetterman, Jessica L; Liu, Poching; Luo, Yan; Larson, Martin G; Vasan, Ramachandran S; Zhu, Jun; Levy, Daniel

2018-03-01

Increasing evidence implicates mitochondrial dysfunction in aging and age-related conditions. But little is known about the molecular basis for this connection. A possible cause may be mutations in the mitochondrial DNA (mtDNA), which are often heteroplasmic-the joint presence of different alleles at a single locus in the same individual. However, the involvement of mtDNA heteroplasmy in aging and age-related conditions has not been investigated thoroughly. We deep-sequenced the complete mtDNA genomes of 356 Framingham Heart Study participants (52% women, mean age 43, mean coverage 4570-fold), identified 2880 unique mutations and comprehensively annotated them by MITOMAP and PolyPhen-2. We discovered 11 heteroplasmic "hot" spots [NADH dehydrogenase (ND) subunit 1, 4, 5 and 6 genes, n = 7; cytochrome c oxidase I (COI), n = 2; 16S rRNA, n = 1; D-loop, n = 1] for which the alternative-to-reference allele ratios significantly increased with advancing age (Bonferroni correction p < 0.001). Four of these heteroplasmic mutations in ND and COI genes were predicted to be deleterious nonsynonymous mutations which may have direct impact on ATP production. We confirmed previous findings that healthy individuals carry many low-frequency heteroplasmy mutations with potentially deleterious effects. We hypothesize that the effect of a single deleterious heteroplasmy may be minimal due to a low mutant-to-wildtype allele ratio, whereas the aggregate effects of many deleterious mutations may cause changes in mitochondrial function and contribute to age-related diseases. The identification of age-related mtDNA mutations is an important step to understand the genetic architecture of age-related diseases and may uncover novel therapeutic targets for such diseases.

Guidance for effective discipline. American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and Family Health.

PubMed

1998-04-01

When advising families about discipline strategies, pediatricians should use a comprehensive approach that includes consideration of the parent-child relationship, reinforcement of desired behaviors, and consequences for negative behaviors. Corporal punishment is of limited effectiveness and has potentially deleterious side effects. The American Academy of Pediatrics recommends that parents be encouraged and assisted in the development of methods other than spanking for managing undesired behavior.

Genetic Allee effects and their interaction with ecological Allee effects.

PubMed

Wittmann, Meike J; Stuis, Hanna; Metzler, Dirk

2018-01-01

It is now widely accepted that genetic processes such as inbreeding depression and loss of genetic variation can increase the extinction risk of small populations. However, it is generally unclear whether extinction risk from genetic causes gradually increases with decreasing population size or whether there is a sharp transition around a specific threshold population size. In the ecological literature, such threshold phenomena are called 'strong Allee effects' and they can arise for example from mate limitation in small populations. In this study, we aim to (i) develop a meaningful notion of a 'strong genetic Allee effect', (ii) explore whether and under what conditions such an effect can arise from inbreeding depression due to recessive deleterious mutations, and (iii) quantify the interaction of potential genetic Allee effects with the well-known mate-finding Allee effect. We define a strong genetic Allee effect as a genetic process that causes a population's survival probability to be a sigmoid function of its initial size. The inflection point of this function defines the critical population size. To characterize survival-probability curves, we develop and analyse simple stochastic models for the ecology and genetics of small populations. Our results indicate that inbreeding depression can indeed cause a strong genetic Allee effect, but only if individuals carry sufficiently many deleterious mutations (lethal equivalents). Populations suffering from a genetic Allee effect often first grow, then decline as inbreeding depression sets in and then potentially recover as deleterious mutations are purged. Critical population sizes of ecological and genetic Allee effects appear to be often additive, but even superadditive interactions are possible. Many published estimates for the number of lethal equivalents in birds and mammals fall in the parameter range where strong genetic Allee effects are expected. Unfortunately, extinction risk due to genetic Allee effects can easily be underestimated as populations with genetic problems often grow initially, but then crash later. Also interactions between ecological and genetic Allee effects can be strong and should not be neglected when assessing the viability of endangered or introduced populations. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Background Selection in Partially Selfing Populations

PubMed Central

Roze, Denis

2016-01-01

Self-fertilizing species often present lower levels of neutral polymorphism than their outcrossing relatives. Indeed, selfing automatically increases the rate of coalescence per generation, but also enhances the effects of background selection and genetic hitchhiking by reducing the efficiency of recombination. Approximations for the effect of background selection in partially selfing populations have been derived previously, assuming tight linkage between deleterious alleles and neutral loci. However, loosely linked deleterious mutations may have important effects on neutral diversity in highly selfing populations. In this article, I use a general method based on multilocus population genetics theory to express the effect of a deleterious allele on diversity at a linked neutral locus in terms of moments of genetic associations between loci. Expressions for these genetic moments at equilibrium are then computed for arbitrary rates of selfing and recombination. An extrapolation of the results to the case where deleterious alleles segregate at multiple loci is checked using individual-based simulations. At high selfing rates, the tight linkage approximation underestimates the effect of background selection in genomes with moderate to high map length; however, another simple approximation can be obtained for this situation and provides accurate predictions as long as the deleterious mutation rate is not too high. PMID:27075726

Treatment Outcome Research with the Non-Offending Parents of Sexually Abused Children: A Critical Review

ERIC Educational Resources Information Center

Corcoran, Jacqueline

2004-01-01

Potentially deleterious effects arise from the experience of childhood sexual abuse, but maternal supportiveness has been identified as a crucial mediator. Consequently, a body of knowledge has begun to develop on interventions designed to improve the supportiveness and adjustment of the non-offending parent. The present paper attempts to provide…

Patterns of Genetic Coding Variation in a Native American Population before and after European Contact.

PubMed

Lindo, John; Rogers, Mary; Mallott, Elizabeth K; Petzelt, Barbara; Mitchell, Joycelynn; Archer, David; Cybulski, Jerome S; Malhi, Ripan S; DeGiorgio, Michael

2018-05-03

The effects of European colonization on the genomes of Native Americans may have produced excesses of potentially deleterious features, mainly due to the severe reductions in population size and corresponding losses of genetic diversity. This assumption, however, neither considers actual genomic patterns that existed before colonization nor does it adequately capture the effects of admixture. In this study, we analyze the whole-exome sequences of modern and ancient individuals from a Northwest Coast First Nation, with a demographic history similar to other indigenous populations from the Americas. We show that in approximately ten generations from initial European contact, the modern individuals exhibit reduced levels of novel and low-frequency variants, a lower proportion of potentially deleterious alleles, and decreased heterozygosity when compared to their ancestors. This pattern can be explained by a dramatic population decline, resulting in the loss of potentially damaging low-frequency variants, and subsequent admixture. We also find evidence that the indigenous population was on a steady decline in effective population size for several thousand years before contact, which emphasizes regional demography over the common conception of a uniform expansion after entry into the Americas. This study examines the genomic consequences of colonialism on an indigenous group and describes the continuing role of gene flow among modern populations. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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.

Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations

NASA Astrophysics Data System (ADS)

Sardanyés, Josep; Simó, Carles; Martínez, Regina; Solé, Ricard V.; Elena, Santiago F.

2014-04-01

The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.

Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury

PubMed Central

Ellis, Amanda; Grace, Peter M.; Wieseler, Julie; Favret, Jacob; Springer, Kendra; Skarda, Bryce; Hutchinson, Mark R.; Falci, Scott; Rice, Kenner C.; Maier, Steven F.; Watkins, Linda R.

2016-01-01

Central neuropathic pain (CNP) is a pervasive, debilitating problem that impacts thousands of people living with central nervous system disorders, including spinal cord injury (SCI). Current therapies for treating this type of pain are ineffective and often have dose-limiting side effects. Although opioids are one of the most commonly used CNP treatments, recent animal literature has indicated that administering opioids shortly after a traumatic injury can actually have deleterious effects on long-term health and recovery. In order to study the deleterious effects of administering morphine shortly after trauma, we employed our low thoracic (T13) dorsal root avulsion model (Spinal Neuropathic Avulsion Pain, SNAP). Administering a weeklong course of 10 mg/kg/day morphine beginning 24 hr after SNAP resulted in amplified mechanical allodynia. Co-administering the non-opioid toll-like receptor 4 (TLR4) antagonist (+)-naltrexone throughout the morphine regimen prevented morphine-induced amplification of SNAP. Exploration of changes induced by early post-trauma morphine revealed that this elevated gene expression of TLR4, TNF, IL-1β, and NLRP3, as well as IL-1β protein at the site of spinal cord injury. These data suggest that a short course of morphine administered early after spinal trauma can exacerbate CNP in the long term. TLR4 initiates this phenomenon and, as such, may be potential therapeutic targets for preventing the deleterious effects of administering opioids after traumatic injury. PMID:27519154

Deleterious Mutations, Apparent Stabilizing Selection and the Maintenance of Quantitative Variation

PubMed Central

Kondrashov, A. S.; Turelli, M.

1992-01-01

Apparent stabilizing selection on a quantitative trait that is not causally connected to fitness can result from the pleiotropic effects of unconditionally deleterious mutations, because as N. Barton noted, ``... individuals with extreme values of the trait will tend to carry more deleterious alleles ....'' We use a simple model to investigate the dependence of this apparent selection on the genomic deleterious mutation rate, U; the equilibrium distribution of K, the number of deleterious mutations per genome; and the parameters describing directional selection against deleterious mutations. Unlike previous analyses, we allow for epistatic selection against deleterious alleles. For various selection functions and realistic parameter values, the distribution of K, the distribution of breeding values for a pleiotropically affected trait, and the apparent stabilizing selection function are all nearly Gaussian. The additive genetic variance for the quantitative trait is kQa(2), where k is the average number of deleterious mutations per genome, Q is the proportion of deleterious mutations that affect the trait, and a(2) is the variance of pleiotropic effects for individual mutations that do affect the trait. In contrast, when the trait is measured in units of its additive standard deviation, the apparent fitness function is essentially independent of Q and a(2); and β, the intensity of selection, measured as the ratio of additive genetic variance to the ``variance'' of the fitness curve, is very close to s = U/k, the selection coefficient against individual deleterious mutations at equilibrium. Therefore, this model predicts appreciable apparent stabilizing selection if s exceeds about 0.03, which is consistent with various data. However, the model also predicts that β must equal V(m)/V(G), the ratio of new additive variance for the trait introduced each generation by mutation to the standing additive variance. Most, although not all, estimates of this ratio imply apparent stabilizing selection weaker than generally observed. A qualitative argument suggests that even when direct selection is responsible for most of the selection observed on a character, it may be essentially irrelevant to the maintenance of variation for the character by mutation-selection balance. Simple experiments can indicate the fraction of observed stabilizing selection attributable to the pleiotropic effects of deleterious mutations. PMID:1427047

Similarity of Deleterious Effects of Divorce on Chinese and American Children.

ERIC Educational Resources Information Center

Zhou, Zheng; Bray, Melissa A.; Kehle, Thomas J.; Xin, Tao

2001-01-01

Reviews and contrasts the effects of divorce on Chinese children's adjustment to American children of divorce. Results indicate that the deleterious effects of divorce on children's academic and social functioning appear to be similar to that experienced by American children. (Contains 23 references.) (GCP)

A Comparative Analysis of Four Individualized Instructional Delivery Systems with Adult Learners. Final Report.

ERIC Educational Resources Information Center

Holzbauer, Ida; Florell, Robert J.

Because many pesticides are potentially injurious to their users and can have a deleterious effect on the environment when misused, the Environmental Protection Agency has restricted the use of some chemicals to certified users only. A program was developed to assess the need for training in pesticide use, to develop the necessary curriculum, to…

Radio-induced inherited sterility in Heliothis zea (Boddie)

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

Carpenter, J.E.

1985-01-01

Heliothis zea (Boddie) (Lepidoptera: Noctuidae) males and females were irradiated with substerilizing doses of radiation. These moths were inbred and outcrossed and observed for their ability to reproduce. The inherited deleterious effects resulting from the irradiated P/sub 1/ males were recorded for several generations. Larvae from both irradiated (10 krad) and normal parents were compared for their ability to survive under field conditions on whole-stage sweet corn and these results were compared with those from a laboratory study using meridic diet. Irradiated males and females and F/sub 1/ males from an irradiated (10 krad) male x normal female cross weremore » released in the field and in field cages and observed for their ability to search/attract and secure a mate. Females that had mated with normal and irradiated (10 krad) males were studied to determine the effect of different mating histories on the subsequent mating propensity of the females. A 10-krad dose of radiation induced deleterious effects which were inherited through the F/sub 2/ generation. These radiation-induced deleterious effects were similar to those reported in other species of Lepidoptera. The relationship between the survival of normal larvae and larvae from irradiated parents was similar under laboratory and field rearing conditions. Females mated to normal males and males irradiated with 10 krad had the same mating propensity and experienced the same intermating interval. These effects of substerilizing doses of radiation and inherited sterility on the reproductive ability and behavior of H. zea suggest that a great potential exists for population suppression.« less

Opposite in vivo effects of agents that stimulate or inhibit the glutamate/cysteine exchanger system xc- on the inhibition of hippocampal LTP by Aß.

PubMed

Zhang, Dainan; Jin, Baozhe; Ondrejcak, Tomas; Rowan, Michael J

2016-12-01

Aggregated amyloid ß-protein (Aß) is pathognomonic of Alzheimer's disease and certain assemblies of Aß are synaptotoxic. Excess glutamate or diminished glutathione reserve are both implicated in mediating or modulating Aß-induced disruption of synaptic plasticity. The system xc- antiporter promotes Na + -independent exchange of cystine with glutamate thereby providing a major source of extracellular glutamate and intracellular glutathione concentrations. Here we probed the ability of two drugs with opposite effects on system xc-, the inhibitor sulfasalazine and facilitator N-acetylcysteine, to modulate the ability of Aß1-42 to inhibit long-term potentiation (LTP) in the CA1 area of the anaesthetized rat. Whereas acute systemic treatment with sulfasalazine lowered the threshold for Aß to interfere with synaptic plasticity, N-acetylcysteine prevented the inhibition of LTP by Aß alone or in combination with sulfasalazine. Moreover acute N-acetylcysteine also prevented the inhibition of LTP by TNFα, a putative mediator of Aß actions, and repeated systemic N-acetylcysteine treatment for 7 days reversed the delayed deleterious effect of Aß on LTP. Since both of these drugs are widely used clinically, further evaluation of their potential beneficial and deleterious actions in early Alzheimer's disease seems warranted. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Screening and Evaluation of Deleterious SNPs in APOE Gene of Alzheimer's Disease.

PubMed

Masoodi, Tariq Ahmad; Al Shammari, Sulaiman A; Al-Muammar, May N; Alhamdan, Adel A

2012-01-01

Introduction. Apolipoprotein E (APOE) is an important risk factor for Alzheimer's disease (AD) and is present in 30-50% of patients who develop late-onset AD. Several single-nucleotide polymorphisms (SNPs) are present in APOE gene which act as the biomarkers for exploring the genetic basis of this disease. The objective of this study is to identify deleterious nsSNPs associated with APOE gene. Methods. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nonsynonymous (ns) SNPs and their effect on protein was predicted by PolyPhen and SIFT, respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the APOE protein was evaluated by using Swiss PDB viewer and NOMAD-Ref server. Results. Six nsSNPs were found to be least stable by I-Mutant 2.0 with DDG value of >-1.0. Four nsSNPs showed a highly deleterious tolerance index score of 0.00. Nine nsSNPs were found to be probably damaging with position-specific independent counts (PSICs) score of ≥2.0. Seven nsSNPs were found to be highly polymorphic with a risk score of 3-4. The total energies and root-mean-square deviation (RMSD) values were higher for three mutant-type structures compared to the native modeled structure. Conclusion. We concluded that three nsSNPs, namely, rs11542041, rs11542040, and rs11542034, to be potentially functional polymorphic.

Evaluation of a new website design for iwantthekit for chlamydia, gonorrhea, and trichomonas screening.

PubMed

Kuder, Margaret; Goheen, Mary Jett; Dize, Laura; Barnes, Mathilda; Gaydos, Charlotte A

2015-05-01

The www.iwantthekit.org provides Internet-based, at-home sexually transmitted infection screening. The Web site implemented an automated test result access system. To evaluate potential deleterious effects of the new system, we analyzed demographics, Web site usage, and treatment. The post-Web site design captured more participant information and no decrease in requests, kit return, or treatment adherence.

Genomic instability and bystander effects: a paradigm shift in radiation biology?

NASA Technical Reports Server (NTRS)

Morgan, William F.

2002-01-01

A basic paradigm in radiobiology is that, following exposure to ionizing radiation, the deposition of energy in the cell nucleus and the resulting damage to DNA, the principal target, are responsible for the radiation's deleterious biological effects. Findings in two rapidly expanding fields of research--radiation-induced genomic instability and bystander effects--have caused us to reevaluate these central tenets. In this article, the potential influence of induced genomic instability and bystander effects on cellular injury after exposure to low-level radiation will be reviewed.

Betel nut chewing and its deleterious effects on oral cavity.

PubMed

Anand, Richa; Dhingra, Chandan; Prasad, Sumanth; Menon, Ipseeta

2014-01-01

The habit of chewing betel nut has a long history of use. Betel nut and products derived from it are widely used as a masticatory product among various communities and in several countries across the world. Over a long period, several additives have been added to a simple betel nut preparation; thus, creating the betel quid (BQ) and encompassing chewing tobacco in the preparation. Betel nut has deleterious effects on oral soft tissues. Its effects on dental caries and periodontal diseases, two major oral diseases are less well-documented. Betel-induced lichenoid lesions mainly on buccal mucosa have been reported at quid retained sites. In chronic chewers, a condition called betel chewers mucosa is often found where the quid is placed. Betel nut chewing is implicated in oral submucous fibrosis (OSF) and its use along with tobacco can cause leukoplakia, both of which are potentially malignant in the oral cavity. Oral cancer often arises from such precancerous changes. Thus, public health measures to quit betel use are recommended to control disabling conditions such as OSF and oral cancer.

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

Szovenyi, Peter; Shaw, Jon; Yang, Xiaohan

In diploid organisms, selfing reduces the efficiency of selection in removing deleterious mutations from a population. This need not be the case for all organisms. Some plants, for example, undergo an extreme form of selfing known as intragametophytic selfing, which immediately exposes all recessive deleterious mutations in a parental genome to selective purging. Here we ask how effectively deleterious mutations are removed from such plants. Specifically, we study the extent to which deleterious mutations accumulate in a predominantly selfing and a predominantly outcrossing pair of moss species, using genome-wide transcriptome data. We find that the selfing species purge significantly moremore » non-synonymous mutations, as well as a greater proportion of radical amino acid changes which alter physicochemical properties of amino acids. Moreover, their purging of deleterious mutation is especially strong in conserved regions of protein-coding genes. Our observations show that selfing need not impede but can even accelerate the removal of deleterious mutations, and do so on a genome-wide scale.« less

Computational Methods to Work as First-Pass Filter in Deleterious SNP Analysis of Alkaptonuria

PubMed Central

Magesh, R.; George Priya Doss, C.

2012-01-01

A major challenge in the analysis of human genetic variation is to distinguish functional from nonfunctional SNPs. Discovering these functional SNPs is one of the main goals of modern genetics and genomics studies. There is a need to effectively and efficiently identify functionally important nsSNPs which may be deleterious or disease causing and to identify their molecular effects. The prediction of phenotype of nsSNPs by computational analysis may provide a good way to explore the function of nsSNPs and its relationship with susceptibility to disease. In this context, we surveyed and compared variation databases along with in silico prediction programs to assess the effects of deleterious functional variants on protein functions. In other respects, we attempted these methods to work as first-pass filter to identify the deleterious substitutions worth pursuing for further experimental research. In this analysis, we used the existing computational methods to explore the mutation-structure-function relationship in HGD gene causing alkaptonuria. PMID:22606059

PATHOPHYSIOLOGICAL CONSEQUENCES OF TAT-HKII PEPTIDE ADMINISTRATION ARE INDEPENDENT OF IMPAIRED VASCULAR FUNCTION AND ENSUING ISCHEMIA

PubMed Central

Nederlof, Rianne; Xie, Chaoqin; Eerbeek, Otto; Koeman, Anneke; Milstein, Dan MJ; Hollmann, Markus W; Mik, Egbert G; Warley, Alice; Southworth, Richard; Akar, Fadi G.; Zuurbier, Coert J

2013-01-01

Rationale We have shown that partial dissociation of HKII from mitochondria in the intact heart using low dose (200 nM) TAT-HKII prevents the cardioprotective effects of ischemic preconditioning (IPC) whereas high-dose (10 μM) TAT-HKII administration results in rapid myocardial dysfunction, mitochondrial depolarization and disintegration. In this issue of Circulation Research, Pasdois et al argue that the deleterious effects of TAT-HKII administration on cardiac function are likely due to vasoconstriction and ensuing ischemia. Objective To investigate whether altered vascular function and ensuing ischemia recapitulate the deleterious effects of TAT-HKII in intact myocardium. Methods and Results Using a variety of complementary techniques, including mitochondrial membrane potential (ΔΨm) imaging, high-resolution optical action potential (AP) mapping, analysis of lactate production, NADH epifluorescence, lactate dehydrogenase (LDH) release, and electron microscopy, we provide direct evidence that refutes the notion that acute myocardial dysfunction by high-dose TAT-HKII peptide administration is a consequence of impaired vascular function. Moreover, we demonstrate that low-dose TAT-HKII treatment, which abrogates the protective effects of IPC, is not associated with ischemia or ischemic-injury. Conclusions Our findings challenge the notion that the effects of TAT-HKII are attributable to impaired vascular function and ensuing ischemia; thereby, lending further credence to the role of mitochondria bound HKII as a critical regulator of cardiac function, ischemia-reperfusion (IR) injury, and cardioprotection by IPC. PMID:23329797

Pathway to neural resilience: Self-esteem buffers against deleterious effects of poverty on the hippocampus.

PubMed

Wang, Yinan; Zhang, Lin; Kong, Xiangzhen; Hong, Yingyi; Cheon, Bobby; Liu, Jia

2016-11-01

Human neuroimaging studies have shown that people living in poverty tend to suffer hippocampal atrophy, which leads to impaired memory and learning throughout life. However, behavioral studies demonstrate that poor people with high self-esteem are often exempt from the deleterious effect of poverty and instead possess a happy and successful life. Here we investigated whether high self-esteem can buffer against the deleterious effects of poverty, as indicated by low subjective socioeconomic status (SSS), on the hippocampal gray matter volume (GMV) in a large cohort of young participants (N = 280). As expected, findings revealed that although low (vs. high) SSS was linked with a smaller hippocampal GMV, the deleterious effect of low SSS on hippocampal GMV was alleviated when the participants have high self-esteem. Commonality analyses further confirmed this observation. The current study suggests that positive psychological resources such as self-esteem may provide protection for the hippocampal atrophy in adversity. Hum Brain Mapp 37:3757-3766, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Accumulation of Spontaneous Mutations in the Ciliate Tetrahymena thermophila

PubMed Central

Long, Hong-An; Paixão, Tiago; Azevedo, Ricardo B. R.; Zufall, Rebecca A.

2013-01-01

Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes. PMID:23934880

Social Stigma and Sexual Minorities’ Romantic Relationship Functioning: A Meta-Analytic Review

PubMed Central

Doyle, David Matthew; Molix, Lisa

2015-01-01

To bolster knowledge of determinants of relationship functioning among sexual minorities, the current meta-analysis aimed to quantitatively review evidence for the association between social stigma and relationship functioning as well as examine potential moderators. Thirty-five studies were identified, including 130 effect sizes (39 independent; N = 10,745). Across studies, evidence was found for a small but significant inverse association between social stigma and relationship functioning. Furthermore, this association was moderated by stigma type (with more deleterious associations for internalized relative to perceived stigma) and dimension of relationship functioning (with more deleterious associations for affective relative to cognitive and negative relative to positive). Evidence for demographic moderators (region, sex, race, age) was generally mixed although important limitations related to unique characteristics of study samples are discussed. We conclude by highlighting the importance of social stigma for relationship functioning and point toward directions for future research and policy action. PMID:26199218

Increased burden of deleterious variants in essential genes in autism spectrum disorder.

PubMed

Ji, Xiao; Kember, Rachel L; Brown, Christopher D; Bućan, Maja

2016-12-27

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.

Increased burden of deleterious variants in essential genes in autism spectrum disorder

PubMed Central

Kember, Rachel L.; Brown, Christopher D.; Bućan, Maja

2016-01-01

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease. PMID:27956632

Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset.

PubMed

Gordon, Adam S; Tabor, Holly K; Johnson, Andrew D; Snively, Beverly M; Assimes, Themistocles L; Auer, Paul L; Ioannidis, John P A; Peters, Ulrike; Robinson, Jennifer G; Sucheston, Lara E; Wang, Danxin; Sotoodehnia, Nona; Rotter, Jerome I; Psaty, Bruce M; Jackson, Rebecca D; Herrington, David M; O'Donnell, Christopher J; Reiner, Alexander P; Rich, Stephen S; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A

2014-04-15

The study of genetic influences on drug response and efficacy ('pharmacogenetics') has existed for over 50 years. Yet, we still lack a complete picture of how genetic variation, both common and rare, affects each individual's responses to medications. Exome sequencing is a promising alternative method for pharmacogenetic discovery as it provides information on both common and rare variation in large numbers of individuals. Using exome data from 2203 AA and 4300 Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a survey of coding variation within 12 Cytochrome P450 (CYP) genes that are collectively responsible for catalyzing nearly 75% of all known Phase I drug oxidation reactions. In addition to identifying many polymorphisms with known pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles across the 12 CYP genes of interest. These alleles include many with diverse functional effects such as premature stop codons, aberrant splicesites and mutations at conserved active site residues. Our analysis considering both novel, predicted functional alleles as well as known, actionable CYP alleles reveals that rare, deleterious variation contributes markedly to the overall burden of pharmacogenetic alleles within the populations considered, and that the contribution of rare variation to this burden is over three times greater in AA individuals as compared with Caucasians. While most of these impactful alleles are individually rare, 7.6-11.7% of individuals interrogated in the study carry at least one newly described potentially deleterious alleles in a major drug-metabolizing CYP.

Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline.

PubMed

Valcarcel-Ares, Marta Noa; Tucsek, Zsuzsanna; Kiss, Tamas; Giles, Cory B; Tarantini, Stefano; Yabluchanskiy, Andriy; Balasubramanian, Priya; Gautam, Tripti; Galvan, Veronica; Ballabh, Praveen; Richardson, Arlan; Freeman, Willard M; Wren, Jonathan D; Deak, Ferenc; Ungvari, Zoltan; Csiszar, Anna

2018-06-08

There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate that obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood brain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis that synergistic effects of obesity and aging on inflammatory processes exert deleterious effects on hippocampal function, young and aged C57BL/6 mice were rendered obese by chronic feeding of a high fat diet followed by assessment of learning and memory function, measurement of hippocampal long-term potentiation (LTP), assessment of changes in hippocampal expression of genes relevant for synaptic function and determination of synaptic density. Because there is increasing evidence that altered production of lipid mediators modulate LTP, neuroinflammation and neurovascular coupling responses, the effects of obesity on hippocampal levels of relevant eicosanoid mediators were also assessed. We found that aging exacerbates obesity-induced microglia activation, which is associated with deficits in hippocampal-dependent learning and memory tests, impaired LTP, decreased synaptic density and dysregulation of genes involved in regulation of synaptic plasticity. Obesity in aging also resulted in an altered hippocampal eicosanoid profile, including decreases in vasodilator and pro-LTP epoxy-eicosatrienoic acids (EETs). Collectively, our results taken together with previous findings suggest that obesity in aging promotes hippocampal inflammation, which in turn may contribute to synaptic dysfunction and cognitive impairment.

A novel histone deacetylase inhibitor prevents IL‐1β induced metabolic dysfunction in pancreatic β‐cells

PubMed Central

Susick, Laura; Senanayake, Thulani; Veluthakal, Rajakrishnan; Woster, Patrick M.

2009-01-01

Abstract The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has recently been shown to inhibit deleterious effects of cytokines on β‐cells, but it is unable to protect β‐cells from death due to its own cytotoxicity. Herein, we investigated novel HDAC inhibitors for their cytoprotective effects against IL‐1β‐induced damage to isolated β‐cells. We report that three novel compounds (THS‐73–44, THS‐72–5 and THS‐78–5) significantly inhibited HDAC activity and increased the acetylation of histone H4 in isolated β‐cells. Further, these compounds exerted no toxic effects on metabolic cell viability in these cells. However, among the three compounds tested, only THS‐78–5 protected against IL‐1β‐mediated loss in β‐cell viability. THS‐78–5 was also able to attenuate IL‐1β‐induced inducible nitric oxide synthase expression and subsequent NO release. Our data also indicate that the cytoprotective properties of THS‐78–5 against IL‐1β‐mediated effects may, in part, be due to inhibition of IL‐1β‐induced transactivation of nuclear factor κB (NF‐κB) in these cells. Together, we provide evidence for a novel HDAC inhibitor with a significant potential to prevent IL‐1β‐mediated effects on isolated β‐cells. Potential implications of these findings in the development of novel therapeutics to prevent deleterious effects of cytokines and the onset of autoimmune diabetes are discussed. PMID:20141611

Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism

PubMed Central

Shaik, Shahnoor S.; Obata, Toshihiro; Hebelstrup, Kim H.; Schwahn, Kevin; Fernie, Alisdair R.; Mateiu, Ramona V.; Blennow, Andreas

2016-01-01

Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and β-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD. PMID:26891365

Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies

PubMed Central

N, Nagasundaram; Zhu, Hailong; Liu, Jiming; V, Karthick; C, George Priya Doss; Chakraborty, Chiranjib; Chen, Luonan

2015-01-01

The cyclin-dependent kinase 4 (CDK4)-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1) and protein-ligand (CDK4-flavopiridol) interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL) _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment. PMID:26252490

Assessing potential health risks to fish and humans using mercury concentrations in inland fish from across western Canada and the United States

USGS Publications Warehouse

Lepak, Jesse M.; Hooten, Mevin B.; Eagles-Smith, Collin A.; Tate, Michael T.; Lutz, Michelle A.; Ackerman, Joshua T.; Willacker, James J.; Jackson, Allyson K.; Evers, David C.; Wiener, James G.; Pritz, Colleen Flanagan; Davis, Jay

2016-01-01

Fish represent high quality protein and nutrient sources, but Hg contamination is ubiquitous in aquatic ecosystems and can pose health risks to fish and their consumers. Potential health risks posed to fish and humans by Hg contamination in fish were assessed in western Canada and the United States. A large compilation of inland fish Hg concentrations was evaluated in terms of potential health risk to the fish themselves, health risk to predatory fish that consume Hg contaminated fish, and to humans that consume Hg contaminated fish. The probability that a fish collected from a given location would exceed a Hg concentration benchmark relevant to a health risk was calculated. These exceedance probabilities and their associated uncertainties were characterized for fish of multiple size classes at multiple health-relevant benchmarks. The approach was novel and allowed for the assessment of the potential for deleterious health effects in fish and humans associated with Hg contamination in fish across this broad study area. Exceedance probabilities were relatively common at low Hg concentration benchmarks, particularly for fish in larger size classes. Specifically, median exceedances for the largest size classes of fish evaluated at the lowest Hg concentration benchmarks were 0.73 (potential health risks to fish themselves), 0.90 (potential health risk to predatory fish that consume Hg contaminated fish), and 0.97 (potential for restricted fish consumption by humans), but diminished to essentially zero at the highest benchmarks and smallest fish size classes. Exceedances of benchmarks are likely to have deleterious health effects on fish and limit recommended amounts of fish humans consume in western Canada and the United States. Results presented here are not intended to subvert or replace local fish Hg data or consumption advice, but provide a basis for identifying areas of potential health risk and developing more focused future research and monitoring efforts.

The effect of glycerol, propylene glycol and polyethylene glycol 400 on the partition coefficient of benzophenone-3 (oxybenzone).

PubMed

Mbah, C J

2007-01-01

Sunscreen products are widely used to protect the skin from sun-related deleterious effects. The objective of the study was to investigate the potential effect of glycerol, propylene glycol and polyethylene glycol 400 on dermal absorption of oxybenzone by studying their effects on its partition coefficient. The partition coefficient was evaluated in a chloroform-water system at room temperature. It was found that glycerol and propylene glycol decreased the partition coefficient of oxybenzone, while an increase in partition coefficient was observed with polyethylene glycol 400. The findings suggest that polyethylene glycol 400 in contrast to glycerol and propylene glycol has the potential of increasing the vehicle-skin partition coefficient of oxybenzone when cosmetic products containing such an UV absorber are topically applied to the skin.

Effects of a metabolic syndrome induced by a fructose-rich diet on bone metabolism in rats.

PubMed

Felice, Juan Ignacio; Gangoiti, María Virginia; Molinuevo, María Silvina; McCarthy, Antonio Desmond; Cortizo, Ana María

2014-02-01

The aims of this study were: first, to evaluate the possible effects of a fructose rich diet (FRD)-induced metabolic syndrome (MS) on different aspects of long bone histomorphometry in young male rats; second, to investigate the effects of this diet on bone tissue regeneration; and third, to correlate these morphometric alterations with changes in the osteogenic/adipogenic potential and expression of specific transcription factors, of marrow stromal cells (MSC) isolated from rats with fructose-induced MS. MS was induced in rats by treatment with a FRD for 28 days. Halfway through treatment, a parietal wound was made and bone healing was evaluated 14 days later. After treatments, histomorphometric analysis was performed in dissected femoral and parietal bones. MSC were isolated from the femora of control or fructose-treated rats and differentiated either to osteoblasts (evaluated by type 1 collagen, Alkaline phosphatase and extracellular nodule mineralization) or to adipocytes (evaluated by intracellular triglyceride accumulation). Expression of Runx2 and PPARγ was assessed by Western blot. Fructose-induced MS induced deleterious effects on femoral metaphysis microarchitecture and impaired bone regeneration. Fructose treatment decreased the osteogenic potential of MSC and Runx2 expression. In addition, it increased the adipogenic commitment of MSC and PPARγ expression. Fructose-induced MS is associated with deleterious effects on bone microarchitecture and with a decrease in bone repair. These alterations could be due to a deviation in the adipogenic/osteogenic commitment of MSC, probably by modulation of the Runx2/PPARγ ratio. Copyright © 2014 Elsevier Inc. All rights reserved.

Are There Deleterious Cardiac Effects of Acute and Chronic Endurance Exercise?

PubMed Central

Eijsvogels, Thijs M. H.; Fernandez, Antonio B.; Thompson, Paul D.

2015-01-01

Multiple epidemiological studies document that habitual physical activity reduces the risk of atherosclerotic cardiovascular disease (ASCVD), and most demonstrate progressively lower rates of ASCVD with progressively more physical activity. Few studies have included individuals performing high-intensity, lifelong endurance exercise, however, and recent reports suggest that prodigious amounts of exercise may increase markers for, and even the incidence of, cardiovascular disease. This review examines the evidence that extremes of endurance exercise may increase cardiovascular disease risk by reviewing the causes and incidence of exercise-related cardiac events, and the acute effects of exercise on cardiovascular function, the effect of exercise on cardiac biomarkers, including “myocardial” creatine kinase, cardiac troponins, and cardiac natriuretic peptides. This review also examines the effect of exercise on coronary atherosclerosis and calcification, the frequency of atrial fibrillation in aging athletes, and the possibility that exercise may be deleterious in individuals genetically predisposed to such cardiac abnormalities as long QT syndrome, right ventricular cardiomyopathy, and hypertrophic cardiomyopathy. This review is to our knowledge unique because it addresses all known potentially adverse cardiovascular effects of endurance exercise. The best evidence remains that physical activity and exercise training benefit the population, but it is possible that prolonged exercise and exercise training can adversely affect cardiac function in some individuals. This hypothesis warrants further examination. PMID:26607287

Military Retirement: Background and Recent Developments

DTIC Science & Technology

2016-09-12

be made. However, others have argued that past modifications intended to save money have had a deleterious effect on military recruiting and...In addition, some have argued that past modifications to the system intended to save money have had a deleterious effect on military recruiting and...to accrue tax- free . As such, a Roth plan is typically a better savings vehicle for young, low-income individuals who typically

Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators of Inflammation to Ameliorate the Deleterious Effects of Blast Overpressure on Eye and Brain Visual Processing Centers in Rats

DTIC Science & Technology

2013-10-01

Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators 5a. CONTRACT NUMBER of Inflammation to Ameliorate the Deleterious Effects...studies have not been carried out as yet. Our hypothesis is that novel polyunsaturated fatty acid derived lipid mediators of inflammation, i.e., lipoxins

IN VITRO AND IN VIVO EVALUATION OF ANTIMICROBIAL AND ANTIOXIDANT POTENTIAL OF STEVIA EXTRACT.

PubMed

Moselhy, Said S; Ghoneim, Magdy A; Khan, Jehan A

2016-01-01

The current trend globally is the utilization of natural products as therapeutic agents given its minimum side effects. The leaves of Stevia contain several active ingredient compounds such as rebaudioside. Stevia extract have been used for many purposes. Active oxygen radicals can induce base modifications, DNA breakage, and intracellular protein crosslink's. This study was done to evaluate the potential of stevia extract as antibacterial and antioxidants actions. Antibacterial activity of different extracts of stevia was tested in vitro against different species of bacteria and hepato-protective efficacy was testes in rats injected with CCl 4 as hepatotoxic. Acetone extract exhibited antibacterial activity against selected five bacteria species. The acetone extract suppressed the elevation of serum ALT (p <0.05) and AST (p <0.001) activities induced by CCl 4 . Animals given stevia extract showed prevention against deleterious effects of CCl 4 by lowering lipid peroxidation and enhancement of antioxidant activities as SOD and CAT. The protection trial is better than treatment trial. Total phenolic content of aqueous and acetone extracts were found 30 mg and 85 mg gallic /gm extract respectively. While the total flavonoids were 40 mg and 80 mg quercetin/g respectively. The GC-MS analysis showed that monoterpene and indole are the main components. Aqueous extract don't show any antibacterial activity against the tested strains. The antioxidant properties were attributable to its phenolic content to scavenge free radicals. Acetone extract possess a potent antimicrobial and activity against deleterious effect of CCl 4 -caused liver damage.

Immune competence of rats fed with beluga whale blubber from the contaminated St. Lawrence estuary

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

Brousseau, P.; Lapierre, P.; Guise, S. De

1995-12-31

Over the last decades, high concentrations of environmental contaminants such as PCBs have been measured in the tissues of many species of marine mammals from different parts of the world. Even though many deleterious effects of these compounds have been reported in laboratory animals, the overall risk associated with these contaminants in wild animals is still not clearly understood. However, necropsy of St. Lawrence belugas showed numerous severe and disseminated infections with rather mildly pathogenic bacteria. Moreover, 37% of all the tumors reported in cetaceans were observed in St. Lawrence beluga whales. Indeed, both observations suggest immunosuppression. The aim ofmore » the study was to determine if contaminants present in fat tissues of belugas might provoke deleterious effect to their immune system if, under some circumstances, they are released into the circulation. To assess their immunotoxic potential, rats were fed for two months on a diet in which the lipids originated from the blubber of either highly polluted St. Lawrence belugas or relatively uncontaminated arctic belugas. Then, multiple immune responses were monitored. Those include phagocytosis, plaque forming cells, oxidative burst, natural killer cells, immunophenotyping and mitogenic assay. The results obtained show that only the humoral response of rats was impaired by the treatment. By combining all this information, the authors propose possible mechanisms of action to explain potential long-term consequences of environmental pollution.« less

Efficient algorithms for probing the RNA mutation landscape.

PubMed

Waldispühl, Jérôme; Devadas, Srinivas; Berger, Bonnie; Clote, Peter

2008-08-08

The diversity and importance of the role played by RNAs in the regulation and development of the cell are now well-known and well-documented. This broad range of functions is achieved through specific structures that have been (presumably) optimized through evolution. State-of-the-art methods, such as McCaskill's algorithm, use a statistical mechanics framework based on the computation of the partition function over the canonical ensemble of all possible secondary structures on a given sequence. Although secondary structure predictions from thermodynamics-based algorithms are not as accurate as methods employing comparative genomics, the former methods are the only available tools to investigate novel RNAs, such as the many RNAs of unknown function recently reported by the ENCODE consortium. In this paper, we generalize the McCaskill partition function algorithm to sum over the grand canonical ensemble of all secondary structures of all mutants of the given sequence. Specifically, our new program, RNAmutants, simultaneously computes for each integer k the minimum free energy structure MFE(k) and the partition function Z(k) over all secondary structures of all k-point mutants, even allowing the user to specify certain positions required not to mutate and certain positions required to base-pair or remain unpaired. This technically important extension allows us to study the resilience of an RNA molecule to pointwise mutations. By computing the mutation profile of a sequence, a novel graphical representation of the mutational tendency of nucleotide positions, we analyze the deleterious nature of mutating specific nucleotide positions or groups of positions. We have successfully applied RNAmutants to investigate deleterious mutations (mutations that radically modify the secondary structure) in the Hepatitis C virus cis-acting replication element and to evaluate the evolutionary pressure applied on different regions of the HIV trans-activation response element. In particular, we show qualitative agreement between published Hepatitis C and HIV experimental mutagenesis studies and our analysis of deleterious mutations using RNAmutants. Our work also predicts other deleterious mutations, which could be verified experimentally. Finally, we provide evidence that the 3' UTR of the GB RNA virus C has been optimized to preserve evolutionarily conserved stem regions from a deleterious effect of pointwise mutations. We hope that there will be long-term potential applications of RNAmutants in de novo RNA design and drug design against RNA viruses. This work also suggests potential applications for large-scale exploration of the RNA sequence-structure network. Binary distributions are available at http://RNAmutants.csail.mit.edu/.

Effects of televised alcohol messages on teenage drinking patterns.

PubMed

Atkin, C K

1990-01-01

This paper presents an overview of theoretical perspectives applicable to the effects of television drinking portrayals on adolescent audiences, focusing on the influence of beer and wine advertising and entertainment depictions of drinking behavior. A critical review of survey research evidence indicates that alcohol commercials contribute to a modest increase in overall consumption by teenagers and may have a slight impact on alcohol misuse and drunk driving. There are no studies measuring the effects of entertainment programming on adolescents, but content analyses suggest the potential for increased prodrinking attitudes and behaviors. Policy implications for addressing the deleterious effects of televised drinking are discussed, and priorities for future research are identified.

Skin cell protection against UVA by Sideroxyl, a new antioxidant complementary to sunscreens.

PubMed

Pygmalion, Marie-Jocelyne; Ruiz, Laetitia; Popovic, Evelyne; Gizard, Julie; Portes, Pascal; Marat, Xavier; Lucet-Levannier, Karine; Muller, Benoit; Galey, Jean-Baptiste

2010-12-01

Oxidative stress resulting from photosensitized ROS production in skin is widely accepted as the main contributor to the deleterious effects of UVA exposure. Among the mechanisms known to be involved in UVA-induced oxidative damage, iron plays a central role. UVA radiation of skin cells induces an immediate release of iron, which can then act as a catalyst for uncontrolled oxidation reactions of cell components. Such site-specific damage can scarcely be counteracted by classical antioxidants. In contrast, iron chelators potentially offer an effective way to protect skin against UVA insults. However, iron chelation is very difficult to achieve without disturbing iron homeostasis or inducing iron depletion. A novel compound was developed to avoid these potentially harmful side effects. Sideroxyl was designed to acquire its strong chelating capability only during oxidative stress according to an original process of intramolecular hydroxylation. Herein, we describe in vitro results demonstrating the protective efficiency of Sideroxyl against deleterious effects of UVA at the molecular, cellular, and tissular levels. First, the Sideroxyl diacid form protects a model protein against UVA-induced photosensitized carbonylation. Second, intracellular ROS are dose-dependently decreased in the presence of Sideroxyl in both human cultured fibroblasts and human keratinocytes. Third, Sideroxyl protects normal human fibroblasts against UVA-induced DNA damage as measured by the comet assay and MMP-1 production. Finally, Sideroxyl provides protection against UVA-induced alterations in human reconstructed skin. These results suggest that Sideroxyl may prevent UVA-induced damage in human skin as a complement to sunscreens, especially in the long-wavelength UVA range. Copyright © 2010 Elsevier Inc. All rights reserved.

Comparative effects of avocado oil and losartan on blood pressure, renal vascular function, and mitochondrial oxidative stress in hypertensive rats.

PubMed

Márquez-Ramírez, Cristian Adrián; Hernández de la Paz, José Lucio; Ortiz-Avila, Omar; Raya-Farias, Andrés; González-Hernández, Juan Carlos; Rodríguez-Orozco, Alain Raimundo; Salgado-Garciglia, Rafael; Saavedra-Molina, Alfredo; Godínez-Hernández, Daniel; Cortés-Rojo, Christian

2018-03-20

Angiotensin II (Ang-II) antagonism alleviates hypertensive kidney damage by improving mitochondrial function and decreasing oxidative stress. This condition also is associated with altered renal vascular tone due to enhanced constriction by Ang-II. Thus, approaches ameliorating these events are desirable to alleviate kidney damage. Avocado oil, a source of antioxidants and oleic acid, is known to improve mitochondrial function, while oleic acid has antihypertensive effects. Therefore, the aim of this study was to test whether avocado oil counteracts, to a similar degree as the Ang-II blocker losartan, the deleterious effects of hypertension on blood pressure, renal vascular performance, kidney mitochondrial function, and oxidative stress. Hypertensive rats induced with Nω-nitro-l-arginine methyl ester (L-NAME) were supplemented during 45 d with avocado oil or losartan. Vascular responses were analyzed in perfused kidney. Membrane potential, reactive oxygen species levels, and glutathione were analyzed in isolated kidney mitochondria. In hypertensive rats, avocado oil decreased 21.2% and 15.5% diastolic and systolic blood pressures, respectively, and alleviated impaired renal vasodilation. Hypertension decreased membrane potential by 83.7% and augmented reactive oxygen species levels by 51% in mitochondria fueled with a complex I substrate, whereas it augmented the levels of oxidized glutathione in 48%. These alterations were normalized by avocado oil at a comparable degree to losartan. Because avocado oil mimicked the effects of losartan, we propose that the effects of avocado oil might be mediated by decreasing the actions of Ang-II on mitochondria. These results suggest that avocado oil intake might be a nutritional approach to attenuate the deleterious effects of hypertension on kidney. Copyright © 2018 Elsevier Inc. All rights reserved.

Resuscitation of severe but brief haemorrhagic shock with PFC in rabbits restores skeletal muscle oxygen delivery and does not alter skeletal muscle metabolism.

PubMed

Audonnet-Blaise, Sandra; Krafft, Marie-Pierre; Smani, Younes; Mertes, Paul-Michel; Marie, Pierre-Yves; Labrude, Pierre; Longrois, Dan; Menu, Patrick

2006-07-01

Studies have demonstrated that perfluorocarbon (PFC) emulsions associated with hyperoxia improved whole body oxygen delivery during resuscitation of acute haemorrhagic shock (HS). Nevertheless the microcirculatory effects of PFC and the potential deleterious effects of hyperoxic reperfusion are still of concern. We investigated (i) the ability of a newly formulated, small sized and highly stable PFC emulsion to increase skeletal muscle oxygen delivery and (ii) the effect of hyperoxic reperfusion on skeletal muscle metabolism after a brief period of ischaemia using an original, microdialysis-based method that allowed simultaneous measurement tissue oxygen pressure (PtiO2) and interstitial lactate and pyruvate. These measurements were carried out in anaesthetised and ventilated (FiO2 = 1) rabbits subjected to acute HS (50% of blood volume withdrawal) and either resuscitated with a PFC emulsion diluted with a 5% albumin solution (16.2 g PFC per kg body weight) (n = 10) or with a modified fluid gelatin solution (Gelofusine) (n = 10). We found no difference between the two groups for the haemodynamic and haematological variables (except for the venous oxygen partial pressure). However, a significant difference was observed in the slope of the regression linear relationship exhibited between the mean arterial pressure (MAP) and the PtiO2, PFC group showing a much steeper slope than Gelofusine group. In addition, PtiO2 values increased linearly with decreasing haematocrit (Hct) values in PFC-resuscitated animals and decreased linearly with decreasing Hct values in Gelofusine-resuscitated animals. There were no differences between the two groups concerning the blood and interstitial lactate/pyruvate ratios suggesting no deleterious effect of hyperoxic resuscitation in skeletal muscle. In conclusion these results suggest that resuscitation of severe, but brief, HS with PFC increased skeletal muscle oxygen delivery without measurable deleterious effects.

Herbivory versus corallivory: are parrotfish good or bad for Caribbean coral reefs?

NASA Astrophysics Data System (ADS)

Mumby, Peter J.

2009-09-01

With coral cover in decline on many Caribbean reefs, any process of coral mortality is of potential concern. While sparisomid parrotfishes are major grazers of Caribbean reefs and help control algal blooms, the fact that they also undertake corallivory has prompted some to question the rationale for their conservation. Here the weight of evidence for beneficial effects of parrotfishes, in terms of reducing algal cover and facilitating demographic processes in corals, and the deleterious effects of parrotfishes in terms of causing coral mortality and chronic stress, are reviewed. While elevated parrotfish density will likely increase the predation rate upon juvenile corals, the net effect appears to be positive in enhancing coral recruitment through removal of macroalgal competitors. Parrotfish corallivory can cause modest partial colony mortality in the most intensively grazed species of Montastraea but the generation and healing of bite scars appear to be in near equilibrium, even when coral cover is low. Whole colony mortality in adult corals can lead to complete exclusion of some delicate, lagoonal species of Porites from forereef environments but is only reported for one reef species ( Porites astreoides), for one habitat (backreef), and with uncertain incidence (though likely <<10%). No deleterious effects of predation on coral growth or fecundity have been reported, though recovery of zooxanthellae after bleaching events may be retarded. The balance of evidence to date finds strong support for the herbivory role of parrotfishes in facilitating coral recruitment, growth, and fecundity. In contrast, no net deleterious effects of corallivory have been reported for reef corals. Corallivory is unlikely to constrain overall coral cover but contraints upon dwindling populations of the Montastraea annularis species complex are feasible and the role of parrotfishes as a vector of coral disease requires evaluation. However, any assertion that conservation practices should guard against protecting corallivorous parrotfishes appears to be unwarranted at this stage.

Optimal physiological structure of small neurons to guarantee stable information processing

NASA Astrophysics Data System (ADS)

Zeng, S. Y.; Zhang, Z. Z.; Wei, D. Q.; Luo, X. S.; Tang, W. Y.; Zeng, S. W.; Wang, R. F.

2013-02-01

Spike is the basic element for neuronal information processing and the spontaneous spiking frequency should be less than 1 Hz for stable information processing. If the neuronal membrane area is small, the frequency of neuronal spontaneous spiking caused by ion channel noise may be high. Therefore, it is important to suppress the deleterious spontaneous spiking of the small neurons. We find by simulation of stochastic neurons with Hodgkin-Huxley-type channels that the leakage system is critical and extremely efficient to suppress the spontaneous spiking and guarantee stable information processing of the small neurons. However, within the physiological limit the potassium system cannot do so. The suppression effect of the leakage system is super-exponential, but that of the potassium system is quasi-linear. With the minor physiological cost and the minimal consumption of metabolic energy, a slightly lower reversal potential and a relatively larger conductance of the leakage system give the optimal physiological structure to suppress the deleterious spontaneous spiking and guarantee stable information processing of small neurons, dendrites and axons.

Social Stigma and Sexual Minorities' Romantic Relationship Functioning: A Meta-Analytic Review.

PubMed

Doyle, David Matthew; Molix, Lisa

2015-10-01

To bolster knowledge of determinants of relationship functioning among sexual minorities, the current meta-analysis aimed to quantitatively review evidence for the association between social stigma and relationship functioning as well as examine potential moderators. Thirty-five studies were identified, including 130 effect sizes (39 independent; N = 10,745). Across studies, evidence was found for a small but significant inverse association between social stigma and relationship functioning. Furthermore, this association was moderated by stigma type (with more deleterious associations for internalized relative to perceived stigma) and dimension of relationship functioning (with more deleterious associations for affective relative to cognitive and negative relative to positive). Evidence for demographic moderators (region, sex, race, age) was generally mixed although important limitations related to unique characteristics of study samples are discussed. We conclude by highlighting the importance of social stigma for relationship functioning and point toward directions for future research and policy action. © 2015 by the Society for Personality and Social Psychology, Inc.

Smoker-free workplace policies: developing a model of public health consequences of workplace policies barring employment to smokers.

PubMed

Houle, B; Siegel, M

2009-02-01

A marked shift in tobacco-related workplace health promotion intervention involves the adoption of policies barring employment to smokers. We discuss the potential public health consequences of these policies on those affected-smokers, their families, the surrounding community and society at large. We find a lack of published evidence evaluating the effectiveness and consequences of these policies. By developing a model of policy effects, we outline possible unintended consequences. With such large gaps in the evidence base and the potential for deleterious consequences, we argue for increased discussion about the use of smoker-free employment policies as a public health intervention and for increased engagement of employers by the public health community in worksite health promotion.

Cyclic Voltammetric Wave-Shapes for Microdisk Electrodes: Coupled Effects of Solution Resistance, Double-Layer Capacitance, and Finite Electrochemical Kinetics

DTIC Science & Technology

1991-05-01

vaveshapea. While the use of high scan rates enhances the effect of electrode kinetics upon the voltametry , the deleterious coupled influence of pa 20...waveshapes. While the use of high scan rates enhances the effect of electrode kinetics upon the voltametry , the deleterious coupled influence of P...2 1 󈧚 Aoki et al have in- 23 vestigated linear sweep voltammetry at microdisks in the reversible case, and Zoski and co-workers have developed

Effects and mechanisms of the combined pollution of lanthanum and acid rain on the root phenotype of soybean seedlings.

PubMed

Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2013-09-01

Rare earth pollution and acid rain pollution are both important environmental issues worldwide. In regions which simultaneously occur, the combined pollution of rare earth and acid rain becomes a new environmental issue, and the relevant research is rarely reported. Accordingly, we investigated the combined effects and mechanisms of lanthanum ion (La(3+)) and acid rain on the root phenotype of soybean seedlings. The combined pollution of low-concentration La(3+) and acid rain exerted deleterious effects on the phenotype and growth of roots, which were aggravated by the combined pollution of high-concentration La(3+) and acid rain. The deleterious effects of the combined pollution were stronger than those of single La(3+) or acid rain pollution. These stronger deleterious effects on the root phenotype and growth of roots were due to the increased disturbance of absorption and utilization of mineral nutrients in roots. Copyright © 2013 Elsevier Ltd. All rights reserved.

Combined effects of lanthanum(III) and elevated ultraviolet-B radiation on root growth and ion absorption in soybean seedlings.

PubMed

Huang, Guang Rong; Wang, Li Hong; Zhou, Qing

2014-03-01

Rare earth element accumulation in the soil and elevated ultraviolet (UV)-B radiation (280-315 nm) are important environmental issues worldwide. To date, there have been no reports concerning the combined effects of lanthanum (La)(III) and elevated UV-B radiation on plant roots in regions where the two issues occur simultaneously. Here, the combined effects of La(III) and elevated UV-B radiation on the growth, biomass, ion absorption, activities, and membrane permeability of roots in soybean (Glycine max L.) seedlings were investigated. A 0.08 mmol L(-1) La(III) treatment improved the root growth and biomass of soybean seedlings, while ion absorption, activities, and membrane permeability were obviously unchanged; a combined treatment with 0.08 mmol L(-1) La(III) and elevated UV-B radiation (2.63/6.17 kJ m(-2) day(-1)) exerted deleterious effects on the investigated indices. The deleterious effects were aggravated in the other combined treatments and were stronger than those of treatments with La(III) or elevated UV-B radiation alone. The combined treatment with 0.24/1.20 mmol L(-1) La(III) and elevated UV-B radiation exerted synergistically deleterious effects on the growth, biomass, ion absorption, activities, and membrane permeability of roots in soybean seedlings. In addition, the deleterious effects of the combined treatment on the root growth were due to the inhibition of ion absorption induced by the changes in the root activity and membrane permeability.

The Joint Effects of Background Selection and Genetic Recombination on Local Gene Genealogies

PubMed Central

Zeng, Kai; Charlesworth, Brian

2011-01-01

Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the structured coalescent model against forward-in-time simulations and show that it accurately captures the effects of background selection. The model produces more accurate predictions of the mean coalescent time than the existing formula and supports the conclusion that the effect of background selection is greater in the interior of a deleterious region than at its boundaries. The level of linkage disequilibrium between sites is elevated by background selection, to an extent that is well summarized by a change in effective population size. The structured coalescent model is readily extendable to more realistic situations and should prove useful for analyzing genome-wide polymorphism data. PMID:21705759

The joint effects of background selection and genetic recombination on local gene genealogies.

PubMed

Zeng, Kai; Charlesworth, Brian

2011-09-01

Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the structured coalescent model against forward-in-time simulations and show that it accurately captures the effects of background selection. The model produces more accurate predictions of the mean coalescent time than the existing formula and supports the conclusion that the effect of background selection is greater in the interior of a deleterious region than at its boundaries. The level of linkage disequilibrium between sites is elevated by background selection, to an extent that is well summarized by a change in effective population size. The structured coalescent model is readily extendable to more realistic situations and should prove useful for analyzing genome-wide polymorphism data.

Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome: design, development, and potential place in therapy.

PubMed

Graf, Solomon A; Garcia, Jose M

2017-01-01

Cancer anorexia-cachexia syndrome (CACS) is a complex and largely untreatable paraneoplastic complication common in advanced cancer. It is associated with profoundly deleterious effects on quality of life and survival. Since its discovery over a decade ago, anamorelin hydrochloride (anamorelin), a mimetic of the growth hormone secretagogue ghrelin, has shown considerable promise in ameliorating components of CACS when administered to patients with advanced cancer, including loss of lean body mass and reversal of anorexia. This review summarizes the development of anamorelin and its safety and efficacy in clinical investigations. The potential future role of anamorelin in treating CACS is also discussed.

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials.

PubMed

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models-of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells-to investigate the relative effects of reducing two important voltage-gated Ca currents-the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action.

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

PubMed Central

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J.

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models—of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells—to investigate the relative effects of reducing two important voltage-gated Ca currents—the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action. PMID:25360118

Consuming fire ants reduces northern bobwhite survival and weight gain

USGS Publications Warehouse

Myers, P.E.; Allen, Craig R.; Birge, Hannah E.

2014-01-01

Northern bobwhite quail, Colinus virginianus (L.) (Galliformes: Odontophoridae), population declines are well documented, but pinpointing the reasons for these decreases has proven elusive. Bobwhite population declines are attributed primarily to loss of habitat and land use changes. This, however, does not entirely explain population declines in areas intensively managed for bobwhites. Although previous research demonstrates the negative impact of red imported fire ant (Solenopsis invicta Buren) (Hymenoptera: Formicidae) on northern bobwhites, the mechanisms underlying this effect are largely unknown. To meet the protein demands of early growth and development, bobwhite chicks predominantly consume small insects, of which ants are a substantial proportion. Fire ants alter ant community dynamics by often reducing native ant diversity and abundance while concurrently increasing the abundance of individuals. Fire ants have negative effects on chicks, but they are also a large potential protein source, making it difficult to disentangle their net effect on bobwhite chicks. To help investigate these effects, we conducted a laboratory experiment to understand (1) whether or not bobwhites consume fire ants, and (2) how the benefits of this consumption compare to the deleterious impacts of bobwhite chick exposure to fire ants. Sixty bobwhite chicks were separated into two groups of 30; one group was provided with starter feed only and the second group was provided with feed and fire ants. Bobwhite chicks were observed feeding on fire ants. Chicks that fed on fire ants had reduced survival and weight gain. Our results show that, while fire ants increase potential food sources for northern bobwhite, their net effect on bobwhite chicks is deleterious. This information will help inform land managers and commercial bobwhite rearing operations.

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.

Uremic Toxicity of Advanced Glycation End Products in CKD

PubMed Central

Stinghen, Andréa E.M.; Massy, Ziad A.; Vlassara, Helen; Striker, Gary E.

2016-01-01

Advanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product–specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD. PMID:26311460

Effects of high salinity from desalination brine on growth, photosynthesis, water relations and osmolyte concentrations of seagrass Posidonia australis.

PubMed

Cambridge, M L; Zavala-Perez, A; Cawthray, G R; Mondon, J; Kendrick, G A

2017-02-15

Highly saline brines from desalination plants expose seagrass communities to salt stress. We examined effects of raised salinity (46 and 54psu) compared with seawater controls (37psu) over 6weeks on the seagrass, Posidonia australis, growing in tanks with the aim of separating effects of salinity from other potentially deleterious components of brine and determining appropriate bioindicators. Plants survived exposures of 2-4weeks at 54psu, the maximum salinity of brine released from a nearby desalination plant. Salinity significantly reduced maximum quantum yield of PSII (chlorophyll a fluorescence emissions). Leaf water potential (Ψ w ) and osmotic potential (Ψ π ) were more negative at increased salinity, while turgor pressure (Ψ p ) was unaffected. Leaf concentrations of K + and Ca 2+ decreased, whereas concentrations of sugars (mainly sucrose) and amino acids increased. We recommend leaf osmolarity, ion, sugar and amino acid concentrations as bioindicators for salinity effects, associated with brine released in desalination plant outfalls. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of phosphate on glyphosate uptake and toxicity in willow.

PubMed

Gomes, Marcelo Pedrosa; Le Manac'h, Sarah Gingras; Moingt, Matthieu; Smedbol, Elise; Paquet, Serge; Labrecque, Michel; Lucotte, Marc; Juneau, Philippe

2016-03-05

Phosphate (PO4(3-)) has been shown to increase glyphosate uptake by willow, a plant species known for its phytoremediation potential. However, it remains unclear if this stimulation of glyphosate uptake can result in an elevated glyphosate toxicity to plants (which could prevent the use of willows in glyphosate-remediation programs). Consequently, we studied the effects of PO4(3-) on glyphosate uptake and toxicity in a fast growing willow cultivar (Salix miyabeana SX64). Plants were grown in hydroponic solution with a combination of glyphosate (0, 0.001, 0.065 and 1 mg l(-1)) and PO4(3-) (0, 200 and 400 mg l(-1)). We demonstrated that PO4(3-) fertilization greatly increased glyphosate uptake by roots and its translocation to leaves, which resulted in increased shikimate concentration in leaves. In addition to its deleterious effects in photosynthesis, glyphosate induced oxidative stress through hydrogen peroxide accumulation. Although it has increased glyphosate accumulation, PO4(3-) fertilization attenuated the herbicide's deleterious effects by increasing the activity of antioxidant systems and alleviating glyphosate-induced oxidative stress. Our results indicate that in addition to the glyphosate uptake, PO4(3-) is involved in glyphosate toxicity in willow by preventing glyphosate induced oxidative stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Religious coping moderates the relation between racism and psychological well-being among Christian Asian American college students.

PubMed

Kim, Paul Youngbin; Kendall, Dana L; Webb, Marcia

2015-01-01

The authors examined the moderating role of positive and negative religious coping in the relation between racism and psychological well-being in a sample of Catholic and Protestant Asian American college students (N = 107). On the basis of prior theorizing on the 2 types of religious coping, combined with some limited empirical evidence, they predicted that positive religious coping would have a buffering effect (Hypothesis 1) on the racism-mental health relation and that negative religious coping would have an exacerbating effect (Hypothesis 2). Participants completed an online survey containing measures corresponding to the study variables. Results indicated that the interaction between positive religious coping and racism was nonsignificant, so Hypothesis 1 was not supported. For Hypothesis 2, the negative religious coping and racism interaction term was statistically significant, but the moderating effect was in an unexpected direction, such that negative religious coping actually protected against the deleterious impact of racism on mental health. The findings suggest that the theorized deleterious influence of negative religious coping may need to be reconsidered in an Asian American setting. The findings have the potential to inform practitioners who work with Asian American college students to better cope with the detrimental consequences of racism. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Multiple deleterious effects of experimentally aged sperm in a monogamous bird

USGS Publications Warehouse

White, J.; Wagner, R.H.; Helfenstein, F.; Hatch, Shyla A.; Mulard, Hervé; Naves, L.C.; Danchin, E.

2008-01-01

Sperm aging is known to be detrimental to reproductive performance. However, this apparently general phenomenon has seldom been studied in an evolutionary context. The negative impact of sperm aging on parental fitness should constitute a strong selective pressure for adaptations to avoid its effects. We studied the impact of sperm aging on black-legged kittiwakes (Rissa tridactyla), a monogamous seabird. Kittiwakes comprise a model system because (i) of evidence that females eject their mates' sperm to prevent fertilization by sperm that would be old and degraded by the time of fertilization and result in reduced reproductive performance and (ii) the lack of extra-pair fertilization in this species makes cryptic female choice an unlikely explanation of postcopulatory sperm ejection by females. We experimentally manipulated the age of the sperm fertilizing kittiwake eggs by fitting males with anti-insemination rings for variable periods of time preceding egg-laying. We found evidence that sperm aging negatively affected four sequential stages of reproduction: fertilization potential, rate of embryonic development, embryonic mortality, and chick condition at hatching. These results may be produced by a continuum of a single process of sperm aging that differentially affects various aspects of development, depending on the degree of damage incurred to the spermatozoa. The marked impact of sperm age on female fitness may thus drive postcopulatory sperm ejection by females. These results provide experimental evidence of deleterious effects of sperm aging on a nondomestic vertebrate, underlining its taxonomic generality and its potential to select for a wide array of adaptations. ?? 2008 by The National Academy of Sciences of the USA.

IN VITRO AND IN VIVO EVALUATION OF ANTIMICROBIAL AND ANTIOXIDANT POTENTIAL OF STEVIA EXTRACT.

PubMed Central

Moselhy, Said S.; Ghoneim, Magdy A.; Khan, Jehan A.

2016-01-01

Background: The current trend globally is the utilization of natural products as therapeutic agents given its minimum side effects. The leaves of Stevia contain several active ingredient compounds such as rebaudioside. Stevia extract have been used for many purposes. Active oxygen radicals can induce base modifications, DNA breakage, and intracellular protein crosslink’s. This study was done to evaluate the potential of stevia extract as antibacterial and antioxidants actions. Materials and methods: Antibacterial activity of different extracts of stevia was tested in vitro against different species of bacteria and hepato-protective efficacy was testes in rats injected with CCl4 as hepatotoxic. Results: Acetone extract exhibited antibacterial activity against selected five bacteria species. The acetone extract suppressed the elevation of serum ALT (p <0.05) and AST (p <0.001) activities induced by CCl4. Animals given stevia extract showed prevention against deleterious effects of CCl4 by lowering lipid peroxidation and enhancement of antioxidant activities as SOD and CAT. The protection trial is better than treatment trial. Total phenolic content of aqueous and acetone extracts were found 30 mg and 85 mg gallic /gm extract respectively. While the total flavonoids were 40 mg and 80 mg quercetin/g respectively. The GC-MS analysis showed that monoterpene and indole are the main components. Aqueous extract don’t show any antibacterial activity against the tested strains. The antioxidant properties were attributable to its phenolic content to scavenge free radicals. Conclusion: Acetone extract possess a potent antimicrobial and activity against deleterious effect of CCl4-caused liver damage. PMID:28480355

Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

PubMed

Marsden, Clare D; Ortega-Del Vecchyo, Diego; O'Brien, Dennis P; Taylor, Jeremy F; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D; Wayne, Robert K; Lohmueller, Kirk E

2016-01-05

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.

Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs

PubMed Central

Marsden, Clare D.; Ortega-Del Vecchyo, Diego; O’Brien, Dennis P.; Taylor, Jeremy F.; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D.; Wayne, Robert K.; Lohmueller, Kirk E.

2016-01-01

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508

The seleno-organic compound ebselen impairs mitochondrial physiology and induces cell death in AR42J cells.

PubMed

Santofimia-Castaño, Patricia; Garcia-Sanchez, Lourdes; Ruy, Deborah Clea; Fernandez-Bermejo, Miguel; Salido, Gines M; Gonzalez, Antonio

2014-09-17

Ebselen is a seleno-organic compound that causes cell death in several cancer cell types. The mechanisms underlying its deleterious effects have not been fully elucidated. In this study, the effects of ebselen (1 μM-40 μM) on AR42J tumor cells have been examined. Cell viability was studied using AlamarBlue(®) test. Cell cycle phase determination was carried out by flow cytometry. Changes in intracellular free Ca(2+) concentration were followed by fluorimetry analysis of fura-2-loaded cells. Distribution of mitochondria, mitochondrial Ca(2+) concentration and mitochondrial membrane potential were monitored by confocal microscopy of cells loaded with Mitotracker Green™ FM, rhod-2 or TMRM respectively. Caspase-3 activity was calculated following the luorogenic substrate ACDEVD-AMC signal with a spectrofluorimeter. Results show that cell viability decreased in the presence of ebselen. An increase in the number of cells in the S-phase of the cell cycle was observed. Ebselen induced a concentration-dependent mobilization of Ca(2+) from agonist- and thapsigargin-sensitive Ca(2+) pools. Ebselen induced also a transient increase in mitochondrial Ca(2+) concentration, a progressive decrease of the mitochondrial membrane potential and a disruption of the mitochondrial network. Finally, a concentration-dependent increase in caspase-3 activity was detected. We conclude that ebselen exerts deleterious actions on the cells that involve the impairment of mitochondrial physiology and the activation of caspase-3-mediated apoptotic pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cirrus Cloud Seeding has Potential to Cool Climate

NASA Technical Reports Server (NTRS)

Storelvmo, T.; Kristjansson, J. E.; Muri, H.; Pfeffer, M.; Barahona, D.; Nenes, A.

2013-01-01

Cirrus clouds, thin ice clouds in the upper troposphere, have a net warming effect on Earth s climate. Consequently, a reduction in cirrus cloud amount or optical thickness would cool the climate. Recent research indicates that by seeding cirrus clouds with particles that promote ice nucleation, their lifetimes and coverage could be reduced. We have tested this hypothesis in a global climate model with a state-of-the-art representation of cirrus clouds and find that cirrus cloud seeding has the potential to cancel the entire warming caused by human activity from pre-industrial times to present day. However, the desired effect is only obtained for seeding particle concentrations that lie within an optimal range. With lower than optimal particle concentrations, a seeding exercise would have no effect. Moreover, a higher than optimal concentration results in an over-seeding that could have the deleterious effect of prolonging cirrus lifetime and contributing to global warming.

Matrix Metalloproteinase-9 Mediates the Deleterious Effects of α2-Antiplasmin on Blood-Brain Barrier Breakdown and Ischemic Brain Injury in Experimental Stroke.

PubMed

Singh, Satish; Houng, Aiilyan K; Reed, Guy L

2018-04-15

During acute brain ischemia, α2-antiplasmin markedly enhances brain injury, blood-brain barrier breakdown and matrix metalloproteinase-9 (MMP-9) expression. Although α2-antiplasmin inhibits fibrin thrombus-degradation, and MMP-9 is a collagen-degrading enzyme altering blood-brain barrier, both have similar deleterious effects on the ischemic brain. We examined the hypothesis that MMP-9 is an essential downstream mediator of α2-antiplasmin's deleterious effects during brain ischemia. Middle cerebral artery thromboembolic stroke was induced in a randomized, blinded fashion in mice with increased blood levels of α2-antiplasmin. There was a robust increase in MMP-9 expression (immunofluorescence) in the ischemic vs. the non-ischemic hemisphere of MMP-9 +/+ but not MMP-9 -/- mice, 24 h after stroke. Brain swelling and hemorrhage were significantly increased in the ischemic vs. the non-ischemic hemisphere of MMP-9 +/+ mice. By comparison to MMP-9 +/+ mice, the ischemic hemispheres of MMP-9 -/- mice showed a ∼6-fold reduction in brain swelling (p < 0.001) and a ∼9-fold reduction in brain hemorrhage. Brain infarction (p < 0.0001) and TUNEL-positive cell death (p < 0.001) were significantly diminished in the ischemic hemisphere of MMP-9 -/- mice vs. MMP-9 +/+ mice. Ischemic breakdown of the blood-brain barrier and fibrin deposition were also significantly reduced in MMP-9 -/- mice vs. MMP-9 +/+ mice (p < 0.05), as measured by quantitative immunofluorescence. We conclude that MMP-9 deficiency ablates many of the deleterious effects of high α2-antiplasmin levels, significantly reducing blood-brain barrier breakdown, TUNEL-positive cell death, brain hemorrhage, swelling and infarction. This suggests that the two molecules may be in a shared pathway in which MMP-9 is essential downstream for the deleterious effects of α2-antiplasmin in ischemic stroke. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis

PubMed Central

Huang, Wei; Booth, David M; Cane, Matthew C; Chvanov, Michael; Javed, Muhammad A; Elliott, Victoria L; Armstrong, Jane A; Dingsdale, Hayley; Cash, Nicole; Li, Yan; Greenhalf, William; Mukherjee, Rajarshi; Kaphalia, Bhupendra S; Jaffar, Mohammed; Petersen, Ole H; Tepikin, Alexei V; Sutton, Robert; Criddle, David N

2014-01-01

Objective Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. Design Intracellular calcium ([Ca2+]C), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. Results Inhibition of OME with 4-MP converted predominantly transient [Ca2+]C rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. Conclusions A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation. PMID:24162590

Smoker-Free Workplace Policies: Developing a Model of Public Health Consequences of Workplace Policies Barring Employment to Smokers

PubMed Central

Houle, Brian; Siegel, Michael

2009-01-01

A marked shift in tobacco-related workplace health promotion intervention involves the adoption of policies barring employment to smokers. We discuss the potential public health consequences of these policies on those affected – smokers, their families, the surrounding community, and society at large. We find a lack of published evidence evaluating the effectiveness and consequences of these policies. By developing a model of policy effects, we outline possible unintended consequences. With such large gaps in the evidence base and the potential for deleterious consequences, we argue for increased discussion about the use of smoker-free employment policies as a public health intervention and for increased engagement of employers by the public health community in worksite health promotion. PMID:19168490

Beneficial or Deleterious Effects of a Preexisting Hypersensitivity to Bacterial Components on the Course and Outcome of Infection

PubMed Central

Gumenscheimer, Marina; Mitov, Ivan; Galanos, Chris; Freudenberg, Marina A.

2002-01-01

Priming with heat-killed Propionibacterium acnes enhances the sensitivity of mice to lipopolysaccharide (LPS) and other biologically active bacterial components. We show that P. acnes priming has protective and deleterious effects on a subsequent serovar Typhimurium infection. It may result in a complete protection or prolonged survival, or it may accelerate mortality of the infected mice, depending on the number of serovar Typhimurium bacteria administered and on the degree of LPS hypersensitivity at the time of infection. Both effects of P. acnes-induced hypersensitivity are mediated by gamma interferon (IFN-γ) and are based on a differential activation of the innate immune mechanisms which recognize and react against the LPS present in infecting bacteria. In P. acnes-primed mice null for LPS-binding protein (LBP−/− mice), the impaired LPS recognition, due to the absence of LBP, resulted in a higher resistance to serovar Typhimurium infection. A similar P. acnes priming of mice had a protective, but no deleterious effect on a subsequent L. monocytogenes infection. This effect was IFN-γ dependent but independent of LBP. PMID:12228287

Comet assay: a reliable tool for the assessment of DNA damage in different models.

PubMed

Dhawan, Alok; Bajpayee, Mahima; Parmar, Devendra

2009-02-01

New chemicals are being added each year to the existing burden of toxic substances in the environment. This has led to increased pollution of ecosystems as well as deterioration of the air, water, and soil quality. Excessive agricultural and industrial activities adversely affect biodiversity, threatening the survival of species in a particular habitat as well as posing disease risks to humans. Some of the chemicals, e.g., pesticides and heavy metals, may be genotoxic to the sentinel species and/or to non-target species, causing deleterious effects in somatic or germ cells. Test systems which help in hazard prediction and risk assessment are important to assess the genotoxic potential of chemicals before their release into the environment or commercial use as well as DNA damage in flora and fauna affected by contaminated/polluted habitats. The Comet assay has been widely accepted as a simple, sensitive, and rapid tool for assessing DNA damage and repair in individual eukaryotic as well as some prokaryotic cells, and has increasingly found application in diverse fields ranging from genetic toxicology to human epidemiology. This review is an attempt to comprehensively encase the use of Comet assay in different models from bacteria to man, employing diverse cell types to assess the DNA-damaging potential of chemicals and/or environmental conditions. Sentinel species are the first to be affected by adverse changes in their environment. Determination of DNA damage using the Comet assay in these indicator organisms would thus provide information about the genotoxic potential of their habitat at an early stage. This would allow for intervention strategies to be implemented for prevention or reduction of deleterious health effects in the sentinel species as well as in humans.

Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity: a strategy for the treatment of genetic diseases.

PubMed

Shulman, Eli; Belakhov, Valery; Wei, Gao; Kendall, Ann; Meyron-Holtz, Esther G; Ben-Shachar, Dorit; Schacht, Jochen; Baasov, Timor

2014-01-24

There is compelling evidence that aminoglycoside (AG) antibiotics can induce the mammalian ribosome to suppress disease-causing nonsense mutations and partially restore the expression of functional proteins. However, prolonged AG treatment can cause detrimental side effects in patients, including most prominently, ototoxicity. Recent mechanistic discussions have considered the relative contributions of mitochondrial and cytoplasmic protein synthesis inhibition to AG-induced ototoxicity. We show that AGs inhibit mitochondrial protein synthesis in mammalian cells and perturb cell respiration, leading to a time- and dose-dependent increase in superoxide overproduction and accumulation of free ferrous iron in mitochondria caused by oxidative damage of mitochondrial aconitase, ultimately leading to cell apoptosis via the Fenton reaction. These deleterious effects increase with the increased potency of AG to inhibit the mitochondrial rather than cytoplasmic protein synthesis, which in turn correlates with their ototoxic potential in both murine cochlear explants and the guinea pig in vivo. The deleterious effects of AGs were alleviated in synthetic derivatives specially designed for the treatment of genetic diseases caused by nonsense mutations and possessing low affinity toward mitochondrial ribosomes. This work highlights the benefit of a mechanism-based drug redesign strategy that can maximize the translational value of "readthrough therapy" while mitigating drug-induced side effects. This approach holds promise for patients suffering from genetic diseases caused by nonsense mutations.

Cannabinoids and the kidney: effects in health and disease.

PubMed

Park, Frank; Potukuchi, Praveen K; Moradi, Hamid; Kovesdy, Csaba P

2017-11-01

Consumption of cannabis and various related products (cannabinoids) for both medicinal and recreational use is gaining popularity. Furthermore, regulatory changes are fostering a cultural shift toward increasing liberalization of cannabis use, thereby increasing the likelihood of even larger numbers of individuals being exposed in the future. The two different types of receptors (CB 1 and CB 2 ) that are activated by the pharmacologically active ingredients of cannabis are found in numerous tissues, including the kidneys. Experimental studies suggest that stimulation of these receptors using pharmacologic agents or their naturally occurring ligands could have both deleterious and beneficial effects on the kidneys, depending on receptor distribution, type of renal insult, or the timing of the activation during acute or chronic states of kidney injury. To date, the mechanisms by which the CB 1 or CB 2 receptors are involved in the pathology of these renal conditions remain to be fully described. Furthermore, a better understanding of the impact of exocannabinoids and endocannabinoids on the renal system may lead to the development of new drugs to treat kidney disease and its complications. Given the increasing public health relevance of cannabis exposure, it is clear that more research is necessary to clarify the various physiological and pathophysiological effects of cannabis and related analogs on the kidney. This will help limit the deleterious effects of these substances while promoting their potential beneficial impact on renal function in various types of kidney diseases.

K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid beta-protein precursor genes and neuronal death in rat hippocampus.

PubMed Central

Heurteaux, C; Bertaina, V; Widmann, C; Lazdunski, M

1993-01-01

Transient global forebrain ischemia induces in rat brain a large increase of expression of the immediate early genes c-fos and c-jun and of the mRNAs for the 70-kDa heat-shock protein and for the form of the amyloid beta-protein precursor including the Kunitz-type protease-inhibitor domain. At 24 hr after ischemia, this increased expression is particularly observed in regions that are vulnerable to the deleterious effects of ischemia, such as pyramidal cells of the CA1 field in the hippocampus. In an attempt to find conditions which prevent the deleterious effects of ischemia, representatives of three different classes of K+ channel openers, (-)-cromakalim, nicorandil, and pinacidil, were administered both before ischemia and during the reperfusion period. This treatment totally blocked the ischemia-induced expression of the different genes. In addition it markedly protected neuronal cells against degeneration. The mechanism of the neuroprotective effects involves the opening of ATP-sensitive K+ channels since glipizide, a specific blocker of that type of channel, abolished the beneficial effects of K+ channel openers. The various classes of K+ channel openers seem to deserve attention as potential drugs for cerebral ischemia. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8415718

A Postsecondary Transition Model for Low-Income, Minority Youth in Philadelphia

ERIC Educational Resources Information Center

Brown, Alexis Tolbert

2016-01-01

School administrators are in the best position, but often lack the knowledge, to help low-income, minority youth transition to college. Consequently, some youth are not meeting their full potential and there are long-term, deleterious consequences on local economies as wage earning potential stagnates. Using Aslanargun's, Farmer-Hinton's, and…

Never Let the Opportunity to Prepare for a Crisis Go to Waste: The Need for Proactive Measures in the Asia-Pacific Region to Mitigate the Impacts of Climate Change

DTIC Science & Technology

2015-05-21

mitigation plan in place. In the long term, it is likely that the Filipinos will contend with both rising sea levels and acidification of the ocean . The... acidification of the oceans will likely have a deleterious effect on fisheries, increasing the potential for food...Persian Gulf to both the South China Sea and the Pacific Ocean . 34 With such enormous economic value, it should come as no surprise that nations

An Overview of Live Attenuated Recombinant Pseudorabies Viruses for Use as Novel Vaccines

PubMed Central

Dong, Bo; Zarlenga, Dante S.; Ren, Xiaofeng

2014-01-01

Pseudorabies virus (PRV) is a double-stranded, DNA-based swine virus with a genome approximating 150 kb in size. PRV has many nonessential genes which can be replaced with genes encoding heterologous antigens but without deleterious effects on virus propagation. Recombinant PRVs expressing both native and foreign antigens are able to stimulate immune responses. In this paper, we review the current status of live attenuated recombinant PRVs and live PRV-based vector vaccines with potential for controlling viral infections in animals. PMID:24995348

Mistranslation can enhance fitness through purging of deleterious mutations

PubMed Central

Bratulic, Sinisa; Toll-Riera, Macarena; Wagner, Andreas

2017-01-01

Phenotypic mutations are amino acid changes caused by mistranslation. How phenotypic mutations affect the adaptive evolution of new protein functions is unknown. Here we evolve the antibiotic resistance protein TEM-1 towards resistance on the antibiotic cefotaxime in an Escherichia coli strain with a high mistranslation rate. TEM-1 populations evolved in such strains endow host cells with a general growth advantage, not only on cefotaxime but also on several other antibiotics that ancestral TEM-1 had been unable to deactivate. High-throughput sequencing of TEM-1 populations shows that this advantage is associated with a lower incidence of weakly deleterious genotypic mutations. Our observations show that mistranslation is not just a source of noise that delays adaptive evolution. It could even facilitate adaptive evolution by exacerbating the effects of deleterious mutations and leading to their more efficient purging. The ubiquity of mistranslation and its effects render mistranslation an important factor in adaptive protein evolution. PMID:28524864

Impact of substance use on the onset and course of early psychosis.

PubMed

Verdoux, Hélène; Tournier, Marie; Cougnard, Audrey

2005-11-01

The strong comorbidity between psychosis and substance use is already identifiable in early psychosis, raising the question of the direction of the association between substance use and psychosis onset. It has long been considered that this association was explained by the self-medication hypothesis. This hypothesis has been recently challenged by several prospective studies carried out in population-based samples, showing a dose-response relationship between cannabis exposure and risk of psychosis. This association was independent from potential confounding factors such as exposure to other drugs and pre-existence of psychotic symptoms. As a large percentage of subjects from the general population is now exposed to this drug, even a small increase in the risk of adverse effects may have significant deleterious consequences for the health of the population. Hence, reducing exposure to cannabis may contribute to prevention of some incident cases of psychosis. Regarding prognosis, persistent substance misuse after the onset of psychosis has a deleterious impact on clinical outcome. Therapeutic programs for subjects with dual diagnosis should be implemented early in the course of psychosis to maximise their impact on the course of illness.

Secondary Traumatic Stress and Burnout Among Refugee Resettlement Workers: The Role of Coping and Emotional Intelligence.

PubMed

Akinsulure-Smith, Adeyinka M; Espinosa, Adriana; Chu, Tracy; Hallock, Ryan

2018-04-01

To promote a better understanding of the impact of refugee resettlement work on refugee resettlement workers, this study examined the prevalence rates of deleterious mental health and occupational outcomes, such as secondary traumatic stress and burnout, among a sample of 210 refugee resettlement workers at six refugee resettlement agencies in the United States. The study also explored coping mechanisms used by service providers to manage work-related stress and the influence of such strategies and emotional intelligence on secondary traumatic stress and burnout. Our findings show that certain coping strategies, including self-distraction, humor, venting, substance use, behavioral disengagement, and self-blame, were strongly related to deleterious outcomes, βs = .18 to .38, ps = .023 to < .001. Emotional intelligence was a negative correlate for all outcomes, βs = -.25 to -.30, ps < .001, above and beyond the effects of trauma, coping styles, job, and demographic characteristics. These findings have potential implications for clinical training and organizational policy regarding refugee mental health. Copyright © 2018 International Society for Traumatic Stress Studies.

Evidence for Hitchhiking of Deleterious Mutations within the Human Genome

PubMed Central

Chun, Sung; Fay, Justin C.

2011-01-01

Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles. PMID:21901107

A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans

PubMed Central

Koch, Evan; Novembre, John

2017-01-01

When mutations have small effects on fitness, population size plays an important role in determining the amount and nature of deleterious genetic variation. The extent to which recent population size changes have impacted deleterious variation in humans has been a question of considerable interest and debate. An emerging consensus is that the Out-of-Africa bottleneck and subsequent growth events have been too short to cause meaningful differences in genetic load between populations; though changes in the number and average frequencies of deleterious variants have taken place. To provide more support for this view and to offer additional insight into the divergent evolution of deleterious variation across populations, we numerically solve time-inhomogeneous diffusion equations and study the temporal dynamics of the frequency spectra in models of population size change for modern humans. We observe how the response to demographic change differs by the strength of selection, and we then assess whether similar patterns are observed in exome sequence data from 33,370 and 5203 individuals of non-Finnish European and West African ancestry, respectively. Our theoretical results highlight how even simple summaries of the frequency spectrum can have complex responses to demographic change. These results support the finding that some apparent discrepancies between previous results have been driven by the behaviors of the precise summaries of deleterious variation. Further, our empirical results make clear the difficulty of inferring slight differences in frequency spectra using recent next-generation sequence data. PMID:28159863

A Ruby in the Rubbish: Beneficial Mutations, Deleterious Mutations and the Evolution of Sex

PubMed Central

Peck, J. R.

1994-01-01

This study presents a mathematical model in which a single beneficial mutation arises in a very large population that is subject to frequent deleterious mutations. The results suggest that, if the population is sexual, then the deleterious mutations will have little effect on the ultimate fate of the beneficial mutation. However, if most offspring are produced asexually, then the probability that the beneficial mutation will be lost from the population may be greatly enhanced by the deleterious mutations. Thus, sexual populations may adapt much more quickly than populations where most reproduction is asexual. Some of the results were produced using computer simulation methods, and a technique was developed that allows treatment of arbitrarily large numbers of individuals in a reasonable amount of computer time. This technique may be of prove useful for the analysis of a wide variety of models, though there are some constraints on its applicability. For example, the technique requires that reproduction can be described by Poisson processes. PMID:8070669

Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

PubMed Central

Ajaltouni, Jean

2015-01-01

The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

A red orange extract modulates the vascular response to a recreational dive: a pilot study on the effect of anthocyanins on the physiological consequences of scuba diving.

PubMed

Balestra, C; Cimino, F; Theunissen, S; Snoeck, T; Provyn, S; Canali, R; Bonina, A; Virgili, F

2016-09-01

Nutritional antioxidants have been proposed as an expedient strategy to counter the potentially deleterious effects of scuba diving on endothelial function, flow-mediated dilation (FMD) and heart function. Sixteen volunteers performing a single standard dive (20 min at 33 m) according to US Navy diving procedures were randomly assigned to two groups: one was administered with two doses of 200 mg of an anthocyanins (AC)-rich extract from red oranges, 12 and 4 h before diving. Anthocyanins supplementation significantly modulated the effects of diving on haematocrit, body water distribution and FMD. AC administration significantly reduces the potentially harmful endothelial effects of a recreational single dive. The lack of any significant effect on the most common markers of plasma antioxidant capacity suggests that the mechanism underlying this protective activity is independent of the putative antioxidant effect of AC and possibly involves cellular signalling modulation of the response to high oxygen.

Simulation of deleterious processes in a static-cell diode pumped alkali laser

NASA Astrophysics Data System (ADS)

Oliker, Benjamin Q.; Haiducek, John D.; Hostutler, David A.; Pitz, Greg A.; Rudolph, Wolfgang; Madden, Timothy J.

2014-02-01

The complex interactions in a diode pumped alkali laser (DPAL) gain cell provide opportunities for multiple deleterious processes to occur. Effects that may be attributable to deleterious processes have been observed experimentally in a cesium static-cell DPAL at the United States Air Force Academy [B.V. Zhdanov, J. Sell, R.J. Knize, "Multiple laser diode array pumped Cs laser with 48 W output power," Electronics Letters, 44, 9 (2008)]. The power output in the experiment was seen to go through a "roll-over"; the maximum power output was obtained with about 70 W of pump power, then power output decreased as the pump power was increased beyond this point. Research to determine the deleterious processes that caused this result has been done at the Air Force Research Laboratory utilizing physically detailed simulation. The simulations utilized coupled computational fluid dynamics (CFD) and optics solvers, which were three-dimensional and time-dependent. The CFD code used a cell-centered, conservative, finite-volume discretization of the integral form of the Navier-Stokes equations. It included thermal energy transport and mass conservation, which accounted for chemical reactions and state kinetics. Optical models included pumping, lasing, and fluorescence. The deleterious effects investigated were: alkali number density decrease in high temperature regions, convective flow, pressure broadening and shifting of the absorption lineshape including hyperfine structure, radiative decay, quenching, energy pooling, off-resonant absorption, Penning ionization, photoionization, radiative recombination, three-body recombination due to free electron and buffer gas collisions, ambipolar diffusion, thermal aberration, dissociative recombination, multi-photon ionization, alkali-hydrocarbon reactions, and electron impact ionization.

Efficacy of an extract from garlic, Allium sativum, against infection with the furunculosis bacterium, Aeromonas salmonicida, in rainbow trout, Oncorhynchus mykiss

USGS Publications Warehouse

Breyer, Kate E.; Getchell, Rodman G.; Cornwell, Emily R.; Wooster, Gregory A.; Ketola, H. George; Bowser, Paul R.

2015-01-01

Juvenile rainbow trout, Oncorhynchus mykiss, were fed diets containing 0, 0.5, 1.0, and 2.0% of a garlic extract, challenged with a modified 50% lethal dose of Aeromonas salmonicida and monitored for 28 d. There were significant increases in survival of trout fed 0.5 and 1.0% garlic extract as compared to the control and 2.0% garlic extract groups. A target animal safety study was performed at varying increments using the target dose of 0.5% garlic extract at 0× (0% garlic extract), 1× (0.5% garlic extract), 3× (1.5% garlic extract), and 5× (2.5% garlic extract) for 3× (6 wk) the duration of the original study. There was a significant increase in the level of circulating lymphocytes and a significant decrease in the level of circulating monocytes. The latter correlated to an increased level of pigment-containing macrophage centers within the renal tissue as garlic extract dosing increased, denoting a potential deleterious inflammatory effect as macrophage infiltration became severe at the highest dose. These studies suggest that feeding low-dose (0.5% or 1.0%) garlic extract improves survivability in rainbow trout when challenged with A. salmonicida and appears safe; however, higher levels do not appear to be effective and may cause deleterious effects on health.

Diabetic Nephropathy Induced by Increased Ace Gene Dosage Is Associated with High Renal Levels of Angiotensin (1–7) and Bradykinin

PubMed Central

Bertoncello, Nádia; Moreira, Roseli Peres; Arita, Danielle Yuri; Aragão, Danielle S.; Watanabe, Ingrid Kazue Mizuno; Dantas, Patricia S.; Santos, Ralmony; Mattar-Rosa, Rodolfo; Yokota, Rodrigo; Cunha, Tatiana Sousa; Casarini, Dulce Elena

2015-01-01

Population studies have shown an association between diabetic nephropathy (DN) and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE in humans, Ace in mice). The aim was to evaluate the modulation of Ace copies number and diabetes mellitus (DM) on renal RAS and correlate it with indicators of kidney function. Increased number of copies of the Ace gene, associated with DM, induces renal dysfunction. The susceptibility to the development of DN in 3 copies of animals is associated with an imbalance in activity of RAS enzymes leading to increased synthesis of Ang II and Ang-(1–7). Increased concentration of renal Ang-(1–7) appears to potentiate the deleterious effects triggered by Ang II on kidney structure and function. Results also show increased bradykinin concentration in 3 copies diabetic group. Taken together, results indicate that the deleterious effects described in 3 copies diabetic group are, at least in part, due to a combination of factors not usually described in the literature. Thus, the data presented here show up innovative and contribute to understanding the complex mechanisms involved in the development of DN, in order to optimize the treatment of patients with this complication. PMID:26442284

High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.

PubMed

Kelleher, Raymond J; Geigenmüller, Ute; Hovhannisyan, Hayk; Trautman, Edwin; Pinard, Robert; Rathmell, Barbara; Carpenter, Randall; Margulies, David

2012-01-01

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism.

High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism

PubMed Central

Hovhannisyan, Hayk; Trautman, Edwin; Pinard, Robert; Rathmell, Barbara; Carpenter, Randall; Margulies, David

2012-01-01

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism. PMID:22558107

Long-Acting β2-Agonists in Asthma: Enantioselective Safety Studies are Needed.

PubMed

Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten; Calzetta, Luigino; Wood-Baker, Richard; Farber, Mark O; Page, Clive P; Walters, E Haydn

2018-05-01

Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without ICS. LABAs clearly demonstrate effective bronchodilatation and steroid-sparing activity, but long-term treatment can lead to tolerance of their bronchodilator effects. There are also concerns with regard to the effects of LABAs on bronchial hyperresponsiveness (BHR), where long-term use is associated with increased BHR and loss of bronchoprotection. A complicating factor is that formoterol and salmeterol are both chiral compounds, usually administered as 50:50 racemic (rac-) mixtures of two enantiomers. The chiral nature of these compounds has been largely forgotten in the debate regarding LABA safety and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from the short-acting β2-agonist (SABA) salbutamol. Supportive clinical findings include the fact that patients in emergency departments who demonstrate a blunted response to salbutamol are more likely to benefit from (R)-salbutamol than rac-salbutamol, and resistance to salbutamol appears to be a contributory mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue.

Plant polyphenols as natural drugs for the management of Down syndrome and related disorders.

PubMed

Vacca, Rosa Anna; Valenti, Daniela; Caccamese, Salvatore; Daglia, Maria; Braidy, Nady; Nabavi, Seyed Mohammad

2016-12-01

Polyphenols are secondary metabolites of plants largely found in fruits, vegetables, cereals and beverages, and therefore represent important constituents of the human diet. Increasing studies have demonstrated the potential beneficial effects of polyphenols on human health. Extensive reviews have discussed the protective effects of polyphenols against a series of diseases such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders. Limited studies have investigated the potential therapeutic effects of these natural compounds on neurodevelopmental disorders associated with intellectual disability, such as Down syndrome (DS), for which mitochondrial dysfunctions and oxidative stress are hallmarks and contribute to the deleterious symptoms and cognitive decline. This review, starting from the structure, source, bioavailability and pharmacokinetics of relevant polyphenols, highlights recent studies on the effect and potential molecular mechanism(s) of action of the phenolic compounds epigallocatechin-3-gallate, resveratrol and hydroxytyrosol in restoring mitochondrial energy deficit and in reversing phenotypical alteration in DS. The clinical implications of plant polyphenol dietary supplements as therapeutic tools in managing DS and other intellectual disability-related diseases, is also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional and Structural Consequence of Rare Exonic Single Nucleotide Polymorphisms: One Story, Two Tales

PubMed Central

Gu, Wanjun; Gurguis, Christopher I.; Zhou, Jin J.; Zhu, Yihua; Ko, Eun-A.; Ko, Jae-Hong; Wang, Ting; Zhou, Tong

2015-01-01

Genetic variation arising from single nucleotide polymorphisms (SNPs) is ubiquitously found among human populations. While disease-causing variants are known in some cases, identifying functional or causative variants for most human diseases remains a challenging task. Rare SNPs, rather than common ones, are thought to be more important in the pathology of most human diseases. We propose that rare SNPs should be divided into two categories dependent on whether the minor alleles are derived or ancestral. Derived alleles are less likely to have been purified by evolutionary processes and may be more likely to induce deleterious effects. We therefore hypothesized that the rare SNPs with derived minor alleles would be more important for human diseases and predicted that these variants would have larger functional or structural consequences relative to the rare variants for which the minor alleles are ancestral. We systematically investigated the consequences of the exonic SNPs on protein function, mRNA structure, and translation. We found that the functional and structural consequences are more significant for the rare exonic variants for which the minor alleles are derived. However, this pattern is reversed when the minor alleles are ancestral. Thus, the rare exonic SNPs with derived minor alleles are more likely to be deleterious. Age estimation of rare SNPs confirms that these potentially deleterious SNPs are recently evolved in the human population. These results have important implications for understanding the function of genetic variations in human exonic regions and for prioritizing functional SNPs in genome-wide association studies of human diseases. PMID:26454016

Elevated Proportions of Deleterious Genetic Variation in Domestic Animals and Plants

PubMed Central

Rubin, Carl-Johan; Carneiro, Miguel; Axelsson, Erik; Andersson, Leif

2018-01-01

Abstract A fraction of genetic variants segregating in any population are deleterious, which negatively impacts individual fitness. The domestication of animals and plants is associated with population bottlenecks and artificial selection, which are predicted to increase the proportion of deleterious variants. However, the extent to which this is a general feature of domestic species is unclear. Here, we examine the effects of domestication on the prevalence of deleterious variation using pooled whole-genome resequencing data from five domestic animal species (dog, pig, rabbit, chicken, and silkworm) and two domestic plant species (rice and soybean) compared with their wild ancestors. We find significantly reduced genetic variation and increased proportion of nonsynonymous amino acid changes in all but one of the domestic species. These differences are observable across a range of allele frequencies, both common and rare. We find proportionally more single nucleotide polymorphisms in highly conserved elements in domestic species and a tendency for domestic species to harbor a higher proportion of changes classified as damaging. Our findings most likely reflect an increased incidence of deleterious variants in domestic species, which is most likely attributable to population bottlenecks that lead to a reduction in the efficacy of selection. An exception to this pattern is displayed by European domestic pigs, which do not show traces of a strong population bottleneck and probably continued to exchange genes with wild boar populations after domestication. The results presented here indicate that an elevated proportion of deleterious variants is a common, but not ubiquitous, feature of domestic species. PMID:29325102

Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1)

PubMed Central

Hauke, Jan; Heitz, Florian; Reuss, Alexander; Kommoss, Stefan; Marmé, Frederik; Heimbach, André; Prieske, Katharina; Richters, Lisa; Burges, Alexander; Neidhardt, Guido; de Gregorio, Nikolaus; El-Balat, Ahmed; Hilpert, Felix; Meier, Werner; Kimmig, Rainer; Kast, Karin; Sehouli, Jalid; Baumann, Klaus; Jackisch, Christian; Park-Simon, Tjoung-Won; Hanker, Lars; Kröber, Sandra; Pfisterer, Jacobus; Gevensleben, Heidrun; Schnelzer, Andreas; Dietrich, Dimo; Neunhöffer, Tanja; Krockenberger, Mathias; Brucker, Sara Y.; Nürnberg, Peter; Thiele, Holger; Altmüller, Janine; Lamla, Josefin; Elser, Gabriele; du Bois, Andreas; Hahnen, Eric; Schmutzler, Rita

2017-01-01

Background Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated. Methods Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history. Results In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16–93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the BRCA1 (15.5%), BRCA2 (5.5%), RAD51C (2.5%) and PALB2 (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in BRCA1/2 (and in all 16 risk genes) in patients <60 years was 30.2% (33.2%) versus 10.6% (18.9%) in patients ≥60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants of 31.6% (36.0%) versus 11.4% (17.6%) and histologic subtype of high grade serous ovarian cancer versus other showed a prevalence of deleterious variants of 23.2% (29.1%) and 10.2% (14.8%), respectively. Testing only for BRCA1/2 would miss in our series more than 5% of the patients with a deleterious variant in established risk genes. Conclusions 26.4% of all patients harbor at least one deleterious variant in established risk genes. The threshold of 10% mutation rate which is accepted for reimbursement by health care providers in Germany was observed in all subgroups analyzed and neither age at primary diagnosis nor histo-type or family history sufficiently enough could identify a subgroup not eligible for genetic counselling and testing. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer and limiting testing to BRCA1/2 seems to be not sufficient. PMID:29053726

Liquid Water Restricts Habitability in Extreme Deserts

NASA Astrophysics Data System (ADS)

Cockell, Charles S.; Brown, Sarah; Landenmark, Hanna; Samuels, Toby; Siddall, Rebecca; Wadsworth, Jennifer

2017-04-01

Liquid water is a requirement for biochemistry, yet under some circumstances it is deleterious to life. Here, we show that liquid water reduces the upper temperature survival limit for two extremophilic photosynthetic microorganisms (Gloeocapsa and Chroococcidiopsis spp.) by greater than 40°C under hydrated conditions compared to desiccated conditions. Under hydrated conditions, thermal stress causes protein inactivation as shown by the fluorescein diacetate assay. The presence of water was also found to enhance the deleterious effects of freeze-thaw in Chroococcidiopsis sp. In the presence of water, short-wavelength UV radiation more effectively kills Gloeocapsa sp. colonies, which we hypothesize is caused by factors including the greater penetration of UV radiation into hydrated colonies compared to desiccated colonies. The data predict that deserts where maximum thermal stress or irradiation occurs in conjunction with the presence of liquid water may be less habitable to some organisms than more extreme arid deserts where organisms can dehydrate prior to being exposed to these extremes, thus minimizing thermal and radiation damage. Life in extreme deserts is poised between the deleterious effects of the presence and the lack of liquid water.

Lineage dynamics and mutation-selection balance in non-adapting asexual populations

NASA Astrophysics Data System (ADS)

Pénisson, Sophie; Sniegowski, Paul D.; Colato, Alexandre; Gerrish, Philip J.

2013-02-01

In classical population genetics, mutation-selection balance refers to the equilibrium frequency of a deleterious allele established and maintained under two opposing forces: recurrent mutation, which tends to increase the frequency of the allele; and selection, which tends to decrease its frequency. In a haploid population, if μ denotes the per capita rate of production of the deleterious allele by mutation and s denotes the selective disadvantage of carrying the allele, then the classical mutation-selection balance frequency of the allele is approximated by μ/s. This calculation assumes that lineages carrying the mutant allele in question—the ‘focal allele’—do not accumulate deleterious mutations linked to the focal allele. In principle, indirect selection against the focal allele caused by such additional mutations can decrease the frequency of the focal allele below the classical mutation-selection balance. This effect of indirect selection will be strongest in an asexual population, in which the entire genome is in linkage. Here, we use an approach based on a multitype branching process to investigate this effect, analyzing lineage dynamics under mutation, direct selection, and indirect selection in a non-adapting asexual population. We find that the equilibrium balance between recurrent mutation to the focal allele and the forces of direct and indirect selection against the focal allele is closely approximated by γμ/(s + U) (s = 0 if the focal allele is neutral), where γ ≈ eθθ-(ω+θ)(ω + θ)(Γ(ω + θ) - Γ(ω + θ,θ)), \\theta =U/\\tilde {s}, and \\omega =s/\\tilde {s}; U denotes the genomic deleterious mutation rate and \\tilde {s} denotes the geometric mean selective disadvantage of deleterious mutations elsewhere on the genome. This mutation-selection balance for asexual populations can remain surprisingly invariant over wide ranges of the mutation rate.

Risk of population extinction from fixation of deleterious and reverse mutations.

PubMed

Lande, R

1998-01-01

A model is developed for alternate fixations of mildly deleterious and wild-type alleles arising by forward and reverse mutation in a finite population. For almost all parameter values, this gives an equilibrium load that agrees closely with the general expression derived from diffusion theory. Nearly neutral mutations with selection coefficient a few times larger than 1/(2N(e)) do the most damage by increasing the equilibrium load. The model of alternate fixations facilitates dynamical analysis of the expected load and the mean time to extinction in a population that has been suddenly reduced from a very large size to a small size. Reverse mutation can substantially improve population viability, increasing the mean time to extinction by an order of magnitude or more, but because many mutations are irreversible the effects may not be large. Populations with initially high mean fitness and small effective size, N(e) below a few hundred individuals, may be at serious risk of extinction from fixation of deleterious mutations within 10(3) to 10(4) generations.

Ammonia toxicity: from head to toe?

PubMed

Dasarathy, Srinivasan; Mookerjee, Rajeshwar P; Rackayova, Veronika; Rangroo Thrane, Vinita; Vairappan, Balasubramaniyan; Ott, Peter; Rose, Christopher F

2017-04-01

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction.

Uncovering disease mechanisms through network biology in the era of Next Generation Sequencing

NASA Astrophysics Data System (ADS)

Piñero, Janet; Berenstein, Ariel; Gonzalez-Perez, Abel; Chernomoretz, Ariel; Furlong, Laura I.

2016-04-01

Characterizing the behavior of disease genes in the context of biological networks has the potential to shed light on disease mechanisms, and to reveal both new candidate disease genes and therapeutic targets. Previous studies addressing the network properties of disease genes have produced contradictory results. Here we have explored the causes of these discrepancies and assessed the relationship between the network roles of disease genes and their tolerance to deleterious germline variants in human populations leveraging on: the abundance of interactome resources, a comprehensive catalog of disease genes and exome variation data. We found that the most salient network features of disease genes are driven by cancer genes and that genes related to different types of diseases play network roles whose centrality is inversely correlated to their tolerance to likely deleterious germline mutations. This proved to be a multiscale signature, including global, mesoscopic and local network centrality features. Cancer driver genes, the most sensitive to deleterious variants, occupy the most central positions, followed by dominant disease genes and then by recessive disease genes, which are tolerant to variants and isolated within their network modules.

Uncovering disease mechanisms through network biology in the era of Next Generation Sequencing

PubMed Central

Piñero, Janet; Berenstein, Ariel; Gonzalez-Perez, Abel; Chernomoretz, Ariel; Furlong, Laura I.

2016-01-01

Characterizing the behavior of disease genes in the context of biological networks has the potential to shed light on disease mechanisms, and to reveal both new candidate disease genes and therapeutic targets. Previous studies addressing the network properties of disease genes have produced contradictory results. Here we have explored the causes of these discrepancies and assessed the relationship between the network roles of disease genes and their tolerance to deleterious germline variants in human populations leveraging on: the abundance of interactome resources, a comprehensive catalog of disease genes and exome variation data. We found that the most salient network features of disease genes are driven by cancer genes and that genes related to different types of diseases play network roles whose centrality is inversely correlated to their tolerance to likely deleterious germline mutations. This proved to be a multiscale signature, including global, mesoscopic and local network centrality features. Cancer driver genes, the most sensitive to deleterious variants, occupy the most central positions, followed by dominant disease genes and then by recessive disease genes, which are tolerant to variants and isolated within their network modules. PMID:27080396

Rare beneficial mutations can halt Muller's ratchet

NASA Astrophysics Data System (ADS)

Balick, Daniel; Goyal, Sidhartha; Jerison, Elizabeth; Neher, Richard; Shraiman, Boris; Desai, Michael

2012-02-01

In viral, bacterial, and other asexual populations, the vast majority of non-neutral mutations are deleterious. This motivates the application of models without beneficial mutations. Here we show that the presence of surprisingly few compensatory mutations halts fitness decay in these models. Production of deleterious mutations is balanced by purifying selection, stabilizing the fitness distribution. However, stochastic vanishing of fitness classes can lead to slow fitness decay (i.e. Muller's ratchet). For weakly deleterious mutations, production overwhelms purification, rapidly decreasing population fitness. We show that when beneficial mutations are introduced, a stable steady state emerges in the form of a dynamic mutation-selection balance. We argue this state is generic for all mutation rates and population sizes, and is reached as an end state as genomes become saturated by either beneficial or deleterious mutations. Assuming all mutations have the same magnitude selective effect, we calculate the fraction of beneficial mutations necessary to maintain the dynamic balance. This may explain the unexpected maintenance of asexual genomes, as in mitochondria, in the presence of selection. This will affect in the statistics of genetic diversity in these populations.

Overview of proteomics studies in obstructive sleep apnea

PubMed Central

Feliciano, Amélia; Torres, Vukosava Milic; Vaz, Fátima; Carvalho, Ana Sofia; Matthiesen, Rune; Pinto, Paula; Malhotra, Atul; Bárbara, Cristina; Penque, Deborah

2015-01-01

Obstructive sleep apnea (OSA) is an underdiagnosed common public health concern causing deleterious effects on metabolic and cardiovascular health. Although much has been learned regarding the pathophysiology and consequences of OSA in the past decades, the molecular mechanisms associated with such processes remain poorly defined. The advanced high-throughput proteomics-based technologies have become a fundamental approach for identifying novel disease mediators as potential diagnostic and therapeutic targets for many diseases, including OSA. Here, we briefly review OSA pathophysiology and the technological advances in proteomics and the first results of its application to address critical issues in the OSA field. PMID:25770042

Current Status of Bicarbonate in CKD

PubMed Central

Dobre, Mirela; Rahman, Mahboob

2015-01-01

Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been tested very little, especially with respect to standard clinical outcomes. On the basis of fundamental research and small alkali supplementation trials, correcting metabolic acidosis has a strikingly broad array of potential benefits. This review summarizes the published evidence on the association between serum bicarbonate and clinical outcomes. We discuss the role of alkali supplementation in CKD as it relates to retarding kidney disease progression, improving metabolic and musculoskeletal complications. PMID:25150154

Optically Phase-Locked Electronic Speckle Pattern Interferometer (OPL-ESPI)

NASA Astrophysics Data System (ADS)

Moran, Steven E.; Law, Robert L.; Craig, Peter N.; Goldberg, Warren M.

1986-10-01

This report describes the design, theory, operation, and characteristics of the OPL-ESPI, which generates real time equal Doppler speckle contours of vibrating objects from unstable sensor platforms with a Doppler resolution of 30 Hz and a maximum tracking range of + or - 5 HMz. The optical phase locked loop compensates for the deleterious effects of ambient background vibration and provides the bases for a new ESPI video signal processing technique, which produces high contrast speckle contours. The OPL-ESPI system has local oscillator phase modulation capability, offering the potential for detection of vibrations with the amplitudes less than lambda/100.

Berry Fruit Consumption and Metabolic Syndrome

PubMed Central

Vendrame, Stefano; Del Bo’, Cristian; Ciappellano, Salvatore; Riso, Patrizia; Klimis-Zacas, Dorothy

2016-01-01

Metabolic Syndrome is a cluster of risk factors which often includes central obesity, dyslipidemia, insulin resistance, glucose intolerance, hypertension, endothelial dysfunction, as well as a pro-inflammatory, pro-oxidant, and pro-thrombotic environment. This leads to a dramatically increased risk of developing type II diabetes mellitus and cardiovascular disease, which is the leading cause of death both in the United States and worldwide. Increasing evidence suggests that berry fruit consumption has a significant potential in the prevention and treatment of most risk factors associated with Metabolic Syndrome and its cardiovascular complications in the human population. This is likely due to the presence of polyphenols with known antioxidant and anti-inflammatory effects, such as anthocyanins and/or phenolic acids. The present review summarizes the findings of recent dietary interventions with berry fruits on human subjects with or at risk of Metabolic Syndrome. It also discusses the potential role of berries as part of a dietary strategy which could greatly reduce the need for pharmacotherapy, associated with potentially deleterious side effects and constituting a considerable financial burden. PMID:27706020

Recent Advances on Endocrine Disrupting Effects of UV Filters.

PubMed

Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

2016-08-03

Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives.

49 CFR 192.620 - Alternative maximum allowable operating pressure for certain steel pipelines.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY...) At points where gas with potentially deleterious contaminants enters the pipeline, use filter...

N-acetyl-L-cysteine pre-treatment protects cryopreserved bovine spermatozoa from reactive oxygen species without compromising the in vitro developmental potential of intracytoplasmic sperm injection embryos.

PubMed

Pérez, L; Arias, M E; Sánchez, R; Felmer, R

2015-12-01

Excess of reactive oxygen species (ROS) on in vitro embryo production systems negatively affects the quality and developmental potential of embryos, as result of a decreased sperm quality and increased DNA fragmentation. This issue is of major importance in assisted fertilisation procedures such as intracytoplasmic sperm injection (ICSI), because this technique does not allow the natural selection of competent spermatozoa, and therefore, DNA-damaged spermatozoa might be used to fertilise an egg. The aim of this study was to investigate a new strategy to prevent the potential deleterious effect of ROS on cryopreserved bovine spermatozoa. We evaluated the effect of a sperm pre-treatment with different concentrations of N-acetyl-L-cysteine (NAC) on ROS production, viability and DNA fragmentation and assessed the effect of this treatment on the in vitro developmental potential and quality of embryos generated by ICSI. The results show a strong scavenging effect of 1 and 10 mm NAC after exposure of spermatozoa to a ROS inducer, without compromising the viability and DNA integrity. Importantly, in vitro developmental potential and quality of embryos generated by ICSI with spermatozoa treated with NAC were not affected, confirming the feasibility of using this treatment before an ICSI cycle. © 2015 Blackwell Verlag GmbH.

CaMKII in Vascular Signalling: "Friend or Foe"?

PubMed

Ebenebe, Obialunanma V; Heather, Alison; Erickson, Jeffrey R

2018-05-01

Signalling mechanisms within and between cells of the vasculature enable function and maintain homeostasis. However, a number of these mechanisms also contribute to the pathophysiology of vascular disease states. The multifunctional signalling molecule calcium/calmodulin-dependent kinase II (CaMKII) has been shown to have critical functional effects in many tissue types. For example, CaMKII is known to have a dual role in cardiac physiology and pathology. The function of CaMKII within the vasculature is incompletely understood, but emerging evidence points to potential physiological and pathological roles. This review discusses the evidence for CaMKII signalling within the vasculature, with the aim to better understand both positive and potentially deleterious effects of CaMKII activation in vascular tissue. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Light at night pollution of the internal clock, a public health issue.

PubMed

Touitou, Yvan

2015-10-01

Light is the major synchronizer of the internal clock located in the suprachiasmatic nuclei of the anterior hypothalamus. Retinal ganglion cells contain melanopsin, a photoreceptor with a peak sensitivity to blue wavelength (460-480 nm). Light signal is transmitted from the eye to the clock, then to the pineal gland which produces melatonin, considered as the hand of the clock. Even a weak intensity of light (LEDs, tablets, mobile phones, computers...) is able to block the secretion of melatonin, the hormone of darkness. Light is also able to phase advance or phase delay the circadian system according to the timing of exposure. This Phase Response Curve (PRC) is used to resynchronize the clock in various situations of circadian desynchronization. Exposure to Light at Night (LAN) results in a disruption of the circadian system which is deleterious to health. In industrialized countries, including France, 75 % of the total workforce is estimated to be involved in atypical hours, far from the classical diurnal hours of work. Of interest, shift work and night work involve 15.4 % of the French workforce. A number of epidemiologic studies, peiformed mainly on nurses, showed an association between sustained night work (3 to 20 years) and an increased risk of breast cancer Health problems faced by flight attendants have also been reported, though other causes like exposure to radiations cannot be ruled out. Other deleterious effects are reported in this paper. The potential mechanisms of the deleterious effects of LAN on health are suppression of melatonin andsleep deprivation. The International Agencyfor Cancer Research (IARC) classified shift work that involves circadian disruption as ( probably carcinogenic to humans". Countermeasures (e.g melatonin, bright light, use of psychotropic drugs) have been proposed as a means to improve adaptation to shift work and night work and to fight " clock pollution " and circadian desynchronization by LAN.

Graphic tobacco health warnings: which genre to choose?

PubMed

Sobani, Z; Nizami, S; Raza, E; ul Ain Baloch, N; Khan, J A

2010-03-01

Tobacco prevention studies show that graphic health warnings are more effective than text warnings, but there are no data on the effectiveness of different types of graphic health warnings in a Pakistani population. Even marginal differences in the effectiveness of genres can be of potential significance for public health. To study the effectiveness of different types of graphic tobacco warnings in a Pakistani population. We presented ten anti-smoking warnings to randomly selected volunteers (n = 170) and recorded their opinion on the effectiveness of each warning. The warnings were based on a range of images aimed at the diverse population interviewed. A grading scale based on appeal, application, educational potential and motivation towards cessation was used to produce a composite grade of perceived effectiveness of the warning. Our results indicate that graphic warnings reach a greater proportion of the population than text warnings. Those appealing to logic, and those inculcating a sense of fear by showing a deleterious outcome of smoking, were judged likely to be most effective in motivating smokers to quit and preventing experimental smokers from forming a habit.

Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.

PubMed

Bonnet, N; Laroche, N; Beaupied, H; Vico, L; Dolleans, E; Benhamou, C L; Courteix, D

2007-08-01

Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta(2)-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta(2)-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, -1.8%; P < 0.01) and quality (-8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.

Oxidative stress, testosterone, and cognition among Caucasian and Mexican-American men with and without Alzheimer's disease.

PubMed

Cunningham, Rebecca L; Singh, Meharvan; O'Bryant, Sid E; Hall, James R; Barber, Robert C

2014-01-01

The use of testosterone among aging men has been increasing, but results from studies addressing the effectiveness of testosterone replacement therapy have been equivocal. Given our prior pre-clinical studies that reported a major influence of oxidative stress on testosterone's neuroprotective effects, we investigated whether the negative effects of testosterone on brain function were predicted by oxidative load. In order to test our hypothesis, we determined whether circulating total testosterone and luteinizing hormone correlated with cognition in a subset of the Texas Alzheimer's Research & Care Consortium (TARCC) cohort, consisting of Caucasian (n = 116) and Mexican-American (n = 117) men. We also assessed whether oxidative stress (as indexed by homocysteine levels) modified this relationship between sex hormones and cognition, and whether the levels of two antioxidants, superoxide dismutase-1 and glutathione S-transferase (GST), varied as a function of circulating testosterone. In a low oxidative stress environment, testosterone was positively associated with the level of the antioxidant, GST, while no deleterious effects on cognitive function were noted. In contrast, under conditions of high oxidative stress (homocysteine levels >12 μmol/L), testosterone and luteinizing hormone were associated with cognitive impairment, but only among Caucasians. The ethnic difference was attributed to significantly higher GST levels among Mexican-Americans. While testosterone may be beneficial under conditions of low oxidative stress, testosterone appears to have negative consequences under conditions of elevated oxidative stress, but only in Caucasians. Mexican-Americans, however, were protected from any deleterious effects of testosterone, potentially due to higher levels of endogenous antioxidant defenses such as GST.

In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

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

Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna

2006-04-01

Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 gmore » of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in combination with creatine and ascorbic acid on cancer-bearing animals had been investigated by measuring the increase in life span and tumor cell growth inhibition. The results indicated that anticancer effect of methylglyoxal was significantly augmented by ascorbic acid and further augmented by ascorbic acid and creatine. Nearly 80% of the animals treated with methylglyoxal plus ascorbic acid plus creatine were completely cured and devoid of any malignant cells within the peritoneal cavity.« less

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 109.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Added poisonous or deleterious substances. 109.6...-PACKAGING MATERIAL General Provisions § 109.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 109.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Added poisonous or deleterious substances. 109.6...-PACKAGING MATERIAL General Provisions § 109.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 109.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Added poisonous or deleterious substances. 109.6...-PACKAGING MATERIAL General Provisions § 109.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

Mutation predicts 40 million years of fly wing evolution.

PubMed

Houle, David; Bolstad, Geir H; van der Linde, Kim; Hansen, Thomas F

2017-08-24

Mutation enables evolution, but the idea that adaptation is also shaped by mutational variation is controversial. Simple evolutionary hypotheses predict such a relationship if the supply of mutations constrains evolution, but it is not clear that constraints exist, and, even if they do, they may be overcome by long-term natural selection. Quantification of the relationship between mutation and phenotypic divergence among species will help to resolve these issues. Here we use precise data on over 50,000 Drosophilid fly wings to demonstrate unexpectedly strong positive relationships between variation produced by mutation, standing genetic variation, and the rate of evolution over the last 40 million years. Our results are inconsistent with simple constraint hypotheses because the rate of evolution is very low relative to what both mutational and standing variation could allow. In principle, the constraint hypothesis could be rescued if the vast majority of mutations are so deleterious that they cannot contribute to evolution, but this also requires the implausible assumption that deleterious mutations have the same pattern of effects as potentially advantageous ones. Our evidence for a strong relationship between mutation and divergence in a slowly evolving structure challenges the existing models of mutation in evolution.

CHEK2 contribution to hereditary breast cancer in non-BRCA families.

PubMed

Desrichard, Alexis; Bidet, Yannick; Uhrhammer, Nancy; Bignon, Yves-Jean

2011-01-01

Mutations in the BRCA1 and BRCA2 genes are responsible for only a part of hereditary breast cancer (HBC). The origins of "non-BRCA" HBC in families may be attributed in part to rare mutations in genes conferring moderate risk, such as CHEK2, which encodes for an upstream regulator of BRCA1. Previous studies have demonstrated an association between CHEK2 founder mutations and non-BRCA HBC. However, very few data on the entire coding sequence of this gene are available. We investigated the contribution of CHEK2 mutations to non-BRCA HBC by direct sequencing of its whole coding sequence in 507 non-BRCA HBC cases and 513 controls. We observed 16 mutations in cases and 4 in controls, including 9 missense variants of uncertain consequence. Using both in silico tools and an in vitro kinase activity test, the majority of the variants were found likely to be deleterious for protein function. One variant present in both cases and controls was proposed to be neutral. Removing this variant from the pool of potentially deleterious variants gave a mutation frequency of 1.48% for cases and 0.29% for controls (P = 0.0040). The odds ratio of breast cancer in the presence of a deleterious CHEK2 mutation was 5.18. Our work indicates that a variety of deleterious CHEK2 alleles make an appreciable contribution to breast cancer susceptibility, and their identification could help in the clinical management of patients carrying a CHEK2 mutation.

The efficiency of close inbreeding to reduce genetic adaptation to captivity

PubMed Central

Theodorou, K; Couvet, D

2015-01-01

Although ex situ conservation is indispensable for thousands of species, captive breeding is associated with negative genetic changes: loss of genetic variance and genetic adaptation to captivity that is deleterious in the wild. We used quantitative genetic individual-based simulations to model the effect of genetic management on the evolution of a quantitative trait and the associated fitness of wild-born individuals that are brought to captivity. We also examined the feasibility of the breeding strategies under a scenario of a large number of loci subject to deleterious mutations. We compared two breeding strategies: repeated half-sib mating and a method of minimizing mean coancestry (referred to as gc/mc). Our major finding was that half-sib mating is more effective in reducing genetic adaptation to captivity than the gc/mc method. Moreover, half-sib mating retains larger allelic and adaptive genetic variance. Relative to initial standing variation, the additive variance of the quantitative trait increased under half-sib mating during the sojourn in captivity. Although fragmentation into smaller populations improves the efficiency of the gc/mc method, half-sib mating still performs better in the scenarios tested. Half-sib mating shows two caveats that could mitigate its beneficial effects: low heterozygosity and high risk of extinction when populations are of low fecundity and size and one of the following conditions are met: (i) the strength of selection in captivity is comparable with that in the wild, (ii) deleterious mutations are numerous and only slightly deleterious. Experimental validation of half-sib mating is therefore needed for the advancement of captive breeding programs. PMID:25052417

Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications.

PubMed

Belaidi, Elise; Morand, Jessica; Gras, Emmanuelle; Pépin, Jean-Louis; Godin-Ribuot, Diane

2016-12-01

Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endothelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications

PubMed Central

Belaidi, Elise; Morand, Jessica; Gras, Emmanuelle; Pépin, Jean-Louis; Godin-Ribuot, Diane

2016-01-01

Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endotelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients. PMID:27492897

Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer

PubMed Central

Carvalho, S; Catarino, TA; Dias, AM; Kato, M; Almeida, A; Hessling, B; Figueiredo, J; Gärtner, F; Sanches, JM; Ruppert, T; Miyoshi, E; Pierce, M; Carneiro, F; Kolarich, D; Seruca, R; Yamaguchi, Y; Taniguchi, N; Reis, CA; Pinho, SS

2016-01-01

E-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with β1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell–cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression. PMID:26189796

Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.

PubMed

Tarantini, Stefano; Valcarcel-Ares, M Noa; Yabluchanskiy, Andriy; Tucsek, Zsuzsanna; Hertelendy, Peter; Kiss, Tamas; Gautam, Tripti; Zhang, Xin A; Sonntag, William E; de Cabo, Rafael; Farkas, Eszter; Elliott, Michael H; Kinter, Michael T; Deak, Ferenc; Ungvari, Zoltan; Csiszar, Anna

2018-06-14

Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2+/+ and Nrf2-/-, mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2-/- mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CA1 area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.

Unraveling the Deleterious Effects of Cancer-Driven STK11 Mutants Through Conformational Sampling Approach.

PubMed

Lopus, Merlin; Paul, D Meshach; Rajasekaran, R

2016-01-01

Tumor suppressor gene, STK11, encodes for serine-threonine kinase, which has a critical role in regulating cell growth and apoptosis. Mutations of the same lead to the inactivation of STK11, which eventually causes different types of cancer. In this study, we focused on identifying those driver mutations through analyzing structural variations of mutants, viz., D194N, E199K, L160P, and Y49D. Native and the mutants were analyzed to determine their geometrical deviations such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, potential energy, and solvent-accessible surface area using conformational sampling technique. Additionally, the global minimized structure of native and mutants was further analyzed to compute their intramolecular interactions and distribution of secondary structure. Subsequently, simulated thermal denaturation and docking studies were performed to determine their structural variations, which in turn alter the formation of active complex that comprises STK11, STRAD, and MO25. The deleterious effect of the mutants would result in a comparative loss of enzyme function due to variations in their binding energy pertaining to spatial conformation and flexibility. Hence, the structural variations in binding energy exhibited by the mutants, viz., D194N, E199K, L160P, and Y49D, to that of the native, consequently lead to pathogenesis.

Duration of Sexual Harassment and Generalized Harassment in the Workplace Over Ten Years: Effects on Deleterious Drinking Outcomes

PubMed Central

McGinley, Meredith; Richman, Judith A.; Rospenda, Kathleen M.

2012-01-01

While harassment in the workplace has been linked to deleterious drinking outcomes, researchers have yet to examine the long-term effects of chronic workplace harassment. During a ten year longitudinal mail survey, university employees (N = 2265) were administered measures of sexual harassment, generalized workplace harassment, and problematic drinking. Using growth mixture modeling, two latent classes of workplace harassment emerged: infrequent and chronic. Demographic characteristics (gender, age, and race) predicted the shape of the trajectories and likelihood of class membership. As hypothesized, membership in the chronic harassment classes was linked to future problematic drinking, even after controlling for previous drinking. PMID:21745045

Duration of sexual harassment and generalized harassment in the workplace over ten years: effects on deleterious drinking outcomes.

PubMed

McGinley, Meredith; Richman, Judith A; Rospenda, Kathleen M

2011-01-01

Although harassment in the workplace has been linked to deleterious drinking outcomes, researchers have yet to examine the long-term effects of chronic workplace harassment. During a 10-year longitudinal mail survey, university employees (N = 2,265) were administered measures of sexual harassment, generalized workplace harassment, and problematic drinking. Using growth mixture modeling, two latent classes of workplace harassment emerged: infrequent and chronic. Demographic characteristics (gender, age, and race) predicted the shape of the trajectories and likelihood of class membership. As hypothesized, membership in the chronic harassment classes was linked to future problematic drinking, even after controlling for previous drinking.

Testing the ability of non-methylamine osmolytes present in kidney cells to counteract the deleterious effects of urea on structure, stability and function of proteins.

PubMed

Khan, Sheeza; Bano, Zehra; Singh, Laishram R; Hassan, Md Imtaiyaz; Islam, Asimul; Ahmad, Faizan

2013-01-01

Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D (o)) and functional activity parameters (K m and k cat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively.

Liquid Water Restricts Habitability in Extreme Deserts.

PubMed

Cockell, Charles S; Brown, Sarah; Landenmark, Hanna; Samuels, Toby; Siddall, Rebecca; Wadsworth, Jennifer

2017-04-01

Liquid water is a requirement for biochemistry, yet under some circumstances it is deleterious to life. Here, we show that liquid water reduces the upper temperature survival limit for two extremophilic photosynthetic microorganisms (Gloeocapsa and Chroococcidiopsis spp.) by greater than 40°C under hydrated conditions compared to desiccated conditions. Under hydrated conditions, thermal stress causes protein inactivation as shown by the fluorescein diacetate assay. The presence of water was also found to enhance the deleterious effects of freeze-thaw in Chroococcidiopsis sp. In the presence of water, short-wavelength UV radiation more effectively kills Gloeocapsa sp. colonies, which we hypothesize is caused by factors including the greater penetration of UV radiation into hydrated colonies compared to desiccated colonies. The data predict that deserts where maximum thermal stress or irradiation occurs in conjunction with the presence of liquid water may be less habitable to some organisms than more extreme arid deserts where organisms can dehydrate prior to being exposed to these extremes, thus minimizing thermal and radiation damage. Life in extreme deserts is poised between the deleterious effects of the presence and the lack of liquid water. Key Words: Deserts-Extremophiles-Stress-High temperatures-UV radiation-Desiccation. Astrobiology 17, 309-318.

Testing the Ability of Non-Methylamine Osmolytes Present in Kidney Cells to Counteract the Deleterious Effects of Urea on Structure, Stability and Function of Proteins

PubMed Central

Khan, Sheeza; Bano, Zehra; Singh, Laishram R.; Hassan, Md. Imtaiyaz; Islam, Asimul; Ahmad, Faizan

2013-01-01

Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D o) and functional activity parameters (K m and k cat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively. PMID:24039776

The Janus face of iron on anoxic worlds: iron oxides are both protective and destructive to life on the early Earth and present-day Mars.

PubMed

Wadsworth, Jennifer; Cockell, Charles S

2017-05-01

The surface of the early Earth was probably subjected to a higher flux of ultraviolet (UV) radiation than today. UV radiation is known to severely damage DNA and other key molecules of life. Using a liquid culture and a rock analogue system, we investigated the interplay of protective and deleterious effects of iron oxides under UV radiation on the viability of the model organism, Bacillus subtilis. In the presence of hydrogen peroxide, there exists a fine balance between iron oxide's protective effects against this radiation and its deleterious effects caused by Photo-Fenton reactions. The maximum damage was caused by a concentration of hematite of ∼1 mg/mL. Concentrations above this confer increasing protection by physical blockage of the UV radiation, concentrations below this cause less effective UV radiation blockage, but also a correspondingly less effective Photo-Fenton reaction, providing an overall advantage. These results show that on anoxic worlds, surface habitability under a high UV flux leaves life precariously poised between the beneficial and deleterious effects of iron oxides. These results have relevance to the Archean Earth, but also the habitability of the Martian surface, where high levels of UV radiation in combination with iron oxides and hydrogen peroxide can be found. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart

PubMed Central

Sárközy, Márta; Pipicz, Márton; Dux, László; Csont, Tamás

2016-01-01

Hypercholesterolemia is a frequent metabolic disorder associated with increased risk for cardiovascular morbidity and mortality. In addition to its well-known proatherogenic effect, hypercholesterolemia may exert direct effects on the myocardium resulting in contractile dysfunction, aggravated ischemia/reperfusion injury, and diminished stress adaptation. Both preclinical and clinical studies suggested that elevated oxidative and/or nitrative stress plays a key role in cardiac complications induced by hypercholesterolemia. Therefore, modulation of hypercholesterolemia-induced myocardial oxidative/nitrative stress is a feasible approach to prevent or treat deleterious cardiac consequences. In this review, we discuss the effects of various pharmaceuticals, nutraceuticals, some novel potential pharmacological approaches, and physical exercise on hypercholesterolemia-induced oxidative/nitrative stress and subsequent cardiac dysfunction as well as impaired ischemic stress adaptation of the heart in hypercholesterolemia. PMID:26788247

[Signaling mechanisms involved in resolution of inflammation].

PubMed

Cervantes-Villagrana, Rodolfo Daniel; Cervantes-Villagrana, Alberto Rafael; Presno-Bernal, José Miguel

2014-01-01

Inflammation is a physiological process, which eliminates pathogens and induces repair of damaged tissue. This process is controlled by negative feedback mechanisms, but if the inflammation persists, it generates a deleterious autoimmune process or can to contribute with diseases such as obesity or cancer. The inflammation resolution involves mechanisms such as decrease of proliferation and maturation of immune cells, phagocytosis and apoptosis of immune cells, and decrease of proinflammatory mediators. Therefore, is relevant to study the physiological effects of specific receptors that participate in inflammation resolution and the design of specific agonists as conventional anti-inflammatory therapeutics, without dramatic collateral effects. In this review, we study some mechanisms associated with inflammation inhibition, particularly the transduction of receptors for ligands with anti-inflammatory effects and that are relevant for their potential therapeutic.

Neuropsychology of Child Maltreatment and Implications for School Psychologists

ERIC Educational Resources Information Center

Davis, Andrew S.; Moss, Lauren E.; Nogin, Margarita M.; Webb, Nadia Elizabeth

2015-01-01

Child maltreatment has the potential to alter a child's neurodevelopmental trajectory and substantially increase the risk of later psychiatric disorders, as well as to deleteriously impact neurocognitive functioning throughout the lifespan. Child maltreatment has been linked to multiple domains of neurocognitive impairment, including…

Modeling the dynamics of chromosomal alteration progression in cervical cancer: A computational model

PubMed Central

2017-01-01

Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC) is a process in which the cell acquires dynamic behavior from non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamics of deleterious and non-deleterious mutations as an outcome of tumor progression. The analysis of chromosomal alterations mediated by our model reveals that multiple deleterious mutations are more frequent in precursor lesions than in CC. Cells with lethal deleterious mutations would be eliminated, which would mitigate cancer progression; on the other hand, cells with non-deleterious mutations would become dominant, which could predispose them to cancer progression. The study of somatic alterations through computer simulations of cancer progression provides a feasible pathway for insights into the transformation of cell mechanisms in humans. During cancer progression, tumors may acquire new phenotype traits, such as the ability to invade and metastasize or to become clinically important when they develop drug resistance. Non-deleterious chromosomal alterations contribute to this progression. PMID:28723940

Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants.

PubMed

Fu, Wenqing; O'Connor, Timothy D; Jun, Goo; Kang, Hyun Min; Abecasis, Goncalo; Leal, Suzanne M; Gabriel, Stacey; Rieder, Mark J; Altshuler, David; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J; Akey, Joshua M

2013-01-10

Establishing the age of each mutation segregating in contemporary human populations is important to fully understand our evolutionary history and will help to facilitate the development of new approaches for disease-gene discovery. Large-scale surveys of human genetic variation have reported signatures of recent explosive population growth, notable for an excess of rare genetic variants, suggesting that many mutations arose recently. To more quantitatively assess the distribution of mutation ages, we resequenced 15,336 genes in 6,515 individuals of European American and African American ancestry and inferred the age of 1,146,401 autosomal single nucleotide variants (SNVs). We estimate that approximately 73% of all protein-coding SNVs and approximately 86% of SNVs predicted to be deleterious arose in the past 5,000-10,000 years. The average age of deleterious SNVs varied significantly across molecular pathways, and disease genes contained a significantly higher proportion of recently arisen deleterious SNVs than other genes. Furthermore, European Americans had an excess of deleterious variants in essential and Mendelian disease genes compared to African Americans, consistent with weaker purifying selection due to the Out-of-Africa dispersal. Our results better delimit the historical details of human protein-coding variation, show the profound effect of recent human history on the burden of deleterious SNVs segregating in contemporary populations, and provide important practical information that can be used to prioritize variants in disease-gene discovery.

Effects of microcystin-LR and cylindrospermopsin on plant-soil systems: A review of their relevance for agricultural plant quality and public health

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

Machado, J.; Campos, A.

Toxic cyanobacterial blooms are recognized as an emerging environmental threat worldwide. Although microcystin-LR is the most frequently documented cyanotoxin, studies on cylindrospermopsin have been increasing due to the invasive nature of cylindrospermopsin-producing cyanobacteria. The number of studies regarding the effects of cyanotoxins on agricultural plants has increased in recent years, and it has been suggested that the presence of microcystin-LR and cylindrospermopsin in irrigation water may cause toxic effects in edible plants. The uptake of these cyanotoxins by agricultural plants has been shown to induce morphological and physiological changes that lead to a potential loss of productivity. There is alsomore » evidence that edible terrestrial plants can bioaccumulate cyanotoxins in their tissues in a concentration dependent-manner. Moreover, the number of consecutive cycles of watering and planting in addition to the potential persistence of microcystin-LR and cylindrospermopsin in the environment are likely to result in groundwater contamination. The use of cyanotoxin-contaminated water for agricultural purposes may therefore represent a threat to both food security and food safety. However, the deleterious effects of cyanotoxins on agricultural plants and public health seem to be dependent on the concentrations studied, which in most cases are non-environmentally relevant. Interestingly, at ecologically relevant concentrations, the productivity and nutritional quality of some agricultural plants seem not to be impaired and may even be enhanced. However, studies assessing if the potential tolerance of agricultural plants to these concentrations can result in cyanotoxin and allergen accumulation in the edible tissues are lacking. This review combines the most current information available regarding this topic with a realistic assessment of the impact of cyanobacterial toxins on agricultural plants, groundwater quality and public health. - Highlights: • Deleterious effects of MC-LR/CYN on agricultural plants are concentration-dependent. • Toxic effects of MC-LR and CYN at ecological conditions are scarce. • The bioaccumulation of MC-LR/CYN in vegetables is time- and concentration-dependent. • The persistence of MC-LR/CYN on soil systems can result in groundwater contamination. • A realistic assessment of the impact of MC-LR/CYN on agricultural plants was made.« less

Distance from sub-Saharan Africa predicts mutational load in diverse human genomes.

PubMed

Henn, Brenna M; Botigué, Laura R; Peischl, Stephan; Dupanloup, Isabelle; Lipatov, Mikhail; Maples, Brian K; Martin, Alicia R; Musharoff, Shaila; Cann, Howard; Snyder, Michael P; Excoffier, Laurent; Kidd, Jeffrey M; Bustamante, Carlos D

2016-01-26

The Out-of-Africa (OOA) dispersal ∼ 50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

Environmental Toxicity and Poor Cognitive Outcomes in Children and Adults

PubMed Central

Liu, Jianghong; Lewis, Gary

2014-01-01

Extensive literature has already documented the deleterious effects of heavy metal toxins on the human brain and nervous system. These toxins, however, represent only a fraction of the environmental hazards that may pose harm to cognitive ability in humans. Lead and mercury exposure, air pollution, and organic compounds all have the potential to damage brain functioning yet remain understudied. In order to provide comprehensive and effective public health and health care initiatives for prevention and treatment, we must first fully understand the potential risks, mechanisms of action, and outcomes surrounding exposure to these elements in the context of neurocognitive ability. This article provides a review of the negative effects on cognitive ability of these lesser-studied environmental toxins, with an emphasis on delineating effects observed in child versus adult populations. Possible differential effects across sociodemographic populations (e.g., urban versus rural residents; ethnic minorities) are discussed as important contributors to risk assessment and the development of prevention measures. The public health and clinical implications are significant and offer ample opportunities for clinicians and researchers to help combat this growing problem. PMID:24645424

Environmental toxicity and poor cognitive outcomes in children and adults.

PubMed

Liu, Jianghong; Lewis, Gary

2014-01-01

Extensive literature has already documented the deleterious effects of heavy metal toxins on the human brain and nervous system. These toxins, however, represent only a fraction of the environmental hazards that may pose harm to cognitive ability in humans. Lead and mercury exposure, air pollution, and organic compounds all have the potential to damage brain functioning yet remain understudied. In order to provide comprehensive and effective public health and health care initiatives for prevention and treatment, we must first fully understand the potential risks, mechanisms of action, and outcomes surrounding exposure to these elements in the context of neurocognitive ability. This article provides a review of the negative effects on cognitive ability of these lesser-studied environmental toxins, with an emphasis on delineating effects observed in child versus adult populations. Possible differential effects across sociodemographic populations (e.g., urban versus rural residents; ethnic minorities) are discussed as important contributors to risk assessment and the development of prevention measures. The public health and clinical implications are significant and offer ample opportunities for clinicians and researchers to help combat this growing problem.

Relieving feelings of strain among women with elderly mothers.

PubMed

Scharlach, A E

1987-03-01

I hypothesized that feelings of strain experienced by an adult daughter are likely to interfere with the nature of her relationship with her aging mother and to have a potentially deleterious effect on the mother. To test this proposition, I devised a study that examined the impact of two brief interventions on 37 middle-aged women and 24 of their elderly mothers: (a) a cognitive-behavioral presentation designed to reduce the daughter's unrealistic feelings of responsibility and (b) a supportive-educational presentation designed to increase the daughter's awareness of her mother's needs. I found that the first procedure was more effective than the second in reducing the daughter's burden, improving the mother-daughter relationship, and decreasing the loneliness experienced by the elderly mother.

Risk of brain tumors from wireless phone use.

PubMed

Dubey, Rash Bihari; Hanmandlu, Madasu; Gupta, Suresh Kumar

2010-01-01

The debate regarding the health effects of low-intensity electromagnetic radiation from sources such as power lines, base stations, and cell phones has recently been reignited. Wireless communication has dramatically influenced our lifestyle; its impact on human health has not been completely assessed. Widespread concern continues in the community about the deleterious effects of radiofrequency radiations on human tissues and the subsequent potential threat of carcinogenesis. Exposure to low-frequency electromagnetic field has been linked to a variety of adverse health outcomes. This article surveys the results of early cell phone studies, where exposure duration was too short to expect tumor genesis, and 2 sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Hardell.

Substance use in the perinatal period

PubMed Central

Forray, Ariadna; Foster, Dawn

2015-01-01

Perinatal substance use remains a major public health problem and is associated with a number of deleterious maternal and fetal effects. Polysubstance use in pregnancy is common, and can potentiate adverse maternal and fetal outcomes. Tobacco is the most commonly used substance in pregnancy, followed by alcohol and illicit substances. The treatments for perinatal substance use are limited and consist mostly of behavioral and psychosocial interventions. Of these contingency management has shown the most efficacy. More recently, novel interventions such as progesterone for postpartum cocaine use have shown promise. The purpose of this review is to examine the recent literature on the use of tobacco, alcohol, cannabis, stimulants, and opioids in the perinatal period, their effects on maternal and fetal health and current treatments. PMID:26386836

Hypokalemia causing rhabdomyolysis in a patient with short bowel syndrome.

PubMed

Balhara, Kamna S; Highet, Bridget; Omron, Rodney

2015-04-01

Rhabdomyolysis, usually in the setting of trauma or drug use, is frequently seen in the emergency setting, and often leads to hyperkalemia at presentation. Hypokalemia, however, is a potentially underrecognized cause of rhabdomyolysis. We present a case of rhabdomyolysis likely due to hypokalemia in the setting of short bowel syndrome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although less common, hypokalemia can be a significant cause of rhabdomyolysis via its effects on muscle. This scenario should be considered in the differential diagnosis of patients at risk for hypokalemia who present with weakness. Rapid recognition of this relationship and rapid correction of hypokalemia may prove very important in preventing the deleterious effects of rhabdomyolysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Genotoxicity of gemfibrozil in the gilthead seabream (Sparus aurata).

PubMed

Barreto, A; Luis, L G; Soares, A M V M; Paíga, P; Santos, L H M L M; Delerue-Matos, C; Hylland, K; Loureiro, S; Oliveira, M

2017-09-01

Widespread use of pharmaceuticals and suboptimal wastewater treatment have led to increased levels of these substances in aquatic ecosystems. Lipid-lowering drugs such as gemfibrozil, which are among the most abundant human pharmaceuticals in the environment, may have deleterious effects on aquatic organisms. We examined the genotoxicity of gemfibrozil in a fish species, the gilthead seabream (Sparus aurata), which is commercially important in southern Europe. Following 96-h waterborne exposure, molecular (erythrocyte DNA strand breaks) and cytogenetic (micronuclei and other nuclear abnormalities in cells) endpoints were measured. Gemfibrozil was positive in both endpoints, at environmentally relevant concentrations, a result that raises concerns about the potential genotoxic effects of the drug in recipient waters. Copyright © 2017 Elsevier B.V. All rights reserved.

The legacy of domestication: accumulation of deleterious mutations in the dog genome.

PubMed

Cruz, Fernando; Vilà, Carles; Webster, Matthew T

2008-11-01

Dogs exhibit more phenotypic variation than any other mammal and are affected by a wide variety of genetic diseases. However, the origin and genetic basis of this variation is still poorly understood. We examined the effect of domestication on the dog genome by comparison with its wild ancestor, the gray wolf. We compared variation in dog and wolf genes using whole-genome single nucleotide polymorphism (SNP) data. The d(N)/d(S) ratio (omega) was around 50% greater for SNPs found in dogs than in wolves, indicating that a higher proportion of nonsynonymous alleles segregate in dogs compared with nonfunctional genetic variation. We suggest that the majority of these alleles are slightly deleterious and that two main factors may have contributed to their increase. The first is a relaxation of selective constraint due to a population bottleneck and altered breeding patterns accompanying domestication. The second is a reduction of effective population size at loci linked to those under positive selection due to Hill-Robertson interference. An increase in slightly deleterious genetic variation could contribute to the prevalence of disease in modern dog breeds.

Heavy Metal Pollution from Gold Mines: Environmental Effects and Bacterial Strategies for Resistance.

PubMed

Fashola, Muibat Omotola; Ngole-Jeme, Veronica Mpode; Babalola, Olubukola Oluranti

2016-10-26

Mining activities can lead to the generation of large quantities of heavy metal laden wastes which are released in an uncontrolled manner, causing widespread contamination of the ecosystem. Though some heavy metals classified as essential are important for normal life physiological processes, higher concentrations above stipulated levels have deleterious effects on human health and biota. Bacteria able to withstand high concentrations of these heavy metals are found in the environment as a result of various inherent biochemical, physiological, and/or genetic mechanisms. These mechanisms can serve as potential tools for bioremediation of heavy metal polluted sites. This review focuses on the effects of heavy metal wastes generated from gold mining activities on the environment and the various mechanisms used by bacteria to counteract the effect of these heavy metals in their immediate environment.

Cognitive Load Mediates the Effect of Emotion on Analytical Thinking.

PubMed

Trémolière, Bastien; Gagnon, Marie-Ève; Blanchette, Isabelle

2016-11-01

Although the detrimental effect of emotion on reasoning has been evidenced many times, the cognitive mechanism underlying this effect remains unclear. In the present paper, we explore the cognitive load hypothesis as a potential explanation. In an experiment, participants solved syllogistic reasoning problems with either neutral or emotional contents. Participants were also presented with a secondary task, for which the difficult version requires the mobilization of cognitive resources to be correctly solved. Participants performed overall worse and took longer on emotional problems than on neutral problems. Performance on the secondary task, in the difficult version, was poorer when participants were reasoning about emotional, compared to neutral contents, consistent with the idea that processing emotion requires more cognitive resources. Taken together, the findings afford evidence that the deleterious effect of emotion on reasoning is mediated by cognitive load.

Heavy Metal Pollution from Gold Mines: Environmental Effects and Bacterial Strategies for Resistance

PubMed Central

Fashola, Muibat Omotola; Ngole-Jeme, Veronica Mpode; Babalola, Olubukola Oluranti

2016-01-01

Mining activities can lead to the generation of large quantities of heavy metal laden wastes which are released in an uncontrolled manner, causing widespread contamination of the ecosystem. Though some heavy metals classified as essential are important for normal life physiological processes, higher concentrations above stipulated levels have deleterious effects on human health and biota. Bacteria able to withstand high concentrations of these heavy metals are found in the environment as a result of various inherent biochemical, physiological, and/or genetic mechanisms. These mechanisms can serve as potential tools for bioremediation of heavy metal polluted sites. This review focuses on the effects of heavy metal wastes generated from gold mining activities on the environment and the various mechanisms used by bacteria to counteract the effect of these heavy metals in their immediate environment. PMID:27792205

Recent Advances on Endocrine Disrupting Effects of UV Filters

PubMed Central

Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

2016-01-01

Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives. PMID:27527194

A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients

PubMed Central

Sun, Yishan; Paşca, Sergiu P; Portmann, Thomas; Goold, Carleton; Worringer, Kathleen A; Guan, Wendy; Chan, Karen C; Gai, Hui; Vogt, Daniel; Chen, Ying-Jiun J; Mao, Rong; Chan, Karrie; Rubenstein, John LR; Madison, Daniel V; Hallmayer, Joachim; Froehlich-Santino, Wendy M; Bernstein, Jonathan A; Dolmetsch, Ricardo E

2016-01-01

Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixed results regarding the importance of Nav1.1 in human inhibitory versus excitatory neurons. We studied a Nav1.1 mutation (p.S1328P) identified in a pair of twins with Dravet Syndrome and generated iPSC-derived neurons from these patients. Characterization of the mutant channel revealed a decrease in current amplitude and hypersensitivity to steady-state inactivation. We then differentiated Dravet-Syndrome and control iPSCs into telencephalic excitatory neurons or medial ganglionic eminence (MGE)-like inhibitory neurons. Dravet inhibitory neurons showed deficits in sodium currents and action potential firing, which were rescued by a Nav1.1 transgene, whereas Dravet excitatory neurons were normal. Our study identifies biophysical impairments underlying a deleterious Nav1.1 mutation and supports the hypothesis that Dravet Syndrome arises from defective inhibitory neurons. DOI: http://dx.doi.org/10.7554/eLife.13073.001 PMID:27458797

The effect of polyandry on a distorter system with differential viabilities in the sexes.

PubMed

Manser, Andri; Lindholm, Anna K; König, Barbara; Bagheri, Homayoun C

2012-11-01

The presence of selfish genetic elements can have fatal consequences for populations that harbor them. In the well known t haplotype in wild house mice, large proportions of the population die from t/t recessive lethal effects. Due to strong advantages at the gamete level (drive), t haplotypes nevertheless occur at substantial frequencies. The stable presence of a lethal is not the only effect of the t. It also distorts the fate of mutations that differentially affect male and female survival and reproduction (such as in sexual conflict), by giving male selective effects a strong advantage over female selective effects. In a recent study, we proposed polyandry as a potential counterstrategy against t deleterious effects. Here, we show that (1) the efficiency of polyandry in reducing the t frequency strongly depends on the selective context and (2) polyandry helps to reduce male-biased leverage in sex dependent selection.

Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning.

PubMed

Zubedat, Salman; Aga-Mizrachi, Shlomit; Cymerblit-Sabba, Adi; Ritter, Ami; Nachmani, Maayan; Avital, Avi

2015-01-01

Either pre- or post-natal environmental factors seem to play a key role in brain and behavioral development and to exert long-term effects. Increasing evidence suggests that exposure to prenatal stress (PS) leads to motor and learning deficits and elevated anxiety, while enriched environment (EE) shows protective effects. The dopaminergic system is also sensitive to environmental life circumstances and affects attention functioning, which serves as the preliminary gate to cognitive processes. However, the effects of methylphenidate (MPH) on the dopaminergic system and attentional functioning, in the context of these life experiences, remain unclear. Therefore, we aimed to examine the effects of EE or PS on distinct types of attention, along with possible effects of MPH exposure. We found that PS impaired selective attention as well as partial sustained attention, while EE had beneficial effects. Both EE and MPH ameliorated the deleterious effects of PS on attention functioning. Considering the possible psychostimulant effect of MPH, we examined both anxiety-like behavior as well as motor learning. We found that PS had a clear anxiogenic effect, whereas EE had an anxiolytic effect. Nevertheless, the treatment with both MPH and/or EE recovered the deleterious effects of PS. In the motor-learning task, the PS group showed superior performance while MPH led to impaired motor learning. Performance decrements were prevented in both the PS + MPH and EE + MPH groups. This study provides evidence that peripubertal exposure to EE (by providing enhanced sensory, motor, and social opportunities) or MPH treatments might be an optional therapeutic intervention in preventing the PS long-term adverse consequences.

The Role of piRNA-Mediated Epigenetic Silencing in the Population Dynamics of Transposable Elements in Drosophila melanogaster

PubMed Central

Lee, Yuh Chwen G.

2015-01-01

The piwi-interacting RNAs (piRNA) are small RNAs that target selfish transposable elements (TEs) in many animal genomes. Until now, piRNAs’ role in TE population dynamics has only been discussed in the context of their suppression of TE transposition, which alone is not sufficient to account for the skewed frequency spectrum and stable containment of TEs. On the other hand, euchromatic TEs can be epigenetically silenced via piRNA-dependent heterochromatin formation and, similar to the widely known “Position-effect variegation”, heterochromatin induced by TEs can “spread” into nearby genes. We hypothesized that the piRNA-mediated spread of heterochromatin from TEs into adjacent genes has deleterious functional effects and leads to selection against individual TEs. Unlike previously identified deleterious effects of TEs due to the physical disruption of DNA, the functional effect we investigated here is mediated through the epigenetic influences of TEs. We found that the repressive chromatin mark, H3K9me, is elevated in sequences adjacent to euchromatic TEs at multiple developmental stages in Drosophila melanogaster. Furthermore, the heterochromatic states of genes depend not only on the number of and distance from adjacent TEs, but also on the likelihood that their nearest TEs are targeted by piRNAs. These variations in chromatin status probably have functional consequences, causing genes near TEs to have lower expression. Importantly, we found stronger selection against TEs that lead to higher H3K9me enrichment of adjacent genes, demonstrating the pervasive evolutionary consequences of TE-induced epigenetic silencing. Because of the intrinsic biological mechanism of piRNA amplification, spread of TE heterochromatin could result in the theoretically required synergistic deleterious effects of TE insertions for stable containment of TE copy number. The indirect deleterious impact of piRNA-mediated epigenetic silencing of TEs is a previously unexplored, yet important, element for the evolutionary dynamics of TEs. PMID:26042931

The Role of Chronic Inflammation in Obesity-Associated Cancers

PubMed Central

2013-01-01

There is a strong relationship between metabolism and immunity, which can become deleterious under conditions of metabolic stress. Obesity, considered a chronic inflammatory disease, is one example of this link. Chronic inflammation is increasingly being recognized as an etiology in several cancers, particularly those of epithelial origin, and therefore a potential link between obesity and cancer. In this review, the connection between the different factors that can lead to the chronic inflammatory state in the obese individual, as well as their effect in tumorigenesis, is addressed. Furthermore, the association between obesity, inflammation, and esophageal, liver, colon, postmenopausal breast, and endometrial cancers is discussed. PMID:23819063

Endocannabinoids as mediators in the heart: a potential target for therapy of remodelling after myocardial infarction?

PubMed Central

Hiley, C Robin; Ford, William R

2003-01-01

Endocannabinoid production by platelets and macrophages is increased in circulatory shock. This may be protective of the cardiovascular system as blockade of CB1 cannabinoid receptors exacerbates endothelial dysfunction in haemorrhagic and endotoxin shock and reduces survival. Now evidence suggests that blockade of CB1 receptors starting 24 h after myocardial infarction in rats has a deleterious effect on cardiac performance, while use of a nonselective cannabinoid receptor agonist prevents hypotension and reduces endothelial dysfunction, although left ventricular end diastolic pressure is elevated. Cannabinoids and endocannabinoid systems may therefore present useful targets for therapy following myocardial infarction. PMID:12711614

Hyperspectral near-infrared reflectance imaging for detection of defect tomatoes

USDA-ARS?s Scientific Manuscript database

Cuticle cracks on tomatoes are potential sites of pathogenic infection that may cause deleterious consequences both to consumer health and to fresh and fresh-cut produce markets. The feasibility of a hyperspectral near-infrared imaging technique in the spectral range of 1000 nm to 1700 nm was inves...

A New Era for Research Education in Australia?

ERIC Educational Resources Information Center

Marsh, Helene; Smith, Bradley; King, Max; Evans, Terry

2012-01-01

Use of the Australian research assessment exercise, Excellence in Research for Australia (ERA) to influence the policy and practice of research education in Australia will undoubtedly have many consequences, some of them unintended and potentially deleterious. ERA is a retrospective measure of research quality; research education is prospective.…

Using SNPs with varying specificity to quantify hybridization between closely related but genetically distinct moth populations in the wild

USDA-ARS?s Scientific Manuscript database

Invasive insect species can potentially hybridize with closely related native populations to produce new phenotypes with deleterious economic and environmental consequences. Monitoring such events is often problematic because populations that can interbreed are typically sufficiently similar that it...

On the genetic parameter determining the efficiency of purging: an estimate for Drosophila egg-to-pupae viability.

PubMed

Bersabé, D; García-Dorado, A

2013-02-01

The consequences of inbreeding on fitness can be crucial in evolutionary and conservation grounds and depend upon the efficiency of purging against deleterious recessive alleles. Recently, analytical expressions have been derived to predict the evolution of mean fitness, taking into account both inbreeding and purging, which depend on an 'effective purging coefficient (d(e) )'. Here, we explore the validity of that predictive approach and assay the strength of purging by estimating d(e) for egg-to-pupae viability (EPV) after a drastic reduction in population size in a recently captured base population of Drosophila melanogaster. For this purpose, we first obtained estimates of the inbreeding depression rate (δ) for EPV in the base population, and we found that about 40% was due to segregating recessive lethals. Then, two sets of lines were founded from this base population and were maintained with different effective size throughout the rest of the experiment (N = 6; N = 12), their mean EPV being assayed at different generations. Due to purging, the reductions in mean EPV experienced by these lines were considerably smaller than the corresponding neutral predictions. For the 60% of δ attributable to nonlethal deleterious alleles, our results suggest an effective purging coefficient d(e) > 0.02. Similarly, we obtain that d(e) > 0.09 is required to roughly account for purging against the pooled inbreeding depression from lethal and nonlethal deleterious alleles. This implies that purging should be efficient for population sizes of the order of a few tens and larger, but might be inefficient against nonlethal deleterious alleles in smaller populations. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

CHEK2 contribution to hereditary breast cancer in non-BRCA families

PubMed Central

2011-01-01

Background Mutations in the BRCA1 and BRCA2 genes are responsible for only a part of hereditary breast cancer (HBC). The origins of "non-BRCA" HBC in families may be attributed in part to rare mutations in genes conferring moderate risk, such as CHEK2, which encodes for an upstream regulator of BRCA1. Previous studies have demonstrated an association between CHEK2 founder mutations and non-BRCA HBC. However, very few data on the entire coding sequence of this gene are available. Methods We investigated the contribution of CHEK2 mutations to non-BRCA HBC by direct sequencing of its whole coding sequence in 507 non-BRCA HBC cases and 513 controls. Results We observed 16 mutations in cases and 4 in controls, including 9 missense variants of uncertain consequence. Using both in silico tools and an in vitro kinase activity test, the majority of the variants were found likely to be deleterious for protein function. One variant present in both cases and controls was proposed to be neutral. Removing this variant from the pool of potentially deleterious variants gave a mutation frequency of 1.48% for cases and 0.29% for controls (P = 0.0040). The odds ratio of breast cancer in the presence of a deleterious CHEK2 mutation was 5.18. Conclusions Our work indicates that a variety of deleterious CHEK2 alleles make an appreciable contribution to breast cancer susceptibility, and their identification could help in the clinical management of patients carrying a CHEK2 mutation. PMID:22114986

ANMCO/AIOM/AICO Consensus Document on clinical and management pathways of cardio-oncology: executive summary.

PubMed

Tarantini, Luigi; Massimo Gulizia, Michele; Di Lenarda, Andrea; Maurea, Nicola; Giuseppe Abrignani, Maurizio; Bisceglia, Irma; Bovelli, Daniella; De Gennaro, Luisa; Del Sindaco, Donatella; Macera, Francesca; Parrini, Iris; Radini, Donatella; Russo, Giulia; Beatrice Scardovi, Angela; Inno, Alessandro

2017-05-01

Cardiovascular disease and cancer are leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system. The above considerations have led to the development of a new branch of clinical cardiology based on the principles of multidisciplinary collaboration between cardiologists and oncologists: Cardio-oncology, which aims to find solutions to the prevention, monitoring, diagnosis and treatment of heart damage induced by cancer care in order to pursue, in the individual patient, the best possible care for cancer while minimizing the risk of cardiac toxicity. In this consensus document we provide practical recommendations on how to assess, monitor, treat and supervise the candidate or patient treated with potentially cardiotoxic cancer therapy in order to treat cancer and protect the heart at all stages of the oncological disease. Cardiovascular diseases and cancer often share the same risk factors and can coexist in the same individual. Such possibility is amplified by the deleterious effects of cancer treatment on the heart. The above considerations have led to the development of a new branch of clinical cardiology, based on multidisciplinary collaboration between cardiologist and oncologist: the cardio-oncology. It aims to prevent, monitor, and treat heart damages induced by cancer therapies in order to achieve the most effective cancer treatment, while minimizing the risk of cardiac toxicity. In this paper, we provide practical recommendations on how to assess, monitor, treat and supervise patients treated with potential cardiotoxic cancer therapies.

ANMCO/AIOM/AICO Consensus Document on clinical and management pathways of cardio-oncology: executive summary

PubMed Central

Tarantini, Luigi; Massimo Gulizia, Michele; Di Lenarda, Andrea; Maurea, Nicola; Giuseppe Abrignani, Maurizio; Bisceglia, Irma; Bovelli, Daniella; De Gennaro, Luisa; Del Sindaco, Donatella; Macera, Francesca; Parrini, Iris; Radini, Donatella; Russo, Giulia; Beatrice Scardovi, Angela; Inno, Alessandro

2017-01-01

Abstract Cardiovascular disease and cancer are leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system. The above considerations have led to the development of a new branch of clinical cardiology based on the principles of multidisciplinary collaboration between cardiologists and oncologists: Cardio-oncology, which aims to find solutions to the prevention, monitoring, diagnosis and treatment of heart damage induced by cancer care in order to pursue, in the individual patient, the best possible care for cancer while minimizing the risk of cardiac toxicity. In this consensus document we provide practical recommendations on how to assess, monitor, treat and supervise the candidate or patient treated with potentially cardiotoxic cancer therapy in order to treat cancer and protect the heart at all stages of the oncological disease. Cardiovascular diseases and cancer often share the same risk factors and can coexist in the same individual. Such possibility is amplified by the deleterious effects of cancer treatment on the heart. The above considerations have led to the development of a new branch of clinical cardiology, based on multidisciplinary collaboration between cardiologist and oncologist: the cardio-oncology. It aims to prevent, monitor, and treat heart damages induced by cancer therapies in order to achieve the most effective cancer treatment, while minimizing the risk of cardiac toxicity. In this paper, we provide practical recommendations on how to assess, monitor, treat and supervise patients treated with potential cardiotoxic cancer therapies. PMID:28751851

CRISPR-STOP: gene silencing through base-editing-induced nonsense mutations.

PubMed

Kuscu, Cem; Parlak, Mahmut; Tufan, Turan; Yang, Jiekun; Szlachta, Karol; Wei, Xiaolong; Mammadov, Rashad; Adli, Mazhar

2017-07-01

CRISPR-Cas9-induced DNA damage may have deleterious effects at high-copy-number genomic regions. Here, we use CRISPR base editors to knock out genes by changing single nucleotides to create stop codons. We show that the CRISPR-STOP method is an efficient and less deleterious alternative to wild-type Cas9 for gene-knockout studies. Early stop codons can be introduced in ∼17,000 human genes. CRISPR-STOP-mediated targeted screening demonstrates comparable efficiency to WT Cas9, which indicates the suitability of our approach for genome-wide functional screenings.

Combined sequence and sequence-structure-based methods for analyzing RAAS gene SNPs: a computational approach.

PubMed

Singh, Kh Dhanachandra; Karthikeyan, Muthusamy

2014-12-01

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure (BP). Mutations on the genes that encode components of the RAAS have played a significant role in genetic susceptibility to hypertension and have been intensively scrutinized. The identification of such probably causal mutations not only provides insight into the RAAS but may also serve as antihypertensive therapeutic targets and diagnostic markers. The methods for analyzing the SNPs from the huge dataset of SNPs, containing both functional and neutral SNPs is challenging by the experimental approach on every SNPs to determine their biological significance. To explore the functional significance of genetic mutation (SNPs), we adopted combined sequence and sequence-structure-based SNP analysis algorithm. Out of 3864 SNPs reported in dbSNP, we found 108 missense SNPs in the coding region and remaining in the non-coding region. In this study, we are reporting only those SNPs in coding region to be deleterious when three or more tools are predicted to be deleterious and which have high RMSD from the native structure. Based on these analyses, we have identified two SNPs of REN gene, eight SNPs of AGT gene, three SNPs of ACE gene, two SNPs of AT1R gene, three SNPs of CYP11B2 gene and three SNPs of CMA1 gene in the coding region were found to be deleterious. Further this type of study will be helpful in reducing the cost and time for identification of potential SNP and also helpful in selecting potential SNP for experimental study out of SNP pool.

Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African Buffalo: a plausible new mechanism for a high frequency anomaly.

PubMed

van Hooft, Pim; Greyling, Ben J; Getz, Wayne M; van Helden, Paul D; Zwaan, Bas J; Bastos, Armanda D S

2014-01-01

Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has important implications for our understanding not only of the evolutionary and ecological dynamics of sex-ratio distorters and suppressors, but also of the functioning of deleterious and sexually-antagonistic alleles, and their impact on population viability.

Indoor terpene emissions from cooking with herbs and pepper and their secondary organic aerosol production potential

PubMed Central

Klein, Felix; Farren, Naomi J.; Bozzetti, Carlo; Daellenbach, Kaspar R.; Kilic, Dogushan; Kumar, Nivedita K.; Pieber, Simone M.; Slowik, Jay G.; Tuthill, Rosemary N.; Hamilton, Jacqueline F.; Baltensperger, Urs; Prévôt, André S. H.; El Haddad, Imad

2016-01-01

Cooking is widely recognized as an important source of indoor and outdoor particle and volatile organic compound emissions with potential deleterious effects on human health. Nevertheless, cooking emissions remain poorly characterized. Here the effect of herbs and pepper on cooking emissions was investigated for the first time to the best of our knowledge using state of the art mass spectrometric analysis of particle and gas-phase composition. Further, the secondary organic aerosol production potential of the gas-phase emissions was determined by smog chamber aging experiments. The emissions of frying meat with herbs and pepper include large amounts of mono-, sesqui- and diterpenes as well as various terpenoids and p-cymene. The average total terpene emission rate from the use of herbs and pepper during cooking is estimated to be 46 ± 5 gg-1Herbs min-1. These compounds are highly reactive in the atmosphere and lead to significant amounts of secondary organic aerosol upon aging. In summary we demonstrate that cooking with condiments can constitute an important yet overlooked source of terpenes in indoor air. PMID:27830718

Indoor terpene emissions from cooking with herbs and pepper and their secondary organic aerosol production potential

NASA Astrophysics Data System (ADS)

Klein, Felix; Farren, Naomi J.; Bozzetti, Carlo; Daellenbach, Kaspar R.; Kilic, Dogushan; Kumar, Nivedita K.; Pieber, Simone M.; Slowik, Jay G.; Tuthill, Rosemary N.; Hamilton, Jacqueline F.; Baltensperger, Urs; Prévôt, André S. H.; El Haddad, Imad

2016-11-01

Cooking is widely recognized as an important source of indoor and outdoor particle and volatile organic compound emissions with potential deleterious effects on human health. Nevertheless, cooking emissions remain poorly characterized. Here the effect of herbs and pepper on cooking emissions was investigated for the first time to the best of our knowledge using state of the art mass spectrometric analysis of particle and gas-phase composition. Further, the secondary organic aerosol production potential of the gas-phase emissions was determined by smog chamber aging experiments. The emissions of frying meat with herbs and pepper include large amounts of mono-, sesqui- and diterpenes as well as various terpenoids and p-cymene. The average total terpene emission rate from the use of herbs and pepper during cooking is estimated to be 46 ± 5 gg-1Herbs min-1. These compounds are highly reactive in the atmosphere and lead to significant amounts of secondary organic aerosol upon aging. In summary we demonstrate that cooking with condiments can constitute an important yet overlooked source of terpenes in indoor air.

Indoor terpene emissions from cooking with herbs and pepper and their secondary organic aerosol production potential.

PubMed

Klein, Felix; Farren, Naomi J; Bozzetti, Carlo; Daellenbach, Kaspar R; Kilic, Dogushan; Kumar, Nivedita K; Pieber, Simone M; Slowik, Jay G; Tuthill, Rosemary N; Hamilton, Jacqueline F; Baltensperger, Urs; Prévôt, André S H; El Haddad, Imad

2016-11-10

Cooking is widely recognized as an important source of indoor and outdoor particle and volatile organic compound emissions with potential deleterious effects on human health. Nevertheless, cooking emissions remain poorly characterized. Here the effect of herbs and pepper on cooking emissions was investigated for the first time to the best of our knowledge using state of the art mass spectrometric analysis of particle and gas-phase composition. Further, the secondary organic aerosol production potential of the gas-phase emissions was determined by smog chamber aging experiments. The emissions of frying meat with herbs and pepper include large amounts of mono-, sesqui- and diterpenes as well as various terpenoids and p-cymene. The average total terpene emission rate from the use of herbs and pepper during cooking is estimated to be 46 ± 5 gg -1 Herbs min -1 . These compounds are highly reactive in the atmosphere and lead to significant amounts of secondary organic aerosol upon aging. In summary we demonstrate that cooking with condiments can constitute an important yet overlooked source of terpenes in indoor air.

Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

PubMed Central

Kwon, Jee Young; Koedrith, Preeyaporn; Seo, Young Rok

2014-01-01

Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. PMID:25565845

Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats.

PubMed

Marques-Neto, Silvio Rodrigues; Castiglione, Raquel Carvalho; Pontes, Aiza; Oliveira, Dahienne Ferreira; Ferraz, Emanuelle Baptista; Nascimento, José Hamilton Matheus; Bouskela, Eliete

2016-01-01

Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats. We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet. Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders.

Deleterious Effects From Occupational Exposure to Ethylene Thiourea in Pregnant Women.

PubMed

Mutic, Abby D; Baker, Brenda J; McCauley, Linda A

2017-12-01

Human exposure to endocrine disrupting chemicals (EDCs) has become common as a result of widespread application of these chemicals to the food supply, environmental contamination, and occupational exposures (Caserta et al., 2011). However, relatively little is known about the effects of EDCs such as ethylene thiourea (ETU) in developing fetuses and the lasting implications of this disruption on human development from birth through adulthood. Of highest concern are chronic, low-dose exposures among industrial and agricultural workers. Current knowledge regarding the significance of endocrine thyroid signaling on normal human development raises serious concerns about the possible deleterious effects of EDCs in the developing fetus, children, and mature adults. Occupational health nurses are critical in identifying women and families at increased risk of ETU exposure and mitigating early exposures in pregnancy.

Videoconferencing at psychology internships: interns' perceptions of interactive television experiences and prospects.

PubMed

Yozwiak, John A; Robiner, William N; Victor, Andrea M; Durmusoglu, Gokce

2010-09-01

This article reviews the use and perceptions of videoconferencing in psychology internship training from the perspective of interns. Videoconferencing offers a means of expanding training beyond conventional on-site models. Psychology interns completed an online survey about their experiences with videoconferencing and perspectives of its impact on training. Most participants encountered it in their didactics. Some used it for supervision or other purposes. Interns' perspectives were complex, with videoconferencing seen as supporting learning similar to conventional training in some ways, yet as less desirable overall. Direct comparisons between videoconferencing and on-site training revealed interns perceived videoconferencing as somewhat less effective, and as deleteriously affecting learning dynamics. Challenges and potential benefits of incorporating videoconferencing into psychology internship training were identified. Potential benefits include augmenting available internship training and increasing rural sites' access to training.

Antipsychotics activate the TGFβ pathway effector SMAD3

PubMed Central

Cohen, T.; Sundaresh, S.; Levine, F.

2014-01-01

Although effective in treating an array of neurological disorders, antipsychotics are associated with deleterious metabolic side effects. Through high-throughput screening, we previously identified phenothiazine antipsychotics as modulators of the human insulin promoter. Here, we extended our initial finding to structurally diverse typical and atypical antipsychotics. We then identified the TGFβ pathway as being involved in the effect of antipsychotics on the insulin promoter, finding that antipsychotics activated SMAD3, a downstream effector of the TGFβ pathway, through a receptor distinct from the TGFβ receptor family and known neurotransmitter receptor targets of antipsychotics. Of note, antipsychotics that do not cause metabolic side effects did not activate SMAD3. In vivo relevance was demonstrated by reanalysis of gene expression data from human brains treated with antipsychotics, which showed altered expression of SMAD3 responsive genes. This work raises the possibility that antipsychotics could be designed that retain beneficial CNS activity while lacking deleterious metabolic side effects. PMID:22290122

Effects of Marijuana Use on Brain Structure and Function: Neuroimaging Findings from a Neurodevelopmental Perspective

PubMed Central

Brumback, T.; Castro, N.; Jacobus, J.; Tapert, S.

2016-01-01

Marijuana, behind only tobacco and alcohol, is the most popular recreational drug in America with prevalence rates of use rising over the past decade. A wide range of research has highlighted neurocognitive deficits associated with marijuana use, particularly when initiated during childhood or adolescence. Neuroimaging, describing alterations to brain structure and function, has begun to provide a picture of possible mechanisms associated with the deleterious effects of marijuana use. This chapter provides a neurodevelopmental framework from which recent data on brain structural and functional abnormalities associated with marijuana use is reviewed. Based on the current data, we provide aims for future studies to more clearly delineate the effects of marijuana on the developing brain and to define underlying mechanisms of the potential long-term negative consequences of marijuana use. PMID:27503447

Counteraction of the deleterious effects of urea on structure and stability of mammalian kidney proteins by osmolytes.

PubMed

Dar, Mohammad Aasif; Wahiduzzaman; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

2018-02-01

Owing to the urine concentrating mechanism of kidney cells, urea concentration is very high (3.0-5.0M) in mammalian kidneys which may denature many kidney proteins. Methylamines are known to counteract the deleterious effects of urea on structure, stability and function of proteins at 2:1 molar ratio of urea to methylamines. It is known that mammalian kidney cells also contain stabilizing osmolytes, non-methylamines (myo-inositol and sorbitol). A question arises: Do these non-methylmine osmolytes have ability to counteract the deleterious effects of urea on kidney proteins? To answer this question, we took two kidney proteins, namely, sheep serum albumin and Human carbonic anhydrase II. We measured their thermodynamic stability (ΔG 0 N↔D , the Gibbs free energy change in absence of GdmCl (guanidinium chloride) associated with the equilibrium, native (N) state↔denatured (D) state) from the GdmCl-induced denaturation curves in the presence of different concentrations of urea and each kidney osmolyte individually and in combination. For both proteins, we observed that (i) glycine betaine and myo-inositol provide perfect counteraction at 2:1 molar ratio of urea to osmolyte, i.e., denaturing effect of 2M urea is 100% neutralized by 1M of glycine betaine (or myo-inositol), and (ii) sorbitol fails to refold urea denatured proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

The Nitrate-nitrite-NO pathway and its implications for Heart Failure and Preserved Ejection Fraction

PubMed Central

Chirinos, Julio A.; Zamani, Payman

2016-01-01

The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic LV load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term “disease-modifying” effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway. PMID:26792295

Mechanisms of nitrogen deposition effects on temperate forest lichens and trees

USGS Publications Warehouse

Carter, Therese S.; Clark, Christopher M.; Fenn, Mark E.; Jovan, Sarah E.; Perakis, Steven; Riddell, Jennifer; Schaberg, Paul G.; Greaver, Tara; Hastings, Meredith

2017-01-01

We review the mechanisms of deleterious nitrogen (N) deposition impacts on temperate forests, with a particular focus on trees and lichens. Elevated anthropogenic N deposition to forests has varied effects on individual organisms depending on characteristics both of the N inputs (form, timing, amount) and of the organisms (ecology, physiology) involved. Improved mechanistic knowledge of these effects can aid in developing robust predictions of how organisms respond to either increases or decreases in N deposition. Rising N levels affect forests in micro- and macroscopic ways from physiological responses at the cellular, tissue, and organism levels to influencing individual species and entire communities and ecosystems. A synthesis of these processes forms the basis for the overarching themes of this paper, which focuses on N effects at different levels of biological organization in temperate forests. For lichens, the mechanisms of direct effects of N are relatively well known at cellular, organismal, and community levels, though interactions of N with other stressors merit further research. For trees, effects of N deposition are better understood for N as an acidifying agent than as a nutrient; in both cases, the impacts can reflect direct effects on short time scales and indirect effects mediated through long-term soil and belowground changes. There are many gaps on fundamental N use and cycling in ecosystems, and we highlight the most critical gaps for understanding potential deleterious effects of N deposition. For lichens, these gaps include both how N affects specific metabolic pathways and how N is metabolized. For trees, these gaps include understanding the direct effects of N deposition onto forest canopies, the sensitivity of different tree species and mycorrhizal symbionts to N, the influence of soil properties, and the reversibility of N and acidification effects on plants and soils. Continued study of how these N response mechanisms interact with one another, and with other dimensions of global change, remains essential for predicting ongoing changes in lichen and tree populations across North American temperate forests.

Response of understory vegetation to salvage logging following a high-severity wildfire

Treesearch

Eric E. Knapp; Martin W. Ritchie

2016-01-01

Timber is frequently salvage-logged following high-severity stand-replacing wildfire, but the practice is controversial. One concern is that compound disturbances could result in more deleterious impacts than either disturbance individually, with mechanical operations having the potential to set back recovering native species and increase invasion by non-...

Rare deleterious mutations are associated with disease in bipolar disorder families.

PubMed

Rao, A R; Yourshaw, M; Christensen, B; Nelson, S F; Kerner, B

2017-07-01

Bipolar disorder (BD) is a common, complex and heritable psychiatric disorder characterized by episodes of severe mood swings. The identification of rare, damaging genomic mutations in families with BD could inform about disease mechanisms and lead to new therapeutic interventions. To determine whether rare, damaging mutations shared identity-by-descent in families with BD could be associated with disease, exome sequencing was performed in multigenerational families of the NIMH BD Family Study followed by in silico functional prediction. Disease association and disease specificity was determined using 5090 exomes from the Sweden-Schizophrenia (SZ) Population-Based Case-Control Exome Sequencing study. We identified 14 rare and likely deleterious mutations in 14 genes that were shared identity-by-descent among affected family members. The variants were associated with BD (P<0.05 after Bonferroni's correction) and disease specificity was supported by the absence of the mutations in patients with SZ. In addition, we found rare, functional mutations in known causal genes for neuropsychiatric disorders including holoprosencephaly and epilepsy. Our results demonstrate that exome sequencing in multigenerational families with BD is effective in identifying rare genomic variants of potential clinical relevance and also disease modifiers related to coexisting medical conditions. Replication of our results and experimental validation are required before disease causation could be assumed.

Plant water potential improves prediction of empirical stomatal models.

PubMed

Anderegg, William R L; Wolf, Adam; Arango-Velez, Adriana; Choat, Brendan; Chmura, Daniel J; Jansen, Steven; Kolb, Thomas; Li, Shan; Meinzer, Frederick; Pita, Pilar; Resco de Dios, Víctor; Sperry, John S; Wolfe, Brett T; Pacala, Stephen

2017-01-01

Climate change is expected to lead to increases in drought frequency and severity, with deleterious effects on many ecosystems. Stomatal responses to changing environmental conditions form the backbone of all ecosystem models, but are based on empirical relationships and are not well-tested during drought conditions. Here, we use a dataset of 34 woody plant species spanning global forest biomes to examine the effect of leaf water potential on stomatal conductance and test the predictive accuracy of three major stomatal models and a recently proposed model. We find that current leaf-level empirical models have consistent biases of over-prediction of stomatal conductance during dry conditions, particularly at low soil water potentials. Furthermore, the recently proposed stomatal conductance model yields increases in predictive capability compared to current models, and with particular improvement during drought conditions. Our results reveal that including stomatal sensitivity to declining water potential and consequent impairment of plant water transport will improve predictions during drought conditions and show that many biomes contain a diversity of plant stomatal strategies that range from risky to conservative stomatal regulation during water stress. Such improvements in stomatal simulation are greatly needed to help unravel and predict the response of ecosystems to future climate extremes.

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age.

PubMed

Bedarida, Tatiana; Baron, Stephanie; Vessieres, Emilie; Vibert, Francoise; Ayer, Audrey; Marchiol-Fournigault, Carmen; Henrion, Daniel; Paul, Jean-Louis; Noble, Florence; Golmard, Jean-Louis; Beaudeux, Jean-Louis; Cottart, Charles-Henry; Nivet-Antoine, Valerie

2014-09-01

High-protein-low-carbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet. Copyright © 2014 the American Physiological Society.

Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.

PubMed

Felice, Juan Ignacio; Schurman, León; McCarthy, Antonio Desmond; Sedlinsky, Claudia; Aguirre, José Ignacio; Cortizo, Ana María

2017-04-01

Deleterious effects of metabolic syndrome (MS) on bone are still controversial. In this study we evaluated the effects of a fructose-induced MS, and/or an oral treatment with metformin on the osteogenic potential of bone marrow mesenchymal stromal cells (MSC), as well as on bone formation and architecture. 32 male 8week-old Wistar rats were assigned to four groups: control (C), control plus oral metformin (CM), rats receiving 10% fructose in drinking water (FRD), and FRD plus metformin (FRDM). Samples were collected to measure blood parameters, and to perform pQCT analysis and static and dynamic histomorphometry. MSC were isolated to determine their osteogenic potential. Metformin improved blood parameters in FRDM rats. pQCT and static and dynamic histomorphometry showed no significant differences in trabecular and cortical bone parameters among groups. FRD reduced TRAP expression and osteocyte density in trabecular bone and metformin only normalized osteocyte density. FRD decreased the osteogenic potential of MSC and metformin administration could revert some of these parameters. FRD-induced MS shows reduction in MSC osteogenic potential, in osteocyte density and in TRAP activity. Oral metformin treatment was able to prevent trabecular osteocyte loss and the reduction in extracellular mineralization induced by FRD-induced MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders.

PubMed

Lorenz, Carmen; Lesimple, Pierre; Bukowiecki, Raul; Zink, Annika; Inak, Gizem; Mlody, Barbara; Singh, Manvendra; Semtner, Marcus; Mah, Nancy; Auré, Karine; Leong, Megan; Zabiegalov, Oleksandr; Lyras, Ekaterini-Maria; Pfiffer, Vanessa; Fauler, Beatrix; Eichhorst, Jenny; Wiesner, Burkhard; Huebner, Norbert; Priller, Josef; Mielke, Thorsten; Meierhofer, David; Izsvák, Zsuzsanna; Meier, Jochen C; Bouillaud, Frédéric; Adjaye, James; Schuelke, Markus; Wanker, Erich E; Lombès, Anne; Prigione, Alessandro

2017-05-04

Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment. High-content screening of FDA-approved drugs using the MMP phenotype highlighted avanafil, which we found was able to partially rescue the calcium defect in patient NPCs and differentiated neurons. Overall, our results show that iPSC-derived NPCs provide an effective model for drug screening to target mtDNA disorders that affect the nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

A Case Report of Cannabis Induced Hemoptysis

PubMed Central

Hashmi, Hafiz Rizwan Talib; Duncalf, Richard; Khaja, Misbahuddin

2016-01-01

Abstract As the principal route of marijuana use is by inhalation, potential harmful consequences on pulmonary structure and function can be anticipated. Here, we present a case of hemoptysis attributed to smoking cannabis in a 38-year-old man. The patient experienced an episode of hemoptysis and shortness of breath immediately after smoking marijuana. Chest radiograph and computed tomography (CT) scans of the chest showed bilateral diffuse ground-glass opacities. A fiber optic bronchoscopy confirmed bilateral diffuse bleeding from respiratory tract. Additional evaluation of hemoptysis indicated no infection or immunological responses. Urine toxicology was positive for cannabis. Chronic marijuana smoking causes visible and microscopic injury to the larger airways responsible for symptoms or chronic bronchitis. We review the beneficial and deleterious effects of marijuana and describe a case of significant hemoptysis attributed to smoking marijuana. In addition to other respiratory complications of marijuana use, physicians should educate their patients about this potentially lethal effect of marijuana smoking in the form of hemoptysis. PMID:27043693

Antiepileptic drugs and brain maturation: fetal exposure to lamotrigine generates cortical malformations in rats.

PubMed

Manent, Jean-Bernard; Jorquera, Isabel; Franco, Valentina; Ben-Ari, Yehezkel; Perucca, Emilio; Represa, Alfonso

2008-02-01

Intake of antiepileptic drugs (AEDs) during pregnancy can provoke severe and subtle fetal malformations associated with deleterious sequelae, reflecting the need for experimental investigations on the comparative teratogenic potential of these agents. We recently reported that prenatal exposure to vigabatrin and valproate, two AEDs which act through GABAergic mechanisms, induces hippocampal and cortical dysplasias in rodents. We have now investigated the effects of phenobarbital (PB, 30 mg/kg day) i.p.), a drug also endowed with GABAergic effects, and the new generation AEDs lamotrigine (LTG, 5-20mg/kg/day i.p.), topiramate (TPM, 10mg/kg/day i.p.), and levetiracetam (LEV, 50mg/kg/day i.p.) on brain development. Prenatal exposure to LTG induced hippocampal and cortical malformations in a dose-dependent manner, at maternal plasma concentrations within the clinically occurring range. These abnormalities were not observed after exposure to PB, TP and LEV. These observations raise concerns about potential clinical correlates and call for detailed comparative investigations on the consequences of AED use during pregnancy.

Combined effects of gamma radiation doses and sodium nitrite content on the lipid oxidation and color of mortadella.

PubMed

Dutra, Monalisa Pereira; Cardoso, Giselle Pereira; Fontes, Paulo Rogério; Silva, Douglas Roberto Guimarães; Pereira, Marcio Tadeu; Ramos, Alcinéia de Lemos Souza; Ramos, Eduardo Mendes

2017-12-15

The effects of different doses of gamma radiation (0-20kGy) on the color and lipid oxidation of mortadella prepared with increasing nitrite levels (0-300ppm) were evaluated using a central composite rotatable design. Higher radiation doses increased the redox potential, promoted the lipid oxidation and elevating the hue color of the mortadellas. Nevertheless, higher addition of sodium nitrite elevated the residual nitrite content, reduced the lipid oxidation and promoted the increase of redness and the reduce of hue color of the mortadellas, regardless of the radiation dose applied. Nitrite addition had a greater effect than irradiation on the quality parameters evaluated, and even at low levels (∼75ppm), its use decreased the deleterious effects of irradiation at doses as high as 20kGy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Salt potentiates methylamine counteraction system to offset the deleterious effects of urea on protein stability and function.

PubMed

Rahman, Safikur; Rehman, Md Tabish; Singh, Laishram R; Warepam, Marina; Ahmad, Faizan; Dar, Tanveer Ali

2015-01-01

Cellular methylamines are osmolytes (low molecular weight organic compounds) believed to offset the urea's harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea's effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction.

Marijuana for Glaucoma: A Recipe for Disaster or Treatment?

PubMed Central

Sun, Xiaoshen; Xu, Chaoying S.; Chadha, Nisha; Chen, Allshine; Liu, Ji

2015-01-01

Marijuana has been shown to lower intraocular pressure (IOP) but with limited duration of action and numerous adverse effects. Use of marijuana to lower IOP as a means of glaucoma treatment would require frequent use throughout the day, leading to significant adverse effects, possible progression toward Cannabis Use Disorder (CUD), and/or withdrawal symptoms. The treatment of glaucoma based on the cannabis plant or drugs based on the cannabinoid molecule should be considered carefully before being prescribed. Considerations should include the adverse physical and psychological adverse effects, including substance abuse. Currently, the deleterious effects of marijuana outweigh the benefits of its IOP-lowering capacity in most glaucoma patients. Under extremely rare circumstances, a few categories of glaucoma patients may be potential candidates for treatment with medical marijuana. Further studies on alternate routes and more focused means of cannabinoid molecule delivery to the eye for glaucoma treatment are needed. PMID:26339209

The impact of sleep loss on hippocampal function

PubMed Central

Prince, Toni-Moi; Abel, Ted

2013-01-01

Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep deprivation to impair memory consolidation and plasticity. In this review, we address these topics with a focus on the detrimental effects of post-learning sleep deprivation on memory consolidation. Obtaining adequate sleep is challenging in a society that values “work around the clock.” Therefore, the development of interventions to combat the negative cognitive effects of sleep deprivation is key. However, there are a limited number of therapeutics that are able to enhance cognition in the face of insufficient sleep. The identification of molecular pathways implicated in the deleterious effects of sleep deprivation on memory could potentially yield new targets for the development of more effective drugs. PMID:24045505

Marijuana for Glaucoma: A Recipe for Disaster or Treatment?

PubMed

Sun, Xiaoshen; Xu, Chaoying S; Chadha, Nisha; Chen, Allshine; Liu, Ji

2015-09-01

Marijuana has been shown to lower intraocular pressure (IOP) but with limited duration of action and numerous adverse effects. Use of marijuana to lower IOP as a means of glaucoma treatment would require frequent use throughout the day, leading to significant adverse effects, possible progression toward Cannabis Use Disorder (CUD), and/or withdrawal symptoms. The treatment of glaucoma based on the cannabis plant or drugs based on the cannabinoid molecule should be considered carefully before being prescribed. Considerations should include the adverse physical and psychological adverse effects, including substance abuse. Currently, the deleterious effects of marijuana outweigh the benefits of its IOP-lowering capacity in most glaucoma patients. Under extremely rare circumstances, a few categories of glaucoma patients may be potential candidates for treatment with medical marijuana. Further studies on alternate routes and more focused means of cannabinoid molecule delivery to the eye for glaucoma treatment are needed.

Sex-differential heterologous (non-specific) effects of vaccines: an emerging public health issue that needs to be understood and exploited.

PubMed

Flanagan, Katie L; Plebanski, Magdalena

2017-01-01

Vaccines have heterologous effects on the immune system, leading to altered susceptibility to a range of pathogens, and possibly allergy and autoimmunity. Effects are often sex-differential. This review discusses the evidence, mechanisms and public health implications of the non-specific effects of vaccines (NSEs). Areas covered: This article firstly discusses the World Health Organization systematic review of the evidence for sex-differential heterologous effects of vaccines, and further PubMed indexed studies on NSEs on susceptibility to infectious diseases, allergy, autoimmunity and malignancy in animals and humans. Potential immunological mechanisms are evaluated, including sex-differential effects. Finally it describes how advances in systems biology might be applied to study such effects. Expert commentary: This section points out the need to understand immune mechanisms in order to exploit beneficial vaccine effects, and diminish deleterious ones. It suggests analysis of vaccine effects by sex is important, and discusses the future for personalised vaccines that take these effects into account.

Economic growth and mortality: do social protection policies matter?

PubMed

Bilal, Usama; Cooper, Richard; Abreu, Francis; Nau, Claudia; Franco, Manuel; Glass, Thomas A

2017-08-01

In the 20th century, periods of macroeconomic growth have been associated with increases in population mortality. Factors that cause or mitigate this association are not well understood. Evidence suggests that social policy may buffer the deleterious impact of economic growth. We sought to explore associations between changing unemployment (as a proxy for economic change) and trends in mortality over 30 years in the context of varying social protection expenditures. We model change in all-cause mortality in 21 OECD (Organization for Economic Cooperation and Development) countries from 1980 to 2010. Data from the Comparative Welfare States Data Set and the WHO Mortality Database were used. A decrease in the unemployment rate was used as a proxy for economic growth and age-adjusted mortality rates as the outcome. Social protection expenditure was measured as percentage of gross domestic product expended. A 1% decrease in unemployment (i.e. the proxy for economic growth) was associated with a 0.24% increase in the overall mortality rate (95% confidence interval: 0.07;0.42) in countries with no changes in social protection. Reductions in social protection expenditure strengthened this association between unemployment and mortality. The magnitude of the association was diminished over time. Our results are consistent with the hypothesis that social protection policies that accompany economic growth can mitigate its potential deleterious effects on health. Further research should identify specific policies that are most effective. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Polyoxometalates as antitumor agents: Bioactivity of a new polyoxometalate with copper on a human osteosarcoma model.

PubMed

León, I E; Porro, V; Astrada, S; Egusquiza, M G; Cabello, C I; Bollati-Fogolin, M; Etcheverry, S B

2014-10-05

Polyoxometalates (POMs) are early transition metal oxygen anion clusters. They display interesting biological effects mainly related to their antiviral and antitumor properties. On the other hand, copper compounds also show different biological and pharmacological effects in cell culture and in animal models. We report herein for the first time, a detailed study of the mechanisms of action of a copper(II) compound of the group of HPOMs with the formula K7Na3[Cu4(H2O)2(PW9034)2]20H2O (PW9Cu), in a model of human osteosarcoma derived cell line, MG-63. The compound inhibited selectively the viability of the osteosarcoma cells in the range of 25-100μM (p<0.01). Besides, we have clearly shown a more deleterious action of PW9Cu on tumor osteoblasts than in normal cells. Cytotoxicity studies also showed deleterious effects for PW9Cu. The increment of reactive oxygen species (ROS) and the decrease of the GSH/GSSG ratio were involved in the antiproliferative effects of PW9Cu. Moreover, the compound caused cell cycle arrest in G2 phase, triggering apoptosis as determined by flow cytometry. As a whole, these results showed the main mechanisms of the deleterious effects of PW9Cu in the osteosarcoma cell line MG-63, demonstrating that this compound is a promissory agent for cancer treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

EPA Science Inventory

Ozone (03) is a criteria air pollutant that is associated with numerous adverse health effects, including altered respiratory immune responses. Despite its deleterious health effects, possible epigenetic mechanisms underlying 03-induced health effects remain understudied. MicroRN...

Mice housed on coal dust-contaminated sand: A model to evaluate the impacts of coal mining on health.

PubMed

Caballero-Gallardo, Karina; Olivero-Verbel, Jesus

2016-03-01

Coal dust is the most important air pollutant in coal mining in regards to producing deleterious health effects. It permeates the surrounding environment threatening public health. The aim of this study was to evaluate the toxic effects associated with exposure to sand contaminated with coal dust particles below 38 μm in diameter, obtained from a mineral sample collected in the largest coal mine in South America, La Loma, Cesar, Colombia. Sterilized sand was spiked with coal dust to obtain concentrations ranging from zero to 4% coal dust. To model natural exposure, mice were housed for eight weeks in boxes containing this mixture as bedding after which, they were euthanized and blood and tissue samples were collected. Real time PCR analysis revealed an increase in Cyp1A1 mRNA for living on sand with coal dust concentrations greater than 2% compared to mice living on sand without coal dust. Unexpectedly, for mice on coal dust-polluted sand, Sod1, Scd1 and Nqo1 hepatic mRNA were downregulated. The Comet assay in peripheral blood cells and the micronucleus test in blood smears, showed a significant potential genotoxic effect only at the highest coal dust concentration. Histopathological analysis revealed vascular congestion and peribronchial inflammation in the lungs. A dose-response relationship for the presence of hepatic steatosis, vacuolization and nuclei enlargements was observed in the exposed animals. The data suggest living on a soil polluted with coal dust induces molecular, cellular and histopathological changes in mice. Accordingly, the proposed model can be used to identify deleterious effects of exposure to coal dust deposited in soils that may pose health risks for surrounding wildlife populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

PubMed

Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

2015-01-01

Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

PubMed Central

Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

2015-01-01

Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

Dose and Chemical Modification Considerations for Continuous Cyclic AMP Analog Delivery to the Injured CNS

PubMed Central

Fouad, Karim; Ghosh, Mousumi; Vavrek, Romana; Tse, Arthur D.

2009-01-01

Abstract In this investigation, two cell-permeable synthetic analogs of cAMP, dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP, which are widely used to elevate intracellular cAMP levels under experimental conditions, were investigated for their ability to dose-dependently improve histological and functional outcomes following continuous delivery in two models of incomplete spinal cord injury (SCI). The cAMP analogs were delivered via osmotic minipumps at 1–250 mM through an indwelling cortical cannula or by intrathecal infusion for up to 4 weeks after either a T8 unilateral over-hemisection or a C2-3 dorsolateral quadrant lesion, respectively. In both SCI models, continuous db-cAMP delivery was associated with histopathological changes that included sporadic micro-hemorrhage formation and cavitation, enhanced macrophage infiltration and tissue damage at regions beyond the immediate application site; no deleterious or beneficial effect of agent delivery was observed at the spinal injury site. Furthermore, these changes were accompanied by pronounced behavioral deficits that included an absence of progressive locomotor recovery, increased extensor tone, paralysis, and sensory abnormalities. These deleterious effects were not observed in saline-treated animals, in animals in which the db-cAMP dose did not exceed 1 mM, or in those animals that received a high dose (250 mM) of the alternative cAMP analog, 8-bromo-cAMP. These results demonstrate that, for continuous intraparenchymal or intrathecal administration of cAMP analogs for the study of biological or therapeutic effects within the central nervous system (CNS), consideration of the effective concentration applied as well as the potential toxicity of chemical moieties on the parent molecule and/or their activity needs to be taken into account. PMID:19397425

Meteorite Impacts and Planetary Habitability: The Good, the Bad, and the Ugly

NASA Astrophysics Data System (ADS)

Osinski, G. R.

2012-12-01

It is now widely accepted that meteorite impacts negatively affect life on a planet, as evidenced by the deleterious effects associated with the formation of the Chicxulub impact structure, Mexico, 65 Myr. ago and its link to the Cretaceous-Paleogene mass extinction event. This impact event had a profound affect on the evolution of life on Earth by ending the age of the dinosaurs and paving the way for mammals to ascend to dominance. In terms of the origin of life, despite the controversy over when exactly life appeared on Earth, it is likely that it did so during one of the harshest, most inhospitable times in Earth history: the Late Heavy Bombardment Period ~4.0-3.8 Ga. During this time, asteroid and comet impacts were ~10-20 times as frequent as they are at the present day. This may seem counterintuitive until one considers that these cataclysmic, initially destructive impact events may also have had beneficial effects with respect to life. This contribution will present a synthesis of information concerning the role that meteorite impacts may have played in the origin and evolution of life on Earth and, by analogy, with other planetary bodies throughout the Universe. It will hopefully be demonstrated that impact events do not just frustrate life, but that impact craters, once formed, may represent protected niches where life can survive and evolve and, potentially, where life may have originated. It is proposed that the geological, biological, and environmental changes known to be caused by an impact allow for the formulation of key cross-cutting hypotheses concerning the potential deleterious and beneficial effects of meteorite impact events. Most notably, it is proposed that impact events produce new, unique habitats for life and, therefore, can have an overall positive effect on planetary habitability. Habitats include: 1) impact-generated hydrothermal systems, which could provide habitats for thermophilic and hyperthermophilic microorganisms, 2) impact-processed crystalline rocks, which have increased porosity and translucence compared to unshocked materials, improving microbial colonization, 3) impact glasses, which, similar to volcanic glasses, provide an excellent readily available source of bioessential elements, and 4) impact crater lakes, which form protected sedimentary basins with various niches and that increase the preservation potential of fossils and organic material.

Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations.

PubMed

Auré, Karine; Dubourg, Odile; Jardel, Claude; Clarysse, Lucie; Sternberg, Damien; Fournier, Emmanuel; Laforêt, Pascal; Streichenberger, Nathalie; Petiot, Philippe; Gervais-Bernard, Hélène; Vial, Christophe; Bedat-Millet, Anne-Laure; Drouin-Garraud, Valérie; Bouillaud, Frédéric; Vandier, Christophe; Fontaine, Bertrand; Lombès, Anne

2013-11-19

To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide. Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts. Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations. The MT-ATP6 m.9185T>C p.Leu220Pro mutation, previously associated with Leigh syndrome, was present in all family members, while the MT-TL1 m.3271T>C mutation, a known cause of MELAS syndrome, was observed in the sole patient with MELAS presentation. Significant defect of complexes V and I as well as oxidative stress were observed in both primary fibroblasts and cybrid cells with 100% m.9185T>C mutation. Permanent plasma membrane depolarization and altered permeability to K(+) in fibroblasts provided a link with the paralysis episodes. Screening of 9 patients, based on their clinical phenotype, identified 4 patients with similar deleterious MT-ATP6 mutations (twice m.9185T>C and once m.9176T>C or m.8893T>C). A fifth patient presented with an original potentially deleterious MT-ATP8 mutation (m.8403T>C). All mutations were associated with almost-normal complex V activity but significant oxidative stress and permanent plasma membrane depolarization. Homoplasmic mutations in the MT-ATP6/8 genes may cause episodic weakness responding to acetazolamide treatment.

Radiographic followup of joints injected with triamcinolone hexacetonide for the management of childhood arthritis.

PubMed

Sparling, M; Malleson, P; Wood, B; Petty, R

1990-06-01

Evidence of deleterious effects following intraarticular injection of triamcinolone hexacetonide was sought through a review of radiographs of 145 joints of 55 children with chronic arthritis. Possible deleterious effects were noted in 16 joints of 11 patients. These effects included: small patella (2 joints), patellar osteochondritis dissecans (1 joint), periarticular calcification (9 joints), intraarticular tibial bony spur (1 joint), avascular necrosis of the distal radial epiphysis (2 joints), and avascular necrosis of the proximal femoral epiphysis (1 joint). Only the latter possible complication was symptomatic. Serial radiographs of 76 joints of 30 children showed mild progressive changes compatible with the underlying disease, except in the hip joint, where changes were more severe. The intraarticular injection of triamcinolone hexacetonide is a procedure that appears to be associated with an acceptably low frequency of radiologic abnormalities for many joints in children with chronic arthritis, but its effects on the hip joint remain uncertain.

Method and system for reducing device performance degradation of organic devices

DOEpatents

Teague, Lucile C.

2014-09-02

Methods and systems for reducing the deleterious effects of gate bias stress on the drain current of an organic device, such as an organic thin film transistor, are provided. In a particular aspect, the organic layer of an organic device is illuminated with light having characteristics selected to reduce the gate bias voltage effects on the drain current of the organic device. For instance, the wavelength and intensity of the light are selected to provide a desired recovery of drain current of the organic device. If the characteristics of the light are appropriately matched to the organic device, recovery of the deleterious effects caused by gate bias voltage stress effects on the drain current of the organic device can be achieved. In a particular aspect, the organic device is selectively illuminated with light to operate the organic device in multiple modes of operation.

How voluntary prenatal diagnosis and selective abortion increase the abnormal human gene pool.

PubMed

Boss, J A

1990-06-01

It is often assumed that prenatal diagnosis followed by the selective abortion of "defective" fetuses has a positive eugenic effect. Although mandatory selective abortion of "defective" fetuses and, more important, carriers would tend to reduce the number of deleterious genes in the gene pool, the present program of voluntary prenatal diagnosis and selective abortion actually increases the number of deleterious genes. This raises the issue of freedom of choice regarding selective abortion and societal pressure on parents to undergo prenatal testing and to abort their fetus should it have a genetic disorder or be a carrier of one.

A model for evaluating radiological impacts on organisms other than man for use in post-closure assessments of geological repositories for radioactive wastes.

PubMed

Thorn, M C; Kelly, M; Rees, J H; Sánchez-Friera, P; Calvez, M

2002-09-01

Bioaccumulation and dosimetric models have been developed that allow the computation of dose rates to a wide variety of plants and animals in the context of the deep geological disposal of solid radioactive wastes. These dose rates can be compared with the threshold dose rates at which significant deleterious effects have been observed in field and laboratory observations. This provides a general indication of whether effects on ecosystems could be observable, but does not quantify the level of those effects. To address this latter issue, two indicator organisms were identified and exposure-response relationships were developed for endpoints of potential interest (mortality in conifers and the induction of skeletal malformations in rodents irradiated in utero). The bioaccumulation, dosimetry and exposure-response models were implemented and used to evaluate the potential significance of radionuclide releases from a proposed deep geological repository for radioactive wastes in France. This evaluation was undertaken in the context of a programme of assessment studies being performed by the Agence nationale pour la gestion des déchets radioactifs (ANDRA).

How regulatory T cells work

PubMed Central

Vignali, Dario A. A.; Collison, Lauren W.; Workman, Creg J.

2009-01-01

Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting anti-tumour immunity. Given that Treg cells can have both beneficial and deleterious effects, there is considerable interest in determining their mechanisms of action. In this Review, we discuss the basic mechanisms used by Treg cells to mediate suppression, and discuss whether one or many of these mechanisms are likely to be crucial for Treg-cell function. In addition, we present the hypothesis that effector T cells may not be ‘innocent’ parties in this suppressive process and might in fact potentiate Treg-cell function. PMID:18566595

Time, money, and morality.

PubMed

Gino, Francesca; Mogilner, Cassie

2014-02-01

Money, a resource that absorbs much daily attention, seems to be involved in much unethical behavior, which suggests that money itself may corrupt. This research examined a way to offset such potentially deleterious effects-by focusing on time, a resource that tends to receive less attention than money but is equally ubiquitous in daily life. Across four experiments, we examined whether shifting focus onto time can salvage individuals' ethicality. We found that implicitly activating the construct of time, rather than money, leads individuals to behave more ethically by cheating less. We further found that priming time reduces cheating by making people reflect on who they are. Implications for the use of time primes in discouraging dishonesty are discussed.

Treatment Effects for Common Outcomes of Child Sexual Abuse: A Current Meta-Analysis

PubMed Central

Trask, Emily V.; Walsh, Kate; DiLillo, David

2010-01-01

The present meta-analysis examined the effects of psychosocial treatments at reducing deleterious outcomes of sexual abuse. The meta-analysis included a total of 35 published and unpublished studies written in English, focusing on youth under the age of 18, and evaluating the effectiveness of treatments for the most common negative outcomes of sexual abuse: PTSD symptoms, externalizing problems, and internalizing problems. Results revealed medium effect sizes for PTSD symptoms, externalizing problems, and internalizing problems following treatment for sexual abuse. This study also examined the potential moderating effects of treatment (e.g., modality, duration, inclusion of caregiver) and participant (e.g., age, gender, ethnicity) characteristics. Results indicated that longer interventions were associated with greater treatment gains while group and individual treatments were equally effective. These findings shed new light on treatment effectiveness and provide useful information regarding the conditions under which treatment may be most effective. Future directions for research in this area are discussed. PMID:21603060

MutaBind estimates and interprets the effects of sequence variants on protein-protein interactions.

PubMed

Li, Minghui; Simonetti, Franco L; Goncearenco, Alexander; Panchenko, Anna R

2016-07-08

Proteins engage in highly selective interactions with their macromolecular partners. Sequence variants that alter protein binding affinity may cause significant perturbations or complete abolishment of function, potentially leading to diseases. There exists a persistent need to develop a mechanistic understanding of impacts of variants on proteins. To address this need we introduce a new computational method MutaBind to evaluate the effects of sequence variants and disease mutations on protein interactions and calculate the quantitative changes in binding affinity. The MutaBind method uses molecular mechanics force fields, statistical potentials and fast side-chain optimization algorithms. The MutaBind server maps mutations on a structural protein complex, calculates the associated changes in binding affinity, determines the deleterious effect of a mutation, estimates the confidence of this prediction and produces a mutant structural model for download. MutaBind can be applied to a large number of problems, including determination of potential driver mutations in cancer and other diseases, elucidation of the effects of sequence variants on protein fitness in evolution and protein design. MutaBind is available at http://www.ncbi.nlm.nih.gov/projects/mutabind/. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa.

PubMed

McGee, Terri L; Seyedahmadi, Babak Jian; Sweeney, Meredith O; Dryja, Thaddeus P; Berson, Eliot L

2010-07-01

Usher syndrome type II (USH2) is an autosomal recessive disorder characterised by retinitis pigmentosa (RP) and mild to moderate sensorineural hearing loss. Mutations in the USH2A gene are the most common cause of USH2 and are also a cause of some forms of RP without hearing loss (ie, non-syndromic RP). The USH2A gene was initially identified as a transcript comprised of 21 exons but subsequently a longer isoform containing 72 exons was identified. The 51 exons unique to the long isoform of USH2A were screened for mutations among a core set of 108 patients diagnosed with USH2 and 80 patients with non-syndromic RP who were all included in a previously reported screen of the short isoform of USH2A. For several exons, additional patients were screened. In total, 35 deleterious mutations were identified including 17 nonsense mutations, 9 frameshift mutations, 5 splice-site mutations, and 4 small in-frame deletions or insertions. Twenty-seven mutations were novel. In addition, 65 rare missense changes were identified. A method of classifying the deleterious effect of the missense changes was developed using the summed results of four different mutation assessment algorithms, SIFT, pMUT, PolyPhen, and AGVGD. This system classified 8 of the 65 changes as 'likely deleterious' and 9 as 'possibly deleterious'. At least one mutation was identified in 57-63% of USH2 cases and 19-23% of cases of non-syndromic recessive RP (calculated without and including probable/possible deleterious changes) thus supporting that USH2A is the most common known cause of RP in the USA.

RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.

PubMed

Xiao, Yinghong; Rouzine, Igor M; Bianco, Simone; Acevedo, Ashley; Goldstein, Elizabeth Faul; Farkov, Mikhail; Brodsky, Leonid; Andino, Raul

2016-04-13

Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations. Here we demonstrate that recombination significantly accelerates adaptation and evolution during acute virus infection. We identified a poliovirus recombination determinant within the virus polymerase, mutation of which reduces recombination rates without altering replication fidelity. By generating a panel of variants with distinct mutation rates and recombination ability, we demonstrate that recombination is essential to enrich the population in beneficial mutations and purge it from deleterious mutations. The concerted activities of mutation and recombination are key to virus spread and virulence in infected animals. These findings inform a mathematical model to demonstrate that poliovirus adapts most rapidly at an optimal mutation rate determined by the trade-off between selection and accumulation of detrimental mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

Cassava haplotype map highlights fixation of deleterious mutations during clonal propagation

USDA-ARS?s Scientific Manuscript database

Cassava (Manihot esculenta Crantz) is an important staple food crop in Africa and South America whose fitness may be severely reduced by ubiquitous deleterious variation. To evaluate these deleterious mutations in cassava genome, we constructed a cassava haplotype map by deep sequencing of 241 diver...

Carotenoid distribution in wild Japanese tree frogs (Hyla japonica) exposed to ionizing radiation in Fukushima.

PubMed

Giraudeau, Mathieu; Bonzom, Jean-Marc; Ducatez, Simon; Beaugelin-Seiller, Karine; Deviche, Pierre; Lengagne, Thierry; Cavalie, Isabelle; Camilleri, Virginie; Adam-Guillermin, Christelle; McGraw, Kevin J

2018-05-09

The nuclear accident in the Fukushima prefecture released a large amount of artificial radionuclides that might have short- and long-term biological effects on wildlife. Ionizing radiation can be a harmful source of reactive oxygen species, and previous studies have already shown reduced fitness effects in exposed animals in Chernobyl. Due to their potential health benefits, carotenoid pigments might be used by animals to limit detrimental effects of ionizing radiation exposure. Here, we examined concentrations of carotenoids in blood (i.e. a snapshot of levels in circulation), liver (endogenous carotenoid reserves), and the vocal sac skin (sexual signal) in relation to the total radiation dose rates absorbed by individual (TDR from 0.2 to 34 µGy/h) Japanese tree frogs (Hyla japonica). We found high within-site variability of TDRs, but no significant effects of the TDR on tissue carotenoid levels, suggesting that carotenoid distribution in amphibians might be less sensitive to ionizing radiation exposure than in other organisms or that the potential deleterious effects of radiation exposure might be less significant or more difficult to detect in Fukushima than in Chernobyl due to, among other things, differences in the abundance and mixture of each radionuclide.

A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera.

PubMed

Charreton, Mercédès; Decourtye, Axel; Henry, Mickaël; Rodet, Guy; Sandoz, Jean-Christophe; Charnet, Pierre; Collet, Claude

2015-01-01

The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee's locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…), before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence) since (i) few studies are available on locomotion at this stage and (ii) in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48 h), three pyrethroids, namely cypermethrin (2.5 ng/bee), tetramethrin (70 ng/bee), tau-fluvalinate (33 ng/bee) and the neonicotinoid thiamethoxam (3.8 ng/bee) caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee) had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field, the case of fipronil demonstrates that toxicity evaluation requires information on multiple endpoints (e.g. long term survival) to fully address pesticides risks for honeybees. Pyrethroid-induced locomotor deficits are discussed in light of recent advances regarding their mode of action on honeybee ion channels and current structure-function studies.

A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera

PubMed Central

Charreton, Mercédès; Decourtye, Axel; Henry, Mickaël; Rodet, Guy; Sandoz, Jean-Christophe; Charnet, Pierre; Collet, Claude

2015-01-01

The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee’s locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…), before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence) since (i) few studies are available on locomotion at this stage and (ii) in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48h), three pyrethroids, namely cypermethrin (2.5 ng/bee), tetramethrin (70 ng/bee), tau-fluvalinate (33 ng/bee) and the neonicotinoid thiamethoxam (3.8 ng/bee) caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee) had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field, the case of fipronil demonstrates that toxicity evaluation requires information on multiple endpoints (e.g. long term survival) to fully address pesticides risks for honeybees. Pyrethroid-induced locomotor deficits are discussed in light of recent advances regarding their mode of action on honeybee ion channels and current structure-function studies. PMID:26659095

A Novel Hybrid Approach for Estimating Total Deposition in the United States

EPA Science Inventory

Atmospheric deposition of nitrogen and sulfur causes many deleterious effects on ecosystems including acidification and excess eutrophication. Assessments to support development of strategies to mitigate these effects require spatially and temporally continuous values of nitrogen...

A Hybrid Approach for Estimating Total Deposition in the United States

EPA Science Inventory

Atmospheric deposition of nitrogen and sulfur causes many deleterious effects on ecosystems including acidification and excess eutrophication. Assessments to support development of strategies to mitigate these effects require spatially and temporally continuous values of nitrogen...

On-Command Exoskeleton for Countermeasure Microgravity Effects on Muscles and Bones

NASA Astrophysics Data System (ADS)

Bar-Cohen, Y.; Bao, X.; Badescu, M.; Sherrit, S.; Mavroidis, C.; Unluhisarcikh, O.; Pietrusinski, M.; Rajulu, S.; Berka, R.; Cowley, M.

2012-06-01

On-command exoskeleton with impeding and augmenting elements would support the operation of astronauts traveling to Mars. Thus, countermeasure deleterious effects on the muscles and bones during travel and assist their physical activity on Mars.

The effects of ambient particulate matter on human alveolar machrophage oxidative and inflammatory responses

EPA Science Inventory

Epidemiologic and occupational studies demonstrate that ambient PM and DEP have deleterious effects on human cardiopulmonary health including exacerbation of pre-existing lung disease and development of respiratory infections. The effects of ambient PM on lung cell responsivenes...

Protection of human muscle acetylcholinesterase from soman by pyridostigmine bromide.

PubMed

Maselli, Ricardo A; Henderson, John D; Ng, Jarae; Follette, David; Graves, Gregory; Wilson, Barry W

2011-04-01

Pretreatment with pyridostigmine bromide (PB) of human intercostal muscle fibers exposed to the irreversible acetylcholinesterase (AChE) inhibitor soman was investigated. Muscles were pretreated with 3 × 10(-6) M PB or saline for 20 minutes, then exposed to 10(-7) M soman for 10 minutes. AChE of muscles treated with soman alone was inhibited >95%. In contrast, PB pretreatment of soman-exposed bundles protected 20% of AChE activity. AChE of bundles exposed to PB alone recovered after 4 hours, but bundles exposed to both PB and soman did not. Soman-induced reduction of resting membrane potentials and increment of amplitudes and decay times of miniature endplate potentials (MEPPs) were partially corrected by PB pretreatment. In vitro pretreatment of human muscles with PB protected up to 20% of muscle AChE and ameliorated some deleterious effects on endplate physiology induced by soman. Copyright © 2011 Wiley Periodicals, Inc.

The NMDA receptor as a target for cognitive enhancement

PubMed Central

Collingridge, Graham L.; Volianskis, Arturas; Bannister, Neil; France, Grace; Hanna, Lydia; Mercier, Marion; Tidball, Patrick; Fang, Guangyu; Irvine, Mark W.; Costa, Blaise M.; Monaghan, Daniel T.; Bortolotto, Zuner A.; Molnár, Elek; Lodge, David; Jane, David E.

2015-01-01

NMDA receptors (NMDAR) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal. In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation. There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required. Excessive activation and the resultant deleterious effects will need to be carefully avoided. Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events. PMID:22796429

Cardiac surgery during pregnancy: continuous fetal monitoring using umbilical artery Doppler flow velocity indices.

PubMed

Mishra, Manisha; Sawhney, Ravindra; Kumar, Anil; Bapna, Kumar Ramesh; Kohli, Vijay; Wasir, Harpreet; Trehan, Naresh

2014-01-01

The fetal death rate associated with cardiac surgery with cardiopulmonary bypass (CPB) is as high as 9.5-29%. We report continuous monitoring of fetal heart rate and umbilical artery flow-velocity waveforms by transvaginal ultrasonography and their analyses in relation to events of the CPB in two cases in second trimester of pregnancy undergoing mitral valve replacement. Our findings suggest that the transition of circulation from corporeal to extracorporeal is the most important event during surgery; the associated decrease in mean arterial pressure (MAP) at this stage potentially has deleterious effects on the fetus, which get aggravated with the use of vasopressors. We suggest careful management of CPB at this stage, which include partial controlled CPB at initiation and gradual transition to full CPB; this strategy maintains high MAP and avoids the use of vasopressors. Maternal and fetal monitoring can timely recognize the potential problems and provide window for the required treatment.

Toxic and Beneficial Potential of Silver Nanoparticles: The Two Sides of the Same Coin.

PubMed

Souza, Lilian Rodrigues Rosa; da Silva, Veronica Santana; Franchi, Leonardo Pereira; de Souza, Tiago Alves Jorge

2018-01-01

Nanotechnology has allowed great changes in chemical, biological and physical properties of metals when compared to their bulk counterparts. Within this context, silver nanoparticles (AgNPs) play a major role due to their unique properties, being widely used in daily products such as fabrics, washing machines, water filters, food and medicine. However, AgNPs can enter cells inducing a "Trojan-horse" type mechanism which potentially leads to cellular autophagy, apoptosis or necrosis. On the other hand, this cytotoxicity mechanism can be optimized to develop drug nanocarriers and anticancer therapies. The increasing use of these NPs entails their release into the environment, damaging ecosystems balance and representing a threat to human health. In this context, the possible deleterious effects that these NPs may represent for the biotic and abiotic ecosystems components represent an obstacle that must be overcome in order to guarantee the safety use of their unique properties.

The Effect of Deep Brain Stimulation on the Speech Motor System

ERIC Educational Resources Information Center

Mücke, Doris; Becker, Johannes; Barbe, Michael T.; Meister, Ingo; Liebhart, Lena; Roettger, Timo B.; Dembek, Till; Timmermann, Lars; Grice, Martine

2014-01-01

Purpose: Chronic deep brain stimulation of the nucleus ventralis intermedius is an effective treatment for individuals with medication-resistant essential tremor. However, these individuals report that stimulation has a deleterious effect on their speech. The present study investigates one important factor leading to these effects: the…

Sex speeds adaptation by altering the dynamics of molecular evolution.

PubMed

McDonald, Michael J; Rice, Daniel P; Desai, Michael M

2016-03-10

Sex and recombination are pervasive throughout nature despite their substantial costs. Understanding the evolutionary forces that maintain these phenomena is a central challenge in biology. One longstanding hypothesis argues that sex is beneficial because recombination speeds adaptation. Theory has proposed several distinct population genetic mechanisms that could underlie this advantage. For example, sex can promote the fixation of beneficial mutations either by alleviating interference competition (the Fisher-Muller effect) or by separating them from deleterious load (the ruby in the rubbish effect). Previous experiments confirm that sex can increase the rate of adaptation, but these studies did not observe the evolutionary dynamics that drive this effect at the genomic level. Here we present the first, to our knowledge, comparison between the sequence-level dynamics of adaptation in experimental sexual and asexual Saccharomyces cerevisiae populations, which allows us to identify the specific mechanisms by which sex speeds adaptation. We find that sex alters the molecular signatures of evolution by changing the spectrum of mutations that fix, and confirm theoretical predictions that it does so by alleviating clonal interference. We also show that substantially deleterious mutations hitchhike to fixation in adapting asexual populations. In contrast, recombination prevents such mutations from fixing. Our results demonstrate that sex both speeds adaptation and alters its molecular signature by allowing natural selection to more efficiently sort beneficial from deleterious mutations.

Giardia duodenalis: Number and Fluorescence Reduction Caused by the Advanced Oxidation Process (H2O2/UV)

PubMed Central

Guimarães, José Roberto; Franco, Regina Maura Bueno; Guadagnini, Regiane Aparecida; dos Santos, Luciana Urbano

2014-01-01

This study evaluated the effect of peroxidation assisted by ultraviolet radiation (H2O2/UV), which is an advanced oxidation process (AOP), on Giardia duodenalis cysts. The cysts were inoculated in synthetic and surface water using a concentration of 12 g H2O2 L−1 and a UV dose (λ = 254 nm) of 5,480 mJcm−2. The aqueous solutions were concentrated using membrane filtration, and the organisms were observed using a direct immunofluorescence assay (IFA). The AOP was effective in reducing the number of G. duodenalis cysts in synthetic and surface water and was most effective in reducing the fluorescence of the cyst walls that were present in the surface water. The AOP showed a higher deleterious potential for G. duodenalis cysts than either peroxidation (H2O2) or photolysis (UV) processes alone. PMID:27379301

Social aggravation: Understanding the complex role of social relationships on stress and health-relevant physiology.

PubMed

Birmingham, Wendy C; Holt-Lunstad, Julianne

2018-04-05

There is a rich literature on social support and physical health, but research has focused primarily on the protective effects of social relationship. The stress buffering model asserts that relationships may be protective by being a source of support when coping with stress, thereby blunting health relevant physiological responses. Research also indicates relationships can be a source of stress, also influencing health. In other words, the social buffering influence may have a counterpart, a social aggravating influence that has an opposite or opposing effect. Drawing upon existing conceptual models, we expand these to delineate how social relationships may influence stress processes and ultimately health. This review summarizes the existing literature that points to the potential deleterious physiological effects of our relationships when they are sources of stress or exacerbate stress. Copyright © 2018 Elsevier B.V. All rights reserved.

RCT of a Promising Vocational/Employment Program for High-Risk Juvenile Offenders

PubMed Central

Schaeffer, Cindy M.; Henggeler, Scott W.; Ford, Julian D.; Mann, Marc; Chang, Rocio; Chapman, Jason E.

2013-01-01

Juvenile offenders with substance use problems are at high risk for deleterious long-term outcomes. This study evaluated the capacity of a promising vocational and employment training program in the building sector (i.e., Community Restitution Apprenticeship-Focused Training, CRAFT) to mitigate such outcomes through enhanced employment and education. Participants were 97 high-risk juvenile offenders (mean age = 15.8 years) randomized to CRAFT versus education as usual (EAU) intervention conditions. Multi-method procedures measured employment, education, substance use, mental health, and criminal outcomes through a 30-month post-baseline follow-up. CRAFT was significantly more effective than EAU at increasing rates of youth employment and GED attendance. Intervention effects were not observed, however, for months employed, hours worked, or hourly wage. Measures of youth substance use, mental health symptoms, and criminal activity showed no favorable or iatrogenic effects. The potential of CRAFT was modestly supported, and suggestions were made for future research. PMID:23958035

[Medicines interacting with mitochondria: anti-ischemic effects of trimetazidine].

PubMed

Spedding, M; Tillement, J P; Morin, D; Le Ridant, A

1999-01-01

While mitochondria are key factors in energy production in cells they are also key factors in their life cycle because under certain circumstances they can provoke cellular apoptosis. Some 45 per cent of myocardial volume is taken up by mitochondria. Furthermore, mitochondria are key to many aspects of neuronal activity and can trigger neurodegenerative processes. Lipid oxidation is responsible for the production of much ATP resynthesis in the heart but this process is less oxygen efficient than glucose oxidation. During ischaemia, lipid oxidation is suddenly blocked, but markedly increased during reperfusion, causing accumulation of potentially toxic metabolites (acylcarnitines, acyl-CoA, lysophospholipids). These metabolites can change calcium handling, inducing arrhythmias. Trimetazidine, and another product in development, ranolazine, by inhibiting lipid oxidation favours glucose oxidation and inhibits the production of deleterious lipid metabolites. Thus this class of drugs can have beneficial effects on myocardial metabolism without direct haemodynamic effects.

Fatigue crack growth at elevated temperature 316 stainless steel and H-13 steel

NASA Technical Reports Server (NTRS)

Chen, W. C.; Liu, H. W.

1976-01-01

Crack growths were measured at elevated temperatures under four types of loading: pp, pc, cp, and cc. In H-13 steel, all these four types of loading gave nearly the same crack growth rates, and the length of hold time had negligible effects. In AISI 316 stainless steel, the hold time effects on crack growth rate were negligible if the loading was tension-tension type; however, these effects were significant in reversed bending load, and the crack growth rates under these four types of loading varied considerably. Both tensile and compressive hold times caused increased crack growth rate, but the compressive hold period was more deleterious than the tensile one. Metallographic examination showed that all the crack paths under different types of loading were largely transgranular for both CTS tension-tension specimens and SEN reversed cantilever bending specimens. In addition, an electric potential technique was used to monitor crack growth at elevated temperature.

Effects triggered by platinum nanoparticles on primary keratinocytes.

PubMed

Konieczny, Piotr; Goralczyk, Anna Grazyna; Szmyd, Radoslaw; Skalniak, Lukasz; Koziel, Joanna; Filon, Francesca Larese; Crosera, Matteo; Cierniak, Agnieszka; Zuba-Surma, Ewa K; Borowczyk, Julia; Laczna, Eliza; Drukala, Justyna; Pyza, Elzbieta; Semik, Danuta; Woznicka, Olga; Klein, Andrzej; Jura, Jolanta

2013-01-01

The platinum (Pt)-group elements (PGEs) represent a new kind of environmental pollutant and a new hazard for human health. Since their introduction as vehicle-exhaust catalysts, their emissions into the environment have grown considerably compared with their low natural concentration in the earth crust. PGE emissions from vehicle catalysts can be also in the form of nanometer-sized particles (Pt nanoparticles [PtNPs]). These elements, both in their metallic form or as ions solubilized in biological media, are now recognized as potent allergens and sensitizers. Human skin is always exposed to toxic particles; therefore, in the present study we addressed the question of whether polyvinylpyrrolidone-coated PtNPs may have any negative effects on skin cells, including predominantly epidermal keratinocytes. In this study, PtNPs of two sizes were used: 5.8 nm and 57 nm, in concentrations of 6.25, 12.5, and 25 μg/mL. Both types of NPs were protected with polyvinylpyrrolidone. Primary keratinocytes were treated for 24 and 48 hours, then cytotoxicity, genotoxicity, morphology, metabolic activity, and changes in the activation of signaling pathways were investigated in PtNP-treated cells. We found that PtNPs trigger toxic effects on primary keratinocytes, decreasing cell metabolism, but these changes have no effects on cell viability or migration. Moreover, smaller NPs exhibited more deleterious effect on DNA stability than the big ones. Analyzing activation of caspases, we found changes in activity of caspase 9 and caspase 3/7 triggered mainly by smaller NPs. Changes were not so significant in the case of larger nanoparticles. Importantly, we found that PtNPs have antibacterial properties, as is the case with silver NPs (AgNPs). In comparison to our previous study regarding the effects of AgNPs on cell biology, we found that PtNPs do not exhibit such deleterious effects on primary keratinocytes as AgNPs and that they also can be used as potential antibacterial agents, especially in the treatment of Escherichia coli, representing a group of Gram-negative species.

Quorum-sensing inhibition abrogates the deleterious impact of Pseudomonas aeruginosa on airway epithelial repair.

PubMed

Ruffin, Manon; Bilodeau, Claudia; Maillé, Émilie; LaFayette, Shantelle L; McKay, Geoffrey A; Trinh, Nguyen Thu Ngan; Beaudoin, Trevor; Desrosiers, Martin-Yvon; Rousseau, Simon; Nguyen, Dao; Brochiero, Emmanuelle

2016-09-01

Chronic Pseudomonas aeruginosa lung infections are associated with progressive epithelial damage and lung function decline. In addition to its role in tissue injury, the persistent presence of P. aeruginosa-secreted products may also affect epithelial repair ability, raising the need for new antivirulence therapies. The purpose of our study was to better understand the outcomes of P. aeruginosa exoproducts exposure on airway epithelial repair processes to identify a strategy to counteract their deleterious effect. We found that P. aeruginosa exoproducts significantly decreased wound healing, migration, and proliferation rates, and impaired the ability of directional migration of primary non-cystic fibrosis (CF) human airway epithelial cells. Impact of exoproducts was inhibited after mutations in P. aeruginosa genes that encoded for the quorum-sensing (QS) transcriptional regulator, LasR, and the elastase, LasB, whereas impact was restored by LasB induction in ΔlasR mutants. P. aeruginosa purified elastase also induced a significant decrease in non-CF epithelial repair, whereas protease inhibition with phosphoramidon prevented the effect of P. aeruginosa exoproducts. Furthermore, treatment of P. aeruginosa cultures with 4-hydroxy-2,5-dimethyl-3(2H)-furanone, a QS inhibitor, abrogated the negative impact of P. aeruginosa exoproducts on airway epithelial repair. Finally, we confirmed our findings in human airway epithelial cells from patients with CF, a disease featuring P. aeruginosa chronic respiratory infection. These data demonstrate that secreted proteases under the control of the LasR QS system impair airway epithelial repair and that QS inhibitors could be of benefit to counteract the deleterious effect of P. aeruginosa in infected patients.-Ruffin, M., Bilodeau, C., Maillé, É., LaFayette, S. L., McKay, G. A., Trinh, N. T. N., Beaudoin, T., Desrosiers, M.-Y., Rousseau, S., Nguyen, D., Brochiero, E. Quorum-sensing inhibition abrogates the deleterious impact of Pseudomonas aeruginosa on airway epithelial repair. © FASEB.

Intersection between metabolic dysfunction, high fat diet consumption, and brain aging.

PubMed

Uranga, Romina M; Bruce-Keller, Annadora J; Morrison, Christopher D; Fernandez-Kim, Sun Ok; Ebenezer, Philip J; Zhang, Le; Dasuri, Kalavathi; Keller, Jeffrey N

2010-07-01

Deleterious neurochemical, structural, and behavioral alterations are a seemingly unavoidable aspect of brain aging. However, the basis for these alterations, as well as the basis for the tremendous variability in regards to the degree to which these aspects are altered in aging individuals, remains to be elucidated. An increasing number of individuals regularly consume a diet high in fat, with high-fat diet consumption known to be sufficient to promote metabolic dysfunction, although the links between high-fat diet consumption and aging are only now beginning to be elucidated. In this review we discuss the potential role for age-related metabolic disturbances serving as an important basis for deleterious perturbations in the aging brain. These data not only have important implications for understanding the basis of brain aging, but also may be important to the development of therapeutic interventions which promote successful brain aging.

How Attributional Ambiguity Shapes Physiological and Emotional Responses to Social Rejection and Acceptance

PubMed Central

Mendes, Wendy Berry; McCoy, Shannon; Major, Brenda; Blascovich, Jim

2008-01-01

The authors examined White and Black participants’ emotional, physiological, and behavioral responses to same-race or different-race evaluators, following rejecting social feedback or accepting social feedback. As expected, in ingroup interactions, the authors observed deleterious responses to social rejection and benign responses to social acceptance. Deleterious responses included cardiovascular (CV) reactivity consistent with threat states and poorer performance, whereas benign responses included CV reactivity consistent with challenge states and better performance. In intergroup interactions, however, a more complex pattern of responses emerged. Social rejection from different-race evaluators engendered more anger and activational responses, regardless of participants’ race. In contrast, social acceptance produced an asymmetrical race pattern—White participants responded more positively than did Black participants. The latter appeared vigilant and exhibited threat responses. Discussion centers on implications for attributional ambiguity theory and potential pathways from discrimination to health outcomes. PMID:18211177

Evaluation and identification of damaged single nucleotide polymorphisms in COL1A1 gene involved in osteoporosis

PubMed Central

Alsaif, Mohammed A.; Al Shammari, Sulaiman A.; Alhamdan, Adel A.

2012-01-01

Introduction Single-nucleotide polymorphisms (SNPs) are biomarkers for exploring the genetic basis of many complex human diseases. The prediction of SNPs is promising in modern genetic analysis but it is still a great challenge to identify the functional SNPs in a disease-related gene. The computational approach has overcome this challenge and an increase in the successful rate of genetic association studies and reduced cost of genotyping have been achieved. The objective of this study is to identify deleterious non-synonymous SNPs (nsSNPs) associated with the COL1A1 gene. Material and methods The SNPs were retrieved from the Single Nucleotide Polymorphism Database (dbSNP). Using I-Mutant, protein stability change was calculated. The potentially functional nsSNPs and their effect on proteins were predicted by PolyPhen and SIFT respectively. FASTSNP was used for estimation of risk score. Results Our analysis revealed 247 SNPs as non-synonymous, out of which 5 nsSNPs were found to be least stable by I-Mutant 2.0 with a DDG value of > –1.0. Four nsSNPs, namely rs17853657, rs17857117, rs57377812 and rs1059454, showed a highly deleterious tolerance index score of 0.00 with a change in their physicochemical properties by the SIFT server. Seven nsSNPs, namely rs1059454, rs8179178, rs17853657, rs17857117, rs72656340, rs72656344 and rs72656351, were found to be probably damaging with a PSIC score difference between 2.0 and 3.5 by the PolyPhen server. Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, were found to be highly polymorphic with a risk score of 3-4 with a possible effect of non-conservative change and splicing regulation by FASTSNP. Conclusions Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, are potential functional polymorphisms that are likely to have a functional impact on the COL1A1 gene. PMID:24273577

Hyperspectral data analysis procedures with reduced sensitivity to noise

NASA Technical Reports Server (NTRS)

Landgrebe, David A.

1993-01-01

Multispectral sensor systems have become steadily improved over the years in their ability to deliver increased spectral detail. With the advent of hyperspectral sensors, including imaging spectrometers, this technology is in the process of taking a large leap forward, thus providing the possibility of enabling delivery of much more detailed information. However, this direction of development has drawn even more attention to the matter of noise and other deleterious effects in the data, because reducing the fundamental limitations of spectral detail on information collection raises the limitations presented by noise to even greater importance. Much current effort in remote sensing research is thus being devoted to adjusting the data to mitigate the effects of noise and other deleterious effects. A parallel approach to the problem is to look for analysis approaches and procedures which have reduced sensitivity to such effects. We discuss some of the fundamental principles which define analysis algorithm characteristics providing such reduced sensitivity. One such analysis procedure including an example analysis of a data set is described, illustrating this effect.

Factors affecting drug-induced liver injury: antithyroid drugs as instances

PubMed Central

Niknahad, Hossein; Jamshidzadeh, Akram; Abdoli, Narges

2014-01-01

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed. PMID:25320726

Essentials of Periodontal Medicine in Preventive Medicine

PubMed Central

Gulati, Minkle; Anand, Vishal; Jain, Nikil; Anand, Bhargavi; Bahuguna, Rohit; Govila, Vivek; Rastogi, Pavitra

2013-01-01

Influence of systemic disorders on periodontal diseases is well established. However, of growing interest is the effect of periodontal diseases on numerous systemic diseases or conditions like cardiovascular disease, cerebrovascular disease, diabetes, pre-term low birth weight babies, preeclampsia, respiratory infections and others including osteoporosis, cancer, rheumatoid arthritis, erectile dysfunction, Alzheimer's disease, gastrointestinal disease, prostatitis, renal diseases, which has also been scientifically validated. This side of the oral-systemic link has been termed Periodontal Medicine and is potentially of great public health significance, as periodontal disease is largely preventable and in many instances readily treatable, hence, providing many new opportunities for preventing and improving prognosis of several systemic pathologic conditions. This review article highlights the importance of prevention and treatment of periodontal diseases as an essential part of preventive medicine to circumvent its deleterious effects on general health. PMID:24130938

Essentials of periodontal medicine in preventive medicine.

PubMed

Gulati, Minkle; Anand, Vishal; Jain, Nikil; Anand, Bhargavi; Bahuguna, Rohit; Govila, Vivek; Rastogi, Pavitra

2013-09-01

Influence of systemic disorders on periodontal diseases is well established. However, of growing interest is the effect of periodontal diseases on numerous systemic diseases or conditions like cardiovascular disease, cerebrovascular disease, diabetes, pre-term low birth weight babies, preeclampsia, respiratory infections and others including osteoporosis, cancer, rheumatoid arthritis, erectile dysfunction, Alzheimer's disease, gastrointestinal disease, prostatitis, renal diseases, which has also been scientifically validated. This side of the oral-systemic link has been termed Periodontal Medicine and is potentially of great public health significance, as periodontal disease is largely preventable and in many instances readily treatable, hence, providing many new opportunities for preventing and improving prognosis of several systemic pathologic conditions. This review article highlights the importance of prevention and treatment of periodontal diseases as an essential part of preventive medicine to circumvent its deleterious effects on general health.

Assessing potential radiological harm to fukushima recovery workers.

PubMed

Scott, Bobby R

2011-01-01

A radiological emergency exists at the Fukushima Daiichi (Fukushima I) nuclear power plant in Japan as a result of the March 11, 2011 magnitude 9.0 earthquake and the massive tsunami that arrived later. News media misinformation related to the emergency triggered enormous social fear worldwide of the radioactivity that is being released from damaged fuel rods. The heroic recovery workers are a major concern because they are being exposed to mostly gamma radiation during their work shifts and life-threatening damage to the radiosensitive bone marrow could occur over time. This paper presents a way in which the bone marrow equivalent dose (in millisieverts), as estimated per work shift, could be used along with the hazard function model previously developed for radiological risk assessment to repeatedly check for potential life-threatening harm (hematopoietic system damage) to workers. Three categories of radiation hazard indication are proposed: 1, life-threatening damage unlikely; 2, life-threatening damage possible; 3, life-threatening damage likely. Categories 2 and 3 would be avoided if the whole body effective dose did not exceed the annual effective dose limit of 250 mSv. For down-wind populations, hormetic effects (activated natural protective processes) are much more likely than are deleterious effects.

Fibrin tissue adhesive and autologous concha cartilage for reconstruction of the posterior-superior canal wall of the chinchilla middle ear.

PubMed

Siedentop, Karl H; O'Grady, Kevin; Bhattacharyya, Tapan K; Shah, Ami

2004-05-01

We conducted this study to prove that fibrin tissue adhesive (FTA) is safe, efficacious, biocompatible, and readily biodegradable with no deleterious side effects for fixation of a cartilage graft to bone along the chinchilla canal wall. A posterior-superior canal defect was created in 12 chinchillas. The canal walls of six chinchillas were closed with autologous concha cartilage alone, whereas the canal wall of the remaining six animals were closed with cartilage in conjunction with fibrin tissue adhesive. Animals were killed 8 weeks postoperatively. Three of six cartilage grafts were displaced in the graft alone group, whereas all six grafts in the cartilage with FTA group healed without displacement. Fibrin tissue adhesive was found to be effective, biocompatible, biodegradable, and without any deleterious side effects for reconstruction of the superior-posterior canal wall of chinchillas.

Impact of gene patents on the cost-effective delivery of care: the case of BRCA1 genetic testing.

PubMed

Sevilla, Christine; Julian-Reynier, Claire; Eisinger, François; Stoppa-Lyonnet, Dominique; Bressac-de Paillerets, Brigitte; Sobol, Hagay; Moatti, Jean-Paul

2003-01-01

In 1994/95, two genes, BRCA1/2, associated with a predisposition to breast or ovarian cancer were identified. Genetic testing of deleterious BRCA1/2 mutations consequently can be proposed to individuals with a family history of breast or ovarian cancer to identify who is at risk. The granting of U.S. patents on BRCA1/2 to a privately owned company has led to the monopoly use of a unique technique (Direct Sequencing of the gene, DS) for BRCA1/2 testing in this country. Alternative strategies using prescreening techniques, however, have been experienced worldwide. On the basis of data collected at three laboratories of French public hospitals, we carried out a cost-effectiveness study comparing DS to 19 alternative strategies with the number of deleterious BRCA1 mutations detected as the outcome. Results show that the DS strategy presents the highest average cost per mutation detected (9,882.5 Euro) and that there exist strategies using prescreening techniques that can reach similar effectiveness while reducing total costs. Moreover, other strategies can obtain a four- to sevenfold reduction in the average cost per mutation detected as soon as some rates of false negatives (2% to 13%) are deemed to be acceptable. Results suggest that gene patents with a very broad scope, covering all potential medical applications, may prevent health care systems from identifying and adopting the most efficient genetic testing strategies due to the monopoly granted for the exploitation of the gene. Policy implications for regulatory authorities, in the current context of the extension of BRCA1/2 patents in other countries, are discussed.

Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model.

PubMed

León, I E; Cadavid-Vargas, J F; Tiscornia, I; Porro, V; Castelli, S; Katkar, P; Desideri, A; Bollati-Fogolin, M; Etcheverry, S B

2015-10-01

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na₂[VO(silibinin)₂2]·6H₂O (VOsil) and chrysin [VO(chrysin)₂EtOH]₂(VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments.

Posttraumatic stress, effort regulation, and academic outcomes among college students: A longitudinal study.

PubMed

Boyraz, Güler; Granda, Rebecca; Baker, Camille N; Tidwell, Lacey Lorehn; Waits, J Brandon

2016-07-01

Entering college with posttraumatic stress disorder (PTSD) symptomatology has been linked to poor academic performance and increased risk for dropping out of college; however, little is known regarding the mechanisms by which PTSD symptoms have deleterious effects on college outcomes. Drawing from a self-regulated learning (SRL) perspective, which suggests that students' learning behaviors and outcomes can be influenced by contextual and developmental factors, we hypothesized that students who enter college with high PTSD symptomatology may experience difficulties in effort regulation, which in turn, may have deleterious effects on their academic performance and college persistence. These hypothesized relationships, as well as the potential gender differences in these relationships were examined using a longitudinal study design and a multigroup structural equation modeling approach. Of the 928 1st-year students who participated in the study, 484 (52.2%) students who reported lifetime exposure to traumatic events constituted the final sample of the study. The prevalence of PTSD among the trauma-exposed participants was 12.4%. After controlling for participation in on-campus activities and American College Testing (ACT) assessment scores, the relationship between PTSD symptomatology in the 1st semester of college and 2nd-year enrollment was mediated by effort regulation and 1st-year cumulative grade-point average (GPA). Specifically, participants who started college with higher levels of PTSD symptomatology also reported lower levels of effort regulation, which in turn, had a significant indirect effect on 2nd-year enrollment through 1st-year GPA. Results also indicated that the paths in the hypothesized model were not significantly different for men and women. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Exercise Promotes Healthy Aging of Skeletal Muscle

PubMed Central

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

2016-01-01

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Deleterious ATM Gene Mutation; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Deleterious RAD51C Gene Mutation; Deleterious RAD51D Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Wilms Tumor

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.

PubMed

Solowij, Nadia; Broyd, Samantha J; Beale, Camilla; Prick, Julie-Anne; Greenwood, Lisa-Marie; van Hell, Hendrika; Suo, Chao; Galettis, Peter; Pai, Nagesh; Fu, Shanlin; Croft, Rodney J; Martin, Jennifer H; Yücel, Murat

2018-01-01

Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ 9 -tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial

PubMed Central

Solowij, Nadia; Broyd, Samantha J.; Beale, Camilla; Prick, Julie-Anne; Greenwood, Lisa-marie; van Hell, Hendrika; Suo, Chao; Galettis, Peter; Pai, Nagesh; Fu, Shanlin; Croft, Rodney J.; Martin, Jennifer H.; Yücel, Murat

2018-01-01

Abstract Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence. PMID:29607408

Discovering functional DNA elements using population genomic information: a proof of concept using human mtDNA.

PubMed

Schrider, Daniel R; Kern, Andrew D

2014-06-09

Identifying the complete set of functional elements within the human genome would be a windfall for multiple areas of biological research including medicine, molecular biology, and evolution. Complete knowledge of function would aid in the prioritization of loci when searching for the genetic bases of disease or adaptive phenotypes. Because mutations that disrupt function are disfavored by natural selection, purifying selection leaves a detectable signature within functional elements; accordingly, this signal has been exploited for over a decade through the use of genomic comparisons of distantly related species. While this is so, the functional complement of the genome changes extensively across time and between lineages; therefore, evidence of the current action of purifying selection in humans is essential. Because the removal of deleterious mutations by natural selection also reduces within-species genetic diversity within functional loci, dense population genetic data have the potential to reveal genomic elements that are currently functional. Here, we assess the potential of this approach by examining an ultradeep sample of human mitochondrial genomes (n = 16,411). We show that the high density of polymorphism in this data set precisely delineates regions experiencing purifying selection. Furthermore, we show that the number of segregating alleles at a site is strongly correlated with its divergence across species after accounting for known mutational biases in human mitochondrial DNA (ρ = 0.51; P < 2.2 × 10(-16)). These two measures track one another at a remarkably fine scale across many loci-a correlation that is purely the result of natural selection. Our results demonstrate that genetic variation has the potential to reveal with surprising precision which regions in the genome are currently performing important functions and likely to have deleterious fitness effects when mutated. As more complete human genomes are sequenced, similar power to reveal purifying selection may be achievable in the human nuclear genome. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Effects of Anabolic Steroids on Lipoprotein Profiles of Female Weight Lifters.

ERIC Educational Resources Information Center

Moffatt, Robert J.; And Others

1990-01-01

This study examined the effects of resistance exercise and anabolic steroids on lipoprotein profiles of female weightlifters. The study found that women who participate in resistance training have better lipoprotein profiles than their sedentary counterparts, but these changes do not offset the deleterious effects of steroid use. (SM)

Effects of Belongingness and Synchronicity on Face-to-Face and Computer-Mediated Online Cooperative Pedagogy

ERIC Educational Resources Information Center

Saltarelli, Andrew John

2012-01-01

Previous research suggests asynchronous online computer-mediated communication (CMC) has deleterious effects on certain cooperative learning pedagogies (e.g., constructive controversy), but the processes underlying this effect and how it may be ameliorated remain unclear. This study tests whether asynchronous CMC thwarts belongingness needs…

The effects of perceived racism on psychological distress mediated by venting and disengagement coping in Native Hawaiians.

PubMed

Kaholokula, Joseph Keawe'aimoku; Antonio, Mapuana C K; Ing, Claire K Townsend; Hermosura, Andrea; Hall, Kimberly E; Knight, Rebecca; Wills, Thomas A

2017-01-12

Studies have linked perceived racism to psychological distress via certain coping strategies in several different racial and ethnic groups, but few of these studies included indigenous populations. Elucidating modifiable factors for intervention to reduce the adverse effects of racism on psychological well-being is another avenue to addressing health inequities. We examined the potential mediating effects of 14 distinct coping strategies on the relationship between perceived racism and psychological distress in a community-based sample of 145 Native Hawaiians using structural equation modeling. Perceived racism had a significant indirect effect on psychological distress, mediated through venting and behavioral disengagement coping strategies, with control for age, gender, educational level, and marital status. The findings suggest that certain coping strategies may exacerbate the deleterious effects of racism on a person's psychological well-being. Our study adds Native Hawaiians to the list of U.S. racial and ethnic minorities whose psychological well-being is adversely affected by racism.

Importance of carbon dioxide in the critical patient: Implications at the cellular and clinical levels.

PubMed

Morales Quinteros, Luis; Bringué Roque, Josep; Kaufman, David; Artigas Raventós, Antonio

2018-02-24

Important recent insights have emerged regarding the cellular and molecular role of carbon dioxide (CO 2 ) and the effects of hypercapnia. The latter may have beneficial effects in patients with acute lung injury, affording reductions in pulmonary inflammation, lessened oxidative alveolar damage, and the regulation of innate immunity and host defenses by inhibiting the expression of inflammatory cytokines. However, other studies suggest that CO 2 can have deleterious effects upon the lung, reducing alveolar wound repair in lung injury, decreasing the rate of reabsorption of alveolar fluid, and inhibiting alveolar cell proliferation. Clearly, hypercapnia has both beneficial and harmful consequences, and it is important to determine the net effect under specific conditions. The purpose of this review is to describe the immunological and physiological effects of carbon dioxide, considering their potential consequences in patients with acute respiratory failure. Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Novel method for dynamic control of intracranial pressure.

PubMed

Luciano, Mark G; Dombrowski, Stephen M; Qvarlander, Sara; El-Khoury, Serge; Yang, Jun; Thyagaraj, Suraj; Loth, Francis

2017-05-01

OBJECT Intracranial pressure (ICP) pulsations are generally considered a passive result of the pulsatility of blood flow. Active experimental modification of ICP pulsations would allow investigation of potential active effects on blood and CSF flow and potentially create a new platform for the treatment of acute and chronic low blood flow states as well as a method of CSF substance clearance and delivery. This study presents a novel method and device for altering the ICP waveform via cardiac-gated volume changes. METHODS The novel device used in this experiment (named Cadence) consists of a small air-filled inelastic balloon (approximately 1.0 ml) implanted into the intracranial space and connected to an external programmable pump, triggered by an R-wave detector. Balloons were implanted into the epidural space above 1 of the hemispheres of 19 canines for up to 10 hours. When activated, the balloons were programed to cyclically inflate with the cardiac cycle with variable delay, phase, and volume. The ICP response was measured in both hemispheres. Additionally, cerebral blood flow (heat diffusion and laser Doppler) was studied in 16 canines. RESULTS This system, depending on the inflation pattern of the balloon, allowed a flattening of the ICP waveform, increase in the ICP waveform amplitude, or phase shift of the wave. This occurred with small mean ICP changes, typically around ± 2 mm Hg (15%). Bilateral ICP effects were observed with activation of the device: balloon inflation at each systole increased the systolic ICP pulse (up to 16 mm Hg, 1200%) and deflation at systole decreased or even inverted the systolic ICP pulse (-0.5 to -19 mm Hg, -5% to -1600%) in a dose-(balloon volume) dependent fashion. No aphysiological or deleterious effects on systemic pressure (≤ ±10 mm Hg; 13% change in mean pressure) or cardiac rate (≤ ± 17 beats per minute; 16% change) were observed during up to 4 hours of balloon activity. CONCLUSIONS The results of these initial studies using an intracranially implanted, cardiac-gated, volume-oscillating balloon suggest the Cadence device can be used to modify ICP pulsations, without physiologically deleterious effects on mean ICP, systemic vascular effects, or brain injury. This device and technique may be used to study the role of ICP pulsatility in intracranial hemo- and hydrodynamic processes and introduces the creation of a potential platform of a cardiac-gated system for treatment of acute and chronic low blood flow states, and diseases requiring augmentation of CSF substance clearance or delivery.

75 FR 61871 - Endangered and Threatened Wildlife and Plants; Proposed Listing Determinations for Three Distinct...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

... single facility in one city (ASSRT, 2007). There are currently no fish consumption advisories in effect... substantial deleterious effects on aquatic life. Effects from these elements and compounds on fish include... quality as a result of eutrophication. In a simulation of the effects of water temperature on available...

Role of oxidative stress in diabetic retinopathy and the beneficial effects of flavonoids.

PubMed

Ola, Mohammad Shamsul; Al-Dosari, Dalia; Alhomida, Abdullah S

2018-05-15

Diabetic retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious changes through dysregulation of cellular physiology that damages both neuronal and vascular cells. Here in this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contributes to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by us and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the potential beneficial effects of the six major flavonoid families, such as flavonones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flanonoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in the diabetic retina. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?

PubMed Central

Ristow, Michael

2016-01-01

Abstract A popular belief is that reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced during exercise by the mitochondria and other subcellular compartments ubiquitously cause skeletal muscle damage, fatigue and impair recovery. However, the importance of ROS and RNS as signals in the cellular adaptation process to stress is now evident. In an effort to combat the perceived deleterious effects of ROS and RNS it has become common practice for active individuals to ingest supplements with antioxidant properties, but interfering with ROS/RNS signalling in skeletal muscle during acute exercise may blunt favourable adaptation. There is building evidence that antioxidant supplementation can attenuate endurance training‐induced and ROS/RNS‐mediated enhancements in antioxidant capacity, mitochondrial biogenesis, cellular defence mechanisms and insulin sensitivity. However, this is not a universal finding, potentially indicating that there is redundancy in the mechanisms controlling skeletal muscle adaptation to exercise, meaning that in some circumstances the negative impact of antioxidants on acute exercise response can be overcome by training. Antioxidant supplementation has been more consistently reported to have deleterious effects on the response to overload stress and high‐intensity training, suggesting that remodelling of skeletal muscle following resistance and high‐intensity exercise is more dependent on ROS/RNS signalling. Importantly there is no convincing evidence to suggest that antioxidant supplementation enhances exercise‐training adaptions. Overall, ROS/RNS are likely to exhibit a non‐linear (hormetic) pattern on exercise adaptations, where physiological doses are beneficial and high exposure (which would seldom be achieved during normal exercise training) may be detrimental. PMID:26638792

Impacts of the Invasive European Red Ant (Myrmica rubra (L.): Hymenoptera; Formicidae) on a Myrmecochorous System in the Northeastern United States.

PubMed

Gammans, Nicola; Drummond, Frank; Groden, Eleanor

2018-05-16

We investigated the impact of an invasive ant species from Europe, Myrmica rubra (L.), on a myrmecochorous system (seeds dispersed by ants) in its invaded range in North America. We assessed: 1) how M. rubra process the myrmecochorous diapsores (seeds and elaiosome as a single dispersal unit transported by ants) in comparison with native ants; 2) its preference for common native and invasive diaspore species relative to native ants; 3) how far they disperse diaspores in the field; and 4) the diaspore removal rate by invertebrates and vertebrates in infested areas compared to noninvaded sites. Field experiments demonstrated higher diaspore removal rates over a 10-min and 24-h period by M. rubra compared to native ants. M. rubra's diaspore dispersal distance was 40% greater compared to native ants. In two of three laboratory studies and one field study, there was no significant difference between the seed species which M. rubra and native ants selected. Our data suggest no long-term deleterious effects of M. rubra's invasion on diaspore dispersal in the Maine plant community that is comprised of both native and invasive species. This implies that M. rubra benefits from the myrmechorous plant species' diaspores by increasing their dispersal range away from the parent plant and potentially reducing seed predation. However, it is not known whether the fact that the native ant fauna and M. rubra are attracted to the same plant species' diaspores creates a high level of competition between the ants with deleterious effects on the native ant community.

Evidence for an absence of deleterious effects of ultrasound on human oocytes.

PubMed

Mahadevan, M; Chalder, K; Wiseman, D; Leader, A; Taylor, P J

1987-10-01

Animal and human data would suggest that ultrasound causes deleterious effects to oocytes during meiosis. We directly compared the fertilization rate and embryonic development following in vitro fertilization and embryo transfer of those oocytes exposed to ultrasound and those not exposed in the same patient. In 39 unscreened patients a combination of laparoscopy and ultrasound was used for oocyte recovery. Laparoscopy was performed first on the most accessible ovary (usually the right) and at least one oocyte was obtained. Ultrasound-guided oocyte recovery was successful in the other inaccessible ovary. To assess how oocytes obtained by ultrasound or laparoscopy related to the pregnancy rate, two groups of patients were evaluated in whom the embryos transferred either had been exposed to ultrasound or had not been. The fertilization and the embryo cleavage rates were not significantly different between the ultrasound-exposed and the unexposed groups. The pregnancy rate was also not significantly different [9 of 49 (18.4%) for ultrasound exposed versus 14 of 74 (18.9%) for unexposed]. There was one early spontaneous abortion in each group. Further analysis of a group of 40 patients, in whom the oocytes were exposed to ultrasound in situ, after the endogenous luteinizing hormone (LH) surge had begun 1-27 hr earlier, revealed that 6 became pregnant (15%). This preliminary study suggests that exposure of human oocytes to ultrasonic waves, either during the different phases of meiosis or after the completion of meiosis, did not significantly influence the developmental potential of the in vitro fertilized embryos.

Uric acid and cardiovascular disease.

PubMed

Ndrepepa, Gjin

2018-05-24

Uric acid (UA) is an end product of purine metabolism in humans and great apes. UA acts as an antioxidant and it accounts for 50% of the total antioxidant capacity of biological fluids in humans. When present in cytoplasm of the cells or in acidic/hydrophobic milieu in atherosclerotic plaques, UA converts into a pro-oxidant agent and promotes oxidative stress and through this mechanism participates in the pathophysiology of human disease including cardiovascular disease (CVD). Most epidemiological studies but not all of them suggested the existence of an association between elevated serum UA level and CVD, including coronary heart disease (CHD), stroke, congestive heart failure, arterial hypertension and atrial fibrillation as well as an increased risk for mortality due to CVD in general population and subjects with confirmed CHD. Evidence available also suggests an association between elevated UA and traditional cardiovascular risk factors, metabolic syndrome, insulin resistance, obesity, non-alcoholic fatty liver disease and chronic kidney disease. Experimental and clinical studies have evidenced several mechanisms through which elevated UA level exerts deleterious effects on cardiovascular health including increased oxidative stress, reduced availability of nitric oxide and endothelial dysfunction, promotion of local and systemic inflammation, vasoconstriction and proliferation of vascular smooth muscle cells, insulin resistance and metabolic dysregulation. Although the causality in the relationship between UA and CVD remains unproven, UA may be pathogenic and participate in the pathophysiology of CVD by serving as a bridging mechanism mediating (enabling) or potentiating the deleterious effects of cardiovascular risk factors on vascular tissue and myocardium. Copyright © 2018 Elsevier B.V. All rights reserved.

The role of deleterious mutations in the stability of hybridogenetic water frog complexes

PubMed Central

2014-01-01

Background Some species of water frogs originated from hybridization between different species. Such hybrid populations have a particular reproduction system called hybridogenesis. In this paper we consider the two species Pelophylax ridibundus and Pelophylax lessonae, and their hybrids Pelophylax esculentus. P. lessonae and P. esculentus form stable complexes (L-E complexes) in which P. esculentus are hemiclonal. In L-E complexes all the transmitted genomes by P. esculentus carry deleterious mutations which are lethal in homozygosity. Results We analyze, by means of an individual based computational model, L-E complexes. The results of simulations based on the model show that, by eliminating deleterious mutations, L-E complexes collapse. In addition, simulations show that particular female preferences can contribute to the diffusion of deleterious mutations among all P. esculentus frogs. Finally, simulations show how L-E complexes react to the introduction of translocated P. ridibundus. Conclusions The conclusions are the following: (i) deleterious mutations (combined with sexual preferences) strongly contribute to the stability of L-E complexes; (ii) female sexual choice can contribute to the diffusion of deleterious mutations; and (iii) the introduction of P. ridibundus can destabilize L-E complexes. PMID:24885008

Multilevel biological characterization of exomic variants at the protein level significantly improves the identification of their deleterious effects.

PubMed

Raimondi, Daniele; Gazzo, Andrea M; Rooman, Marianne; Lenaerts, Tom; Vranken, Wim F

2016-06-15

There are now many predictors capable of identifying the likely phenotypic effects of single nucleotide variants (SNVs) or short in-frame Insertions or Deletions (INDELs) on the increasing amount of genome sequence data. Most of these predictors focus on SNVs and use a combination of features related to sequence conservation, biophysical, and/or structural properties to link the observed variant to either neutral or disease phenotype. Despite notable successes, the mapping between genetic variants and their phenotypic effects is riddled with levels of complexity that are not yet fully understood and that are often not taken into account in the predictions, despite their promise of significantly improving the prediction of deleterious mutants. We present DEOGEN, a novel variant effect predictor that can handle both missense SNVs and in-frame INDELs. By integrating information from different biological scales and mimicking the complex mixture of effects that lead from the variant to the phenotype, we obtain significant improvements in the variant-effect prediction results. Next to the typical variant-oriented features based on the evolutionary conservation of the mutated positions, we added a collection of protein-oriented features that are based on functional aspects of the gene affected. We cross-validated DEOGEN on 36 825 polymorphisms, 20 821 deleterious SNVs, and 1038 INDELs from SwissProt. The multilevel contextualization of each (variant, protein) pair in DEOGEN provides a 10% improvement of MCC with respect to current state-of-the-art tools. The software and the data presented here is publicly available at http://ibsquare.be/deogen : wvranken@vub.ac.be Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Obstruction of adaptation in diploids by recessive, strongly deleterious alleles.

PubMed

Assaf, Zoe June; Petrov, Dmitri A; Blundell, Jamie R

2015-05-19

Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a "staggered sweep." It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila.

Under the radar: mitigating enigmatic ecological impacts.

PubMed

Raiter, Keren G; Possingham, Hugh P; Prober, Suzanne M; Hobbs, Richard J

2014-11-01

Identifying the deleterious ecological effects of developments, such as roads, mining, and urban expansion, is essential for informing development decisions and identifying appropriate mitigation actions. However, there are many types of ecological impacts that slip 'under the radar' of conventional impact evaluations and undermine the potential for successful impact mitigation (including offsets). These 'enigmatic' impacts include those that are small but act cumulatively; those outside of the area directly considered in the evaluation; those not detectable with the methods, paradigms, or spatiotemporal scales used to detect them; those facilitated, but not directly caused, by development; and synergistic impact interactions. Here, we propose a framework for conceptualising enigmatic impacts and discuss ways to address them. Copyright © 2014 Elsevier Ltd. All rights reserved.

The respiratory tract and the environment.

PubMed Central

Brain, J D

1977-01-01

The primary determinants of pulmonary disease are environmental. The same thinness and delicacy of the air-blood barrier which allows rapid exchange of oxygen and carbon dioxide also reduce its effectiveness as a barrier to inhaled allergens, carcinogens, toxic particles, and noxious gases, and micro-organisms. Adults breath 10,000 to 20,000 liters of air daily. This volume of air contains potentially hazardous contaminating particles and gases. Future research should explore the diverse physiological mechanisms which prevent the accumulation and deleterious action of inhaled particles and gases. Since most pulmonary diseases are either initiated by or at least aggravated by the inhalagion of particles and gases, the role of environmental factors in the development of respiratory disease is an area worthy of continued support. PMID:598343

Manifestations and mechanisms of stem cell aging

PubMed Central

Liu, Ling

2011-01-01

Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell–based therapy of age-related diseases. PMID:21502357

Soybean hulls as an iron source for bread enrichment

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

Johnson, C.D.; Berry, M.F.; Weaver, C.M.

Soybean hulls, a concentrated source of iron, may have potential as a source of iron fortification in baked products. Retention of /sup 59/Fe in rats from white bread containing intrinsically labeled soybean hulls did not differ significantly (p<0.05) from extrinsically labeled white bread fortified with bakery grade ferrous sulfate (70.4 and 63.1%, respectively). Physical and sensory evaluations of bread containing up to 5% soybean hulls did not differ from white bread in loaf volume, cross-sectional area, tenderness or overall acceptance. These results suggest that soybean hulls are a good source of available iron and may be added to bakery productsmore » without deleterious effects in baking performance and sensory acceptability.« less

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island

PubMed Central

Arriola Apelo, Sebastian I.

2016-01-01

Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging. PMID:27208895

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

The opioid effects of gluten exorphins: asymptomatic celiac disease.

PubMed

Pruimboom, Leo; de Punder, Karin

2015-11-24

Gluten-containing cereals are a main food staple present in the daily human diet, including wheat, barley, and rye. Gluten intake is associated with the development of celiac disease (CD) and related disorders such as diabetes mellitus type I, depression, and schizophrenia. However, until now, there is no consent about the possible deleterious effects of gluten intake because of often failing symptoms even in persons with proven CD. Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function. Here we describe a putative mechanism, explaining how gluten could "mask" its own toxicity by exorphins that are produced through gluten protein digestion.

Cellular and behavioral effects of stilbene resveratrol analogues: implications for reducing the deleterious effects of aging.

PubMed

Joseph, James A; Fisher, Derek R; Cheng, Vivian; Rimando, Agnes M; Shukitt-Hale, Barbara

2008-11-26

Research suggests that polyphenolic compounds contained in fruits and vegetables that are rich in color may have potent antioxidant and anti-inflammatory activities. The present studies determined if stilbene (e.g., resveratrol) compounds would be efficacious in reversing the deleterious effects of aging in 19 month old Fischer 344 rats. Experiment I utilized resveratrol and six resveratrol analogues and examined their efficacies in preventing dopamine-induced decrements in calcium clearance following oxotremorine-induced depolarization in COS-7 cells transfected with M1 muscarinic receptors (MAChR) that we have shown previously to be sensitive to oxidative stressors. Experiment II utilized the most efficacious analogue (pterostilbene) from experiment I and fed aged rats a diet with a low (0.004%) or a high (0.016%) concentration of pterostilbene. Results indicated that pterostilbene was effective in reversing cognitive behavioral deficits, as well as dopamine release, and working memory was correlated with pterostilbene levels in the hippocampus.

Antioxidant activity of hydrated carboxylated nanodiamonds and its influence on water γ-radiolysis

NASA Astrophysics Data System (ADS)

Santacruz-Gomez, Karla; Sarabia-Sainz, A.; Acosta-Elias, M.; Sarabia-Sainz, M.; Janetanakit, Woraphong; Khosla, Nathan; Melendrez, R.; Pedroza Montero, Martin; Lal, Ratnesh

2018-03-01

Water radiolysis involves chemical decomposition of the water molecule into free radicals after exposure to ionizing radiation. These free radicals have deleterious effects on normal cell physiology. Carboxylated nanodiamonds (cNDs) appear to modulate the deleterious effects of γ-irradiation on the pathophysiology of red blood cells (RBCs). In the present work, the antioxidant activity of hydrated cNDs (h-cNDs) on limiting oxidative damage (the water radiolysis effect) by γ-irradiation was confirmed. Our results show that h-cNDs have remarkable free radical scavenging ability and preserve the enzymatic activity of catalase after γ-irradiation. The underlying mechanism through which nanodiamonds exhibit antioxidant activity appears to depend on their colloidal stability. This property of detonation synthesized nanodiamonds is improved after carboxylation, which in turn influences changes in the hydrogen bond strength in water. The observed stability of h-cNDs in water and their antioxidant activity correlates with their protective effect on RBCs against γ-irradiation.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

PubMed Central

Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

Profiling deleterious non-synonymous SNPs of smoker's gene CYP1A1.

PubMed

Ramesh, A Sai; Khan, Imran; Farhan, Md; Thiagarajan, Padma

2013-01-01

CYP1A1 gene belongs to the cytochrome P450 family and is known better as smokers' gene due to its hyperactivation as a consequence of long term smoking. The expression of CYP1A1 induces polycyclic aromatic hydrocarbon production in the lungs, which when over expressed, is known to cause smoking related diseases, such as cardiovascular pathologies, cancer, and diabetes. Single nucleotide polymorphisms (SNPs) are the simplest form of genetic variations that occur at a higher frequency, and are denoted as synonymous and non-synonymous SNPs on the basis of their effects on the amino acids. This study adopts a systematic in silico approach to predict the deleterious SNPs that are associated with disease conditions. It is inferred that four SNPs are highly deleterious, among which the SNP with rs17861094 is commonly predicted to be harmful by all tools. Hydrophobic (isoleucine) to hydrophilic (serine) amino acid variation was observed in the candidate gene. Hence, this investigation aims to characterize a candidate gene from 159 SNPs of CYP1A1.

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2014 CFR

2014-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2010 CFR

2010-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2012 CFR

2012-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2013 CFR

2013-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2011 CFR

2011-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

Double Hits in Schizophrenia.

PubMed

Vorstman, Jacob A S; Olde Loohuis, Loes M; Kahn, René S; Ophoff, Roel A

2018-05-14

The co-occurrence of a Copy Number Variant (CNV) and a functional variant on the other allele may be a relevant genetic mechanism in schizophrenia. We hypothesized that the cumulative burden of such double hits - in particular those composed of a deletion and a coding single nucleotide variation (SNV) - is increased in patients with schizophrenia.We combined CNV data with coding variants data in 795 patients with schizophrenia and 474 controls. To limit false CNV-detection, only CNVs called only by two algorithms we included. CNV-affected genes were subsequently examined for coding SNVs, which we termed "CNV-SNVs". Correcting for total queried sequence, we assessed the CNV-SNV-burden and the combined predicted deleterious effect. We estimated p-values by permutation of the phenotype.We detected 105 CNV-SNVs; 67 in duplicated and 38 in deleted genic sequence. While the difference in CNV-SNVs rates was not significant, the combined deleteriousness inferred by CNV-SNVs in deleted sequence was almost fourfold higher in cases compared to controls (nominal p = 0.009). This effect may be driven by a higher number of CNV-SNVs and/or by a higher degree of predicted deleteriousness of CNV-SNVs. No such effect was observed for duplications.We provide early evidence that deletions co-occurring with a functional variant may be relevant, albeit of modest impact, for the genetic etiology of schizophrenia. Large-scale consortium studies are required to validate our findings. Sequence-based analyses would provide the best resolution for detection of CNVs as well as coding variants genome-wide.

Similar Efficacies of Selection Shape Mitochondrial and Nuclear Genes in Both Drosophila melanogaster and Homo sapiens.

PubMed

Cooper, Brandon S; Burrus, Chad R; Ji, Chao; Hahn, Matthew W; Montooth, Kristi L

2015-08-21

Deleterious mutations contribute to polymorphism even when selection effectively prevents their fixation. The efficacy of selection in removing deleterious mitochondrial mutations from populations depends on the effective population size (Ne) of the mitochondrial DNA and the degree to which a lack of recombination magnifies the effects of linked selection. Using complete mitochondrial genomes from Drosophila melanogaster and nuclear data available from the same samples, we reexamine the hypothesis that nonrecombining animal mitochondrial DNA harbor an excess of deleterious polymorphisms relative to the nuclear genome. We find no evidence of recombination in the mitochondrial genome, and the much-reduced level of mitochondrial synonymous polymorphism relative to nuclear genes is consistent with a reduction in Ne. Nevertheless, we find that the neutrality index, a measure of the excess of nonsynonymous polymorphism relative to the neutral expectation, is only weakly significantly different between mitochondrial and nuclear loci. This difference is likely the result of the larger proportion of beneficial mutations in X-linked relative to autosomal loci, and we find little to no difference between mitochondrial and autosomal neutrality indices. Reanalysis of published data from Homo sapiens reveals a similar lack of a difference between the two genomes, although previous studies have suggested a strong difference in both species. Thus, despite a smaller Ne, mitochondrial loci of both flies and humans appear to experience similar efficacies of purifying selection as do loci in the recombining nuclear genome. Copyright © 2015 Cooper et al.

The sheltered genetic load linked to the s locus in plants: new insights from theoretical and empirical approaches in sporophytic self-incompatibility.

PubMed

Llaurens, Violaine; Gonthier, Lucy; Billiard, Sylvain

2009-11-01

Inbreeding depression and mating systems evolution are closely linked, because the purging of deleterious mutations and the fitness of individuals may depend on outcrossing vs. selfing rates. Further, the accumulation of deleterious mutations may vary among genomic regions, especially for genes closely linked to loci under balancing selection. Sporophytic self-incompatibility (SSI) is a common genetic mechanism in angiosperm that enables hermaphrodite plants to avoid selfing and promote outcrossing. The SSI phenotype is determined by the S locus and may depend on dominance relationships among alleles. Since most individuals are heterozygous at the S locus and recombination is suppressed in the S-locus region, it has been suggested that deleterious mutations could accumulate at genes linked to the S locus, generating a "sheltered load." In this article, we first theoretically investigate the conditions generating sheltered load in SSI. We show that deleterious mutations can accumulate in linkage with specific S alleles, and particularly if those S alleles are dominant. Second, we looked for the presence of sheltered load in Arabidopsis halleri using CO(2) gas treatment to overcome self-incompatibility. By examining the segregation of S alleles and measuring the relative fitness of progeny, we found significant sheltered load associated with the most dominant S allele (S15) of three S alleles tested. This sheltered load seems to be expressed at several stages of the life cycle and to have a larger effect than genomic inbreeding depression.

Inference of the Distribution of Selection Coefficients for New Nonsynonymous Mutations Using Large Samples

PubMed Central

Kim, Bernard Y.; Huber, Christian D.; Lohmueller, Kirk E.

2017-01-01

The distribution of fitness effects (DFE) has considerable importance in population genetics. To date, estimates of the DFE come from studies using a small number of individuals. Thus, estimates of the proportion of moderately to strongly deleterious new mutations may be unreliable because such variants are unlikely to be segregating in the data. Additionally, the true functional form of the DFE is unknown, and estimates of the DFE differ significantly between studies. Here we present a flexible and computationally tractable method, called Fit∂a∂i, to estimate the DFE of new mutations using the site frequency spectrum from a large number of individuals. We apply our approach to the frequency spectrum of 1300 Europeans from the Exome Sequencing Project ESP6400 data set, 1298 Danes from the LuCamp data set, and 432 Europeans from the 1000 Genomes Project to estimate the DFE of deleterious nonsynonymous mutations. We infer significantly fewer (0.38–0.84 fold) strongly deleterious mutations with selection coefficient |s| > 0.01 and more (1.24–1.43 fold) weakly deleterious mutations with selection coefficient |s| < 0.001 compared to previous estimates. Furthermore, a DFE that is a mixture distribution of a point mass at neutrality plus a gamma distribution fits better than a gamma distribution in two of the three data sets. Our results suggest that nearly neutral forces play a larger role in human evolution than previously thought. PMID:28249985

Potential damage of GM crops to the country image of the producing country.

PubMed

Knight, John G; Clark, Allyson; Mather, Damien W

2013-01-01

Frequently heard within New Zealand are arguments that release of genetically modified organisms (GMOs) into the environment will harm the "clean green" image of the country, and therefore do irreparable harm to export markets for food products and also to the New Zealand tourism industry. But where is the evidence? To investigate the likelihood of harmful effects on New Zealand's clean green image in relation to food exports, we have previously used face-to-face interviews with gatekeepers in the food distribution channel in five countries in Europe, in China, and in India. To investigate potential impacts on the New Zealand tourism sector, we have surveyed first-time visitors to New Zealand at Auckland International Airport soon after arrival. We conclude that it is highly unlikely that introduction of GM plants into New Zealand would have any long-term deleterious effect on perceptions in overseas markets of food products sourced from New Zealand. Furthermore it is highly unlikely that New Zealand's image as a tourist destination would suffer if GM plants were introduced.

Salt Potentiates Methylamine Counteraction System to Offset the Deleterious Effects of Urea on Protein Stability and Function

PubMed Central

Singh, Laishram R.; Warepam, Marina; Ahmad, Faizan; Dar, Tanveer Ali

2015-01-01

Cellular methylamines are osmolytes (low molecular weight organic compounds) believed to offset the urea’s harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea’s effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction. PMID:25793733

Effect of Green Macroalgal Blooms on the Survival, Growth, and Behavior of Cockles in Pacific NW Estuaries

EPA Science Inventory

Nutrient over-enrichment of estuaries is a pervasive issue worldwide that often results in blooms of green macroalgae (GMA; Ulva spp.), which can have disruptive and deleterious effects to estuarine flora and fauna. However, little is known of the effects of GMA blooms on the pr...

NAS Report Reveals Dangers From SST

ERIC Educational Resources Information Center

Fowler, Jo Ann V.

1973-01-01

Reported are some harmful effects of supersonic travel on humans and other living organisms. Slight decreases in ozone concentration as a result of emissions from the SST aircrafts reduce absorption of ultraviolet radiation. Effects of this may include skin cancer, distort balance of activity in cells and have a deleterious effect on insects and…

77 FR 62285 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... other markets and thereby allows market participants to react to the execution (an effect known as... BX available shares and routing to other venues' shares will avoid the deleterious effect of market... Orders To Simultaneously Execute Against Exchange Available Shares and Route to Other Markets for...

Effects of prenatal diesel exhaust inhalation on pulmonary inflammation and development of specific immune responses

EPA Science Inventory

There is increasing evidence that exposure to air pollutants during pregnancy can result in a number of deleterious effects including low birth weight and the incidence of allergic asthma. To investigate the in utero effects of DE exposure, timed pregnant BALB/c mice were exposed...

A Theory of Age-Dependent Mutation and Senescence

PubMed Central

Moorad, Jacob A.; Promislow, Daniel E. L.

2008-01-01

Laboratory experiments show us that the deleterious character of accumulated novel age-specific mutations is reduced and made less variable with increased age. While theories of aging predict that the frequency of deleterious mutations at mutation–selection equilibrium will increase with the mutation's age of effect, they do not account for these age-related changes in the distribution of de novo mutational effects. Furthermore, no model predicts why this dependence of mutational effects upon age exists. Because the nature of mutational distributions plays a critical role in shaping patterns of senescence, we need to develop aging theory that explains and incorporates these effects. Here we propose a model that explains the age dependency of mutational effects by extending Fisher's geometrical model of adaptation to include a temporal dimension. Using a combination of simple analytical arguments and simulations, we show that our model predicts age-specific mutational distributions that are consistent with observations from mutation-accumulation experiments. Simulations show us that these age-specific mutational effects may generate patterns of senescence at mutation–selection equilibrium that are consistent with observed demographic patterns that are otherwise difficult to explain. PMID:18660535

Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

PubMed

Hurt, Hallam; Betancourt, Laura M

2016-01-01

It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

Geographical differences in maternal basking behaviour and offspring growth rate in a climatically widespread viviparous reptile.

PubMed

Cadby, Chloé D; Jones, Susan M; Wapstra, Erik

2014-04-01

In reptiles, the thermal environment during embryonic development affects offspring phenotypic traits and potentially offspring fitness. In viviparous species, mothers can potentially manipulate the embryonic thermal environment through their basking behaviour and, thus, may be able to manipulate offspring phenotype and increase offspring fitness. One way in which mothers can maximise offspring phenotype (and thus potentially affect offspring fitness) is by fine-tuning their basking behaviour to the environment in order to buffer the embryo from deleterious developmental temperatures. In widespread species, it is unclear whether populations that have evolved under different climatic conditions will exhibit different maternal behaviours and/or thermal effects on offspring phenotype. To test this, we provided extended or reduced basking opportunity to gravid spotted skinks (Niveoscincus ocellatus) and their offspring from two populations at the climatic extremes of the species' distribution. Gravid females fine-tuned their basking behaviour to the basking opportunity, which allowed them to buffer their embryos from potentially negative thermal effects. This fine-tuning of female basking behaviour appears to have led to the expression of geographical differences in basking behaviour, with females from the cold alpine regions being more opportunistic in their basking behaviour than females from the warmer regions. However, those differences in maternal behaviour did not preclude the evolution of geographic differences in thermal effects: offspring growth varied between populations, potentially suggesting local adaptation to basking conditions. Our results demonstrate that maternal effects and phenotypic plasticity can play a significant role in allowing species to cope in changing environmental conditions, which is particularly relevant in the context of climate change.

Beneficial and Deleterious Bacterial - Host Interactions in Chronic Wound Pathophysiology

DTIC Science & Technology

2015-04-02

Lactobacillus plantarum supernatants disrupted biofilms made by a laboratory strain of P. aeruginosa by 43% and a P. aeruginosa clini- cal strain...that used L. plantarum topically,73–75 Lactobacillus septicemia is possi- ble in severely immunocompromised individuals, and seems to be strain...Bosch A, Yantorno OM, Valdez JC. Antipathogenic properties of Lactobacillus plantarum on Pseudomonas aeruginosa: the potential use of its

Beneficial effects of neotyphodium tembladerae and neotyphodium pampeanum on a wild forage grass

USDA-ARS?s Scientific Manuscript database

Asexual, vertically transmitted fungal endophytes of the genus Neotyphodium are considered to enhance growth, stress resistance and competitiveness of agronomic grasses, but have been suggested to have neutral or deleterious effects on wild grasses. We studied whether the associations between Bromus...

Beneficial effects of Neotyphodium tembladerae and Neotyphodium pampeanum on a wild forage grass

USDA-ARS?s Scientific Manuscript database

Asexual, vertically transmitted fungal endophytes of the genus Neotyphodium are considered to enhance growth, stress resistance and competitiveness of agronomic grasses, but have been suggested to have neutral or deleterious effects on wild grasses. We studied whether the associations between Bromus...

Perturbation of Gene Expression and Steroidogenesis with In vitro Exposure of Fathead Minnow Ovaries to Ketoconazole

EPA Science Inventory

Various chemicals in the environment can disrupt normal endocrine function, including steroid hormone synthesis, causing deleterious effects. Because these compounds can act at different levels of the hypothalamus-pituitary-gonadal (HPG) axis, their effects can lead to a mixture...

Adaptive Appraisals of Anxiety Moderate the Association between Cortisol Reactivity and Performance in Salary Negotiations

PubMed Central

Fridman, Ilona; Mor, Shira; Morris, Michael W.; Crum, Alia J.

2016-01-01

Prior research suggests that stress can be harmful in high-stakes contexts such as negotiations. However, few studies actually measure stress physiologically during negotiations, nor do studies offer interventions to combat the potential negative effects of heightened physiological responses in negotiation contexts. In the current research, we offer evidence that the negative effects of cortisol increases on negotiation performance can be reduced through a reappraisal of anxiety manipulation. We experimentally induced adaptive appraisals by randomly assigning 97 male and female participants to receive either instructions to appraise their anxiety as beneficial to the negotiation or no specific instructions on how to appraise the situation. We also measured participants’ cortisol responses prior to and following the negotiation. Results revealed that cortisol increases were positively related to negotiation performance for participants who were told to view anxiety as beneficial, and not detrimental, for negotiation performance (appraisal condition). In contrast, cortisol increases were negatively related to negotiation performance for participants given no instructions on appraising their anxiety (control condition). These findings offer a means through which to combat the potentially deleterious effects of heightened cortisol reactivity on negotiation outcomes. PMID:27992484

From cooperation to combat: adverse effect of thermal stress in a symbiotic coral-crustacean community.

PubMed

Stella, J S; Munday, P L; Walker, S P W; Pratchett, M S; Jones, G P

2014-04-01

Although mutualisms are ubiquitous in nature, our understanding of the potential impacts of climate change on these important ecological interactions is deficient. Here, we report on a thermal stress-related shift from cooperation to antagonism between members of a mutualistic coral-dwelling community. Increased mortality of coral-defending crustacean symbionts Trapezia cymodoce (coral crab) and Alpheus lottini (snapping shrimp) was observed in response to experimentally elevated temperatures and reduced coral-host (Pocillopora damicornis) condition. However, strong differential numerical effects occurred among crustaceans as a function of species and sex, with shrimp (75%), and female crabs (55%), exhibiting the fastest and greatest declines in numbers. These declines were due to forceful eviction from the coral-host by male crabs. Furthermore, surviving female crabs were impacted by a dramatic decline (85%) in egg production, which could have deleterious consequences for population sustainability. Our results suggest that elevated temperature switches the fundamental nature of this interaction from cooperation to competition, leading to asymmetrical effects on species and/or sexes. Our study illustrates the importance of evaluating not only individual responses to climate change, but also potentially fragile interactions within and among susceptible species.

Adaptive Appraisals of Anxiety Moderate the Association between Cortisol Reactivity and Performance in Salary Negotiations.

PubMed

Akinola, Modupe; Fridman, Ilona; Mor, Shira; Morris, Michael W; Crum, Alia J

2016-01-01

Prior research suggests that stress can be harmful in high-stakes contexts such as negotiations. However, few studies actually measure stress physiologically during negotiations, nor do studies offer interventions to combat the potential negative effects of heightened physiological responses in negotiation contexts. In the current research, we offer evidence that the negative effects of cortisol increases on negotiation performance can be reduced through a reappraisal of anxiety manipulation. We experimentally induced adaptive appraisals by randomly assigning 97 male and female participants to receive either instructions to appraise their anxiety as beneficial to the negotiation or no specific instructions on how to appraise the situation. We also measured participants' cortisol responses prior to and following the negotiation. Results revealed that cortisol increases were positively related to negotiation performance for participants who were told to view anxiety as beneficial, and not detrimental, for negotiation performance (appraisal condition). In contrast, cortisol increases were negatively related to negotiation performance for participants given no instructions on appraising their anxiety (control condition). These findings offer a means through which to combat the potentially deleterious effects of heightened cortisol reactivity on negotiation outcomes.

On hybridising lettuce seedlings with nanoparticles and the resultant effects on the organisms' electrical characteristics.

PubMed

Gizzie, Nina; Mayne, Richard; Patton, David; Kendrick, Paul; Adamatzky, Andrew

2016-09-01

Lettuce seedlings are attracting interest in the computing world due to their capacity to become hybrid circuit components, more specifically, in the creation of living 'wires'. Previous studies have shown that seedlings can be hybridised with gold nanoparticles and withstand mild electrical currents. In this study, lettuce seedlings were hybridised with a variety of metallic and non-metallic nanomaterials: carbon nanotubes, graphene oxide, aluminium oxide and calcium phosphate. Toxic effects and the following electrical properties were monitored: mean potential, resistance and capacitance. Macroscopic observations revealed only slight deleterious health effects after administration with one variety of particle, aluminium oxide. Mean potential in calcium phosphate-hybridised seedlings showed a considerable increase when compared with the control, whereas those administered with graphene oxide showed a small decrease; there were no notable variations across the remaining treatments. Electrical resistance decreased substantially in graphene oxide-treated seedlings whereas slight increases were shown following calcium phosphate and carbon nanotubes applications. Capacitance showed no considerable variation across treated seedlings. These results demonstrate that use of some nanomaterials, specifically graphene oxide and calcium phosphate, may be towards biohybridisation purposes including the generation of living 'wires'. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exercise Promotes Healthy Aging of Skeletal Muscle.

PubMed

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

HUMAN EXPOSURE MODELING: CONCEPTS, METHODS, AND TOOLS

EPA Science Inventory

Understanding human exposure is critical when estimating the occurrence of deleterious effects that could follow contact with environmental contaminants. For many pollutants, the intensity, duration, frequency, route, and timing of exposure is highly variable, particularly whe...

Mitochondrial pathogenic mutations are population-specific.

PubMed

Breen, Michael S; Kondrashov, Fyodor A

2010-12-31

Surveying deleterious variation in human populations is crucial for our understanding, diagnosis and potential treatment of human genetic pathologies. A number of recent genome-wide analyses focused on the prevalence of segregating deleterious alleles in the nuclear genome. However, such studies have not been conducted for the mitochondrial genome. We present a systematic survey of polymorphisms in the human mitochondrial genome, including those predicted to be deleterious and those that correspond to known pathogenic mutations. Analyzing 4458 completely sequenced mitochondrial genomes we characterize the genetic diversity of different types of single nucleotide polymorphisms (SNPs) in African (L haplotypes) and non-African (M and N haplotypes) populations. We find that the overall level of polymorphism is higher in the mitochondrial compared to the nuclear genome, although the mitochondrial genome appears to be under stronger selection as indicated by proportionally fewer nonsynonymous than synonymous substitutions. The African mitochondrial genomes show higher heterozygosity, a greater number of polymorphic sites and higher frequencies of polymorphisms for synonymous, benign and damaging polymorphism than non-African genomes. However, African genomes carry significantly fewer SNPs that have been previously characterized as pathogenic compared to non-African genomes. Finding SNPs classified as pathogenic to be the only category of polymorphisms that are more abundant in non-African genomes is best explained by a systematic ascertainment bias that favours the discovery of pathogenic polymorphisms segregating in non-African populations. This further suggests that, contrary to the common disease-common variant hypothesis, pathogenic mutations are largely population-specific and different SNPs may be associated with the same disease in different populations. Therefore, to obtain a comprehensive picture of the deleterious variability in the human population, as well as to improve the diagnostics of individuals carrying African mitochondrial haplotypes, it is necessary to survey different populations independently. This article was reviewed by Dr Mikhail Gelfand, Dr Vasily Ramensky (nominated by Dr Eugene Koonin) and Dr David Rand (nominated by Dr Laurence Hurst).

Preliminary analysis of data from SRI international transient pulse monitor on board P78-2 SCATHA satellite

NASA Technical Reports Server (NTRS)

Damron, S. A.; Adamo, R. C.; Nanevicz, J. E.

1980-01-01

The satellite charging at high altitudes (SCATHA) program addresses the occurrence of electrostatic discharges causing undesirable effects like deleterious transients in electronic circuits on satellites. The high altitude plasma environment and the effects of the interaction of this environment with the orbiting satellite are studied. The SRI transient pulse monitor (TPM) detects the transient electromagnetic signals induced in selected circuits. As a transient detector the TPM records transient signals, indicates the number of transients observed, and gives peak amplitude of the largest transient during each second's interval. Most of the early data from the TPM contain pulses associated with internal electrical activity and electrostatic charging on the surface of the P78-2 is evidenced. It is found that periods of external discharging do not necessarily coincide with periods in which high potentials are measured on the satellite's surface.

Lung inflammatory response syndrome after cardiac-operations and treatment of lornoxicam

PubMed Central

Tsakiridis, Kosmas; Mpakas, Andreas; Kesisis, George; Arikas, Stamatis; Argyriou, Michael; Siminelakis, Stavros; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Tsiouda, Theodora; Sarika, Eirini; Katamoutou, Ioanna; Zarogoulidis, Konstantinos

2014-01-01

The majority of patients survive after extracorporeal circulation without any clinically apparent deleterious effects. However, disturbances exist in various degrees sometimes, which indicate the harmful effects of cardiopulmonary bypass (CPB) in the body. Several factors during extracorporeal circulation either mechanical dependent (exposure of blood to non-biological area) or mechanical independent (surgical wounds, ischemia and reperfusion, alteration in body temperature, release of endotoxins) have been shown to trigger the inflammatory reaction of the body. The complement activation, the release of cytokines, the leukocyte activation and accumulation as well as the production of several “mediators” such as oxygen free radicals, metabolites of arachidonic acid, platelet activating factors (PAF), nitric acid, and endothelin. The investigation continues today on the three metabolites of lornoxicam (the hydroxylated metabolite and two other metabolites of unknown chemical composition) to search for potential new pharmacological properties and activities. PMID:24672703

Developing standard operating procedures for gene drive research in disease vector mosquitoes.

PubMed

Adelman, Zach N; Pledger, David; Myles, Kevin M

2017-12-01

Numerous arthropod species represent potential targets for gene-drive-based population suppression or replacement, including those that transmit diseases, damage crops, or act as deleterious invasive species. Containment measures for gene drive research in arthropods have been discussed in the literature, but the importance of developing safe and effective standard operating procedures (SOPs) for these types of experiments has not been adequately addressed. Concisely written SOPs link safe work practices, containment measures, institutional training, and research-specific protocols. Here we discuss information to be considered by principal investigators, biosafety officers, and institutional biosafety committees as they work together to develop SOPs for experiments involving gene drive in arthropods, and describe various courses of action that can be used to maintain the effectiveness of SOPs through evaluation and revision. The information provided herein will be especially useful to investigators and regulatory personnel who may lack extensive experience working with arthropods under containment conditions.

Impact of urbanization and gardening practices on common butterfly communities in France.

PubMed

Fontaine, Benoît; Bergerot, Benjamin; Le Viol, Isabelle; Julliard, Romain

2016-11-01

We investigated the interacting impacts of urban landscape and gardening practices on the species richness and total abundance of communities of common butterfly communities across France, using data from a nationwide monitoring scheme. We show that urbanization has a strong negative impact on butterfly richness and abundance but that at a local scale, such impact could be mitigated by gardening practices favoring nectar offer. We found few interactions among these landscape and local scale effects, indicating that butterfly-friendly gardening practices are efficient whatever the level of surrounding urbanization. We further highlight that species being the most negatively affected by urbanization are the most sensitive to gardening practices: Garden management can thus partly counterbalance the deleterious effect of urbanization for butterfly communities. This holds a strong message for park managers and private gardeners, as gardens may act as potential refuge for butterflies when the overall landscape is largely unsuitable.

Assessing the Risks for Modern Diagnostic Ultrasound Imaging

NASA Astrophysics Data System (ADS)

William, Jr.

1998-05-01

Some 35 years after Paul-Jacques and Pierre Curie discovered piezoelectricity, ultrasonic imaging was developed by Paul Langevin. During this work, ultrasonic energy was observed to have a detrimental biological effect. These observations were confirmed a decade later by R. W. Wood and A. L. Loomis. It was not until the early 1950s that ultrasonic exposure conditions were controlled and specified so that studies could focus on the mechanisms by which ultrasound influenced biological materials. In the late 1940s, pioneering work was initiated to image the human body by ultrasonic techniques. These engineers and physicians were aware of the deleterious ultrasound effects at sufficiently high levels; this endeavored them to keep the exposure levels reasonably low. Over the past three decades, diagnostic ultrasound has become a sophisticated technology. Yet, our understanding of the potential risks has not changed appreciably. It is very encouraging that human injury has never been attributed to clinical practice of diagnostic ultrasound.

Male germplasm in relation to environmental conditions: synoptic focus on DNA

USGS Publications Warehouse

Jenkins, Jill A.; Tiersch, Terrence R.; Green, Christopher C.

2011-01-01

Wild animals are generally more sensitive than humans to environmental stressors, thus they act as sentinels for resource degradation. Sublethal stress is generally manifested first at the sub-organismal level, where immune systems are compromised, reproductive success is reduced, and genetic integrity is altered. Biomarkers - variables quantifiably responsive to changes in the environment - provide useful information to resource managers and regulatory agencies. Biomarkers of sperm quality are proving useful in this capacity, as well as in artificial breeding. Cellular and molecular bioassays can help to determine mechanisms of action of deleterious agents, predict fertility and reproductive potential, and model population-wide and community level effects. A sequence of biomarker assays can be tailored to fit species of concern, to study physiological effects responsive to known contamination events, and can be selectively applied to fresh, thawed, and fixed samples, as well as those shipped to the laboratory from field sites.

Polluted Pathways: Mechanisms of Metabolic Disruption by Endocrine Disrupting Chemicals.

PubMed

Mimoto, Mizuho S; Nadal, Angel; Sargis, Robert M

2017-06-01

Environmental toxicants are increasingly implicated in the global decline in metabolic health. Focusing on diabetes, herein, the molecular and cellular mechanisms by which metabolism disrupting chemicals (MDCs) impair energy homeostasis are discussed. Emerging data implicate MDC perturbations in a variety of pathways as contributors to metabolic disease pathogenesis, with effects in diverse tissues regulating fuel utilization. Potentiation of traditional metabolic risk factors, such as caloric excess, and emerging threats to metabolism, such as disruptions in circadian rhythms, are important areas of current and future MDC research. Increasing evidence also implicates deleterious effects of MDCs on metabolic programming that occur during vulnerable developmental windows, such as in utero and early post-natal life as well as pregnancy. Recent insights into the mechanisms by which MDCs alter energy homeostasis will advance the field's ability to predict interactions with classical metabolic disease risk factors and empower studies utilizing targeted therapeutics to treat MDC-mediated diabetes.

Impact of Heavy Metal Pollution on Ammonia Oxidizers in Soils in the Vicinity of a Tailings Dam, Baotou, China.

PubMed

Liu, Jumei; Cao, Weiwei; Jiang, Haiming; Cui, Jing; Shi, Chunfang; Qiao, Xiaohui; Zhao, Ji; Si, Wantong

2018-05-09

Soil heavy metal pollution has received increasing attention due to their toxicity to soil microorganisms. We have analyzed the effects of heavy metal pollution on ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in soils in the vicinity of a tailings dam of Baotou region, China. Results showed that AOB were dominated with Nitrosomonas-like clusters, while AOA was dominated by group1.1b (Nitrososphaera cluster). Single Cd and Cr contents, as well as compound heavy metal pollution levels, had a significant negative impact on soil potential nitrification rate and both diversities of AOA and AOB. No clear relationship was found between any single heavy metal and abundance of AOA or AOB. But compound pollution could significantly decrease AOA abundance. The results indicated that heavy metal pollution had an obviously deleterious effect on the abundance, diversity, activity and composition of ammonia oxidizers in natural soils.

Epidemiology of Substance Use in Reproductive-Age Women

PubMed Central

McHugh, R. Kathryn; Wigderson, Sara; Greenfield, Shelly F.

2014-01-01

Synopsis A significant number of women of reproductive age in the U.S. use addictive substances. In 2012 more than 50% reported current use of alcohol, 20% used tobacco products, and approximately 13% used other drugs. Among women, use of these substances is associated with a number of significant medical, psychiatric, and social consequences, and the course of illness may progress more rapidly in women than men. The lifetime prevalence of alcohol and drug use disorders in women is 19.5% and 7.1%, respectively. In addition, as most addictive substances cross the placenta and have deleterious effects on fetal development, substance use has additional potential adverse consequences for women of reproductive age who may become pregnant. Specific barriers to accessing effective substance use treatment exist for women. The prevalence of substance use and evidence of accelerated illness progression in women highlight the importance of universal substance use screening in women in primary care settings. PMID:24845483

Deleterious effects of recombination and possible nonrecombinatorial advantages of sex in a fungal model.

PubMed

López-Villavicencio, M; Debets, A J M; Slakhorst, M; Giraud, T; Schoustra, S E

2013-09-01

Why sexual reproduction is so prevalent in nature remains a major question in evolutionary biology. Most of the proposed advantages of sex rely on the benefits obtained from recombination. However, it is still unclear whether the conditions under which these recombinatorial benefits would be sufficient to maintain sex in the short term are met in nature. Our study addresses a largely overlooked hypothesis, proposing that sex could be maintained in the short term by advantages due to functions linked with sex, but not related to recombination. These advantages would be so essential that sex could not be lost in the short term. Here, we used the fungus Aspergillus nidulans to experimentally test predictions of this hypothesis. Specifically, we were interested in (i) the short-term deleterious effects of recombination, (ii) possible nonrecombinatorial advantages of sex particularly through the elimination of mutations and (iii) the outcrossing rate under choice conditions in a haploid fungus able to reproduce by both outcrossing and haploid selfing. Our results were consistent with our hypotheses: we found that (i) recombination can be strongly deleterious in the short term, (ii) sexual reproduction between individuals derived from the same clonal lineage provided nonrecombinatorial advantages, likely through a selection arena mechanism, and (iii) under choice conditions, outcrossing occurs in a homothallic species, although at low rates. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

What California sea lions exposed to domoic acid might teach us about autism: lessons for predictive and preventive medicine.

PubMed

Lahvis, Garet Paul

2017-09-01

Autism spectrum disorder (ASD) shares many biological and behavioral similarities with the deleterious effects of domoic acid (DA) exposure. DA is produced by marine algae and most commonly by species of Pseudo-nitzschia . Humans and marine mammals can be exposed to DA when they consume whole fish or shellfish. The mammalian fetus is highly sensitive to the deleterious effects of DA exposure. Both ASD and exposures to toxic levels of DA feature repetitive behaviors, challenges with social interaction, and seizures. They can also share a commonality in brain anatomy and function, particularly the balance between excitatory and inhibitory mechanisms. The current article is relevant to predictive, preventive, and personalized medicine for three reasons. First, shellfish consumption may be a risk factor for ASD and the regulatory limit for DA should be adjusted to prevent this possibility. Human contributions to increased algal production of DA in coastal waters should be identified and reduced. Second, evaluations of sentinel species wild and free-roaming in the environment, though typically outside the purview of biomedical research, should be much more fully employed to gain insights to risk factors for human disease. To better identify and prevent disease, biomedical researchers should study wild populations. Third, studies of DA exposure highlight the possibility that glutamate additives to processed foods may also have deleterious impacts on human brain development and behavior.

A Survey of Caffeine Use and Associated Side Effects in a College Population.

ERIC Educational Resources Information Center

Johnson-Greene, Douglas; And Others

1988-01-01

Surveyed 270 college students concerning their caffeine consumption. Results suggest there is identifiable group using excessive amounts of caffeine. Identified several deleterious effects possibly related to caffeine use. Approximately 75 percent of caffeine users surveyed rarely sought information on caffeine content of products or avoided…

Temporal metabolomic responses of cultured HepG2 liver cells to high fructose and high glucose exposures

USDA-ARS?s Scientific Manuscript database

High fructose consumption has been implicated with deleterious effects on human health, including hyperlipidemia elicited through de novo lipogenesis. However, more global effects of fructose on cellular metabolism have not been elucidated. In order to explore the metabolic impact of fructose-contai...

Water jetting for the mitigation of defects in drilled shafts : a laboratory investigation of jetting effectiveness in different deleterious materials.

DOT National Transportation Integrated Search

2012-09-01

Presented in this report are results of a laboratory investigation designed to examine the effectiveness of water : jetting as a means for mitigating defects in drilled shaft foundations. The primary objective of this research was : to establish an e...

Ecological Engineering Practices for the Reduction of Excess Nitrogen in Human-Influenced Landscapes: A Guide for Watershed Managers

EPA Science Inventory

Excess nitrogen (N) in freshwater systems, estuaries, and coastal areas has well-documented deleterious effects on ecosystems. Ecological engineering practices (EEPs) may be effective at decreasing nonpoint source N leaching to surface and groundwater. However, few studies have s...

The effects of sex-biased gene expression and X-linkage on rates of sequence evolution in Drosophila.

PubMed

Campos, José Luis; Johnston, Keira; Charlesworth, Brian

2017-12-08

A faster rate of adaptive evolution of X-linked genes compared with autosomal genes (the faster-X effect) can be caused by the fixation of recessive or partially recessive advantageous mutations. This effect should be largest for advantageous mutations that affect only male fitness, and least for mutations that affect only female fitness. We tested these predictions in Drosophila melanogaster by using coding and functionally significant non-coding sequences of genes with different levels of sex-biased expression. Consistent with theory, nonsynonymous substitutions in most male-biased and unbiased genes show faster adaptive evolution on the X. However, genes with very low recombination rates do not show such an effect, possibly as a consequence of Hill-Robertson interference. Contrary to expectation, there was a substantial faster-X effect for female-biased genes. After correcting for recombination rate differences, however, female-biased genes did not show a faster X-effect. Similar analyses of non-coding UTRs and long introns showed a faster-X effect for all groups of genes, other than introns of female-biased genes. Given the strong evidence that deleterious mutations are mostly recessive or partially recessive, we would expect a slower rate of evolution of X-linked genes for slightly deleterious mutations that become fixed by genetic drift. Surprisingly, we found little evidence for this after correcting for recombination rate, implying that weakly deleterious mutations are mostly close to being semidominant. This is consistent with evidence from polymorphism data, which we use to test how models of selection that assume semidominance with no sex-specific fitness effects may bias estimates of purifying selection. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Social management of laboratory rhesus macaques housed in large groups using a network approach: A review.

PubMed

McCowan, Brenda; Beisner, Brianne; Hannibal, Darcy

2017-12-07

Biomedical facilities across the nation and worldwide aim to develop cost-effective methods for the reproductive management of macaque breeding groups, typically by housing macaques in large, multi-male multi-female social groups that provide monkey subjects for research as well as appropriate socialization for their psychological well-being. One of the most difficult problems in managing socially housed macaques is their propensity for deleterious aggression. From a management perspective, deleterious aggression (as opposed to less intense aggression that serves to regulate social relationships) is undoubtedly the most problematic behavior observed in group-housed macaques, which can readily escalate to the degree that it causes social instability, increases serious physical trauma leading to group dissolution, and reduces psychological well-being. Thus for both welfare and other management reasons, aggression among rhesus macaques at primate centers and facilities needs to be addressed with a more proactive approach.Management strategies need to be instituted that maximize social housing while also reducing problematic social aggression due to instability using efficacious methods for detection and prevention in the most cost effective manner. Herein we review a new proactive approach using social network analysis to assess and predict deleterious aggression in macaque groups. We discovered three major pathways leading to instability, such as unusually high rates and severity of trauma and social relocations.These pathways are linked either directly or indirectly to network structure in rhesus macaque societies. We define these pathways according to the key intrinsic and extrinsic variables (e.g., demographic, genetic or social factors) that influence network and behavioral measures of stability (see Fig. 1). They are: (1) presence of natal males, (2) matrilineal genetic fragmentation, and (3) the power structure and conflict policing behavior supported by this power structure. We discuss how these three major pathways leading to greater understanding and predictability of deleterious aggression in macaque social groups. Copyright © 2017. Published by Elsevier B.V.

Effects of hyperlipidemia on adaptive responses to repeated zinc exposure

EPA Science Inventory

In individuals with underlying atherosclerosis and coronary heart disease (CHD), exposure to near-road air pollution correlates epidemiologically with deleterious health outcome. Associated cardiotoxicity purportedly involves generation of reactive oxygen species (ROS) and activa...

Financial hardship and psychological distress: Exploring the buffering effects of religion

PubMed Central

Bradshaw, Matt; Ellison, Christopher G.

2013-01-01

Despite ample precedent in theology and social theory, few studies have systematically examined the role of religion in mitigating the harmful effects of socioeconomic deprivation on mental health. The present study outlines several arguments linking objective and subjective measures of financial hardship, as well as multiple aspects of religious life, with psychological distress. Relevant hypotheses are then tested using data on adults aged 18–59 from the 1998 US NORC General Social Survey. Findings confirm that both types of financial hardship are positively associated with distress, and that several different aspects of religious life buffer against these deleterious influences. Specifically, religious attendance and the belief in an afterlife moderate the deleterious effects of financial hardship on both objective and subjective financial hardship, while meditation serves this function only for objective hardship. No interactive relationships were found between frequency of prayer and financial hardship. A number of implications, study limitations, and directions for future research are identified. PMID:20556889

Single season effects of mixed-species cover crops on tomato health (cultivar Celebrity) in multi-state field trials

USDA-ARS?s Scientific Manuscript database

Cover crop use can help mitigate the deleterious effects of common cropping practices (e.g., tillage) and is, therefore, an important component of soil health maintenance. While known to be beneficial in the long term, the short-term effects of cover crops, specifically mixed-species cover crops in ...

Effect of increased systemic concentrations of urea nitrogen in crossbred heifers on in vitro fertilization (IVF)

USDA-ARS?s Scientific Manuscript database

Elevated levels of dietary N and hence systemic concentrations of urea-N have been shown to have a deleterious effect on reproductive processes. The objective of this study was to determine the effect of feeding pubertal crossbred heifers diets with moderate (M-N; 64.8% corn silage, 30.0% alfalfa h...

Distration, Response Mode, Anxiety, and Achievement in Computer Assisted Instruction.

ERIC Educational Resources Information Center

Tobias, Sigmund

The effects of distraction on achievement are particularly important in relation to the acceptability of computer-assisted instructional materials. In addition to these effects, various levels of anxiety may also be deleterious to the learner. In order to measure the effects of both distraction and anxiety 121 subjects were used in a two-by-two…

CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations.

PubMed

Basavarajappa, Balapal S; Subbanna, Shivakumar

2014-02-01

Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as "Spice" or "K2" to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared with vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice. © 2013 Wiley Periodicals, Inc.

Sex-chromosome turnovers: the hot-potato model.

PubMed

Blaser, Olivier; Neuenschwander, Samuel; Perrin, Nicolas

2014-01-01

Sex-determining systems often undergo high rates of turnover but for reasons that remain largely obscure. Two recent evolutionary models assign key roles, respectively, to sex-antagonistic (SA) mutations occurring on autosomes and to deleterious mutations accumulating on sex chromosomes. These two models capture essential but distinct key features of sex-chromosome evolution; accordingly, they make different predictions and present distinct limitations. Here we show that a combination of features from the two models has the potential to generate endless cycles of sex-chromosome transitions: SA alleles accruing on a chromosome after it has been co-opted for sex induce an arrest of recombination; the ensuing accumulation of deleterious mutations will soon make a new transition ineluctable. The dynamics generated by these interactions share several important features with empirical data, namely, (i) that patterns of heterogamety tend to be conserved during transitions and (ii) that autosomes are not recruited randomly, with some chromosome pairs more likely than others to be co-opted for sex.

Aspirin use and endometrial cancer risk and survival.

PubMed

Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

2018-01-01

The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulatory RNA Key Player in p53-Mediated Apoptosis in Embryonic Stem Cells | Center for Cancer Research

Cancer.gov

Embryonic stem cells (ESCs) must maintain the integrity of their genomes or risk passing potentially deleterious mutations on to numerous tissues. Thus, ESCs have a unique genome surveillance system and easily undergo apoptosis or differentiation when DNA damage is detected. The protein p53 is known to promote differentiation in mouse ESCs (mESCs), but its role in DNA

New hosts for the mite Ornithonyssus bursa in Argentina.

PubMed

Santillán, M Á; Grande, J M; Liébana, M S; Martínez, P; Díaz, L A; Bragagnolo, L A; Solaro, C; Galmes, M A; Sarasola, J H

2015-12-01

The mite Ornithonyssus bursa (Berlese) (Mesostigmata: Macronyssidae) is considered a poultry pest causing important infestations in chickens and it is considered a potential vector of arbovirus. Despite being considered a common parasite in wild birds, there is scarce published information about its potential hosts and effects on them. Here we present new bird hosts for O. bursa, assess the presence of Alphavirus, Flavivirus and Bunyavirus in mites from three host species, and discuss its potential impact on wild bird populations. We found O. bursa infecting five raptor and six passerine wild bird species. For nine of these species, this is the first record of infection by O. bursa. Although all analysed mites were negative for the examined arboviruses, the small sample size of mites does not allow further conclusions at the present moment. Because of the general nature of this ectoparasite, its presence in migratory long dispersal and endangered bird species, and the seropositivity for arboviruses in some of the species studied here, we consider it critical to assess the role of O. bursa and other ectoparasites as vectors and reservoirs of pathogens and as potential deleterious agents in wild bird populations. © 2015 The Royal Entomological Society.

Experimental Study of RF Sheaths due to Shear Alfvén Waves in the LAPD

NASA Astrophysics Data System (ADS)

Martin, Michael; Gekelman, Walter; van Compernolle, Bart; Pribyl, Patrick; Carter, Troy

2014-10-01

Ion cyclotron resonance heating (ICRH) is an important tool in current fusion heating experiments and will be an essential part of heating power in ITER. Radio frequency (RF) sheaths in the near-field (at the antenna) and in the far-field (e.g. the divertor region) form during ICRH and may cause deleterious effects, such as destruction of wall materials and plasma impurity generation. In this study a shear Alfvén wave is launched from an antenna in the LAPD bulk plasma (ne ~ 1012 cm-3, Te ~ 5 eV, B0 = 1.8 kG, diameter = 60 cm, length = 18 m) and forms an RF sheath on a limiter plate. Plasma potential rectification is observed with an emissive probe in the bulk plasma only on field lines connected to the limiter. The largest enhancement occurs inside the current channel of the Alfvén wave. Plasma potential measurements at various axial distances from the limiter show the rectification decreases with distance. 2-D maps of plasma potential as well as E = - ∇Φ will be presented. The scaling of sheath potential with wave power and plasma parameters will also be shown.

The effect of path length and display size on memory for spatial information.

PubMed

Guérard, Katherine; Tremblay, Sébastien

2012-01-01

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

Cyanotoxins: bioaccumulation and effects on aquatic animals.

PubMed

Ferrão-Filho, Aloysio da S; Kozlowsky-Suzuki, Betina

2011-12-01

Cyanobacteria are photosynthetic prokaryotes with wide geographic distribution that can produce secondary metabolites named cyanotoxins. These toxins can be classified into three main types according to their mechanism of action in vertebrates: hepatotoxins, dermatotoxins and neurotoxins. Many studies on the effects of cyanobacteria and their toxins over a wide range of aquatic organisms, including invertebrates and vertebrates, have reported acute effects (e.g., reduction in survivorship, feeding inhibition, paralysis), chronic effects (e.g., reduction in growth and fecundity), biochemical alterations (e.g., activity of phosphatases, GST, AChE, proteases), and behavioral alterations. Research has also focused on the potential for bioaccumulation and transferring of these toxins through the food chain. Although the herbivorous zooplankton is hypothesized as the main target of cyanotoxins, there is not unquestionable evidence of the deleterious effects of cyanobacteria and their toxins on these organisms. Also, the low toxin burden in secondary consumers points towards biodilution of microcystins in the food web as the predominant process. In this broad review we discuss important issues on bioaccumulation and the effects of cyanotoxins, with emphasis on microcystins, as well as drawbacks and future needs in this field of research.

Investigating the Structural Impacts of I64T and P311S Mutations in APE1-DNA Complex: A Molecular Dynamics Approach

PubMed Central

Doss, C. George Priya; NagaSundaram, N.

2012-01-01

Background Elucidating the molecular dynamic behavior of Protein-DNA complex upon mutation is crucial in current genomics. Molecular dynamics approach reveals the changes on incorporation of variants that dictate the structure and function of Protein-DNA complexes. Deleterious mutations in APE1 protein modify the physicochemical property of amino acids that affect the protein stability and dynamic behavior. Further, these mutations disrupt the binding sites and prohibit the protein to form complexes with its interacting DNA. Principal Findings In this study, we developed a rapid and cost-effective method to analyze variants in APE1 gene that are associated with disease susceptibility and evaluated their impacts on APE1-DNA complex dynamic behavior. Initially, two different in silico approaches were used to identify deleterious variants in APE1 gene. Deleterious scores that overlap in these approaches were taken in concern and based on it, two nsSNPs with IDs rs61730854 (I64T) and rs1803120 (P311S) were taken further for structural analysis. Significance Different parameters such as RMSD, RMSF, salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that predicted deleterious variants I64T and P311S alters the structure as well as affect the stability of APE1-DNA interacting functions. This study addresses such new methods for validating functional polymorphisms of human APE1 which is critically involved in causing deficit in repair capacity, which in turn leads to genetic instability and carcinogenesis. PMID:22384055

Deleterious BRCA1/2 mutations in an urban population of Black women

PubMed Central

Smith, Karen Lisa; Stein, Julie; DeMarco, Tiffani; Wang, Yiru; Wang, Hongkun; Fries, Melissa; Peshkin, Beth N.; Isaacs, Claudine

2018-01-01

Information on the prevalence of deleterious BRCA1 and BRCA2 (BRCA1/2) mutations in clinic-based populations of Black women is limited. In order to address this gap, we performed a retrospective study to determine the prevalence of deleterious BRCA1/2 mutations, predictors of having a mutation, and acceptance of risk-reducing surgeries in Black women. In an urban unselected clinic-based population, we evaluated 211 self-identified Black women who underwent genetic counseling for hereditary breast–ovarian cancer syndrome. BRCA1/2 mutations were identified in 13.4 % of the participants who received genetic testing. Younger age at diagnosis, higher BRCA-PRO score, significant family history, and diagnosis of triple-negative breast cancer were associated with identification of a BRCA1/2 mutation. Of the affected patients found to have a deleterious mutation, almost half underwent prophylactic measures. In our study population, 1 in 7 Black women who underwent genetic testing harbored a deleterious BRCA1/2 mutation independent of age at diagnosis or family history. PMID:26250392

Lactobacillus rhamnosus reduces parasite load on Toxocara canis experimental infection in mice, but has no effect on the parasite in vitro.

PubMed

Walcher, Débora Liliane; Cruz, Luis Augusto Xavier; de Lima Telmo, Paula; Martins, Lourdes Helena Rodrigues; da Costa de Avila, Luciana Farias; Berne, Maria Elisabeth Aires; Scaini, Carlos James

2018-02-01

Human toxocariasis is a neglected global parasitic zoonosis. The efficacy of drug treatment for this disease has been hindered by the biological complexity of the main etiological agent, the nematode Toxocara canis. Experimental studies have shown the potential of probiotics to promote a reduction in the parasite load of T. canis larvae. This study aimed to evaluate the effect of probiotic Lactobacillus rhamnosus ATCC 7469 on the parasite load of BALB/c mice with acute toxocariasis and evaluate the direct effect of this probiotic on T. canis larvae in vitro. In vivo administration of probiotics reduced the parasite load of T. canis larvae by 53.3% (p = 0.0018) during the early stage of infection in mice. However, when analyzed in vitro, it was observed that the probiotic did not present a deleterious effect on the larvae, as approximately 90% of these remained viable. These results demonstrate the potential of the probiotic L. rhamnosus in the reduction of T. canis larvae in BALB/c mice and suggest it could be used as an alternative means for the controlling of visceral toxocariasis. However, further studies are required to elucidate the mechanisms of action promoted by this probiotic.

Rutin increases critical wavelength of systems containing a single UV filter and with good skin compatibility.

PubMed

Peres, D A; de Oliveira, C A; da Costa, M S; Tokunaga, V K; Mota, J P; Rosado, C; Consiglieri, V O; Kaneko, T M; Velasco, M V R; Baby, A R

2016-08-01

Ultraviolet (UV) radiation is responsible for sunburns, skin cancer, photoaging, and the production of reactive oxygen species (ROS). The awareness on preventing these deleterious effects made the use of anti-UVB formulations an important part of population habits; however, despite the availability of several antioxidants capable of ROS scavenging, the pharmaceutical market lacks products associating UV filters with natural compounds of proven efficacy. Here, we investigated the effect of rutin, a flavonoid with antioxidant activity, associated with UVB filters in dermocosmetic preparations. Formulations were assessed through its antioxidant activity, in vitro photoprotective effectiveness, photostability, and in vivo skin tolerance (hydration, transepidermal water loss, and erythema). Samples containing rutin were compatible with the human skin and presented a pronounced antioxidant potential, with scavenging activity values 75% higher than the ones containing only UVB filters. Although rutin could not prevent the sunscreens photodegradation post-irradiation, the bioactive compound significantly increased the formulations critical wavelengths, showing a photoprotective gain, especially in the UVA range. In conclusion, the absorption in the UVA range, coupled with ROS scavenging potential, proved the positive effect of rutin applied to anti-UVB formulations, making this bioactive compound a promising candidate for photoprotection improvement. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Masculine Discrepancy Stress and Psychosocial Maladjustment: Implications for Behavioral and Mental Health of Adolescent Boys.

PubMed

Reidy, Dennis E; Smith-Darden, Joanne P; Vivolo-Kantor, Alana M; Malone, Carolyn A; Kernsmith, Poco D

2017-01-01

Gender role discrepancy (GRD), or nonconformity to socially prescribed gender roles, has been linked to a multitude of adverse mental and behavioral health outcomes. Masculine discrepancy stress (MDS), stress about being perceived not to conform to one's gender role, may explain the relationship between GRD and deleterious health outcomes. However, research on MDS has primarily been restricted to adult males. This leaves a critical gap pertaining to the potential effect of MDS on adolescent boys, who may be more malleable and susceptible to the influence and pressures of gender socialization. In the current study, data are drawn from a sample of adolescent male students ( N = 592) who completed self-report questionnaires. We employed structural equation modeling to test the effects of GRD and MDS on psychosocial maladjustment measured via sexual behavior, substance use, violence, mood disorder symptoms, and hopelessness. In addition, we controlled for critical risk factors including sociodemographic characteristics, adverse childhood experiences, trauma symptoms, and neighborhood disorganization. Findings indicate significant potentiating effects of MDS on maladjustment while there were direct protective effects of GRD. These data suggest that developing prevention strategies that incorporate social norms pertaining to gender socialization may have an impact on multiple behavioral and mental health problems.

Physiological effects and therapeutic potential of proinsulin C-peptide

PubMed Central

Maric-Bilkan, Christine; Luppi, Patrizia; Wahren, John

2014-01-01

Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes. PMID:25249503

Exercising control over bipolar disorder.

PubMed

Malhi, Gin S; Byrow, Yulisha

2016-11-01

Following extensive research exercise has emerged as an effective treatment for major depressive disorder, and it is now a recognised therapy alongside other interventions. In contrast, there is a paucity of research examining the therapeutic effects of exercise for those with bipolar disorder. Given that dysfunctional reward processing is central to bipolar disorder, research suggests that exercise can perhaps be framed as a reward-related event that may have the potential to precipitate a manic episode. The behavioural activation system (BAS) is a neurobehavioural system that is associated with responding to reward and provides an appropriate framework to theoretically examine and better understand the effects of exercise treatment on bipolar disorder. This article discusses recent research findings and provides an overview of the extant literature related to the neurobiological underpinnings of BAS and exercise as they relate to bipolar disorder. This is important clinically because depending on mood state in bipolar disorder, we postulate that exercise could be either beneficial or deleterious with positive or negative effects on the illness. Clearly, this complicates the evaluation of exercise as a potential treatment in terms of identifying its optimal characteristics in this population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Flight test of ARINC 741 configuration low gain SATCOM system on Boeing 747-400 aircraft

NASA Technical Reports Server (NTRS)

Murphy, Timothy A.; Stapleton, Brian P.

1990-01-01

The Boeing company conducted a flight test of a SATCOM system similar to the ARINC 741 configuration on a production model 747-400. A flight plan was specifically designed to test the system over a wide variety of satellite elevations and aircraft attitudes as well as over land and sea. Interface bit errors, signal quality and aircraft position and navigational inputs were all recorded as a function of time. Special aircraft maneuvers were performed to demonstrate the potential for shadowing by aircraft structures. Both a compass rose test and the flight test indicated that shadowing from the tail is insignificant for the 747-400. However, satellite elevation angles below the aircraft horizon during banking maneuvers were shown to have a significant deleterious effect on SATCOM communications.

Climate and environmental triggers of acute myocardial infarction.

PubMed

Claeys, Marc J; Rajagopalan, Sanjay; Nawrot, Tim S; Brook, Robert D

2017-04-01

Over the past few decades, a growing body of epidemiological and clinical evidence has led to heightened concerns about the potential short- and long-term deleterious effects of the environment on cardiovascular health, including the risk for acute myocardial infarction (AMI). This review highlights the increased risk of AMI caused by exposure to air pollution and cold temperatures. These factors should be considered modifiable risk factors in the prevention of cardiovascular disease. The current body of knowledge about the biological mechanisms linking environmental changes to atherothrombotic events and the impact of climate change on cardiovascular health are discussed. Finally, recommendations for prevention and public policy are presented. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Sports-related concussions - media, science and policy.

PubMed

Mannix, Rebekah; Meehan, William P; Pascual-Leone, Alvaro

2016-08-01

Although growing awareness about the potential long-term deleterious effects of sport-related concussion has led to increased attention to the risks of collision sports, calls to ban these sports, such as American football, might be premature. Collision sports have a relatively high incidence of concussions, but participation in these sports also confers a host of benefits. In addition, the associated risks of participation, including concussion, have not been definitively shown to outweigh the benefits they provide, and the risk-benefit ratio might vary among individuals. The risks of concussion and repetitive concussions associated with collision sports are unknown in the general population and not well characterized even in elite athlete populations. In this article, we discuss current knowledge on sports-related concussion, its neurological consequences, and implications for regulation of the practice of collision sports.

When perspective taking increases taking: reactive egoism in social interaction.

PubMed

Epley, Nicholas; Caruso, Eugene; Bazerman, Max H

2006-11-01

Group members often reason egocentrically, believing that they deserve more than their fair share of group resources. Leading people to consider other members' thoughts and perspectives can reduce these egocentric (self-centered) judgments such that people claim that it is fair for them to take less; however, the consideration of others' thoughts and perspectives actually increases egoistic (selfish) behavior such that people actually take more of available resources. A series of experiments demonstrates this pattern in competitive contexts in which considering others' perspectives activates egoistic theories of their likely behavior, leading people to counter by behaving more egoistically themselves. This reactive egoism is attenuated in cooperative contexts. Discussion focuses on the implications of reactive egoism in social interaction and on strategies for alleviating its potentially deleterious effects.

Flight test of ARINC 741 configuration low gain SATCOM system on Boeing 747-400 aircraft

NASA Astrophysics Data System (ADS)

Murphy, Timothy A.; Stapleton, Brian P.

The Boeing company conducted a flight test of a SATCOM system similar to the ARINC 741 configuration on a production model 747-400. A flight plan was specifically designed to test the system over a wide variety of satellite elevations and aircraft attitudes as well as over land and sea. Interface bit errors, signal quality and aircraft position and navigational inputs were all recorded as a function of time. Special aircraft maneuvers were performed to demonstrate the potential for shadowing by aircraft structures. Both a compass rose test and the flight test indicated that shadowing from the tail is insignificant for the 747-400. However, satellite elevation angles below the aircraft horizon during banking maneuvers were shown to have a significant deleterious effect on SATCOM communications.

Multimodality cardiac imaging in Turner syndrome.

PubMed

Mortensen, Kristian H; Gopalan, Deepa; Nørgaard, Bjarne L; Andersen, Niels H; Gravholt, Claus H

2016-06-01

Congenital and acquired cardiovascular diseases contribute significantly to the threefold elevated risk of premature death in Turner syndrome. A multitude of cardiovascular anomalies and disorders, many of which deleteriously impact morbidity and mortality, is frequently left undetected and untreated because of poor adherence to screening programmes and complex clinical presentations. Imaging is essential for timely and effective primary and secondary disease prophylaxis that may alleviate the severe impact of cardiovascular disease in Turner syndrome. This review illustrates how cardiovascular disease in Turner syndrome manifests in a complex manner that ranges in severity from incidental findings to potentially fatal anomalies. Recommendations regarding the use of imaging for screening and surveillance of cardiovascular disease in Turner syndrome are made, emphasising the key role of non-invasive and invasive cardiovascular imaging to the management of all patients with Turner syndrome.

Exploration of Habitability Factors Influencing Short Duration Spaceflight: Structured Postflight Interviews of Shuttle Crewmembers

NASA Technical Reports Server (NTRS)

Locke, James; Leveton, Lauren; Keeton, Kathryn; Whitmire, Alexandra

2009-01-01

Astronauts report significant difficulties with sleep during Space missions. Psychological, physiological, and habitability factors are all thought to play a role in spaceflight insomnia. Crewmembers gain experience with the spaceflight sleep environment as their missions progress, but this knowledge is not formally collected and communicated to subsequent crews. This lack of information transfer prevents crews from optimizing their capability to sleep during mission, which leads to fatigue and its potentially deleterious effects. The goal of this project is astronauts with recent spaceflight experience to gather their knowledge of and insights into sleep in Space. Structured interviews consisting of standardized closed and open-ended questionnaires are administered to astronauts who have flown on the Space Shuttle since the Columbia disaster. It is hoped that review and analysis of the pooled responses to the interview questions will lead to greater understanding of the sleep environment during short duration spaceflight, with attention placed on problem aspects and their potential solutions.

Uncertainty and research needs for supplementing wild populations of anadromous Pacific salmon

USGS Publications Warehouse

Reisenbichler, R.R.

2005-01-01

Substantial disagreement and uncertainty attend the question of whether the benefits from supplementing wild populations of anadromous salmonids with hatchery fish outweigh the risks. Prudent decisions about supplementation are most likely when the suite of potential benefits and hazards and the various sources of uncertainty are explicitly identified. Models help by indicating the potential consequences of various levels of supplementation but perhaps are most valuable for showing the limitations of available data and helping design studies and monitoring to provide critical data. Information and understanding about the issue are deficient. I discuss various benefits, hazards, and associated uncertainties for supplementation, and implications for the design of monitoring and research. Several studies to reduce uncertainty and facilitate prudent supplementation are described and range from short-term reductionistic studies that help define the issue or help avoid deleterious consequences from supplementation to long-term studies (ca. 10 or more fish generations) that evaluate the net result of positive and negative genetic, behavioral, and ecological effects from supplementation.

Development and characterization of novel electrically conductive PANI-PGS composites for cardiac tissue engineering applications.

PubMed

Qazi, Taimoor H; Rai, Ranjana; Dippold, Dirk; Roether, Judith E; Schubert, Dirk W; Rosellini, Elisabetta; Barbani, Niccoletta; Boccaccini, Aldo R

2014-06-01

Cardiovascular diseases, especially myocardial infarction, are the leading cause of morbidity and mortality in the world, also resulting in huge economic burdens on national economies. A cardiac patch strategy aims at regenerating an infarcted heart by providing healthy functional cells to the injured region via a carrier substrate, and providing mechanical support, thereby preventing deleterious ventricular remodeling. In the present work, polyaniline (PANI) was doped with camphorsulfonic acid and blended with poly(glycerol-sebacate) at ratios of 10, 20 and 30vol.% PANI content to produce electrically conductive composite cardiac patches via the solvent casting method. The composites were characterized in terms of their electrical, mechanical and physicochemical properties. The in vitro biodegradability of the composites was also evaluated. Electrical conductivity increased from 0Scm(-1) for pure PGS to 0.018Scm(-1) for 30vol.% PANI-PGS samples. Moreover, the conductivities were preserved for at least 100h post fabrication. Tensile tests revealed an improvement in the elastic modulus, tensile strength and elasticity with increasing PANI content. The degradation products caused a local drop in pH, which was higher in all composite samples compared with pure PGS, hinting at a buffering effect due to the presence of PANI. Finally, the cytocompatibility of the composites was confirmed when C2C12 cells attached and proliferated on samples with varying PANI content. Furthermore, leaching of acid dopants from the developed composites did not have any deleterious effect on the viability of C2C12 cells. Taken together, these results confirm the potential of PANI-PGS composites for use as substrates to modulate cellular behavior via electrical stimulation, and as biocompatible scaffolds for cardiac tissue engineering applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of 3-keto-1,5-bisphosphonates on obese-liver's rats.

PubMed

Lahbib, Karima; Touil, Soufiane

2016-10-01

Obesity is associated with an oxidative stress status, which is defined by an excess of reactive oxygen species (ROS) vs. the antioxidant defense system. We report in this present work, the link between fat deposition and oxidative stress markers using a High Fat Diet-(HFD) induced rat obesity and liver-oxidative stress. We further determined the impact of chronic administration of 3-keto-1, 5-BPs 1 (a & b) (40μg/kg/8 weeks/i.p.) on liver's level. In fact, exposure of rats to HFD during 16 weeks induced body and liver weight gain and metabolic disruption with an increase on liver Alanine amino transférase (ALAT) and Aspartate aminotransférase (ASAT) concentration. HFD increased liver calcium level as well as free iron, whereas, it provoked a decrease on liver lipase activity. HFD also induced liver-oxidative stress status vocalized by an increase in reactive oxygen species (ROS) as superoxide radical (O 2 ), hydroxyl radical (OH) and Hydrogen peroxide (H 2 O 2 ). Consequently, different deleterious damages as an increase on Malon Dialdehyde MDA, Carbonyl protein PC levels with a decrease in non-protein sulfhydryls NPSH concentrations, have been detected. Interestingly, our results demonstrate a decrease in antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx) and peroxidases (POD). Importantly, 3-keto-1,5-bisphosphonates treatment corrected the majority of the deleterious effects caused by HFD, but it failed to correct some liver's disruptions as mineral profile, oxidative damages (PC and NPSH levels) as well as SOD and lipase activities. Our investigation point that 3-keto-1,5-bisphosphonates could be considered as safe antioxidant agents on the hepatic level that should also find other potential biological applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ebselen alters mitochondrial physiology and reduces viability of rat hippocampal astrocytes.

PubMed

Santofimia-Castaño, Patricia; Salido, Ginés M; González, Antonio

2013-04-01

The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca(2+) concentration ([Ca(2+)]c), the mitochondrial free-Ca(2+) concentration ([Ca(2+)]m), and mitochondrial membrane potential (ψm) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca(2+)]c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca(2+)]m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of ψm and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function.

Mutator dynamics in sexual and asexual experimental populations of yeast.

PubMed

Raynes, Yevgeniy; Gazzara, Matthew R; Sniegowski, Paul D

2011-06-07

In asexual populations, mutators may be expected to hitchhike with associated beneficial mutations. In sexual populations, recombination is predicted to erode such associations, inhibiting mutator hitchhiking. To investigate the effect of recombination on mutators experimentally, we compared the frequency dynamics of a mutator allele (msh2Δ) in sexual and asexual populations of Saccharomyces cerevisiae. Mutator strains increased in frequency at the expense of wild-type strains in all asexual diploid populations, with some approaching fixation in 150 generations of propagation. Over the same period of time, mutators declined toward loss in all corresponding sexual diploid populations as well as in haploid populations propagated asexually. We report the first experimental investigation of mutator dynamics in sexual populations. We show that a strong mutator quickly declines in sexual populations while hitchhiking to high frequency in asexual diploid populations, as predicted by theory. We also show that the msh2Δ mutator has a high and immediate realized cost that is alone sufficient to explain its decline in sexual populations. We postulate that this cost is indirect; namely, that it is due to a very high rate of recessive lethal or strongly deleterious mutation. However, we cannot rule out the possibility that msh2Δ also has unknown directly deleterious effects on fitness, and that these effects may differ between haploid asexual and sexual populations. Despite these reservations, our results prompt us to speculate that the short-term cost of highly deleterious recessive mutations can be as important as recombination in preventing mutator hitchhiking in sexual populations.

[Indications of dexmedetomidine in the current sedoanalgesia tendencies in critical patients].

PubMed

Romera Ortega, M A; Chamorro Jambrina, C; Lipperheide Vallhonrat, I; Fernández Simón, I

2014-01-01

Recently, dexmedetomidine has been marketed in Spain and other European countries. The published experience regarding its use has placed dexmedetomidine on current trends in sedo-analgesic strategies in the adult critically ill patient. Dexmedetomidine has sedative and analgesic properties, without respiratory depressant effects, inducing a degree of depth of sedation in which the patient can open its eyes to verbal stimulation, obey simple commands and cooperate in nursing care. It is therefore a very useful drug in patients who can be maintained on mechanical ventilation with these levels of sedation avoiding the deleterious effects of over or infrasedation. Because of its effects on α2-receptors, it's very useful for the control and prevention of tolerance and withdrawal to other sedatives and psychotropic drugs. The use of dexmedetomidine has been associated with lower incidence of delirium when compared with other sedatives. Moreover, it's a potentially useful drug for sedation of patients in non-invasive ventilation. Copyright © 2013 Elsevier España, S.L. y SEMICYUC. All rights reserved.

Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure.

PubMed

Mrozek, Ségolène; Srairi, Mohamed; Marhar, Fouad; Delmas, Clément; Gaussiat, François; Abaziou, Timothée; Larcher, Claire; Atthar, Vincent; Menut, Rémi; Fourcade, Olivier; Geeraerts, Thomas

2016-01-01

Takotsubo cardiomyopathy can occur at the early phase of severe acute brain injuries. In the case of cardiac output decrease or shock, the optimal treatment is still a matter of debate. Due to massive stress hormone release, the infusion of catecholamines may have limited effects and may even aggravate cardiac failure. Other inotropic agents may be an option. Levosimendan has been shown to have potential beneficial effects in this setting, although milrinone has not been studied. We report a case of a young female presenting with inverted Takotsubo cardiomyopathy syndrome after severe traumatic brain injury. Due to hemodynamic instability and increasing levels of infused norepinephrine, dobutamine infusion was begun but rapidly stopped due to tachyarrhythmia. Milrinone infusion stabilized the patient's hemodynamic status and improved cardiac output without deleterious effects. Milrinone could be a good alternative when inotropes are required in Takotsubo cardiomyopathy and when dobutamine infusion is associated with tachyarrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.

Protective effects of friedelin isolated from Azima tetracantha Lam. against ethanol-induced gastric ulcer in rats and possible underlying mechanisms.

PubMed

Antonisamy, Paulrayer; Duraipandiyan, Veeramuthu; Aravinthan, Adithan; Al-Dhabi, Naif Abdullah; Ignacimuthu, Savarimuthu; Choi, Ki Choon; Kim, Jong-Hoon

2015-03-05

The current study was aimed to investigate the gastroprotective effects of friedelin isolated from the hexane extract of leaves of Azima tetracantha. Ethanol-induced gastric ulcer model was used to investigate the gastroprotective effects of friedelin. Antioxidant enzymes, lipid peroxidation, nitric oxide, gastric vascular permeability, pro and anti-inflammatory cytokines and apoptosis level have been investigated. Ethanol caused severe gastric damage and friedelin pretreatment protected against its deleterious role. Antioxidant enzyme activities, anti-inflammatory cytokines, prostaglandin E2 (PGE2), constitutive nitric oxide synthase (cNOS) and mucus weight have been increased significantly. However, the vascular permeability, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), caspase-3 and apoptosis level have significantly been decreased after friedelin ingestion. The present study has clearly demonstrated the anti-ulcer potential of friedelin, these findings suggested that friedelin could be a new useful natural gastroprotective tool against gastric ulcer. Copyright © 2015 Elsevier B.V. All rights reserved.

Ethnic Identity and Gender as Moderators of the Association between Discrimination and Academic Adjustment among Mexican-origin Adolescents

PubMed Central

Umaña-Taylor, Adriana J.; Wong, Jessie J.; Gonzales, Nancy A.; Dumka, Larry E.

2011-01-01

Existing work has identified perceived discrimination as a risk factor that may contribute to the relatively poorer academic outcomes exhibited by Mexican-origin adolescents in the U.S. The current study examined the longitudinal associations among perceived discrimination and three indices of adolescent adjustment in the school setting (i.e., grade point average, teacher reports of externalizing, adolescents’ deviant peer associations) among 178 Mexican-origin adolescents (53% female). Ethnic identity affirmation was examined as a protective factor expected to reduce the negative effects of discrimination on adolescents’ adjustment, and gender was examined as a potential moderator of the associations of interest. Findings indicated that the deleterious effects of discrimination on adolescents’ adjustment in school were particularly salient for Mexican-origin male adolescents. Importantly, ethnic identity affirmation emerged as a protective factor for Mexican-origin male adolescents by buffering the negative effects of discrimination on their externalizing behaviors in school. PMID:22152761

Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases

PubMed Central

Fleury, Audrey; Martinez, Maria Carmen; Le Lay, Soazig

2014-01-01

Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, are small vesicles secreted from a wide variety of cells. Whereas MVs are particles released by the outward budding of the plasma membrane, exosomes are derived from endocytic compartments. Secretion of EVs can be enhanced by specific stimuli, and increased plasma circulating levels of EVs have been correlated with pathophysiological situations. MVs, already present in the blood of healthy individuals, are considerably elevated in several cardiovascular diseases associated with inflammation, suggesting that they can mediate deleterious effects such as endothelial dysfunction or thrombosis. Nonetheless, very recent studies also demonstrate that MVs may act as biological information vectors transferring proteins or genetic material to maintain cell homeostasis, favor cell repair, or even promote angiogenesis. Additionally, exosomes have also been shown to have pro-angiogenic and cardio-protective properties. These beneficial effects, therefore, reveal the potential therapeutical use of EVs in the field of cardiovascular medicine and regenerative therapy. In this review, we will provide an update of cellular processes modulated by EVs of specific interest in the treatment of cardiovascular pathologies. A special focus will be made on the morphogen sonic hedgehog (Shh) associated with EVs (EVsShh+), which have been shown to mediate many pro-angiogenic effects. In addition to offer a potential source of cardiovascular markers, therapeutical potential of EVs reveal exciting opportunities to deliver specific agents by non-immunogenic means to cardiovascular system. PMID:25136343

Biodegradation of petroleum hydrocarbons in estuarine sediments: metal influence.

PubMed

Almeida, Raquel; Mucha, Ana P; Teixeira, Catarina; Bordalo, Adriano A; Almeida, C Marisa R

2013-02-01

In this work, the potential effect of metals, such as Cd, Cu and Pb, on the biodegradation of petroleum hydrocarbons in estuarine sediments was investigated under laboratory conditions. Sandy and muddy non-vegetated sediments were collected in the Lima River estuary (NW Portugal) and spiked with crude oil and each of the metals. Spiked sediments were left in the dark under constant shaking for 15 days, after which crude oil biodegradation was evaluated. To estimate microbial abundance, total cell counts were obtained by DAPI staining and microbial community structure was characterized by ARISA. Culturable hydrocarbon degraders were determined using a modified most probable number protocol. Total petroleum hydrocarbons concentrations were analysed by Fourier Transform Infrared Spectroscopy after their extraction by sonication, and metal contents were determined by atomic absorption spectrometry. The results obtained showed that microbial communities had the potential to degrade petroleum hydrocarbons, with a maximum of 32 % degradation obtained for sandy sediments. Both crude oil and metals changed the microbial community structure, being the higher effect observed for Cu. Also, among the studied metals, only Cu displayed measurable deleterious effect on the hydrocarbons degradation process, as shown by a decrease in the hydrocarbon degrading microorganisms abundance and in the hydrocarbon degradation rates. Both degradation potential and metal influence varied with sediment characteristics probably due to differences in contaminant bioavailability, a feature that should be taken into account in developing bioremediation strategies for co-contaminated estuarine sites.

Development and Characterization of a High Throughput Screen to investigate the delayed Effects of Radiations Commonly Encountered in Space

NASA Astrophysics Data System (ADS)

Morgan, W. F.

Astronauts based on the space station or on long-term space missions will be exposed to high Z radiations in the cosmic environment In order to evaluate the potentially deleterious effects of exposure to radiations commonly encountered in space we have developed and characterized a high throughput assay to detect mutation deletion events and or hyperrecombination in the progeny of exposed cells This assay is based on a plasmid vector containing a green fluorescence protein reporter construct We have shown that after stable transfection of the vector into human or hamster cells this construct can identify mutations specifically base changes and deletions as well as recombination events e g gene conversion or homologous recombination occurring as a result of exposure to ionizing radiation Our focus has been on those events occurring in the progeny of an irradiated cell that are potentially associated with radiation induced genomic instability rather than the more conventional assays that evaluate the direct immediate effects of radiation exposure Considerable time has been spent automating analysis of surviving colonies as a function of time after irradiation in order to determine when delayed instability is induced and the consequences of this delayed instability The assay is now automated permitting the evaluation of potentially rare events associated with low dose low dose rate radiations commonly encountered in space

Broad phenotypes in heterozygous NR5A1 46,XY patients with a disorder of sex development: an oligogenic origin?

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Audí, Laura; Schaller, André; Flück, Christa E

2018-06-11

SF-1/NR5A1 is a transcriptional regulator of adrenal and gonadal development. NR5A1 disease-causing variants cause disorders of sex development (DSD) and adrenal failure, but most affected individuals show a broad DSD/reproductive phenotype only. Most NR5A1 variants show in vitro pathogenic effects, but not when tested in heterozygote state together with wild-type NR5A1 as usually seen in patients. Thus, the genotype-phenotype correlation for NR5A1 variants remains an unsolved question. We analyzed heterozygous 46,XY SF-1/NR5A1 patients by whole exome sequencing and used an algorithm for data analysis based on selected project-specific DSD- and SF-1-related genes. The variants detected were evaluated for their significance in literature, databases and checked in silico using webtools. We identified 19 potentially deleterious variants (one to seven per patient) in 18 genes in four 46,XY DSD subjects carrying heterozygous NR5A1 disease-causing variants. We constructed a scheme of all these hits within the landscape of currently known genes involved in male sex determination and differentiation. Our results suggest that the broad phenotype in these heterozygous NR5A1 46,XY DSD subjects may well be explained by an oligogenic mode of inheritance, in which multiple hits, individually non-deleterious, may contribute to a DSD phenotype unique to each heterozygous SF-1/NR5A1 individual.

The potential for climate-driven bathymetric range shifts: sustained temperature and pressure exposures on a marine ectotherm, Palaemonetes varians

PubMed Central

Morris, J. P.; Thatje, S.; Cottin, D.; Oliphant, A.; Brown, A.; Shillito, B.; Ravaux, J.; Hauton, C.

2015-01-01

Range shifts are of great importance as a response for species facing climate change. In the light of current ocean-surface warming, many studies have focused on the capacity of marine ectotherms to shift their ranges latitudinally. Bathymetric range shifts offer an important alternative, and may be the sole option for species already at high latitudes or those within enclosed seas; yet relevant data are scant. Hydrostatic pressure (HP) and temperature have wide ranging effects on physiology, importantly acting in synergy thermodynamically, and therefore represent key environmental constraints to bathymetric migration. We present data on transcriptional regulation in a shallow-water marine crustacean (Palaemonetes varians) at atmospheric and high HP following 168-h exposures at three temperatures across the organisms’ thermal scope, to establish the potential physiological limit to bathymetric migration by neritic fauna. We observe changes in gene expression indicative of cellular macromolecular damage, disturbances in metabolic pathways and a lack of acclimation after prolonged exposure to high HP. Importantly, these effects are ameliorated (less deleterious) at higher temperatures, and exacerbated at lower temperatures. These data, alongside previously published behavioural and heat-shock analyses, have important implications for our understanding of the potential for climate-driven bathymetric range shifts PMID:26716003

Phytochemicals reduce aflatoxin-induced toxicity in chicken embryos

USDA-ARS?s Scientific Manuscript database

Aflatoxins (AF) are toxic metabolites produced by molds, Aspergillus flavus and Aspergillus parasiticus, which frequently contaminate poultry feed ingredients. Ingestion of AF-contaminated feed by chickens leads to deleterious effects, including decreased bird performance and reduced egg production....

Phytochemicals reduce aflatoxin-induced toxicity in chicken embryos

USDA-ARS?s Scientific Manuscript database

Aflatoxins (AF) are toxic metabolites produced by molds, Aspergillus flavus and Aspergillus parasicitus, which frequently contaminate chicken feed ingredients. Ingestion of AF-contaminated feed by chickens leads to deleterious effects, including decreased chicken performance and reduced egg producti...

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes.

PubMed

Christie, Joshua R; Beekman, Madeleine

2017-03-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes-specifically their organization into host cells and their uniparental (maternal) inheritance-enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller's ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes-despite their asexual mode of reproduction-can readily undergo adaptive evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Increased Mycoplasma hyopneumoniae Disease Prevalence in Domestic Hybrids Among Free-Living Wild Boar.

PubMed

Goedbloed, Daniel J; van Hooft, Pim; Lutz, Walburga; Megens, Hendrik-Jan; van Wieren, Sip E; Ydenberg, Ron C; Prins, Herbert H T

2015-12-01

Wildlife immune genes are subject to natural selection exerted by pathogens. In contrast, domestic immune genes are largely protected from pathogen selection by veterinary care. Introgression of domestic alleles into the wild could lead to increased disease susceptibility, but observations are scarce due to low introgression rates, low disease prevalence and reduced survival of domestic hybrids. Here we report the first observation of a deleterious effect of domestic introgression on disease prevalence in a free-living large mammal. A fraction of 462 randomly sampled free-living European wild boar (Sus scrofa) was genetically identified as recent wild boar-domestic pig hybrids based on 351 SNP data. Analysis of antibody prevalence against the bacterial pathogen Mycoplasma hyopneumoniae (Mhyo) showed an increased Mhyo prevalence in wild-domestic hybrids. We argue that the most likely mechanism explaining the observed association between domestic hybrid status and Mhyo antibody prevalence would be introgression of deleterious domestic alleles. We hypothesise that large-scale use of antibiotics in the swine breeding sector may have played a role in shaping the relatively deleterious properties of domestic swine immune genes and that domestic introgression may also lead to increased wildlife disease susceptibility in the case of other species.

Undergraduate Students' Achievement Goals for Conducting Research: Examining the Motivational Benefits of Laboratory Classroom Affiliation

ERIC Educational Resources Information Center

Deemer, Eric D.; Dotterer, Aryn M.; Morel, Samantha A.; Bastnagel, Abigail E.

2017-01-01

Rooted in achievement goal theory, the buffering hypothesis posits that contextual factors serve to moderate the deleterious effects of personal achievement goals on relevant outcomes. The present study sought to test this hypothesis by examining the interactive effects of classroom affiliation perceptions and personal achievement goals for…

Mechanisms of nitrogen deposition effects on temperate forest lichens and trees

Treesearch

Therese S. Carter; Christopher M. Clark; Mark E. Fenn; Sarah Jovan; Steven S. Perakis; Jennifer Riddell; Paul G. Schaberg; Tara L. Greaver; Meredith G. Hastings

2017-01-01

We review the mechanisms of deleterious nitrogen (N) deposition impacts on temperate forests, with a particular focus on trees and lichens. Elevated anthropogenic N deposition to forests has varied effects on individual organisms depending on characteristics both of the N inputs (form, timing, amount) and of the organisms (ecology, physiology) involved. Improved...

77 FR 71312 - Irradiation in the Production, Processing and Handling of Food

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-30

... consumption, the Agency must identify the various effects that may result from irradiating the food and assess..., and fish) were irradiated under such conditions, there would be no deleterious effect on the total... foodborne pathogens and extend shelf-life. \\1\\ For the purpose of this final rule, refrigeration temperature...

Loblolly Pine Responds to Mechanical Wounding with Increased Resin Flow

Treesearch

Jonathan J. Ruel; Matthew P. Ayres; Peter L. Lorio

1998-01-01

The oleoresin produced by many conifers has a deleterious effect on numerous associated herbivores, including bark beetles (Coleoptera: Scolytidae), and may have evolved as a plant defense mechanism. Three experiments with juvenile loblolly pine (Pinus taeda L.) used mechanical wounding to drain resin reserves and assess the effects of prior bark wounding on...

Immunizing Children against the Negative Effects of Reward.

ERIC Educational Resources Information Center

Amabile, Teresa M.; And Others

To determine whether training could counter deleterious effects of reward on intrinsic motivation and creativity, 68 students in grades 3, 4, and 5 at a parochial school in Massachusetts were assigned to one of four conditions in which intrinsic motivation training and rewards were either provided or withheld. In the intrinsic motivation training…

Nuclear Weapon Tests and their Consequences,

DTIC Science & Technology

Nuclear weapon research, specifically nuclear bomb tests, and the deleterious effects of heightened radioactivity levels on the world’s biology, are...Soviet Union is discussed. The effects of the U.S.A. bombing of Hiroshima and Nagasaki, as well as the U.S.A. bomb test of March 1, 1954, and listed as

Effects triggered by platinum nanoparticles on primary keratinocytes

PubMed Central

Konieczny, Piotr; Goralczyk, Anna Grazyna; Szmyd, Radoslaw; Skalniak, Lukasz; Koziel, Joanna; Filon, Francesca Larese; Crosera, Matteo; Cierniak, Agnieszka; Zuba-Surma, Ewa K; Borowczyk, Julia; Laczna, Eliza; Drukala, Justyna; Pyza, Elzbieta; Semik, Danuta; Woznicka, Olga; Klein, Andrzej; Jura, Jolanta

2013-01-01

The platinum (Pt)-group elements (PGEs) represent a new kind of environmental pollutant and a new hazard for human health. Since their introduction as vehicle-exhaust catalysts, their emissions into the environment have grown considerably compared with their low natural concentration in the earth crust. PGE emissions from vehicle catalysts can be also in the form of nanometer-sized particles (Pt nanoparticles [PtNPs]). These elements, both in their metallic form or as ions solubilized in biological media, are now recognized as potent allergens and sensitizers. Human skin is always exposed to toxic particles; therefore, in the present study we addressed the question of whether polyvinylpyrrolidone-coated PtNPs may have any negative effects on skin cells, including predominantly epidermal keratinocytes. In this study, PtNPs of two sizes were used: 5.8 nm and 57 nm, in concentrations of 6.25, 12.5, and 25 μg/mL. Both types of NPs were protected with polyvinylpyrrolidone. Primary keratinocytes were treated for 24 and 48 hours, then cytotoxicity, genotoxicity, morphology, metabolic activity, and changes in the activation of signaling pathways were investigated in PtNP-treated cells. We found that PtNPs trigger toxic effects on primary keratinocytes, decreasing cell metabolism, but these changes have no effects on cell viability or migration. Moreover, smaller NPs exhibited more deleterious effect on DNA stability than the big ones. Analyzing activation of caspases, we found changes in activity of caspase 9 and caspase 3/7 triggered mainly by smaller NPs. Changes were not so significant in the case of larger nanoparticles. Importantly, we found that PtNPs have antibacterial properties, as is the case with silver NPs (AgNPs). In comparison to our previous study regarding the effects of AgNPs on cell biology, we found that PtNPs do not exhibit such deleterious effects on primary keratinocytes as AgNPs and that they also can be used as potential antibacterial agents, especially in the treatment of Escherichia coli, representing a group of Gram-negative species. PMID:24204135

Cryptic genetic variation, evolution's hidden substrate

PubMed Central

Paaby, Annalise B.; Rockman, Matthew V.

2016-01-01

Cryptic genetic variation is invisible under normal conditions but fuel for evolution when circumstances change. In theory, CGV can represent a massive cache of adaptive potential or a pool of deleterious alleles in need of constant suppression. CGV emerges from both neutral and selective processes and it may inform how human populations respond to change. In experimental settings, CGV facilitates adaptation, but does it play an important role in the real world? We review the empirical support for widespread CGV in natural populations, including its potential role in emerging human diseases and the growing evidence of its contribution to evolution. PMID:24614309

Copper Contamination Impairs Herbivore Initiation of Seaweed Inducible Defenses and Decreases Their Effectiveness

PubMed Central

2015-01-01

Seaweed-herbivore interactions are often mediated by environmental conditions, yet the roles of emerging anthropogenic stressors on these interactions are poorly understood. For example, chemical contaminants have unknown consequences on seaweed inducible resistance and herbivore response to these defenses despite known deleterious effects of contaminants on animal inducible defenses. Here, we investigated the effect of copper contamination on the interactions between a snail herbivore and a brown seaweed that displays inducible resistance to grazing. We examined seaweed inducible resistance and its effectiveness for organisms exposed to copper at two time points, either during induction or after herbivores had already induced seaweed defenses. Under ambient conditions, non-grazed tissues were more palatable than grazed tissues. However, copper additions negated the preference for non-grazed tissues regardless of the timing of copper exposure, suggesting that copper decreased both how herbivores initiated these inducible defenses and their subsequent effectiveness. Copper decreased stimulation of defenses, at least in part, by suppressing snail grazing pressure—the cue that turns inducible defenses on. Copper decreased effectiveness of defenses by preventing snails from preferentially consuming non-grazed seaweed. Thus, contaminants can potentially stress communities by changing seaweed-herbivore interactions mediated via inducible defenses. Given the ubiquity of seaweed inducible resistance and their potential influence on herbivores, we hypothesize that copper contamination may change the impact of these resistant traits on herbivores. PMID:26274491

Effects of arsenic toxicity on morphological characters in blackgram (Vigna mungo L.) during early growth stage.

PubMed

Shamim, M Z; Pandey, A

2017-07-31

Blackgram is an important pulse crop of the tropic and sub-tropic area and has been identified as a potential crop in many countries. In the south-East Asia arsenic toxicity in soil and water is one of the most environmental problems. Crop productivity is highly affected by cultivation in arsenic polluted soil or irrigation through arsenic polluted water. The present study was conducted to evaluate the effect of arsenic (As) on fresh shoot length, fresh shoot weight, fresh root length, fresh shoot weight and total fresh biomass, The results indicate that root length is more affected than shoot length due to arsenic toxicity. The fresh shoot weight observed was more affected than fresh root weight. This study indicates that arsenic toxicity causes the deleterious effect on blackgram growth. The toxic effect of blackgram depends on the genotypic variability. Some blackgram genotypes show very less toxic effect of arsenic due to its genetic makeup. Experimental findings of study indicate that longer root length and more shoot weight in arsenic stress condition may be tolerant blackgram genotype to arsenic toxicity.

[Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

PubMed

Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

2016-01-01

The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

Transgenerational deleterious effects of ocean acidification on the reproductive success of a keystone crustacean (Gammarus locusta).

PubMed

Borges, Francisco O; Figueiredo, Cátia; Sampaio, Eduardo; Rosa, Rui; Grilo, Tiago F

2018-07-01

Ocean acidification (OA) poses a global threat to marine biodiversity. Notwithstanding, marine organisms may maintain their performance under future OA conditions, either through acclimation or evolutionary adaptation. Surprisingly, the transgenerational effects of high CO 2 exposure in crustaceans are still poorly understood. For the first time, the present study investigated the transgenerational effect of OA, from hatching to maturity, of a key amphipod species (Gammarus locusta). Negative transgenerational effects were observed on survival of the acidified lineage, resulting in significant declines (10-15%) compared to the control groups in each generation. Mate-guarding duration was also significantly reduced under high CO 2 and this effect was not alleviated by transgenerational acclimation, indicating that precopulatory behaviours can be disturbed under a future high CO 2 scenario. Although OA may initially stimulate female investment, transgenerational exposure led to a general decline in egg number and fecundity. Overall, the present findings suggest a potential fitness reduction of natural populations of G. locusta in a future high CO 2 ocean, emphasizing the need of management tools towards species' sustainability. Copyright © 2018 Elsevier Ltd. All rights reserved.

Substance abuse, memory, and post-traumatic stress disorder.

PubMed

Tipps, Megan E; Raybuck, Jonathan D; Lattal, K Matthew

2014-07-01

A large body of literature demonstrates the effects of abused substances on memory. These effects differ depending on the drug, the pattern of delivery (acute or chronic), and the drug state at the time of learning or assessment. Substance use disorders involving these drugs are often comorbid with anxiety disorders, such as post-traumatic stress disorder (PTSD). When the cognitive effects of these drugs are considered in the context of the treatment of these disorders, it becomes clear that these drugs may play a deleterious role in the development, maintenance, and treatment of PTSD. In this review, we examine the literature evaluating the cognitive effects of three commonly abused drugs: nicotine, cocaine, and alcohol. These three drugs operate through both common and distinct neurobiological mechanisms and alter learning and memory in multiple ways. We consider how the cognitive and affective effects of these drugs interact with the acquisition, consolidation, and extinction of learned fear, and we discuss the potential impediments that substance abuse creates for the treatment of PTSD. Copyright © 2013 Elsevier Inc. All rights reserved.

When environmental factors become stressors: interactive effects of vermetid gastropods and sedimentation on corals.

PubMed

Zill, Julie A; Gil, Michael A; Osenberg, Craig W

2017-03-01

Environmental stressors often interact, but most studies of multiple stressors have focused on combinations of abiotic stressors. Here we examined the potential interaction between a biotic stressor, the vermetid snail Ceraesignum maximum , and an abiotic stressor, high sedimentation, on the growth of reef-building corals. In a field experiment, we subjected juvenile massive Porites corals to four treatments: (i) neither stressor, (ii) sedimentation, (iii) vermetids or (iv) both stressors. Unexpectedly, we found no effect of either stressor in isolation, but a significant decrease in coral growth in the presence of both stressors. Additionally, seven times more sediment remained on corals in the presence (versus absence) of vermetids, likely owing to adhesion of sediments to corals via vermetid mucus. Thus, vermetid snails and high sedimentation can interact to drive deleterious effects on reef-building corals. More generally, our study illustrates that environmental factors can combine to have negative interactive effects even when individual effects are not detectable. Such 'ecological surprises' may be easily overlooked, leading to environmental degradation that cannot be anticipated through the study of isolated factors. © 2017 The Author(s).

The Potential of Cannabidiol Treatment for Cannabis Users With Recent-Onset Psychosis.

PubMed

Hahn, Britta

2018-01-13

A major factor associated with poor prognostic outcome after a first psychotic break is cannabis misuse, which is prevalent in schizophrenia and particularly common in individuals with recent-onset psychosis. Behavioral interventions aimed at reducing cannabis use have been unsuccessful in this population. Cannabidiol (CBD) is a phytocannabinoid found in cannabis, although at low concentrations in modern-day strains. CBD has a broad pharmacological profile, but contrary to ∆9-tetrahydrocannabinol (THC), CBD does not activate CB1 or CB2 receptors and has at most subtle subjective effects. Growing evidence indicates that CBD acts as an antipsychotic and anxiolytic, and several reports suggest neuroprotective effects. Moreover, CBD attenuates THC's detrimental effects, both acutely and chronically, including psychotogenic, anxiogenic, and deleterious cognitive effects. This suggests that CBD may improve the disease trajectory of individuals with early psychosis and comorbid cannabis misuse in particular-a population with currently poor prognostic outcome and no specialized effective intervention. © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Controlling coaching and athlete thriving in elite adolescent netballers: The buffering effect of athletes' mental toughness.

PubMed

Gucciardi, Daniel F; Stamatis, Andreas; Ntoumanis, Nikos

2017-08-01

The purposes of this study were to examine the association between controlling coach behaviours and athlete experiences of thriving and test the buffering effect of mental toughness on this relation. A cross-sectional survey. In total, 232 female netballers aged 11 to 17 years (14.97+1.52) with between 1 and 15 years of experience in their sport (7.50+2.28) completed measures of controlling coach interpersonal style, mental toughness and thriving. Latent moderated structural models indicated that (i) controlling coach behaviours were inversely related with experiences of vitality and learning; (ii) mental toughness was positively associated with psychological experiences of both dimensions of thriving; and (iii) mental toughness moderated the effect of coach's controlling interpersonal style on learning but not vitality experiences, such that the effect was weaker for individuals who reported higher levels of mental toughness. This study extends past work and theory to show that mental toughness may enable athletes to counteract the potentially deleterious effect of controlling coach interpersonal styles. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Non-target effects of an introduced biological control agent on deer mouse ecology

Treesearch

Dean E. Pearson; Kevin S. McKelvey; Leonard F. Ruggiero

2000-01-01

Release of exotic insects as biological control agents is a common approach to controlling exotic plants. Though controversy has ensued regarding the deleterious direct effects of biological control agents to non-target species, few have examined the indirect effects of a "well-behaved" biological control agent on native fauna. We studied a grassland in west-...

Feminism and Composition Research: Researching as a Woman.

ERIC Educational Resources Information Center

Gillam, Alice M.

1992-01-01

Discusses the difficulties and frustrations of trying to make explicit connections among teaching, scholarship, and feminism. Points out the deleterious effects of the feminization of the field of composition on the research and scholarship of women in the field. (SR)

0-5997 : structural assessment of "D" regions affected by premature concrete deterioration.

DOT National Transportation Integrated Search

2014-08-01

Reinforced concrete bridge piers in Texas have : shown signs of concrete deterioration in the : form of map cracking within a few years after : construction. The pattern cracking is associated : with the deleterious effects of alkali-silica : reactio...

Slick Science.

ERIC Educational Resources Information Center

Howard, Jane O.

1989-01-01

Some of the background factors and deleterious effects of oil spills are discussed. A classroom activity which demonstrates an oil spill, how the oil affects feathers, and one clean-up method is presented. A list of recent oil spills and three additional resources are included. (CW)

Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.

PubMed

Gayarre, Javier; Martín-Gimeno, Paloma; Osorio, Ana; Paumard, Beatriz; Barroso, Alicia; Fernández, Victoria; de la Hoya, Miguel; Rojo, Alejandro; Caldés, Trinidad; Palacios, José; Urioste, Miguel; Benítez, Javier; García, María J

2017-09-26

Despite a high prevalence of deleterious missense variants, most studies of RAD51C ovarian cancer susceptibility gene only provide in silico pathogenicity predictions of missense changes. We identified a novel deleterious RAD51C missense variant (p.Arg312Trp) in a high-risk family, and propose a criteria to prioritise RAD51C missense changes qualifying for functional analysis. To evaluate pathogenicity of p.Arg312Trp variant we used sequence homology, loss of heterozygosity (LOH) and segregation analysis, and a comprehensive functional characterisation. To define a functional-analysis prioritisation criteria, we used outputs for the known functionally confirmed deleterious and benign RAD51C missense changes from nine pathogenicity prediction algorithms. The p.Arg312Trp variant failed to correct mitomycin and olaparib hypersensitivity and to complement abnormal RAD51C foci formation according to functional assays, which altogether with LOH and segregation data demonstrated deleteriousness. Prioritisation criteria were based on the number of predictors providing a deleterious output, with a minimum of 5 to qualify for testing and a PredictProtein score greater than 33 to assign high-priority indication. Our study points to a non-negligible number of RAD51C missense variants likely to impair protein function, provides a guideline to prioritise and encourage their selection for functional analysis and anticipates that reference laboratories should have available resources to conduct such assays.

The United States Army Concept Capability Plan for Combating Weapons of Mass Destruction for the Futer Modular Force 2015-2024

DTIC Science & Technology

2009-03-25

development and pest control, also have deleterious dual use potential. By replicating themselves after introduction into a target population, a small...N national NATO North Atlantic Treaty Organization NEBC network-enabled battle command NMSCWMD National Military Strategy for Combating...within the continental U.S., Alaska, Hawaii, the District of Columbia, the Commonwealth of Puerto Rico, the U.S. Virgin Islands, Guam, American Samoa

Effect of Fatigue Protocols on Lower Limb Neuromuscular Function and Implications for Anterior Cruciate Ligament Injury Prevention Training: A Systematic Review.

PubMed

Barber-Westin, Sue D; Noyes, Frank R

2017-12-01

Approximately two-thirds of anterior cruciate ligament (ACL) tears are sustained during noncontact situations when an athlete is cutting, pivoting, decelerating, or landing from a jump. Some investigators have postulated that fatigue may result in deleterious alterations in lower limb biomechanics during these activities that could increase the risk of noncontact ACL injuries. However, prior studies have noted a wide variation in fatigue protocols, athletic tasks studied, and effects of fatigue on lower limb kinetics and kinematics. First, to determine if fatigue uniformly alters lower limb biomechanics during athletic tasks that are associated with noncontact ACL injuries. Second, to determine if changes should be made in ACL injury prevention training programs to alter the deleterious effects of fatigue on lower limb kinetics and kinematics. Systematic review; Level of evidence, 4. A systematic review of the literature using MEDLINE was performed. Key terms were fatigue, neuromuscular, exercise, hop test, and single-legged function tests. Inclusion criteria were original research studies involving healthy participants, use of a fatigue protocol, study of at least 1 lower limb task that involved landing from a hop or jump or cutting, and analysis of at least 1 biomechanical variable. Thirty-seven studies involving 806 athletes (485 female, 321 male; mean age, 22.7 years) met the inclusion criteria. General fatigue protocols were used in 20 investigations, peripheral protocols were used in 17 studies, and 21 different athletic tasks were studied (13 single-legged, 8 double-legged). There was no consistency among investigations regarding the effects of fatigue on hip, knee, or ankle joint angles and moments or surface electromyography muscle activation patterns. The fatigue protocols typically did not produce statistically significant changes in ground-reaction forces. Published fatigue protocols did not uniformly produce alterations in lower limb neuromuscular factors that heighten the risk of noncontact ACL injuries. Therefore, justification does not currently exist for major changes in ACL injury prevention training programs to account for potential fatigue effects. However, the effect of fatigue related to ACL injuries is worthy of further investigation, including the refinement of protocols and methods of analysis.

Effects of a chronic l-arginine supplementation on the arginase pathway in aged rats.

PubMed

Moretto, Johnny; Guglielmetti, Anne-Sophie; Tournier-Nappey, Maude; Martin, Hélène; Prigent-Tessier, Anne; Marie, Christine; Demougeot, Céline

2017-04-01

While ageing is frequently associated with l-arginine deficiency, clinical and experimental studies provided controversial data on the interest of a chronic l-arginine supplementation with beneficial, no or even deleterious effects. It was hypothesized that these discrepancies might relate to a deviation of l-arginine metabolism towards production of l-ornithine rather than nitric oxide as a result of age-induced increase in arginase activity. This study investigated the effect of ageing on arginase activity/expression in target tissues and determined whether l-arginine supplementation modulated the effect of ageing on arginase activity. Arginase activity and expression were measured in the heart, vessel, brain, lung, kidney and liver in young rats (3-months old) and aged Wistar rats (22-24-months-old) with or without l-arginine supplementation (2.25% in drinking water for 6weeks). Plasma levels of l-arginine and l-ornithine were quantified in order to calculate the plasma l-arginine/l-ornithine ratio, considered as a reflection of arginase activity. Cardiovascular parameters (blood pressure, heart rate) and aortic vascular reactivity were also studied. Ageing dramatically reduced plasma l-arginine and l-arginine/l-ornithine ratio, decreased liver and kidney arginase activities but did not change activities in other tissues. l-Arginine supplementation normalized plasma l-arginine and l-arginine/l-ornithine ratio, improved endothelial function and decreased systolic blood pressure. These effects were associated with decreased arginase activity in aorta along with no change in the other tissues except in the lung in which activity was increased. A strong mismatch was therefore observed between arginase activity and expression in analyzed tissues. The present study reveals that ageing selectively changes arginase activity in clearance tissues, but does not support a role of the arginase pathway in the potential deleterious effect of the l-arginine supplementation in aged patients. Moreover, our data argue against the use of the measurement of plasma l-arginine/l-ornithine ratio to estimate arginase activity in aged patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxic assessment of the leachates of paddy soils and river sediments from e-waste dismantling sites to microalga, Pseudokirchneriella subcapitata.

PubMed

Nie, Xiangping; Fan, Canpeng; Wang, Zhaohui; Su, Tian; Liu, Xinyu; An, Taicheng

2015-01-01

The potential adverse effects of e-waste recycling activity on environment are getting increasing concern. In this work, a model alga, Pseudokirchneriella subcapitata, was employed to assess the toxic effects of the leachates of paddy soils and river sediments collected from e-waste dismantling sites. Chemical analysis of the paddy soils and river sediments and their leachates were carried out and the growth rate, chlorophyll a fluorescence and anti-oxidative systems of the alga were measured. Results showed that two leachates decreased the amount of PSII active reaction centers and affected photosynthesis performance, interfered with chlorophyll synthesis and inhibited algal growth. Some chemical pollutants in the sediments and soils such as polybrominated diphenyl ethers (PBDEs) and metals derived from e-waste recycling activity may impose oxidative stress on algae and affect the activity of anti-oxidative enzymes such as GST, SOD, CAT and APX. The leachates of both river sediments and paddy soils are potentially toxic to the primary producers, P. subcapitata and the leachate from sediments was more deleterious than that from soils. Copyright © 2014 Elsevier Inc. All rights reserved.

Development of coatings to control electroosmosis in zero gravity electrophoresis

NASA Technical Reports Server (NTRS)

Krupnick, A. C.

1974-01-01

A major problem confronting the operation of free fluid electrophoresis in zero gravity is the control of electrokinetic phenomena and, in particular, electroosmosis. Due to the severity of counter flow, as a result of electroosmosis, the electrical potential developed at the surface of shear must be maintained at near, or as close to, zero millivolts as possible. Based upon this investigation, it has been found that the amount of bound water or the degree of hydroxylation plays a major role in the control of this phenomena. Of necessity, factors, such as adhesion, biocompatibility, protein adsorption, and insolubility were considered in this investigation because of the long buffer-coating exposure times required by present space operations. Based upon tests employing microcapillary electrophoresis, it has been found that gamma amino propyl trihydroxysilane produced a coating which provides the lowest potential (minus 3.86 mv) at the surface of shear between the stationary and mobile layers. This coating has been soaked in both borate and saline buffers, up to three months, in a pH range of 6.5 to 10 without deleterious effects or a change in its ability to control electrokinetic effects.

The Applicability of Resilience Training to the Mitigation of Trauma-Related Mental Illness in Military Personnel [Formula: see text].

PubMed

Thompson, Summer R; Dobbins, Sarah

Ongoing participation by the United States in military operations around the world places military personnel at an increased potential for exposure to trauma, which may directly result in an increased risk for mental health issues. It is important to develop and test new approaches to prevent and mitigate the effects of trauma in military personnel. One such area of research is focused on psychological resilience to prevent the sequelae of trauma. This article examines empirical research of resilience training in military personnel and discusses the potential applicability of such training in this population. In this literature review, four randomized control trials and one retrospective, parallel group study were reviewed. Each intervention had the goal of mitigating behavioral health issues after trauma exposure. The results of the various interventions were wide-ranging from no measurable difference in treatment groups to significant differences in outcomes. Despite the inconclusive results of our review, we have determined that resilience training for active duty service members to help prevent the deleterious effects of trauma on mental health is a compelling and necessary avenue for further research.

PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications.

PubMed

Barreiro, Esther; Gea, Joaquim

2018-01-26

Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.

Blood doping by cobalt. Should we measure cobalt in athletes?

PubMed

Lippi, Giuseppe; Franchini, Massimo; Guidi, Gian Cesare

2006-07-24

Blood doping is commonplace in competitive athletes who seek to enhance their aerobic performances through illicit techniques. Cobalt, a naturally-occurring element with properties similar to those of iron and nickel, induces a marked and stable polycythemic response through a more efficient transcription of the erythropoietin gene. Although little information is available so far on cobalt metabolism, reference value ranges or supplementation in athletes, there is emerging evidence that cobalt is used as a supplement and increased serum concentrations are occasionally observed in athletes. Therefore, given the athlete's connatural inclination to experiment with innovative, unfair and potentially unhealthy doping techniques, cobalt administration might soon become the most suited complement or surrogate for erythropoiesis-stimulating substances. Nevertheless, cobalt administration is not free from unsafe consequences, which involve toxic effects on heart, liver, kidney, thyroid and cancer promotion. Cobalt is easily purchasable, inexpensive and not currently comprehended within the World Anti-Doping Agency prohibited list. Moreover, available techniques for measuring whole blood, serum, plasma or urinary cobalt involve analytic approaches which are currently not practical for antidoping laboratories. Thus more research on cobalt metabolism in athletes is compelling, along with implementation of effective strategies to unmask this potentially deleterious doping practice.

Sustained consumption of cocoa-based dark chocolate enhances seizure-like events in the mouse hippocampus.

PubMed

Cicvaric, Ana; Bulat, Tanja; Bormann, Daniel; Yang, Jiaye; Auer, Bastian; Milenkovic, Ivan; Cabatic, Maureen; Milicevic, Radoslav; Monje, Francisco J

2018-03-01

While the consumption of caffeine and cocoa has been associated with a variety of health benefits to humans, some authors have proposed that excessive caffeine intake may increase the frequency of epileptic seizures in humans and reduce the efficiency of antiepileptic drugs. Little is known, however, about the proconvulsant potential of the sustained, excessive intake of cocoa on hippocampal neural circuits. Using the mouse as an experimental model, we examined the effects of the chronic consumption of food enriched in cocoa-based dark chocolate on motor and mood-related behaviours as well as on the excitability properties of hippocampal neurons. Cocoa food enrichment did not affect body weights or mood-related behaviours but rather promoted general locomotion and improved motor coordination. However, ex vivo electrophysiological analysis revealed a significant enhancement in seizure-like population spike bursting at the neurogenic dentate gyrus, which was paralleled by a significant reduction in the levels of GABA-α1 receptors thus suggesting that an excessive dietary intake of cocoa-enriched food might alter some of the synaptic elements involved in epileptogenesis. These data invite further multidisciplinary research aiming to elucidate the potential deleterious effects of chocolate abuse on behaviour and brain hyperexcitability.

Malignant hyperthermia susceptibility in patients with exertional rhabdomyolysis: a retrospective cohort study and updated systematic review.

PubMed

Kraeva, Natalia; Sapa, Alexander; Dowling, James J; Riazi, Sheila

2017-07-01

Two potentially fatal syndromes, malignant hyperthermia (MH), an adverse reaction to general anesthesia, and exertional rhabdomyolysis (ER) share some clinical features, including hyperthermia, muscle rigidity, tachycardia, and elevated serum creatine kinase. Some patients with ER have experienced an MH event and/or have been diagnosed as MH susceptible (MHS). In order to assess the relationship between ER and MH further, we conducted a retrospective cohort study summarizing clinical and genetic information on Canadian patients with ER who were diagnosed as MHS. In addition, a systematic literature review was performed to compile further evidence on MH susceptibility and RYR1 and CACNA1S variants associated with rhabdomyolysis. Demographic, clinical, and genetic information was collected on Canadian MHS patients who presented with rhabdomyolysis. In addition, we performed a systematic review of the literature published during 1995-2016 on genetic screening of the RYR1 and CACNA1S genes in patients with ER. Retrospective data on Canadian MHS patients with ER showed that ten out of 17 patients carried RYR1 or CACNA1S variants that were either known MH-causative mutations or potentially pathogenic variants. The systematic review revealed 39 different rare RYR1 variants, including 13 MH-causative/associated mutations and five rare potentially deleterious CACNA1S variants in 78% of patients with ER. Findings from the Canadian patient cohort and the systematic review all signal a potential association between MH susceptibility and ER. The presence of MH-causative mutations and putative deleterious RYR1 variants in ER patients without a history of adverse anesthetic reactions suggests their possible increased risk for MH.

Measurement back-action: Listening with quantum dots

NASA Astrophysics Data System (ADS)

Ladd, Thaddeus D.

2012-07-01

Single electrons in quantum dots can be disturbed by the apparatus used to measure them. The disturbance can be mediated by incoherent phonons -- literally, noise. Engineering acoustic interference could negate these deleterious effects and bring quantum dots closer to becoming a robust quantum technology.

Getting Back on Course

ERIC Educational Resources Information Center

Griswold, John S.

2009-01-01

"Spectacular error" sounds euphemistic compared to "devastating," "catastrophic," or "meltdown"--terms more commonly summoned to describe the credit crisis and ensuing global economic carnage. Whatever they are labeled, gross miscalculations on Wall Street are having a deleterious effect on college campuses across the country, with many…

HIGH-THROUGHPUT CHEMICAL SCREENING USING PROTEIN PROFILING OF FISH PLASMA

EPA Science Inventory

Compounds that affect the hormone system, referred to as "endocrine-disrupting chemicals" (EDCs), cause human and animal health problems. It is necessary to test putative EDC chemicals for such deleterious effects, though current testing methodologies are time/animal intensive an...

ASSESSMENT OF BIOFILTER MEDIA PARTICLE SIZES FOR REMOVING AMMONIA

USDA-ARS?s Scientific Manuscript database

With increased concerns over odor and gas emissions from livestock production facilities more efficient technologies of air pollution control are needed to mitigate the deleterious effects of air contaminants. Gas-phase biofilters for treating contaminant gases from poultry and livestock operations ...

Assessment of Biofilter Media Particle Sizes for Removing Ammonia

USDA-ARS?s Scientific Manuscript database

With increased concerns over odor and gas emissions from livestock production facilities more efficient technologies of air pollution control are needed to mitigate the deleterious effects of air contaminants. Gas-phase biofilters for treating contaminant gases from poultry and livestock operations ...

Factors Mediating the Adjustment to Involuntary Childlessness.

ERIC Educational Resources Information Center

Sabatelli, Ronald M.; And Others

1988-01-01

Explored stressors that accompany experience of involuntary childlessness and examined mediators of adjustment to infertility in married individuals. Data showed deleterious effect that coping with infertility can have on couple's sexual relationship. Findings suggest important relationship between self-esteem, marital commitment, and positive…

Properties of Forested Loess Soils After Repeated Prescribed Burns

Treesearch

D.M. Moehring; C.X. Grano; J.R. Bassett

1966-01-01

Nine annual burns have had little effect on the nutrient content and structure of the surface 4 inches of loess soils on flat terrain.Because prescribed burns must often be repeated to obtain desired results, many foresters are apprehensive about the possible deleterious effects on soils. In 1954 the Timber Management Laboratory at Crossett, Arkansas, in co-...

Work, Family, and Mental Health: Testing Different Models of Work-Family Fit.

ERIC Educational Resources Information Center

Grzywacz, Joseph G.; Bass, Brenda L.

2003-01-01

Using family resilience theory, this study examined the effects of work-family conflict and work-family facilitation on mental health among working adults to gain a better understanding of work-family fit. Results suggest that family to work facilitation is a family protective factor that offsets and buffers the deleterious effects of work-family…

Deleterious Effects of Chronic Under-Nutrition on Cognitive Abilities

ERIC Educational Resources Information Center

Ashem, Beatrice; Janes, Margaret D.

1978-01-01

In order to determine the effects of malnutrition on children's cognitive abilities, the McCarthy Scale of Abilities was administered to 118 Nigerian children between the ages of 2 1/2 and 6 years who came from "well-to-do" urban and "poor" urban and rural environments. Scores of malnourished children were lower than those of…

Buffering the Effects of Violence: Communication and Problem-Solving Skills as Protective Factors for Adolescents Exposed to Violence

ERIC Educational Resources Information Center

LeBlanc, Monique; Self-Brown, Shannon; Shepard, Desti; Kelley, Mary Lou

2011-01-01

Although many adolescents exposed to violence evidence negative outcomes, some report few deleterious effects, indicating the presence of moderating variables. This study examined the moderating role of family communication and problem solving on positive and negative outcomes in adolescents exposed to school and neighborhood violence.…

The Impact of Leisure-Time Television on School Learning: A Research Synthesis.

ERIC Educational Resources Information Center

Williams, Patricia A.; And Others

1982-01-01

To integrate empirical findings concerning the impact of leisure time television viewing on student achievement in grades K-12, 274 correlations were assembled from 23 studies. The effects were slightly positive for up to 10 hours of viewing a week, but beyond 10 hours the effects are negative and increasingly more deleterious. (Author/BW)

77 FR 49034 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... to react to the execution (an effect known as ``market impact'' or ``information leakage''). As a...' shares will avoid the deleterious effect of market impact discussed above and result in overall faster...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change To Amend Rule...

77 FR 38875 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... participants to react to the execution (an effect known as ``market impact'' or ``information leakage''). As a... available shares and routing to other venues' shares will avoid the deleterious effect of market impact...-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing of Proposed Rule Change To Amend Rule...

A survey on acquaintance, orientation and behavior of general medical practitioners toward periodontal diseases.

PubMed

Kaur, Supreet; Khurana, Pankaj; Kaur, Harjit

2015-01-01

An association between oral conditions such as periodontal diseases and systemic conditions is noted. As such, periodontal disease is associated with an increased risk of systemic illnesses such as cardiovascular disease, diabetes, adverse pregnancy outcome, atherosclerosis, stroke and hospital acquired pneumonia. The concept of diagnosing and treating a potential patient to minimize the deleterious effects of this chronic infectious and inflammatory condition on systemic conditions represents both an unprecedented challenge and opportunity to our profession. Keeping this in view, the present survey was designed to evaluate the acquaintance, orientation and behavior of general medical practitioners; concerning the effects of periodontal disease on systemic health. A typed questionnaire carrying four sets of questions was distributed among general medical practitioners of seven different government and private medical colleges and hospitals. Questionnaire was developed to assess the acquaintance, orientation and behavior of general medical practitioners toward periodontal disease. Most of the respondents have knowledge regarding the signs and symptoms of periodontal disease and its association with cardiovascular disease. However, majority of them do not know about the potential effect of periodontal disease on other organ systems. General medical practitioners have inadequate knowledge regarding periodontal diseases. Hence, oral health related training should be an integral part of the medical curriculum.

A survey on acquaintance, orientation and behavior of general medical practitioners toward periodontal diseases

PubMed Central

Kaur, Supreet; Khurana, Pankaj; Kaur, Harjit

2015-01-01

Background: An association between oral conditions such as periodontal diseases and systemic conditions is noted. As such, periodontal disease is associated with an increased risk of systemic illnesses such as cardiovascular disease, diabetes, adverse pregnancy outcome, atherosclerosis, stroke and hospital acquired pneumonia. The concept of diagnosing and treating a potential patient to minimize the deleterious effects of this chronic infectious and inflammatory condition on systemic conditions represents both an unprecedented challenge and opportunity to our profession. Keeping this in view, the present survey was designed to evaluate the acquaintance, orientation and behavior of general medical practitioners; concerning the effects of periodontal disease on systemic health. Materials and Methods: A typed questionnaire carrying four sets of questions was distributed among general medical practitioners of seven different government and private medical colleges and hospitals. Questionnaire was developed to assess the acquaintance, orientation and behavior of general medical practitioners toward periodontal disease. Results: Most of the respondents have knowledge regarding the signs and symptoms of periodontal disease and its association with cardiovascular disease. However, majority of them do not know about the potential effect of periodontal disease on other organ systems. Conclusion: General medical practitioners have inadequate knowledge regarding periodontal diseases. Hence, oral health related training should be an integral part of the medical curriculum. PMID:26229276

An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations

PubMed Central

Curnow, Alison; Owen, Sara J.

2016-01-01

As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations. PMID:26953144

The Shared Pathoetiological Effects of Particulate Air Pollution and the Social Environment on Fetal-Placental Development

PubMed Central

2014-01-01

Exposure to particulate air pollution and socioeconomic risk factors are shown to be independently associated with adverse pregnancy outcomes; however, their confounding relationship is an epidemiological challenge that requires understanding of their shared etiologic pathways affecting fetal-placental development. The purpose of this paper is to explore the etiological mechanisms associated with exposure to particulate air pollution in contributing to adverse pregnancy outcomes and how these mechanisms intersect with those related to socioeconomic status. Here we review the role of oxidative stress, inflammation and endocrine modification in the pathoetiology of deficient deep placentation and detail how the physical and social environments can act alone and collectively to mediate the established pathology linked to a spectrum of adverse pregnancy outcomes. We review the experimental and epidemiological literature showing that diet/nutrition, smoking, and psychosocial stress share similar pathways with that of particulate air pollution exposure to potentially exasperate the negative effects of either insult alone. Therefore, socially patterned risk factors often treated as nuisance parameters should be explored as potential effect modifiers that may operate at multiple levels of social geography. The degree to which deleterious exposures can be ameliorated or exacerbated via community-level social and environmental characteristics needs further exploration. PMID:25574176

An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations.

PubMed

Curnow, Alison; Owen, Sara J

2016-01-01

As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations.

Propagation Effects in Space-Based Surveillance Systems

DTIC Science & Technology

1982-02-01

This report describes the first year’s effort to investigate propagation effects in space - based radars. A model was developed for analyzing the...deleterious systems effects by first developing a generalized aperture distribution that ultimately can be applied to any space - based radar configuration...The propagation effects are characterized in terms of the SATCOM model striation parameters. The form of a generalized channel model for space - based radars

Alkylating chemotherapy may exert a uniquely deleterious effect upon neo-antigen-targeting anticancer vaccination

PubMed Central

Litterman, Adam J; Dudek, Arkadiusz Z; Largaespada, David A

2013-01-01

Alkylating chemotherapy exerts both antineoplastic and immunostimulatory effects. However, in addition to depleting regulatory T cells (Treg), alkylating agents also mediate a long lasting antiproliferative effect on responder lymphocytes. Our recent findings indicate that this antiproliferative effect profoundly impairs vaccination-induced immune responses, especially in the case of vaccines that target specific tumor-associated neo-antigens that do not require Treg depletion. PMID:24251080

Quick test for percent of deleterious material.

DOT National Transportation Integrated Search

2009-08-28

The Missouri Department of Transportation (MoDOT) is considering the replacement of its deleterious : materials test method (TM-71) with test methods that are more objective. MoDOT contracted with the Missouri : University of Science and Technology (...

Synthetic cannabinoids: the multi-organ failure and metabolic derangements associated with getting high.

PubMed

Sherpa, Dolkar; Paudel, Bishow M; Subedi, Bishnu H; Chow, Robert Dobbin

2015-01-01

Synthetic cannabinoids (SC), though not detected with routine urine toxicology screening, can cause severe metabolic derangements and widespread deleterious effects in multiple organ systems. The diversity of effects is related to the wide distribution of cannabinoid receptors in multiple organ systems. Both cannabinoid-receptor-mediated and non-receptor-mediated effects can result in severe cardiovascular, renal, and neurologic manifestations. We report the case of a 45-year-old African American male with ST-elevation myocardial infarction, subarachnoid hemorrhage, reversible cardiomyopathy, acute rhabdomyolysis, and severe metabolic derangement associated with the use of K2, an SC. Though each of these complications has been independently associated with SCs, the combination of these effects in a single patient has not been heretofore reported. This case demonstrates the range and severity of complications associated with the recreational use of SCs. Though now banned in the United States, use of systemic cannabinoids is still prevalent, especially among adolescents. Clinicians should be aware of their continued use and the potential for harm. To prevent delay in diagnosis, tests to screen for these substances should be made more readily available.

Fenoterol did not enhance glucocorticoid-induced skeletal changes in male rats.

PubMed

Folwarczna, Joanna; Nowińska, Barbara; Śliwiński, Leszek; Pytlik, Maria; Cegieła, Urszula; Betka, Anna

2011-01-01

Glucocorticoids and β(2)-adrenergic receptor agonists are the most commonly used drugs in the treatment of asthma. Both therapies are potentially dangerous to the skeletal system. The aim of the present study was to investigate the effects of fenoterol, a β(2)-receptor agonist, on the development of bone changes induced by glucocorticoid (prednisolone) administration in mature male rats. The experiments were carried out on 24-week-old male Wistar rats. The effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg s.c. daily) or/and fenoterol hydrobromide (1.4 mg/kg i.p. daily), administered for 4 weeks, on the skeletal system were studied. Bone turnover markers, geometric parameters, mass, mass of bone mineral in the tibia, femur and L-4 vertebra, bone histomorphometric parameters and mechanical properties of tibial metaphysis, femoral diaphysis and femoral neck were determined. Both prednisolone and fenoterol had damaging effects on the skeletal system of mature male rats. However, concurrent administration of fenoterol and prednisolone did not result in the intensification of the deleterious skeletal effect of either drug administered separately.

Ion Engine Plume Interaction Calculations for Prototypical Prometheus 1

NASA Technical Reports Server (NTRS)

Mandell, Myron J.; Kuharski, Robert A.; Gardner, Barbara M.; Katz, Ira; Randolph, Tom; Dougherty, Ryan; Ferguson, Dale C.

2005-01-01

Prometheus 1 is a conceptual mission to demonstrate the use of atomic energy for distant space missions. The hypothetical spacecraft design considered in this paper calls for multiple ion thrusters, each with considerably higher beam energy and beam current than have previously flown in space. The engineering challenges posed by such powerful thrusters relate not only to the thrusters themselves, but also to designing the spacecraft to avoid potentially deleterious effects of the thruster plumes. Accommodation of these thrusters requires good prediction of the highest angle portions of the main beam, as well as knowledge of clastically scattered and charge exchange ions, predictions for grid erosion and contamination of surfaces by eroded grid material, and effects of the plasma plume on radio transmissions. Nonlinear interactions of multiple thrusters are also of concern. In this paper we describe two- and three-dimensional calculations for plume structure and effects of conceptual Prometheus 1 ion engines. Many of the techniques used have been validated by application to ground test data for the NSTAR and NEXT ion engines. Predictions for plume structure and possible sputtering and contamination effects will be presented.

tDCS Stimulation of the dlPFC Selectively Moderates the Detrimental Impact of Emotion on Analytical Reasoning.

PubMed

Trémolière, Bastien; Maheux-Caron, Véronique; Lepage, Jean-François; Blanchette, Isabelle

2018-01-01

There is evidence of a detrimental effect of emotion on reasoning. Recent studies suggest that this relationship is mediated by working memory, a function closely associated with the dorsolateral prefrontal cortex (dlPFC). Relying on transcranial direct current stimulation (tDCS), the present research explores the possibility that anodal stimulation of the dlPFC has the potential to prevent the effect of emotion on analytical reasoning. Thirty-four participants took part in a lab experiment and were tested twice: one session using offline anodal stimulation (with a 2 mA current stimulation applied to the left dlPFC for 20 min), one session using a control (sham) stimulation. In each session, participants solved syllogistic reasoning problems featuring neutral and emotionally negative contents. Results showed that anodal stimulation diminished the deleterious effect of emotion on syllogistic reasoning, but only for a subclass of problems: problems where the conclusion was logically valid. We discuss our results in the light of the reasoning literature as well as the apparent variability of tDCS effects.

Sexual selection on spontaneous mutations strengthens the between-sex genetic correlation for fitness.

PubMed

Allen, Scott L; McGuigan, Katrina; Connallon, Tim; Blows, Mark W; Chenoweth, Stephen F

2017-10-01

A proposed benefit to sexual selection is that it promotes purging of deleterious mutations from populations. For this benefit to be realized, sexual selection, which is usually stronger on males, must purge mutations deleterious to both sexes. Here, we experimentally test the hypothesis that sexual selection on males purges deleterious mutations that affect both male and female fitness. We measured male and female fitness in two panels of spontaneous mutation-accumulation lines of the fly, Drosophila serrata, each established from a common ancestor. One panel of mutation accumulation lines limited both natural and sexual selection (LS lines), whereas the other panel limited natural selection, but allowed sexual selection to operate (SS lines). Although mutation accumulation caused a significant reduction in male and female fitness in both the LS and SS lines, sexual selection had no detectable effect on the extent of the fitness reduction. Similarly, despite evidence of mutational variance for fitness in males and females of both treatments, sexual selection had no significant impact on the amount of mutational genetic variance for fitness. However, sexual selection did reshape the between-sex correlation for fitness: significantly strengthening it in the SS lines. After 25 generations, the between-sex correlation for fitness was positive but considerably less than one in the LS lines, suggesting that, although most mutations had sexually concordant fitness effects, sex-limited, and/or sex-biased mutations contributed substantially to the mutational variance. In the SS lines this correlation was strong and could not be distinguished from unity. Individual-based simulations that mimick the experimental setup reveal two conditions that may drive our results: (1) a modest-to-large fraction of mutations have sex-limited (or highly sex-biased) fitness effects, and (2) the average fitness effect of sex-limited mutations is larger than the average fitness effect of mutations that affect both sexes similarly. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse.

PubMed

Gómez-Hurtado, Nieves; Domínguez-Rodríguez, Alejandro; Mateo, Philippe; Fernández-Velasco, María; Val-Blasco, Almudena; Aizpún, Rafael; Sabourin, Jessica; Gómez, Ana María; Benitah, Jean-Pierre; Delgado, Carmen

2017-07-01

Leptin, is a 16 kDa pleiotropic peptide not only primarily secreted by adipocytes, but also produced by other tissues, including the heart. Controversy exists regarding the adverse and beneficial effects of leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction. We find that leptin activates mechanisms that contribute to cardiac dysfunction under physiological conditions. However, after the establishment of pressure overload, an increase in leptin levels has protective cardiac effects with respect to rescuing the cellular heart failure phenotype. These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca 2+ content via rescue of control sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca 2+ handling parameters. Leptin, is a 16 kDa pleiotropic peptide not only primary secreted by adipocytes, but also produced by other tissues, including the heart. Evidence indicates that leptin may have either adverse or beneficial effects on the heart. To obtain further insights, in the present study, we analysed the effect of leptin treatment on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction (TAC). Three weeks after surgery, animals received either leptin (0.36 mg kg -1  day -1 ) or vehicle via osmotic minipumps for 3 weeks. Echocardiographic measurements showed that, although leptin treatment was deleterious on cardiac function in sham, leptin had a cardioprotective effect following TAC. [Ca 2+ ] i transient in cardiomyocytes followed similar pattern. Patch clamp experiments showed prolongation of action potential duration (APD) in TAC and leptin-treated sham animals, whereas, following TAC, leptin reduced the APD towards control values. APD variations were associated with decreased transient outward potassium current and Kv4.2 and KChIP2 protein expression. TAC myocytes showed a higher incidence of triggered activities and spontaneous Ca 2+ waves. These proarrhythmic manifestations, related to Ca 2+ /calmodulin-dependent protein kinase II and ryanodine receptor phosphorylation, were reduced by leptin. The results of the present study demonstrate that, although leptin treatment was deleterious on cardiac function in control animals, leptin had a cardioprotective effect following TAC, normalizing cardiac function and reducing arrhythmogeneity at the cellular level. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Polarization-based and specular-reflection-based noncontact latent fingerprint imaging and lifting

NASA Astrophysics Data System (ADS)

Lin, Shih-Schön; Yemelyanov, Konstantin M.; Pugh, Edward N., Jr.; Engheta, Nader

2006-09-01

In forensic science the finger marks left unintentionally by people at a crime scene are referred to as latent fingerprints. Most existing techniques to detect and lift latent fingerprints require application of a certain material directly onto the exhibit. The chemical and physical processing applied to the fingerprint potentially degrades or prevents further forensic testing on the same evidence sample. Many existing methods also have deleterious side effects. We introduce a method to detect and extract latent fingerprint images without applying any powder or chemicals on the object. Our method is based on the optical phenomena of polarization and specular reflection together with the physiology of fingerprint formation. The recovered image quality is comparable to existing methods. In some cases, such as the sticky side of tape, our method shows unique advantages.

Flawed gun policy research could endanger public safety.

PubMed Central

Webster, D W; Vernick, J S; Ludwig, J; Lester, K J

1997-01-01

A highly publicized recent study by Lott and Mustard concludes that laws easing restrictions on licenses for carrying concealed firearms in public substantially reduce violent crime. Several serious flaws in the study render the authors' conclusions insupportable. These flaws include misclassification of gun-carrying laws, endogeneity of predictor variables, omission of confounding variables, and failure to control for the cyclical nature of crime trends. Most of these problems should bias results toward overestimating the crime-reducing effects of laws making it easier to carry concealed firearms in public. Lott and Mustard's statistical models produce findings inconsistent with criminological theories and well-established facts about crime, and subsequent reanalysis of their data challenges their conclusions. Public health professionals should understand the methodological issues raised in this commentary, particularly when flawed research could influence the introduction of policies with potentially deleterious consequences. PMID:9224169

Sports-related concussions — media, science and policy

PubMed Central

Mannix, Rebekah; Meehan, William P.; Pascual-Leone, Alvaro

2017-01-01

Although growing awareness about the potential long-term deleterious effects of sport-related concussion has led to increased attention to the risks of collision sports, calls to ban these sports, such as American football, might be premature. Collision sports have a relatively high incidence of concussions, but participation in these sports also confers a host of benefits. In addition, the associated risks of participation, including concussion, have not been definitively shown to outweigh the benefits they provide, and the risk–benefit ratio might vary among individuals. The risks of concussion and repetitive concussions associated with collision sports are unknown in the general population and not well characterized even in elite athlete populations. In this article, we discuss current knowledge on sports-related concussion, its neurological consequences, and implications for regulation of the practice of collision sports. PMID:27364748

Tertiary lymphoid structures in cancer and beyond.

PubMed

Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

2014-11-01

Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hidden genetic variation in the germline genome of Tetrahymena thermophila.

PubMed

Dimond, K L; Zufall, R A

2016-06-01

Genome architecture varies greatly among eukaryotes. This diversity may profoundly affect the origin and maintenance of genetic variation within a population. Ciliates are microbial eukaryotes with unusual genome features, such as the separation of germline and somatic genomes within a single cell and amitotic division. These features have previously been proposed to increase the rate of molecular evolution in these species. Here, we assessed the fitness effects of genetic variation in the two genomes of natural isolates of the ciliate Tetrahymena thermophila. We find more extensive genetic variation in fitness in the transcriptionally silent germline genome than in the expressed somatic genome. Surprisingly, this variation is not primarily deleterious, but has both beneficial and deleterious effects. We conclude that Tetrahymena genome architecture allows for the maintenance of genetic variation that would otherwise be eliminated by selection. We consider the effect of selection on the two genomes and the impacts of reproductive strategies and the mechanism of sex determination on the structure of this variation. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Eutrophication and Hypoxia Degrade Ecosystem Functions and Services of Narragansett Bay Benthic Communities

EPA Science Inventory

Excessive input of nitrogen to estuaries and coastal waters leads to eutrophication; the resulting organic matter over-enrichment of the sediments and seasonal hypoxia of the bottom water have well-known deleterious effects on benthic community biodiversity, abundance, and biomas...

A simplified method for extracting microplastics in laboratory-cultured coral and water samples

EPA Science Inventory

The deleterious effects of microplastic ingestion by marine organisms and the impacts across trophic levels are widely unknown. Due to the extensive ecological and socioeconomic benefits provided by coral reefs, investigating the impacts of microplastics on reef ecosystems is of ...

Mild Developmental Hypothyroidism and Trace Fear Conditioning: Role of Gender and Shock Duration.

EPA Science Inventory

Rodent models of developmental thyroid hormone (TH) deficiency aptly reflect the deleterious effects of severe TH deficiencies on brain structure and function in humans. However, the impact of moderate TH insufficiencies on neurodevelopmental outcomes has proven more difficult to...

Television and the Humanist.

ERIC Educational Resources Information Center

Zigerell, James

The mass media and especially television pose problems for teachers in humanities disciplines traditionally associated with leisure, time for reflection, and the quiet contemplation of the good, true, and beautiful. Although other media have been criticized for their deleterious effects, television most affects humanists in their mission because…

Storming the Citadel: The Fundamental Revolution Against Progressive Education.

ERIC Educational Resources Information Center

Vetterli, Richard

The first four chapters ("Progressive Education,""The Impact of Progressive Education,""The Remedies: Focusing on the Wrong Problems," and "Progressive Education Challenged") examine the deleterious effect that progressive education has had on student achievement and on society as a whole. The last five…

Physiological responses to fluctuating temperatures are characterized by distinct transcriptional profiles in a solitary bee

USDA-ARS?s Scientific Manuscript database

Exposure to stressful, low temperatures during development can result in the accumulation of deleterious physiological effects called chill injury. Metabolic imbalances, disruptions in ion homeostasis, and oxidative stress contribute to the increased mortality of chill-injured insects. Interestingly...

PASSIVE TREATMENT OF ACID ROCK DRAINAGE FROM A SUBSURFACE MINE

EPA Science Inventory

Acidic, metal-contaminated drainages are a critical problem facing many areas of the world. Acid rock drainage results when metal sulfide minerals, particularly pyrite, are oxidized by exposure to oxygen and water. The deleterious effects of these drainages on receiving streams a...

Accelerated test for measuring sulfate resistance of hydraulic cements for Caltrans LLPRS program

DOT National Transportation Integrated Search

2000-04-01

Many California soils are rich in sulfates, which can have deleterious effects on the cements used in rigid pavements. Field experience has demonstrated that sulfate attack usually manifests itself in the form of loss of adhesion and strength. In ord...

Changing Environmentally Relevant Behaviour.

ERIC Educational Resources Information Center

Gudgion, T. J.; Thomas, M. Pugh

1991-01-01

Considered is the role of psychology in helping to change those human behaviors which have deleterious environmental effects. The foremost conclusion is that behavioral psychology can offer practical techniques for such change, yet there are indications that enduring behaviors may be better realized through the intrinsic motivation maintained by…

The Performance of Noncoherent Orthogonal M-FSK in the Presence of Timing and Frequency Errors

NASA Technical Reports Server (NTRS)

Hinedi, Sami; Simon, Marvin K.; Raphaeli, Dan

1993-01-01

Practical M-FSK systems experience a combination of time and frequency offsets (errors). This paper assesses the deleterious effect of these offsets, first individually and then combined, on the average bit error probability performance of the system.

Eutrophication and Hypoxia Diminish Ecosystem Functions of Benthic Communities in a New England Estuary

EPA Science Inventory

Excessive input of nitrogen to estuaries and coastal waters leads to eutrophication; the resulting organic matter over-enrichment of sediments and seasonal hypoxia of bottom water have significant deleterious effects on benthic community biodiversity, abundance, and biomass. Our ...

Songbirds as Sentinels of Mercury in Terrestrial Foodwebs of Eastern North America

EPA Science Inventory

Mercury is a globally distributed environmental contaminant with a variety of deleterious effects in fish, wildlife, and humans. Breeding songbirds may be useful sentinels for mercury because they are relatively easy to sample, have well-defined and small territories, and integra...

Mechanism Underlying the Weight Loss and Complications of Roux-en-Y Gastric Bypass. Review.

PubMed

Abdeen, G; le Roux, C W

2016-02-01

Various bariatric surgical procedures are effective at improving health in patients with obesity associated co-morbidities, but the aim of this review is to specifically describe the mechanisms through which Roux-en-Y gastric bypass (RYGB) surgery enables weight loss for obese patients using observations from both human and animal studies. Perhaps most but not all clinicians would agree that the beneficial effects outweigh the harm of RYGB; however, the mechanisms for both the beneficial and deleterious (for example postprandial hypoglycaemia, vitamin deficiency and bone loss) effects are ill understood. The exaggerated release of the satiety gut hormones, such as GLP-1 and PYY, with their central and peripheral effects on food intake has given new insight into the physiological changes that happen after surgery. The initial enthusiasm after the discovery of the role of the gut hormones following RYGB may need to be tempered as the magnitude of the effects of these hormonal responses on weight loss may have been overestimated. The physiological changes after RYGB are unlikely to be due to a single hormone, or single mechanism, but most likely involve complex gut-brain signalling. Understanding the mechanisms involved with the beneficial and deleterious effects of RYGB will speed up the development of effective, cheaper and safer surgical and non-surgical treatments for obesity.

The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

PubMed Central

Mitwally, Mohamed FM; Casper, Robert F; Diamond, Michael P

2005-01-01

Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality. PMID:16202169

Mechanical Behavior of Advanced Materials for Aerospace Applications

NASA Technical Reports Server (NTRS)

Telesman, Ignancy (Technical Monitor); Kantzos, Peter; Shannon, Brian

2003-01-01

The purpose of this study was to determine whether High Cycle Fatigue (HCF) loading has any deleterious synergistic effect on life when combined with the typical Low Cycle Fatigue (LCF) loading present in engine disks. This interaction is particularly important in the rim region of blisk applications, where fatigue initiations from vibratory stresses (HCF) may be propagated to the disk by LCF. The primary effort in this study was focused on determining and documenting initiation sites and damage mechanisms. Under LCF loading conditions the failures were predominantly surface initiated, while HCF loading favored internal initiations. Deleterious HCF/LCF interactions would always result in a transition from internal to surface initiations. The results indicated that under the relative stress conditions evaluated there was no interaction between HCF and LCF. In FY99 this effort was extended to investigate several other loading conditions (R-ratio effects) as well as interactions between LCF and two-hour tensile dwells. The results will be published as a NASA Technical Memorandum.

Infrared and Skin: Friend or Foe

PubMed Central

Barolet, Daniel; Christiaens, François; Hamblin, Michael R

2016-01-01

In the last decade, it has been proposed that the sun's IR-A wavelengths might be deleterious to human skin and that sunscreens, in addition to their desired effect to protect against UV-B and UV-A, should also protect against IR-A (and perhaps even visible light). Several studies showed that NIR may damage skin collagen content via an increase in MMP-1 activity in the same manner as is known for UVR. Unfortunately, the artificial NIR light sources used in such studies were not representative of the solar irradiance. Yet, little has been said about the other side of the coin. This article will focus on key information suggesting that IR-A may be more beneficial than deleterious when the skin is exposed to the appropriate irradiance/dose of IR-A radiation similar to daily sun exposure received by people in real life. IR-A might even precondition the skin – a process called photoprevention - from an evolutionary standpoint since exposure to early morning IR-A wavelengths in sunlight may ready the skin for the coming mid-day deleterious UVR. Consequently IR-A appears to be the solution, not the problem. It does more good than bad for the skin. It is essentially a question of intensity and how we can learn from the sun. PMID:26745730

Improving drug policy: The potential of broader democratic participation.

PubMed

Ritter, Alison; Lancaster, Kari; Diprose, Rosalyn

2018-05-01

Policies concerned with illicit drugs vex governments. While the 'evidence-based policy' paradigm argues that governments should be informed by 'what works', in practice policy makers rarely operate this way. Moreover the evidence-based policy paradigm fails to account for democratic participatory processes, particularly how community members and people who use drugs might be included. The aim of this paper is to explore the political science thinking about democratic participation and the potential afforded in 'deliberative democracy' approaches, such as Citizens Juries and other mini-publics for improved drug policy processes. Deliberative democracy, through its focus on inclusion, equality and reasoned discussion, shows potential for drug policy reform and shifts the focus from reliance on and privileging of experts and scientific evidence. But the very nature of this kind of 'deliberation' may delimit participation, notably through its insistence on authorised modes of communication. Other forms of participation beyond reasoned deliberation aligned with the ontological view that participatory processes themselves are constitutive of subject positions and policy problems, may generate opportunities for considering how the deleterious effects of authorised modes of communication might be overcome. Copyright © 2018 Elsevier B.V. All rights reserved.

Far-Field RF Sheaths due to Shear Alfvén Waves in the LAPD

NASA Astrophysics Data System (ADS)

Martin, Michael; van Compernolle, Bart; Gekelman, Walter; Pribyl, Pat; Carter, Troy; D'Ippolito, Daniel A.; Myra, James R.

2013-10-01

Ion cyclotron resonance heating (ICRH) is an important tool in current fusion experiments and will be an essential heating component in ITER. ICRH could be limited by deleterious effects due to the formation of radio frequency (RF) sheaths in the near-field (at the antenna) and in the far-field (e.g. in the divertor region). Far-field sheaths are thought to be caused by the direct launch of or mode conversion to a shear Alfvén wave with an electric field component parallel to the background magnetic field at the wall. In this experiment a limiter plate was inserted into a cylindrical plasma in the LAPD (ne ~ 1010-11 cm-3, Te ~ 5 eV, B0 = 1.2 kG) and RF sheaths were created by directly launching the shear Alfven wave. Plasma potential measurements were made with an emissive probe. DC plasma potential rectification was observed along field lines connected to the plate, serving as an indirect measure of RF sheath formation. 2-D maps of plasma properties and rectified plasma potential will be presented. This research is part of an ongoing campaign to study the formation and structure of RF sheaths.

Protein Aggregation and Its Impact on Product Quality

PubMed Central

Roberts, Christopher J.

2014-01-01

Protein pharmaceutical products are typically active as folded monomers that are composed of one or more protein chains, such as the heavy and light chains in monoclonal antibodies that are a mainstay of current drug pipelines. There are numerous possible aggregated states for a given protein, some of which are potentially useful, while most of which are considered deleterious from the perspective of pharmaceutical product quality and performance. This review provides an overview of how and why different aggregated states of proteins occur, how this potentially impacts product quality and performance, fundamental approaches to control aggregate formation, and the practical approaches that are currently used in the pharmaceutical industry. PMID:25173826

Cryptic genetic variation: evolution's hidden substrate.

PubMed

Paaby, Annalise B; Rockman, Matthew V

2014-04-01

Cryptic genetic variation (CGV) is invisible under normal conditions, but it can fuel evolution when circumstances change. In theory, CGV can represent a massive cache of adaptive potential or a pool of deleterious alleles that are in need of constant suppression. CGV emerges from both neutral and selective processes, and it may inform about how human populations respond to change. CGV facilitates adaptation in experimental settings, but does it have an important role in the real world? Here, we review the empirical support for widespread CGV in natural populations, including its potential role in emerging human diseases and the growing evidence of its contribution to evolution.

THERMODYNAMICS OF FE-CU ALLOYS AS DESCRIBED BY A CLASSIC POTENTIALS

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

Caro, A; Caro, M; Lopasso, E M

2005-04-14

The Fe-Cu system is of relevance to the nuclear industry because of the deleterious consequences of Cu precipitates in the mechanical properties of Fe. Several sets of classical potentials are used in molecular dynamics simulations studies of this system, in particular that proposed by Ludwig et al. (Modelling Simul. Mater. Sci. Eng. 6, 19 (1998)). In this work we extract thermodynamic information from this interatomic potentials. We obtain equilibrium phase diagram and find a reasonable agreement with the experimental phases in the regions of relevance to radiation damage studies. We compare the results with the predicted phase diagram based onmore » other potential, as calculated in previous work. We discuss the disagreements found between the phase diagram calculated here and experimental results, focusing on the pure components and discuss the applicability of these potentials; finally we suggest an approach to improve existing potentials for this system.« less

Myo- and cardiotoxic effects of the wild winter mushroom ( Flammulina velutipes) on mice.

PubMed

Mustonen, Anne-Mari; Määttänen, Maija; Kärjä, Vesa; Puukka, Katri; Aho, Jari; Saarela, Seppo; Nieminen, Petteri

2018-04-01

Rhabdomyolysis (destruction of striated muscle) is a novel form of mushroom poisoning in Europe and Asia indicated by increased circulating creatine kinase levels. Particular wild fungi have also been reported to induce elevated creatine kinase activities in mice. Flammulina velutipes (enokitake or winter mushroom) is one of the most actively cultivated mushroom species globally. As it is marketed as a medicinal mushroom and functional food, it is important to examine whether it could induce potentially harmful health effects similar to some previously studied edible fungi. The present study examined the effects of F. velutipes consumption on the plasma clinical chemistry, hematology, and organ histology of laboratory mice. Wild F. velutipes were dried, pulverized, mixed with a regular laboratory rodent diet, and fed to the animals at 0, 3, 6, or 9 g/kg body mass/day for five days ( n = 6/group). F. velutipes consumption caused increased activities of plasma creatine kinase and the MB-fraction of creatine kinase at 6-9 g/kg/d, indicating potentially deleterious effects on both skeletal and cardiac muscle. The plasma total and high-density lipoprotein cholesterol concentrations (at 9 g/kg/d) and white blood cell and lymphocyte counts (at 6-9 g/kg/d) decreased. Although the cholesterol-lowering properties of F. velutipes can be beneficial, the previously unexamined, potentially hazardous side effects of mushroom consumption (myo- and cardiotoxicity) should be thoroughly investigated before recommending this mushroom species as a health-promoting food item. Impact statement This work is important to the field of functional foods, as it provides novel information about the potential myo- and cardiotoxic properties of an edible mushroom, Flammulina velutipes. The results are useful and of importance because F. velutipes is an actively cultivated mushroom and marketed as a health-promoting food item. The findings contribute to the understanding of the complexity of the balance between the beneficial and potentially harmful effects of mushroom consumption.

The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.

PubMed

Raju, S Vamsee; Lin, Vivian Y; Liu, Limbo; McNicholas, Carmel M; Karki, Suman; Sloane, Peter A; Tang, Liping; Jackson, Patricia L; Wang, Wei; Wilson, Landon; Macon, Kevin J; Mazur, Marina; Kappes, John C; DeLucas, Lawrence J; Barnes, Stephen; Kirk, Kevin; Tearney, Guillermo J; Rowe, Steven M

2017-01-01

Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-μm resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis.

Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.

PubMed

Choi, Soo Hyun; Kim, Dae Won; Kim, So Young; An, Jae Jin; Lee, Sun Hwa; Choi, Hee Soon; Sohn, Eun Jung; Hwang, Seok-Il; Won, Moo Ho; Kang, Tae-Cheon; Kwon, Hyung Joo; Kang, Jung Hoon; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2005-12-31

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia

NASA Astrophysics Data System (ADS)

Li, Hongyu; Valkenier, Hennie; Judd, Luke W.; Brotherhood, Peter R.; Hussain, Sabir; Cooper, James A.; Jurček, Ondřej; Sparkes, Hazel A.; Sheppard, David N.; Davis, Anthony P.

2016-01-01

Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.

Ironing out the details of iron overload in myelofibrosis: Lessons from myelodysplastic syndromes.

PubMed

Carreau, Nicole; Tremblay, Douglas; Savona, Michael; Kremyanskaya, Marina; Mascarenhas, John

2016-09-01

Myelofibrosis (MF) and myelodysplastic syndrome (MDS) are hematopoietic stem cell disorders associated with cytopenias and red blood cell (RBC) transfusion dependence. Iron overload (IO) as a consequence of RBC transfusion dependence and its effect on outcomes in MF has not been formally studied. However, IO is a demonstrated poor prognostic feature in patients with MDS and congenital or acquired chronic anemias. Evidence that iron chelation therapy (ICT) reduces the deleterious effects of IO in MDS has led to speculation of benefit in MF. However, data supporting the use of ICT in MF is lacking. Neither disease has clear consensus guidelines for the use of ICT. Moreover, JAK-STAT inhibition, the cornerstone of MF treatment, often contributes to anemia and transfusional requirements. This manuscript reviews known and potential implications of IO in MF and highlights the need for prospective clinical investigations of ICT with consideration in the setting of JAK2 inhibitor therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyperprogressive Disease in Anorectal Melanoma Treated by PD-1 Inhibitors

PubMed Central

Faure, Marjorie; Rochigneux, Philippe; Olive, Daniel; Taix, Sébastien; Brenot-Rossi, Isabelle; Gilabert, Marine

2018-01-01

The 5-year survival rate of primary anorectal malignant melanoma is less than 20%. Optimal treatment of this condition remains controversial regarding locally disease, and whether any preferential survival benefit arises from either abdominoperineal resection or wide local excision remains unknown. The majority of patients progress to metastatic disease, and for decades, the use of chemotherapies, such as platines or dacarbazine, has been advocated to improve overall survival. The therapeutic use of new checkpoint inhibitors in a variety of trials has provided evidence for an antitumoral effect of PD-1 and/or CTL4 inhibitors in mucosal melanomas, but these treatments must still be further evaluated. Some anecdotal occurrences of rapid progression [i.e., hyperprogressive disease (HPD)] while using these immune agents have been described, suggesting potentially deleterious effects of these drugs for some patients. We report a 77-year-old male metastatic anorectal melanoma patient presenting with HPD over 2 months of a PD1 inhibitor treatment course and document this HPD blood phenotype. PMID:29725330

Hyperprogressive Disease in Anorectal Melanoma Treated by PD-1 Inhibitors.

PubMed

Faure, Marjorie; Rochigneux, Philippe; Olive, Daniel; Taix, Sébastien; Brenot-Rossi, Isabelle; Gilabert, Marine

2018-01-01

The 5-year survival rate of primary anorectal malignant melanoma is less than 20%. Optimal treatment of this condition remains controversial regarding locally disease, and whether any preferential survival benefit arises from either abdominoperineal resection or wide local excision remains unknown. The majority of patients progress to metastatic disease, and for decades, the use of chemotherapies, such as platines or dacarbazine, has been advocated to improve overall survival. The therapeutic use of new checkpoint inhibitors in a variety of trials has provided evidence for an antitumoral effect of PD-1 and/or CTL4 inhibitors in mucosal melanomas, but these treatments must still be further evaluated. Some anecdotal occurrences of rapid progression [i.e., hyperprogressive disease (HPD)] while using these immune agents have been described, suggesting potentially deleterious effects of these drugs for some patients. We report a 77-year-old male metastatic anorectal melanoma patient presenting with HPD over 2 months of a PD1 inhibitor treatment course and document this HPD blood phenotype.