Social Media Field Trips: Using Disruptive Technologies without Disrupting the System

ERIC Educational Resources Information Center

Snow, Kathy

2017-01-01

This paper presents a discussion around the question of data protection, privacy, liability and the resultant policy that has developed both in public K-12 education and post secondary education in Canada. With no central regulation of online protection in Canada educators in some provinces face a digital divide caused by more restrictive policy…

Protein synthesis underlies post-retrieval memory consolidation to a restricted degree only when updated information is obtained

PubMed Central

Rodriguez-Ortiz, Carlos J.; De la Cruz, Vanesa; Gutiérrez, Ranier; Bermudez-Rattoni, Federico

2005-01-01

Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here we show that intracortical blockade of protein synthesis in the gustatory cortex after retrieval of taste-recognition memory disrupts previously consolidated memory to a restricted degree only if the experience is updated. Our results suggest that retrieved memory can be modified as part of a mechanism for incorporating updated information into previously consolidated memory. PMID:16166395

Repeated cycles of restricted food intake and binge feeding disrupt sensory-specific satiety in the rat.

PubMed

Ahn, Soyon; Phillips, Anthony G

2012-06-01

The relationship between food restriction and subsequent dysregulation of food intake is complex, variable and long-lasting. The present study investigated in rats whether repeated cycles of food restriction and binge feeding opportunities may alter regulation of food intake by employing a test for sensory-specific satiety. Rats that experienced repeated food restriction-binge cycles maintained heavier body weights compared to rats that remained on continuous food restriction. In contrast to the control subjects, rats that alternated between food restriction and binge feeding failed to display sensory-specific satiety. During the first meal, there was a gradual decrease in the amount of food intake over a 40 min period. When presented with a second meal of the same food, these rats responded to the familiar food in a manner similar as to a novel food (i.e., comparable quantities of both types of food were consumed). Food restriction-binge feeding cycles may be considered as a form of stress, which in turn is associated with cross-sensitization to numerous behavioral responses. Therefore, we propose that stress-induced disruption of sensory-specific satiety reflects a sensitized response to food, in which the interaction between sensory and satiety factors are no longer the key regulators of food choice and meal cessation. Furthermore, a role for sensory-specific satiety in terminating food intake appeared to decline with the progression of the cycles, thereby contributing to a steady increase in body weight of rats that experienced restriction with bouts of binge feeding opportunities. Copyright © 2012 Elsevier B.V. All rights reserved.

Protein malnutrition after weaning disrupts peripheral clock and daily insulin secretion in mice.

PubMed

Borck, Patricia Cristine; Batista, Thiago Martins; Vettorazzi, Jean Franciesco; Camargo, Rafael Ludemann; Boschero, Antonio Carlos; Vieira, Elaine; Carneiro, Everardo Magalhães

2017-12-01

Changes in nutritional state may alter circadian rhythms through alterations in expression of clock genes. Protein deficiency has a profound effect on body metabolism, but the effect of this nutrient restriction after weaning on biological clock has not been explored. Thus, this study aims to investigate whether the protein restriction affects the daily oscillation in the behavior and metabolic rhythms, as well as expression of clock genes in peripheral tissues. Male C57BL/6 J mice, after weaning, were fed a normal-protein (NP) diet or a low-protein (LP) diet for 8 weeks. Mice fed an LP diet did not show difference in locomotor activity and energy expenditure, but the food intake was increased, with parallel increased expression of the orexigenic neuropeptide Npy and disruption of the anorexigenic Pomc oscillatory pattern in the hypothalamus. LP mice showed disruption in the daily rhythmic patterns of plasma glucose, triglycerides and insulin. Also, the rhythmic expression of clock genes in peripheral tissues and pancreatic islets was altered in LP mice. In pancreatic islets, the disruption of clock genes was followed by impairment of daily glucose-stimulated insulin secretion and the expression of genes involved in exocytosis. Pharmacological activation of REV-ERBα could not restore the insulin secretion in LP mice. The present study demonstrates that protein restriction, leading to development of malnutrition, alters the peripheral clock and metabolic outputs, suggesting that this nutrient provides important entraining cues to regulate the daily fluctuation of biological clock. Copyright © 2017 Elsevier Inc. All rights reserved.

Metabolic effects of sleep disruption, links to obesity and diabetes.

PubMed

Nedeltcheva, Arlet V; Scheer, Frank A J L

2014-08-01

To highlight the adverse metabolic effects of sleep disruption and to open ground for research aimed at preventive measures. This area of research is especially relevant given the increasing prevalence of voluntary sleep curtailment, sleep disorders, diabetes, and obesity. Epidemiological studies have established an association between decreased self-reported sleep duration and an increased incidence of type 2 diabetes (T2D), obesity, and cardiovascular disease. Experimental laboratory studies have demonstrated that decreasing either the amount or quality of sleep decreases insulin sensitivity and decreases glucose tolerance. Experimental sleep restriction also causes physiological and behavioral changes that promote a positive energy balance. Although sleep restriction increases energy expenditure because of increased wakefulness, it can lead to a disproportionate increase in food intake, decrease in physical activity, and weight gain. Sleep disruption has detrimental effects on metabolic health. These insights may help in the development of new preventive and therapeutic approaches against obesity and T2D based on increasing the quality and/or quantity of sleep.

Impact of a transition to more restrictive drug formulary on therapy discontinuation and medication adherence.

PubMed

Shirneshan, E; Kyrychenko, P; Matlin, O S; Avila, J P; Brennan, T A; Shrank, W H

2016-02-01

There is conclusive evidence demonstrating that formulary restrictions are associated with reduced utilization and pharmacy spending of the restricted drugs. However, prior efforts to implement restrictive formularies have been associated with inconsistent rates of therapy discontinuation and mixed impacts on adherence to therapy. Also, the impact of transferring patients from an already restrictive formulary to a more aggressive model has not been previously examined. This study evaluated the impact of implementation of a more restrictive formulary on therapy disruption, adherence rates, pharmacy costs and generic utilization among patients with common chronic conditions. In 2014, CVS Health implemented Value Formulary (VF), a restrictive benefit design with the aim of reducing spending while preserving access to and adherence to essential therapy, was used. A retrospective cohort study was conducted to assess changes in therapy disruption rates, pharmacy costs and generic dispensing rate (GDR) (for continuers) and medication adherence (for initiators) following the implementation of VF. The study group was selected from members of three existing employer clients transitioned from standard formulary (SF) to VF on January 2014. The control population was a matched group of six employers with the same preperiod formulary structure, business unit, adherence programmes and patient out-of-pocket cost as the study group. The control group retained SF in 2014. To assess therapy disruption after VF implementation, we categorized patients by their subsequent medication use into three groups: (i) therapy stopped, (ii) therapy continued and (iii) therapy switched. Medication adherence was measured as monthly proportion of days covered (PDC). Pharmacy cost and GDR were measured per utilizer per month (PUPM). Rates of therapy disruption in study and control groups were compared using the chi-square test. Differences in monthly PDC between matched groups were evaluated using multivariate linear regression. Impact of VF on pharmacy cost and GDR was measured through segmented regression of interrupted time series data with generalized estimating equations. A transition from SF to VF influenced drug coverage for approximately 13% of members (as their medications were either no longer covered, or covered restrictively under VF). Compared to patients whose plan sponsors retained SF, the patients that transitioned to VF had a modest (1·3%) but statistically significant increase in therapy discontinuation rates. This was offset by similarly modest improvements in adherence; patients who initiated therapy under VF demonstrated a 1·5% higher adherence to medications as compared to SF patients (P < 0·001). Medication costs in the VF group were lower by $20 PUPM (P < 0·001), and GDR was greater by 4·2% (P < 0·001). Transition of patients to a more restrictive drug formulary led to modest therapy discontinuation, similarly modest improvements in medication adherence and substantial prescription drug cost savings. As healthcare payors search for ways to control the rapid rise in spending for medications without compromising quality, the Value Formulary can serve as a useful tool. © 2016 John Wiley & Sons Ltd.

Interactive Effects of Dorsomedial Hypothalamic Nucleus and Time-Restricted Feeding on Fractal Motor Activity Regulation.

PubMed

Lo, Men-Tzung; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Escobar, Carolina; Buijs, Ruud M; Hu, Kun

2016-01-01

One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations-similar fluctuation structure at different time scales-that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)-a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)-the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the SCN. The differential impacts of food restriction on fractal activity control in intact and DMH-lesioned animals suggest that the DMH plays a crucial role in integrating these different time cues to the circadian network for multiscale regulation of motor activity.

PyRAD: assembly of de novo RADseq loci for phylogenetic analyses.

PubMed

Eaton, Deren A R

2014-07-01

Restriction-site-associated genomic markers are a powerful tool for investigating evolutionary questions at the population level, but are limited in their utility at deeper phylogenetic scales where fewer orthologous loci are typically recovered across disparate taxa. While this limitation stems in part from mutations to restriction recognition sites that disrupt data generation, an additional source of data loss comes from the failure to identify homology during bioinformatic analyses. Clustering methods that allow for lower similarity thresholds and the inclusion of indel variation will perform better at assembling RADseq loci at the phylogenetic scale. PyRAD is a pipeline to assemble de novo RADseq loci with the aim of optimizing coverage across phylogenetic datasets. It uses a wrapper around an alignment-clustering algorithm, which allows for indel variation within and between samples, as well as for incomplete overlap among reads (e.g. paired-end). Here I compare PyRAD with the program Stacks in their performance analyzing a simulated RADseq dataset that includes indel variation. Indels disrupt clustering of homologous loci in Stacks but not in PyRAD, such that the latter recovers more shared loci across disparate taxa. I show through reanalysis of an empirical RADseq dataset that indels are a common feature of such data, even at shallow phylogenetic scales. PyRAD uses parallel processing as well as an optional hierarchical clustering method, which allows it to rapidly assemble phylogenetic datasets with hundreds of sampled individuals. Software is written in Python and freely available at http://www.dereneaton.com/software/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A case study of magnetotail current sheet disruption and diversion

NASA Technical Reports Server (NTRS)

Lui, A. T. Y.; Lopez, R. E.; Krimigis, S. M.; Mcentire, R. W.; Zanetti, L. J.

1988-01-01

On June 1, 1985 the AMPTE/CCE spacecraft (at a geocentric distance of about 8.8 earth radii at the midnight neutral sheet region) observed a dispersionless energetic particle injection and an increase in magnetic field magnitude, which are features commonly attributed to disruption of the near-earth cross-tail current sheet during substorm expansion onsets. An analysis based on high time-resolution measurements from the magnetometer and the energetic particle detector indicates that the current sheet disruption region exhibited localized (less than 1 earth radius) and transient (less than 1 min) particle intensity enhancements, accompanied by complex magnetic field changes with occasional development of a southward magnetic field component. Similar features are seen in other current disruption/diversion events observed by the CCE. The present analysis suggests that the current disruption region is quite turbulent, similar to laboratory experiments on current sheet disruption, with signatures unlike those expected from an X-type neutral line configuration. No clear indication of periodicity in any magnetic field parameter is discernible for this current disruption event.

Time-restricted feeding reduces adiposity in mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Disruption of the circadian rhythm contributes to obesity. The present study investigated the effects of time-restricted feeding (TRF) of a high-fat diet on adiposity in male C57BL/6 mice. Three-week-old mice were fed a low-fat or high-fat diet (16% or 45% of energy from corn oil) ad libitum (ad l...

Using geographic information science to evaluate legal restrictions on freight transportation routing in disruptive scenarios

DOE PAGES

Fialkoff, Marc R.; Omitaomu, Olufemi A.; Peterson, Steven K.; ...

2016-12-23

Disasters have consequences and freight transportation is not immune from the effects of such disruptions. In the aftermath of disasters, planners and policymakers have to utilize scarce resources and work within legal frameworks to provide recovery for affected citizens and business. As seen with Hurricane Sandy, various observers noted the challenge with freight rerouting due to inoperable infrastructure and legal barriers involved with intermodal freight transportation. This paper focuses on how Geographic Information Systems (GIS); specifically WebTRAGIS (Transportation Routing Analysis GIS), a transportation routing platform developed at Oak Ridge National Laboratory, can be used to evaluate different routing options formore » freight transportation. In the case of freight transportation, the Merchant Marine Act of 1920 (also known as the Jones Act) restricts Short Sea Shipping (SSS) between coastwise points within U.S. territorial waters. This restriction leads to reliance on land-side modes for handling increased freight resulting from cargo diversion. Using Hurricane Sandy and the closure of the Port of New York/New Jersey as a case study, different modal studies were conducted; ultimately highlighting the various routes and provides insight into potential review of modal restrictions such as the Jones Act.« less

Using geographic information science to evaluate legal restrictions on freight transportation routing in disruptive scenarios

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

Fialkoff, Marc R.; Omitaomu, Olufemi A.; Peterson, Steven K.

Disasters have consequences and freight transportation is not immune from the effects of such disruptions. In the aftermath of disasters, planners and policymakers have to utilize scarce resources and work within legal frameworks to provide recovery for affected citizens and business. As seen with Hurricane Sandy, various observers noted the challenge with freight rerouting due to inoperable infrastructure and legal barriers involved with intermodal freight transportation. This paper focuses on how Geographic Information Systems (GIS); specifically WebTRAGIS (Transportation Routing Analysis GIS), a transportation routing platform developed at Oak Ridge National Laboratory, can be used to evaluate different routing options formore » freight transportation. In the case of freight transportation, the Merchant Marine Act of 1920 (also known as the Jones Act) restricts Short Sea Shipping (SSS) between coastwise points within U.S. territorial waters. This restriction leads to reliance on land-side modes for handling increased freight resulting from cargo diversion. Using Hurricane Sandy and the closure of the Port of New York/New Jersey as a case study, different modal studies were conducted; ultimately highlighting the various routes and provides insight into potential review of modal restrictions such as the Jones Act.« less

Myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications associated with a novel m.5513G>A mutation in the MT-TW gene.

PubMed

Cardaioli, Elena; Mignarri, Andrea; Cantisani, Teresa Anna; Malandrini, Alessandro; Nesti, Claudia; Rubegni, Anna; Funel, Niccola; Federico, Antonio; Santorelli, Filippo Maria; Dotti, Maria Teresa

2018-06-02

We sequenced the mitochondrial genome from a 40-year-old woman with myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications. Histological and biochemical features of mitochondrial respiratory chain dysfunction were present. Direct sequencing showed a novel heteroplasmic mutation at nucleotide 5513 in the MT-TW gene that encodes tRNA Trp . Restriction Fragment Length Polymorphism analysis confirmed that about 80% of muscle mtDNA harboured the mutation while it was present in minor percentages in mtDNA from other tissues. The mutation is predicted to disrupt a highly conserved base pair within the aminoacyl acceptor stem of the tRNA. This is the 17° mutation in MT-TW gene and expands the known causes of late-onset mitochondrial diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Circadian clock: linking epigenetics to aging

PubMed Central

Orozco-Solis, Ricardo; Sassone-Corsi, Paolo

2015-01-01

Circadian rhythms are generated by an intrinsic cellular mechanism that controls a large array of physiological and metabolic processes. There is erosion in the robustness of circadian rhythms during aging, and disruption of the clock by genetic ablation of specific genes is associated with aging-related features. Importantly, environmental conditions are thought to modulate the aging process. For example, caloric restriction is a very strong environmental effector capable of delaying aging. Intracellular pathways implicating nutrient sensors, such as SIRTs and mTOR complexes, impinge on cellular and epigenetic mechanisms that control the aging process. Strikingly, accumulating evidences indicate that these pathways are involved in both the modulation of the aging process and the control of the clock. Hence, innovative therapeutic strategies focused at controlling the circadian clock and the nutrient sensing pathways might beneficially influence the negative effects of aging. PMID:25033025

Recommendations related to Browns Ferry Fire

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

Not Available

1976-02-01

Based on its review of the events transpiring before, during and after the Browns Ferry fire, the Review Group concludes that the probability of disruptive fires of the magnitude of the Browns Ferry event is small, and that there is no need to restrict operation of nuclear power plants for public safety. However, it is clear that much can and should be done to reduce even further the likelihood of disabling fires and to improve assurance of rapid extinguishment of fires that occur. Consideration should be given also to features that would increase further the ability of nuclear facilities tomore » withstand large fires without loss of important functions should such fires occur. The Review Group believes that improvements, especially in the areas of fire prevention and fire control, can and should be made in most existing facilities.« less

Face Inversion Disproportionately Disrupts Sensitivity to Vertical over Horizontal Changes in Eye Position

ERIC Educational Resources Information Center

Crookes, Kate; Hayward, William G.

2012-01-01

Presenting a face inverted (upside down) disrupts perceptual sensitivity to the spacing between the features. Recently, it has been shown that this disruption is greater for vertical than horizontal changes in eye position. One explanation for this effect proposed that inversion disrupts the processing of long-range (e.g., eye-to-mouth distance)…

The effect of music on repetitive disruptive vocalizations of persons with dementia.

PubMed

Casby, J A; Holm, M B

1994-10-01

This study examined the effect of classical music and favorite music on the repetitive disruptive vocalizations of long-term-care facility (LTCF) residents with dementia of the Alzheimer's type (DAT). Three subjects diagnosed with DAT who had a history of repetitive disruptive vocalizations were selected for the study. Three single-subject withdrawal designs (ABA, ACA, and ABCA) were used to assess subjects' repetitive disruptive vocalizations during each phase: no intervention (A); relaxing, classical music (B); and favorite music (C). Classical music and favorite music significantly decreased the number of vocalizations in two of the three subjects (p < .05). These findings support a method that was effective in decreasing the disruptive vocalization pattern common in those with DAT in the least restrictive manner, as mandated by the Omnibus Budget Reconciliation Act of 1987.

Identification of Chemical Features Linked to Thyroperoxidase Inhibition (SOT)

EPA Science Inventory

Disruption of maternal serum thyroid hormone (TH) adversely affects fetal neurodevelopment. Therefore, assay development within the US EPA ToxCast program is ongoing to enable screening for chemicals that may disrupt TH, in support of the Endocrine Disruption Screening Program (E...

Disaggregation of Amylin Aggregate by Novel Conformationally Restricted Aminobenzoic Acid containing α/β and α/γ Hybrid Peptidomimetics

PubMed Central

Paul, Ashim; Kalita, Sourav; Kalita, Sujan; Sukumar, Piruthivi; Mandal, Bhubaneswar

2017-01-01

Diabetes has emerged as a threat to the current world. More than ninety five per cent of all the diabetic population has type 2 diabetes mellitus (T2DM). Aggregates of Amylin hormone, which is co-secreted with insulin from the pancreatic β-cells, inhibit the activities of insulin and glucagon and cause T2DM. Importance of the conformationally restricted peptides for drug design against T2DM has been invigorated by recent FDA approval of Symlin, which is a large conformationally restricted peptide. However, Symlin still has some issues including solubility, oral bioavailability and cost of preparation. Herein, we introduced a novel strategy for conformationally restricted peptide design adopting a minimalistic approach for cost reduction. We have demonstrated efficient inhibition of amyloid formation of Amylin and its disruption by a novel class of conformationally restricted β-sheet breaker hybrid peptidomimetics (BSBHps). We have inserted β, γ and δ -aminobenzoic acid separately into an amyloidogenic peptide sequence, synthesized α/β, α/γ and α/δ hybrid peptidomimetics, respectively. Interestingly, we observed the aggregation inhibitory efficacy of α/β and α/γ BSBHps, but not of α/δ analogues. They also disrupt existing amyloids into non-toxic forms. Results may be useful for newer drug design against T2DM as well as other amyloidoses and understanding amyloidogenesis. PMID:28054630

Disaggregation of Amylin Aggregate by Novel Conformationally Restricted Aminobenzoic Acid containing α/β and α/γ Hybrid Peptidomimetics

NASA Astrophysics Data System (ADS)

Paul, Ashim; Kalita, Sourav; Kalita, Sujan; Sukumar, Piruthivi; Mandal, Bhubaneswar

2017-01-01

Diabetes has emerged as a threat to the current world. More than ninety five per cent of all the diabetic population has type 2 diabetes mellitus (T2DM). Aggregates of Amylin hormone, which is co-secreted with insulin from the pancreatic β-cells, inhibit the activities of insulin and glucagon and cause T2DM. Importance of the conformationally restricted peptides for drug design against T2DM has been invigorated by recent FDA approval of Symlin, which is a large conformationally restricted peptide. However, Symlin still has some issues including solubility, oral bioavailability and cost of preparation. Herein, we introduced a novel strategy for conformationally restricted peptide design adopting a minimalistic approach for cost reduction. We have demonstrated efficient inhibition of amyloid formation of Amylin and its disruption by a novel class of conformationally restricted β-sheet breaker hybrid peptidomimetics (BSBHps). We have inserted β, γ and δ -aminobenzoic acid separately into an amyloidogenic peptide sequence, synthesized α/β, α/γ and α/δ hybrid peptidomimetics, respectively. Interestingly, we observed the aggregation inhibitory efficacy of α/β and α/γ BSBHps, but not of α/δ analogues. They also disrupt existing amyloids into non-toxic forms. Results may be useful for newer drug design against T2DM as well as other amyloidoses and understanding amyloidogenesis.

Repeated Exposure to Severely Limited Sleep Results in Distinctive and Persistent Physiological Imbalances in Rats

PubMed Central

Everson, Carol A.; Szabo, Aniko

2011-01-01

Chronic sleep disruption in laboratory rats leads to increased energy expenditure, connective tissue abnormalities, and increased weights of major organs relative to body weight. Here we report on expanded findings and the extent to which abnormalities become long-lasting, potentially permanent changes to health status after apparent recuperation from chronic sleep disruption. Rats were exposed 6 times to long periods of disrupted sleep or control conditions during 10 weeks to produce adaptations and then were permitted nearly 4 months of undisturbed sleep. Measurements were made in tissues from these groups and in preserved tissue from the experimental and control groups of an antecedent study that lacked a lengthy recuperation period. Cycles of sleep restriction resulted in energy deficiency marked by a progressive course of hyperphagia and major (15%) weight loss. Analyses of tissue composition in chronically sleep-restricted rats indicated that protein and lipid amounts in internal organs were largely spared, while adipose tissue depots appeared depleted. This suggests high metabolic demands may have preserved the size of the vital organs relative to expectations of severe energy deficiency alone. Low plasma corticosterone and leptin concentrations appear to reflect low substrate availability and diminished adiposity. After nearly 4 months of recuperation, sleep-restricted rats were consuming 20% more food and 35% more water than did comparison control rats, despite normalized weight, normalized adipocytes, and elevated plasma leptin concentrations. Plasma cholesterol levels in recuperated sleep-restricted rats were diminished relative to those of controls. The chronically increased intake of nutriments and water, along with altered negative feedback regulation and substrate use, indicate that internal processes are modified long after a severe period of prolonged and insufficient sleep has ended. PMID:21853062

CRISPR-Mediated Base Editing Enables Efficient Disruption of Eukaryotic Genes through Induction of STOP Codons.

PubMed

Billon, Pierre; Bryant, Eric E; Joseph, Sarah A; Nambiar, Tarun S; Hayward, Samuel B; Rothstein, Rodney; Ciccia, Alberto

2017-09-21

Standard CRISPR-mediated gene disruption strategies rely on Cas9-induced DNA double-strand breaks (DSBs). Here, we show that CRISPR-dependent base editing efficiently inactivates genes by precisely converting four codons (CAA, CAG, CGA, and TGG) into STOP codons without DSB formation. To facilitate gene inactivation by induction of STOP codons (iSTOP), we provide access to a database of over 3.4 million single guide RNAs (sgRNAs) for iSTOP (sgSTOPs) targeting 97%-99% of genes in eight eukaryotic species, and we describe a restriction fragment length polymorphism (RFLP) assay that allows the rapid detection of iSTOP-mediated editing in cell populations and clones. To simplify the selection of sgSTOPs, our resource includes annotations for off-target propensity, percentage of isoforms targeted, prediction of nonsense-mediated decay, and restriction enzymes for RFLP analysis. Additionally, our database includes sgSTOPs that could be employed to precisely model over 32,000 cancer-associated nonsense mutations. Altogether, this work provides a comprehensive resource for DSB-free gene disruption by iSTOP. Copyright © 2017 Elsevier Inc. All rights reserved.

Technology Acquisition Reform

DTIC Science & Technology

2004-03-01

technologies until they are ready to be handed over to an established program. This office would also provide a home for disruptive technologies emerging...the development and acquisition of disruptive technologies .3 Disruptive technologies threaten programs of record but are essential to future Naval...and rarely emerge in response to customer demand. Disruptive technologies have features that a few fringe (and generally new) customers value

Endocrine disruption, parasites and pollutants in wild freshwater fish.

PubMed

Jobling, S; Tyler, C R

2003-01-01

Disruption of the endocrine system has been shown to occur in wild freshwater fish populations across the globe. Effects range from subtle changes in the physiology and sexual behaviour of fish to permanently altered sexual differentiation, impairment of gonad development and/or altered fertility. A wide variety of adverse environmental conditions may induce endocrine disruption, including sub-optimal temperatures, restricted food supply, low pH, environmental pollutants, and/or parasites. Furthermore, it is conceivable that any/all of these factors could act simultaneously to cause a range of disparate or inter-related effects. Some of the strongest evidence for a link between an adverse health effect, as a consequence of endocrine disruption, and a causative agent(s) is between the condition of intersex in wild roach (Rutlius rutilus) in UK rivers and exposure to effluents from sewage treatment works. The evidence to indicate that intersex in roach (and other cyprinid fish living in these rivers) is caused by chemicals that mimic and/or disrupt hormone function/balance in treated sewage effluent is substantial. There are a few parasites that affect the endocrine system directly in fish, including the tape worm Ligula intestinalis and a few parasites from the micropsora phylum. L. intestinalis acts at the level of the hypothalamus restricting GnRH secretion (resulting in poorly developed gonads) and is one of the very few examples where an endocrine disrupting event has been shown to result in a population-level effect (reducing it). It is well established that many parasites affect the immune system and thus the most common effect of parasites on the endocrine system in fish is likely to be an indirect one.

Evolutionarily stable range limits set by interspecific competition.

PubMed

Price, Trevor D; Kirkpatrick, Mark

2009-04-22

A combination of abiotic and biotic factors probably restricts the range of many species. Recent evolutionary models and tests of those models have asked how a gradual change in environmental conditions can set the range limit, with a prominent idea being that gene flow disrupts local adaptation. We investigate how biotic factors, explicitly competition for limited resources, result in evolutionarily stable range limits even in the absence of the disruptive effect of gene flow. We model two competing species occupying different segments of the resource spectrum. If one segment of the resource spectrum declines across space, a species that specializes on that segment can be driven to extinction, even though in the absence of competition it would evolve to exploit other abundant resources and so be saved. The result is that a species range limit is set in both evolutionary and ecological time, as the resources associated with its niche decline. Factors promoting this outcome include: (i) inherent gaps in the resource distribution, (ii) relatively high fitness of the species when in its own niche, and low fitness in the alternative niche, even when resource abundances are similar in each niche, (iii) strong interspecific competition, and (iv) asymmetric interspecific competition. We suggest that these features are likely to be common in multispecies communities, thereby setting evolutionarily stable range limits.

Evolutionarily stable range limits set by interspecific competition

PubMed Central

Price, Trevor D.; Kirkpatrick, Mark

2009-01-01

A combination of abiotic and biotic factors probably restricts the range of many species. Recent evolutionary models and tests of those models have asked how a gradual change in environmental conditions can set the range limit, with a prominent idea being that gene flow disrupts local adaptation. We investigate how biotic factors, explicitly competition for limited resources, result in evolutionarily stable range limits even in the absence of the disruptive effect of gene flow. We model two competing species occupying different segments of the resource spectrum. If one segment of the resource spectrum declines across space, a species that specializes on that segment can be driven to extinction, even though in the absence of competition it would evolve to exploit other abundant resources and so be saved. The result is that a species range limit is set in both evolutionary and ecological time, as the resources associated with its niche decline. Factors promoting this outcome include: (i) inherent gaps in the resource distribution, (ii) relatively high fitness of the species when in its own niche, and low fitness in the alternative niche, even when resource abundances are similar in each niche, (iii) strong interspecific competition, and (iv) asymmetric interspecific competition. We suggest that these features are likely to be common in multispecies communities, thereby setting evolutionarily stable range limits. PMID:19324813

Application of the Disruption Predictor Feature Developer to developing a machine-portable disruption predictor

NASA Astrophysics Data System (ADS)

Parsons, Matthew; Tang, William; Feibush, Eliot

2016-10-01

Plasma disruptions pose a major threat to the operation of tokamaks which confine a large amount of stored energy. In order to effectively mitigate this damage it is necessary to predict an oncoming disruption with sufficient warning time to take mitigative action. Machine learning approaches to this problem have shown promise but require further developments to address (1) the need for machine-portable predictors and (2) the availability of multi-dimensional signal inputs. Here we demonstrate progress in these two areas by applying the Disruption Predictor Feature Developer to data from JET and NSTX, and discuss topics of focus for ongoing work in support of ITER. The author is also supported under the Fulbright U.S. Student Program as a graduate student in the department of Nuclear, Plasma and Radiological Engineering at the University of Illinois at Urbana-Champaign.

DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies

PubMed Central

Ji, Jianling; Lee, Hane; Argiropoulos, Bob; Dorrani, Naghmeh; Mann, John; Martinez-Agosto, Julian A; Gomez-Ospina, Natalia; Gallant, Natalie; Bernstein, Jonathan A; Hudgins, Louanne; Slattery, Leah; Isidor, Bertrand; Le Caignec, Cédric; David, Albert; Obersztyn, Ewa; Wiśniowiecka-Kowalnik, Barbara; Fox, Michelle; Deignan, Joshua L; Vilain, Eric; Hendricks, Emily; Horton Harr, Margaret; Noon, Sarah E; Jackson, Jessi R; Wilkens, Alisha; Mirzaa, Ghayda; Salamon, Noriko; Abramson, Jeff; Zackai, Elaine H; Krantz, Ian; Innes, A Micheil; Nelson, Stanley F; Grody, Wayne W; Quintero-Rivera, Fabiola

2015-01-01

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from −2 SD to −5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype–phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs. PMID:25944381

AREA RESTRICTIONS, RISK, HARM, AND HEALTH CARE ACCESS AMONG PEOPLE WHO USE DRUGS IN VANCOUVER, CANADA: A SPATIALLY ORIENTED QUALITATIVE STUDY

PubMed Central

McNeil, Ryan; Cooper, Hannah; Small, Will; Kerr, Thomas

2015-01-01

Area restrictions prohibiting people from entering drug scenes or areas where they were arrested are a common socio-legal mechanism employed to regulate the spatial practices of people who use drugs (PWUD). To explore how socio-spatial patterns stemming from area restrictions shape risk, harm, and health care access, qualitative interviews and mapping exercises were conducted with 24 PWUD with area restrictions in Vancouver, Canada. Area restrictions disrupted access to health and social resources (e.g., HIV care) concentrated in drug scenes, while territorial stigma prevented PWUD from accessing supports in other neighbourhoods. Rather than preventing involvement in drug-related activities, area restrictions displaced these activities to other locations and increased vulnerability to diverse risks and harms (e.g., unsafe drug use practices, violence). Given the harms stemming from area restrictions there is an urgent need to reconsider this socio-legal strategy. PMID:26241893

The Estrous Cycle of the Ewe Is Resistant to Disruption by Repeated, Acute Psychosocial Stress1

PubMed Central

Wagenmaker, Elizabeth R.; Breen, Kellie M.; Oakley, Amy E.; Tilbrook, Alan J.; Karsch, Fred J.

2010-01-01

Five experiments were conducted to test the hypothesis that psychosocial stress interferes with the estrous cycle of sheep. In experiment 1, ewes were repeatedly isolated during the follicular phase. Timing, amplitude, and duration of the preovulatory luteinizing hormone (LH) surge were not affected. In experiment 2, follicular-phase ewes were subjected twice to a “layered stress” paradigm consisting of sequential, hourly application of isolation, restraint, blindfold, and predator cues. This reduced the LH pulse amplitude but did not affect the LH surge. In experiment 3, different acute stressors were given sequentially within the follicular phase: food denial plus unfamiliar noises and forced exercise, layered stress, exercise around midnight, and transportation. This, too, did not affect the LH surge. In experiment 4, variable acute psychosocial stress was given every 1–2 days for two entire estrous cycles; this did not disrupt any parameter of the cycle monitored. Lastly, experiment 5 examined whether the psychosocial stress paradigms of experiment 4 would disrupt the cycle and estrous behavior if sheep were metabolically stressed by chronic food restriction. Thirty percent of the food-restricted ewes exhibited deterioration of estrous cycle parameters followed by cessation of cycles and failure to express estrous behavior. However, disruption was not more evident in ewes that also encountered psychosocial stress. Collectively, these findings indicate the estrous cycle of sheep is remarkably resistant to disruption by acute bouts of psychosocial stress applied intermittently during either a single follicular phase or repeatedly over two estrous cycles. PMID:20164438

Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork

PubMed Central

Barclay, Johanna L.; Husse, Jana; Bode, Brid; Naujokat, Nadine; Meyer-Kovac, Judit; Schmid, Sebastian M.; Lehnert, Hendrik; Oster, Henrik

2012-01-01

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers. PMID:22629359

75 FR 282 - Restricting the Mailing of Replica or Inert Explosive Devices

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... commitments. We believe this revised proposed rule will minimize the chances of operational disruptions caused... occurrences. Comment: The proposal is in violation of the Second Amendment. We no longer propose to prohibit...

Information Operations

DTIC Science & Technology

2006-02-13

restricted frequency list (JRFL). This list specifies protected, guarded, and taboo frequencies that should not normally be disrupted without prior... frequency list JROC Joint Requirement Oversight Council JSC Joint Spectrum Center JTCB joint targeting coordination board JTF joint task force JWAC joint

Circadian rhythms and obesity in mammals.

PubMed

Froy, Oren

2012-01-01

Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding (RF), calorie restriction (CR), and intermittent fasting (IF), provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. This paper focuses on circadian rhythms and their link to obesity.

Centre-based restricted nearest feature plane with angle classifier for face recognition

NASA Astrophysics Data System (ADS)

Tang, Linlin; Lu, Huifen; Zhao, Liang; Li, Zuohua

2017-10-01

An improved classifier based on the nearest feature plane (NFP), called the centre-based restricted nearest feature plane with the angle (RNFPA) classifier, is proposed for the face recognition problems here. The famous NFP uses the geometrical information of samples to increase the number of training samples, but it increases the computation complexity and it also has an inaccuracy problem coursed by the extended feature plane. To solve the above problems, RNFPA exploits a centre-based feature plane and utilizes a threshold of angle to restrict extended feature space. By choosing the appropriate angle threshold, RNFPA can improve the performance and decrease computation complexity. Experiments in the AT&T face database, AR face database and FERET face database are used to evaluate the proposed classifier. Compared with the original NFP classifier, the nearest feature line (NFL) classifier, the nearest neighbour (NN) classifier and some other improved NFP classifiers, the proposed one achieves competitive performance.

Biomass growth restriction in a packed bed reactor

DOEpatents

Griffith, William L.; Compere, Alicia L.

1978-01-01

When carrying out continuous biologically catalyzed reactions with anaerobic microorganisms attached to a support in an upflow packed bed column, growth of the microorganisms is restricted to prevent the microorganisms from plugging the column by limiting the availability of an essential nutrient and/or by the presence of predatory protozoa which consume the anaerobic microorganisms. A membrane disruptive detergent may be provided in the column to lyse dead microorganisms to make them available as nutrients for live microorganisms.

How sleep and wakefulness influence circadian rhythmicity: effects of insufficient and mistimed sleep on the animal and human transcriptome.

PubMed

Archer, Simon N; Oster, Henrik

2015-10-01

The mammalian circadian system is a multi-oscillator, hierarchically organised system where a central pacemaker synchronises behavioural, physiological and gene expression rhythms in peripheral tissues. Epidemiological studies show that disruption of this internal synchronisation by short sleep and shift work is associated with adverse health outcomes through mechanisms that remain to be elucidated. Here, we review recent animal and human studies demonstrating the profound effects of insufficient and mistimed sleep on the rhythms of gene expression in central and peripheral tissues. In mice, sleep restriction leads to an ~80% reduction in circadian transcripts in the brain and profound disruption of the liver transcriptome. In humans, sleep restriction leads to a 1.9% reduction in circadian transcripts in whole blood, and when sleep is displaced to the daytime, 97% of rhythmic genes become arrhythmic and one-third of all genes show changes in temporal expression profiles. These changes in mice and humans include a significant reduction in the circadian regulation of transcription and translation and core clock genes in the periphery, while at the same time rhythms within the suprachiasmatic nucleus are not disrupted. Although the physiological mediators of these sleep disruption effects on the transcriptome have not been established, altered food intake, changes in hormones such as cortisol, and changes in body and brain temperature may play important roles. Processes and molecular pathways associated with these disruptions include metabolism, immune function, inflammatory and stress responses, and point to the molecular mechanisms underlying the established adverse health outcomes associated with short sleep duration and shift work, such as metabolic syndrome and cancer. © 2015 European Sleep Research Society.

75 FR 38030 - Magnuson-Stevens Act Provisions; Fisheries Off West Coast States; Pacific Coast Groundfish...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... disruption to summer fisheries, as no additional restrictions to fishery management measures are necessary at... impacts within the lowered yelloweye rockfish OY in accordance with the court's order; makes routine in...

Handling Disruptive Innovations in HE: Lessons from Two Contrasting Case Studies

ERIC Educational Resources Information Center

Powell, Stephen; Olivier, Bill; Yuan, Li

2015-01-01

This article aims to show how Higher Education Institutions (HEIs) can recognise and best respond to a disruptive innovation. A disruptive innovation creates a new business model using a new process and usually a new technology to offer a product or service with new features and/or lower cost and initially addresses a group of people who are…

Neuroendocrine disruption without direct endocrine mode of action: Polychloro-biphenyls (PCBs) and bisphenol A (BPA) as case studies.

PubMed

Pinson, Anneline; Franssen, Delphine; Gérard, Arlette; Parent, Anne-Simone; Bourguignon, Jean-Pierre

Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand. Consistent with the WHO definition of an endocrine disrupter, a key issue is the "altered function(s) of the endocrine system". Such altered functions can result from different chemical interactions, beyond agonistic or antagonistic effect at a given receptor. Based on neuroendocrine disruption by polychlorinated biphenyls and bisphenol A, this paper proposes different mechanistic paradigms that can result in adverse health effects. They are a consequence of altered endocrine function(s) secondary to chemical interaction with different steps in the physiological regulatory processes, thus accounting for a possibly indirect endocrine mode of action. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Organizational Conflict: Causes and Manifestations.

ERIC Educational Resources Information Center

Sacks, Eugene

1979-01-01

No group (within an organization) can be entirely harmonious, but conflict is not an altogether disruptive factor. A delicate balance is required to obtain the advantages and restrict the disadvantages of organizational conflict. The causes and forms of organizational conflict are examined. (JMD)

Attentive Tracking Disrupts Feature Binding in Visual Working Memory

PubMed Central

Fougnie, Daryl; Marois, René

2009-01-01

One of the most influential theories in visual cognition proposes that attention is necessary to bind different visual features into coherent object percepts (Treisman & Gelade, 1980). While considerable evidence supports a role for attention in perceptual feature binding, whether attention plays a similar function in visual working memory (VWM) remains controversial. To test the attentional requirements of VWM feature binding, here we gave participants an attention-demanding multiple object tracking task during the retention interval of a VWM task. Results show that the tracking task disrupted memory for color-shape conjunctions above and beyond any impairment to working memory for object features, and that this impairment was larger when the VWM stimuli were presented at different spatial locations. These results demonstrate that the role of visuospatial attention in feature binding is not unique to perception, but extends to the working memory of these perceptual representations as well. PMID:19609460

The effects of war on the control of diseases of livestock in Rhodesia (Zimbabwe).

PubMed

Lawrence, J A; Foggin, C M; Norval, R A

1980-07-26

The disruption of veterinary services in the tribal areas of Rhodesia (now Zimbabwe) during seven years of conflict resulted in serious epidemics of disease. The cessation of dipping was followed by the death of an estimated one million cattle from tick-borne disease. Heavy mortality followed the disruption of control measures for trypanosomiasis. Foot-and-mouth disease and anthrax spread widely in the tribal areas. Rabies, normally restricted to areas bordering Botswana and Mocambique, became widespread. A marked increase in human deaths from anthrax and rabies occurred.

75 FR 30306 - Responding To Disruptive Patients

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-01

... visitations and communications, clothing, personal possessions, money, social interaction, exercise, and... order, these restrictions would take effect upon the signature of the Chief of Staff or designee. We... the proposed rule. VA provides medical care through 21 networks of medical facilities known as...

Impaired search for orientation but not color in hemi-spatial neglect.

PubMed

Wilkinson, David; Ko, Philip; Milberg, William; McGlinchey, Regina

2008-01-01

Patients with hemi-spatial neglect have trouble finding targets defined by a conjunction of visual features. The problem is widely believed to stem from a high-level deficit in attentional deployment, which in turn has led to disagreement over whether the detection of basic features is also disrupted. If one assumes that the detection of salient visual features can be based on the output of spared 'preattentive' processes (Treisman and Gelade, 1980), then feature detection should remain intact. However, if one assumes that all forms of detection require at least a modicum of focused attention (Duncan and Humphreys, 1992), then all forms of search will be disrupted to some degree. Here we measured the detection of feature targets that were defined by either a unique color or orientation. Comparable detection rates were observed in non-neglected space, which indicated that both forms of search placed similar demands on attention. For either of the above accounts to be true, the two targets should therefore be detected with equal efficiency in the neglected field. We found that while the detection rate for color was normal in four of our five patients, all showed an increased reaction time and/or error rate for orientation. This result points to a selective deficit in orientation discrimination, and implies that neglect disrupts specific feature representations. That is, the effects of neglect on visual search are not only attentional but also perceptual.

A mechanical cell disruption microfluidic platform based on an on-chip micropump.

PubMed

Cheng, Yinuo; Wang, Yue; Wang, Zhiyuan; Huang, Liang; Bi, Mingzhao; Xu, Wenxiao; Wang, Wenhui; Ye, Xiongying

2017-03-01

Cell disruption plays a vital role in detection of intracellular components which contain information about genetic and disease characteristics. In this paper, we demonstrate a novel microfluidic platform based on an on-chip micropump for mechanical cell disruption and sample transport. A 50  μ l cell sample can be effectively lysed through on-chip multi-disruption in 36 s without introducing any chemical agent and suffering from clogging by cellular debris. After 30 cycles of circulating disruption, 80.6% and 90.5% cell disruption rates were achieved for the HEK293 cell sample and human natural killer cell sample, respectively. Profiting from the feature of pump-on-chip, the highly integrated platform enables more convenient and cost-effective cell disruption for the analysis of intracellular components.

A mechanical cell disruption microfluidic platform based on an on-chip micropump

PubMed Central

Cheng, Yinuo; Wang, Yue; Wang, Zhiyuan; Bi, Mingzhao; Xu, Wenxiao; Ye, Xiongying

2017-01-01

Cell disruption plays a vital role in detection of intracellular components which contain information about genetic and disease characteristics. In this paper, we demonstrate a novel microfluidic platform based on an on-chip micropump for mechanical cell disruption and sample transport. A 50 μl cell sample can be effectively lysed through on-chip multi-disruption in 36 s without introducing any chemical agent and suffering from clogging by cellular debris. After 30 cycles of circulating disruption, 80.6% and 90.5% cell disruption rates were achieved for the HEK293 cell sample and human natural killer cell sample, respectively. Profiting from the feature of pump-on-chip, the highly integrated platform enables more convenient and cost-effective cell disruption for the analysis of intracellular components. PMID:28798848

Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity.

PubMed

Meerlo, Peter; Sgoifo, Andrea; Suchecki, Deborah

2008-06-01

Frequently disrupted and restricted sleep is a common problem for many people in our modern around-the-clock society. In this context, it is an important question how sleep loss affects the stress systems in our bodies since these systems enable us to deal with everyday challenges. Altered activity and reactivity of these systems following insufficient sleep might have serious repercussions for health and well-being. Studies on both humans and rodents have shown that sleep deprivation and sleep restriction are conditions often associated with mild, temporary increases in the activity of the major neuroendocrine stress systems, i.e., the autonomic sympatho-adrenal system and the hypothalamic-pituitary-adrenal axis. Sleep deprivation may not only have a direct activating effect by itself but, in the long run, it may also affect the reactivity of these systems to other stressors and challenges. Although the first signs of alterations in the way people deal with challenges under conditions of restricted sleep appear to be on the level of emotional perception, chronic sleep restriction may ultimately change the fundamental properties of neuroendocrine stress systems as well. Understandably, few controlled studies in humans have been devoted to this topic. Yet, experimental studies in rodents show that chronic sleep restriction may gradually alter neuroendocrine stress responses as well as the central mechanisms involved in the regulation of these responses. Importantly, the available data from studies in laboratory animals suggest that sleep restriction may gradually change certain brain systems and neuroendocrine systems in a manner that is similar to what is seen in stress-related disorders such as depression (e.g., reduced serotonin receptor sensitivity and altered regulation of the hypothalamic-pituitary-adrenal axis). Such data support the view that insufficient sleep, by acting on stress systems, may sensitize individuals to stress-related disorders. Indeed, epidemiological studies suggest that sleep complaints and sleep restriction may be important risk factors for a variety of diseases that are often linked to stress, including cardiovascular diseases and mood disorders.

Meteorological data for four sites at surface-disruption features in Yucca Flat, Nevada Test Site, Nye County, Nevada, 1985-86

USGS Publications Warehouse

Carman, Rita L.

1994-01-01

Surface-disruption features, or craters, resulting from underground nuclear testing at the Nevada Test Site may increase the potential for ground-water recharge in an area that would normally produce little, if any, recharge. This report presents selected meteorological data resulting from a study of two surface-disruption features during May 1985 through June 1986. The data were collected at four adjacent sites in Yucca Flat, about 56 kilometers north of Mercury, Nevada. Three sites (one in each of two craters and one at an undisturbed site at the original land surface) were instrumented to collect meteorological data for calculating bare-soil evaporation. These data include (1) long-wave radiation, (2) short-wave radiation, (3) net radiation, (4) air temperae, and (5) soil surface temperature. Meteorological data also were collected at a weather station at an undisturbed site near the study craters. Data collected at this site include (1) air temperature, (2) relative humidity, (3) wind velocity, and (4) wind direction.

Humans Have Already Increased the Risk of Basin-wide Disruptions to Pacific Rainfall, and the Risk Increases Even If Global Warming is Restricted to the 2oC Paris Target

NASA Astrophysics Data System (ADS)

Power, S.; Delage, F.; Chung, C.; Ye, H.; Murphy, B.

2017-12-01

The El Nino-Southern Oscillation causes major, intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to approximately one year. These disruptions have major impacts on severe weather, agricultural production, ecosystems, streamflow, and disease within and adjacent to the Pacific, and in many countries beyond. The frequency with which major disruptions to Pacific rainfall occur has been projected to increase over the 21st century, in response to global warming caused by large 21st century greenhouse gas emissions. Here we use the latest generation of climate models to show that the risk of disruption has already increased, and that humans may have contributed to the severity of the 1982/83 and 1997/98 events. We also demonstrate - for the first time - that although marked and sustained reductions in 21st century anthropogenic greenhouse gas emissions can greatly moderate the likelihood of major disruption, elevated risk of occurrence appears locked in now, and for at least the remainder of the 21st century. DOI: 10.1038/ncomms14368

Multiple Antibiotic Resistance Plasmids Allow Scalable,
PCR-Mediated DNA Manipulation and Near-Zero Background Cloning

PubMed Central

Arnak, Remigiusz; Altun, Burcin; Tosato, Valentina

2016-01-01

Summary We have constructed two plasmids that can be used for cloning as templates for PCR- -based gene disruption, mutagenesis and the construction of DNA chromosome translocation cassettes. To our knowledge, these plasmids are the first vectors that confer resistance to ampicillin, kanamycin and hygromycin B in bacteria, and to geneticin (G418) and hygromycin B in Saccharomyces cerevisiae simultaneously. The option of simultaneously using up to three resistance markers provides a highly stringent control of recombinant selection and the almost complete elimination of background resistance, while unique restriction sites allow easy cloning of chosen genetic material. Moreover, we successfully used these new vectors as PCR templates for the induction of chromosome translocation in budding yeast by the bridge-induced translocation system. Cells in which translocation was induced carried chromosomal rearrangements as expected and exhibited resistance to both, G418 and hygromycin B. These features make our constructs very handy tools for many molecular biology applications. PMID:27956856

Single Molecule Analysis of Serotonin Transporter Regulation Using Quantum Dots

NASA Astrophysics Data System (ADS)

Chang, Jerry; Tomlinson, Ian; Warnement, Michael; Ustione, Alessandro; Carneiro, Ana; Piston, David; Blakely, Randy; Rosenthal, Sandra

2011-03-01

For the first time, we implement a novel, single molecule approach to define the localization and mobility of the brain's major target of widely prescribed antidepressant medications, the serotonin transporter (SERT). SERT labeled with single quantum dot (Qdot) revealed unsuspected features of transporter mobility with cholesterol-enriched membrane microdomains (often referred to as ``lipid rafts'') and cytoskeleton network linked to transporter activation. We document two pools of surface SERT proteins defined by their lateral mobility, one that exhibits relatively free diffusion in the plasma membrane and a second that displays significantly restricted mobility and localizes to cholesterol-enriched microdomains. Diffusion model prediction and instantaneous velocity analysis indicated that stimuli that act through p38 MAPK-dependent signaling pathways to activate SERT trigger rapid SERT movements within membrane microdomains. Cytoskeleton disruption showed that SERT lateral mobility behaves a membrane raft-constrained, cytoskeleton-associated manner. Our results identify an unsuspected aspect of neurotransmitter transporter regulation that we propose reflects the dissociation of inhibitory, SERT-associated cytoskeletal anchors.

Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration.

PubMed

Paris, Nicole D; Soroka, Andrew; Klose, Alanna; Liu, Wenxuan; Chakkalakal, Joe V

2016-11-18

Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of Smad4 , the downstream cofactor for canonical TGFβ superfamily signaling, and the target Id1 in aged SCs and MPs during regeneration. Specific deletion of Smad4 in adult mouse SCs led to increased propensity for terminal myogenic commitment connected to impaired proliferative potential. Furthermore, SC-specific Smad4 disruption compromised adult skeletal muscle regeneration. Finally, loss of Smad4 in aged SCs did not promote aged skeletal muscle regeneration. Therefore, SC-specific reduction of Smad4 is a feature of aged regenerating skeletal muscle and Smad4 is a critical regulator of SC and MP amplification during skeletal muscle regeneration.

Genome of the Actinomycete Plant Pathogen Clavibacter michiganensis subsp. sepedonicus Suggests Recent Niche Adaptation▿ †

PubMed Central

Bentley, Stephen D.; Corton, Craig; Brown, Susan E.; Barron, Andrew; Clark, Louise; Doggett, Jon; Harris, Barbara; Ormond, Doug; Quail, Michael A.; May, Georgiana; Francis, David; Knudson, Dennis; Parkhill, Julian; Ishimaru, Carol A.

2008-01-01

Clavibacter michiganensis subsp. sepedonicus is a plant-pathogenic bacterium and the causative agent of bacterial ring rot, a devastating agricultural disease under strict quarantine control and zero tolerance in the seed potato industry. This organism appears to be largely restricted to an endophytic lifestyle, proliferating within plant tissues and unable to persist in the absence of plant material. Analysis of the genome sequence of C. michiganensis subsp. sepedonicus and comparison with the genome sequences of related plant pathogens revealed a dramatic recent evolutionary history. The genome contains 106 insertion sequence elements, which appear to have been active in extensive rearrangement of the chromosome compared to that of Clavibacter michiganensis subsp. michiganensis. There are 110 pseudogenes with overrepresentation in functions associated with carbohydrate metabolism, transcriptional regulation, and pathogenicity. Genome comparisons also indicated that there is substantial gene content diversity within the species, probably due to differential gene acquisition and loss. These genomic features and evolutionary dating suggest that there was recent adaptation for life in a restricted niche where nutrient diversity and perhaps competition are low, correlated with a reduced ability to exploit previously occupied complex niches outside the plant. Toleration of factors such as multiplication and integration of insertion sequence elements, genome rearrangements, and functional disruption of many genes and operons seems to indicate that there has been general relaxation of selective pressure on a large proportion of the genome. PMID:18192393

The Female Athlete Triad

ERIC Educational Resources Information Center

Sherman, Roberta Trattner; Thompson, Ron A.

2004-01-01

The Female Athlete Triad is a syndrome of the interrelated components of disordered eating, amenorrhea, and osteoporosis. Sometimes inadvertently, but more often by willful dietary restriction, many female athletes do not ingest sufficient calories to adequately fuel their physical or sport activities, which can disrupt menstrual functioning,…

Framework for resilience in material supply chains, with a case study from the 2010 Rare Earth Crisis.

PubMed

Sprecher, Benjamin; Daigo, Ichiro; Murakami, Shinsuke; Kleijn, Rene; Vos, Matthijs; Kramer, Gert Jan

2015-06-02

In 2010, Chinese export restrictions caused the price of the rare earth element neodymium to increase by a factor of 10, only to return to almost normal levels in the following months. This despite the fact that the restrictions were not lifted. The significant price peak shows that this material supply chain was only weakly resistant to a major supply disruption. However, the fact that prices rapidly returned to lower levels implies a certain resilience. With the help of a novel approach, based on resilience theory combined with a material flow analysis (MFA) based representation of the neodymium magnet (NdFeB) supply chain, we show that supply chain resilience is composed of various mechanisms, including (a) resistance, (b) rapidity, and (c) flexibility, that originate from different parts of the supply chain. We make recommendations to improve the capacity of the NdFeB system to deal with future disruptions and discuss potential generalities for the resilience of other material supply chains.

Muscle mitochondrial density after exhaustive exercise in dogs - Prolonged restricted activity and retraining

NASA Technical Reports Server (NTRS)

Nazar, K.; Greenleaf, J. E.; Philpott, D.; Pohoska, E.; Olszewska, K.; Kaciuba-Uscilko, H.

1993-01-01

The effect of exhaustive treadmill exercise on mitochondrial density (MD) and ultrastructural changes in quadriceps femoris muscle was studied in 7 normal, healthy, male mongrel dogs before and after restricted activity (RA) and following a subsequent 2-month exercise retraining period. Mean time to exhaustion in the 2-month group decreased from 177 +/- 11 min before to 90 +/- 16 min after RA; retraining increased tolerance to 219 +/- 36 min above the pre-RA and 143 percent above the post-RA time. Post-RA exhaustion time in the 5-months group was 25 and 45 min. Muscle samples taken after RA showed abnormalities indicative of degeneration, which were reversed by retraining. Resting MD decreased from a control level of 27.8 percent to 14.7 percent and 16.3 percent, and was restored to 27.1 percent after retraining. Exhaustive exercise caused an increase in MD under control conditions and after RA, but not following retraining. Disruption of mitochondria after exercise was evident after 5-month confinement. Factors causing mitochondrial changes and eventually their disruption during exercise after restricted activity are not related as much to the state of fatigue as to the pre-exercise quality of the muscle modified by disease or training.

Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging

PubMed Central

Arum, Oge; Saleh, Jamal; Boparai, Ravneet; Turner, Jeremy; Kopchick, John; Khardori, Romesh; Bartke, Andrzej

2014-01-01

The correlation of physiological sensitivity to insulin ( vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice. PMID:25789159

Necroplanetology: Disrupted Planetary Material Transiting WD 1145+017

NASA Astrophysics Data System (ADS)

Manideep Duvvuri, Girish; Redfield, Seth; Veras, Dimitri

2018-06-01

The WD 1145+017 system shows irregular transit features that are consistent with the tidal disruption of differentiated asteroids with bulk densities < 4 g cm-3 and bulk masses < 1021 kg. We use the open-source N-body code REBOUND to simulate this disruption with different internal structures: varying the core volume fraction, mantle/core density ratio, and the presence/absence of a thin low-density crust. We show that these parameters have observationally distinguishable effects on the transit light curve as the asteroid is disrupted and fit the simulation-generated lightcurves to data. We find that an asteroid with a low core fraction, low mantle/density ratio, and without a crust is most consistent with the A1 feature present for multiple weeks circa April 2017. This combination of observations and simulations to study the interior structure and chemistry of exoplanetary bodies via their destruction in action is an early example of necroplanetology, a field that will hopefully grow with the discovery of other systems like WD 1145+017.

Face Inversion Disproportionately Impairs the Perception of Vertical but Not Horizontal Relations between Features

ERIC Educational Resources Information Center

Goffaux, Valerie; Rossion, Bruno

2007-01-01

Upside-down inversion disrupts the processing of spatial relations between the features of a face, while largely preserving local feature analysis. However, recent studies on face inversion failed to observe a clear dissociation between relational and featural processing. To resolve these discrepancies and clarify how inversion affects face…

ISOTONIC DOSE-RESPONSE MODELING OF THE TRANSCRIPTIONAL RESPONSE OF RAT CEREBROCORTICAL TISSUE AFTER ACUTE PYRETHROID EXPOSURE IN VIVO.

EPA Science Inventory

Pyrethroid insecticides produce neurotoxicity in mammals by disrupting ion channel function in excitable nerve membranes. Pyrethroid use has increased as regulatory guidelines have restricted the use of other pesticide classes. Currently, a sensitive, specific, and dose-responsiv...

BRACEROS, MEXICO, AND FOREIGN TRADE.

ERIC Educational Resources Information Center

1966

CRITICISM OF GOVERNMENTAL POLICY RESTRICTING USE OF FOREIGN CONTRACT WORKERS ON AMERICAN FARMS IN 1965 EXPRESSES THREE POSSIBILITIES -- (1) A SEVERE DISRUPTION OF DOMESTIC FRUIT AND VEGETABLE PRODUCTION, (2) AN INCREASE OF AMERICAN INVESTMENT IN FOREIGN, PARTICULARLY MEXICAN, AGRICULTURAL PRODUCTION, AND (3) A LOSS OF UNITED STATES EXPORT MARKET…

Interval Timing Is Preserved Despite Circadian Desynchrony in Rats: Constant Light and Heavy Water Studies.

PubMed

Petersen, Christian C; Mistlberger, Ralph E

2017-08-01

The mechanisms that enable mammals to time events that recur at 24-h intervals (circadian timing) and at arbitrary intervals in the seconds-to-minutes range (interval timing) are thought to be distinct at the computational and neurobiological levels. Recent evidence that disruption of circadian rhythmicity by constant light (LL) abolishes interval timing in mice challenges this assumption and suggests a critical role for circadian clocks in short interval timing. We sought to confirm and extend this finding by examining interval timing in rats in which circadian rhythmicity was disrupted by long-term exposure to LL or by chronic intake of 25% D 2 O. Adult, male Sprague-Dawley rats were housed in a light-dark (LD) cycle or in LL until free-running circadian rhythmicity was markedly disrupted or abolished. The rats were then trained and tested on 15- and 30-sec peak-interval procedures, with water restriction used to motivate task performance. Interval timing was found to be unimpaired in LL rats, but a weak circadian activity rhythm was apparently rescued by the training procedure, possibly due to binge feeding that occurred during the 15-min water access period that followed training each day. A second group of rats in LL were therefore restricted to 6 daily meals scheduled at 4-h intervals. Despite a complete absence of circadian rhythmicity in this group, interval timing was again unaffected. To eliminate all possible temporal cues, we tested a third group of rats in LL by using a pseudo-randomized schedule. Again, interval timing remained accurate. Finally, rats tested in LD received 25% D 2 O in place of drinking water. This markedly lengthened the circadian period and caused a failure of LD entrainment but did not disrupt interval timing. These results indicate that interval timing in rats is resistant to disruption by manipulations of circadian timekeeping previously shown to impair interval timing in mice.

Disruption of direct 3D telomere-TRF2 interaction through two molecularly disparate mechanisms is a hallmark of primary Hodgkin and Reed-Sternberg cells.

PubMed

Knecht, Hans; Johnson, Nathalie A; Haliotis, Tina; Lichtensztejn, Daniel; Mai, Sabine

2017-07-01

In classical Hodgkin's lymphoma (cHL), specific changes in the 3D telomere organization cause progression from mononuclear Hodgkin cells (H) to multinucleated Reed-Sternberg cells (RS). In a post-germinal center B-cell in vitro model, permanent latent membrane protein 1 (LMP1) expression, as observed in Epstein-Barr virus (EBV)-associated cHL, results in multinuclearity and complex chromosomal aberrations through downregulation of key element of the shelterin complex, the telomere repeat binding factor 2 (TRF2). Thus, we hypothesized that the three-dimensional (3D) telomere-TRF2 interaction was progressively disturbed during transition from H to RS cells. To this end, we developed and applied for the first time a combined quantitative 3D TRF2-telomere immune fluorescent in situ hybridization (3D TRF2/Telo-Q-FISH) technique to monolayers of primary H and RS cells, and adjacent benign internal control lymphocytes of lymph node biopsy suspensions from diagnostic lymph node biopsies of 14 patients with cHL. We show that H and RS cells are characterized by two distinct patterns of disruption of 3D telomere-TRF2 interaction. Disruption pattern A is defined by massive attrition of telomere signals and a considerable increase of TRF2 signals not associated with telomeres. This pattern is restricted to EBV-negative cHL. Disruption pattern B is defined by telomere de-protection due to an impressive loss of TRF2 signals, physically linked to telomeres. This pattern is typical of, but is not restricted to, LMP1+EBV-associated cHL. In the disruption pattern B group, so-called 'ghost' end-stage RS cells, void of both TRF2 and telomere signals, were identified, whether or not associated with EBV. Our findings demonstrate that two molecularly disparate mechanisms converge on the level of 3D telomere-TRF2 interaction in the formation of RS cells.

Structure of the runaway electron loss during induced disruptions in TEXTOR

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

Wongrach, K.; Finken, K. H.; Willi, O.

2015-10-15

The loss of runaway electrons during an induced disruption is recorded by a synchrotron imaging technique using a fast infrared CCD camera. The loss is predominantly diffuse. During the “spiky-loss phase”, when the runaway beam moves close to the wall, a narrow channel between the runaway column and a scintillator probe is formed and lasts until the runaway beam is terminated. In some cases, the processed images show a stripe pattern at the plasma edge. A comparison between the MHD dominated disruptions and the MHD-free disruption is performed. A new mechanism of plasma disruptions with the runaway electron generation andmore » a novel model which reproduces many characteristic features of the plasma beam evolution during a disruption is briefly described.« less

Disruption of Smad4 Expression in T Cells Leads to IgA Nephropathy-Like Manifestations

PubMed Central

Yamashita, Michifumi; Choi, Sung Hee; Tomino, Yasuhiko; Letterio, John J.; Emancipator, Steven N.

2013-01-01

The link between glomerular IgA nephropathy (IgAN) and T helper 2 (Th2) response has been implicated, however, the mechanisms are poorly defined because of the lack of an appropriate model. Here we report a novel murine model characterized by lineage-restricted deletion of the gene encoding MAD homologue 4 (Smad4) in T cells (Smad4co/co;Lck-cre). Loss of Smad4 expression in T cells results in overproduction of Th2 cytokines and high serum IgA levels. We found that Smad4co/co;Lck-cre mice exhibited massive glomerular IgA deposition, increased albumin creatinine ratio, aberrant glycosylated IgA, IgA complexed with IgG1 and IgG2a, and polymeric IgA, all known features of IgAN in humans. Furthermore, we examined the β1, 4-galactosyltransferases (β4GalT) enzyme which is involved in the synthesis of glycosylated murine IgA, and we found reduced β4GalT2 and β4GalT4 mRNA levels in B cells. These findings indicate that Smad4co/co;Lck-cre mice could be a useful model for studying the mechanisms between IgAN and Th2 response, and further, disruption of Smad4-dependent signaling in T cells may play an important role in the pathogenesis of human IgAN and contributing to a Th2 T cell phenotype. PMID:24223846

Electronic Combat in Space: Examining the Legality of Fielding a Space-Based Disruptive Electromagnetic Jamming System

DTIC Science & Technology

2007-06-15

particles ( asteroids and meteoroids), energetic charged particles (ions, protons, electrons, etc.), and electromagnetic and ionizing radiation (x-rays...These protocols include a ban on Non-Detectable Fragments; restrictions on the use of Mines , Booby Traps, and Other Devices; prohibitions on certain...

Nigeria Country Analysis Brief

EIA Publications

2016-01-01

Nigeria is currently the largest oil producer in Africa and was the world's fourth-largest exporter of LNG in 2015. Nigeria's oil production is hampered by instability and supply disruptions, while its natural gas sector is restricted by the lack of infrastructure to commercialize natural gas that is currently flared (burned off).

The Florida Child Welfare Behavior Analysis Services Program

ERIC Educational Resources Information Center

Stoutimore, Michael R.; Williams, Catherine E.; Neff, Bryon; Foster, Margie

2008-01-01

Abuse, neglect, or both often result in removing children from their homes and placing them in foster care. As a result of these experiences, many children learn unhealthy behaviors. These "behavioral challenges" often lead to a cycle of multiple placement disruptions and progressively more restrictive placements. The philosophy,…

Review: Neuroinflammation in intrauterine growth restriction.

PubMed

Wixey, Julie A; Chand, Kirat K; Colditz, Paul B; Bjorkman, S Tracey

2017-06-01

Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tidal Disruptions of Main Sequence Stars: Inferences from the Composition of the Fallback Material

NASA Astrophysics Data System (ADS)

Gallegos, Monica; Law-Smith, Jamie; Ramírez-Ruiz, Enrico

2018-01-01

We study black holes within galactic nuclei by analyzing the motions of stars swarming around them. When the conditions are right we can observe and analyze characteristics of the black hole’s destructive power. In this paper we analyze the case when a star lurks close enough to these gravity giants to be ripped apart. After disruption, material that is bound to the supermassive black hole accretes onto it and creates a powerful flare. The standard light curve of these flares is classically described by a t-5/3 power law in time. In this paper we adopt an analytical method to calculate the fallback rate and use Modules for Experiments in Stellar Astrophysics (MESA) to study the disruption of stars with masses between 0.8-3 M⊙ at various evolutionary stages. We move beyond the analysis of the light curve and peer into the interiors of the disrupted stars by studying the compositional features of the fallback material. With this work we can begin to constrain the nature of the stars that are tidally disrupted. We find that most stars develop nitrogen (14N) enhancements with carbon (12C) and oxygen (16O) depletion relative to solar abundance and find that these features are more pronounced for higher mass stars. We also find that these features become prominent only after the time of maximum fallback rate, tpeak, and are observed to appear at earlier times for stars of increasing mass. This work provides a clear spectral method to help classify the transient events we observe at the centers of galaxies.

"Stain in life": The meaning of urinary incontinence in the context of Muslim postmenopausal women through hermeneutic phenomenology.

PubMed

Hamid, Tengku Aizan; Pakgohar, Minoo; Ibrahim, Rahimah; Dastjerdi, Marzieh Vahid

2015-01-01

UI is a worldwide chronic condition among postmenopausal women. Little is known about the meaning of lived experiences of urinary incontinence of these women's viewpoints in their context. The aim of this study was to illuminate the experience of Muslim community-dwelling postmenopausal women who were living with urinary incontinence (UI). Seventeen women with UI (range: 52-68 years) who had experienced it for more than ten years were interviewed. A phenomenological hermeneutic method was used to analyze and interpret the interview texts. The women's experiences of living with urinary incontinence have been presented in terms of three main themes: disruption of normal functioning, self-imposed restriction, and feelings of despair. Disruption of normal functioning meant emotional, spiritual, physical, and daily life disruption. Self-imposed restriction meant suppression of delights and needs and avoidance of social interactions. Feelings of despair referred to predictions of a bad and dark future of living with urinary incontinence, ambiguity, and hopelessness. The meaning of living with UI has been considered a 'stain in life'. Health care providers should be familiar with the different manifestations of urinary incontinence for early diagnosis and prevention of the negative effects of this condition to improve quality of life. In addition, symbolic interactionism theory can help health care providers to understand the meaning of urinary incontinence for women. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hepatic autophagy contributes to the metabolic response to dietary protein restriction.

PubMed

Henagan, Tara M; Laeger, Thomas; Navard, Alexandra M; Albarado, Diana; Noland, Robert C; Stadler, Krisztian; Elks, Carrie M; Burk, David; Morrison, Christopher D

2016-06-01

Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number. Importantly, these effects were also associated with an induction of hepatic autophagy. To determine if the induction of autophagy contributes to these metabolic effects, we tested the metabolic response to dietary protein restriction in BCL2-AAA mice, which bear a genetic mutation that impairs autophagy induction. Interestingly, BCL2-AAA mice exhibit exaggerated responses in terms of both food intake and energy expenditure, whereas the effects of protein restriction on hepatic metabolism were significantly blunted. These data demonstrate that restriction of dietary protein is sufficient to trigger hepatic autophagy, and that disruption of autophagy significantly alters both hepatic and whole animal metabolic response to dietary protein restriction. Copyright © 2016 Elsevier Inc. All rights reserved.

BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis.

PubMed

Gupta, Sunny; Zhu, Hao; Zon, Leonard I; Evans, Todd

2006-06-01

The bone morphogenetic protein (BMP) signaling pathway is essential during gastrulation for the generation of ventral mesoderm, which makes it a challenge to define functions for this pathway at later stages of development. We have established an approach to disrupt BMP signaling specifically in lateral mesoderm during somitogenesis, by targeting a dominant-negative BMP receptor to Lmo2+ cells in developing zebrafish embryos. This results in expansion of hematopoietic and endothelial cells, while restricting the expression domain of the pronephric marker pax2.1. Expression of a constitutively active receptor and transplantation experiments were used to confirm that BMP signaling in lateral mesoderm restricts subsequent hemato-vascular development. The results show that the BMP signaling pathway continues to function after cells are committed to a lateral mesoderm fate, and influences subsequent lineage decisions by restricting hemato-vascular fate in favor of pronephric development.

The Effects of Sleep Continuity Disruption on Positive Mood and Sleep Architecture in Healthy Adults

PubMed Central

Finan, Patrick H.; Quartana, Phillip J.; Smith, Michael T.

2015-01-01

Objective: The purpose of this study was to test an experimental model of the effects of sleep continuity disturbance on sleep architecture and positive mood in order to better understand the mechanisms linking insomnia and depression. Design: Participants were randomized to receive 3 consecutive nights of sleep continuity disruption via forced nocturnal awakenings (FA, n = 21), or one of two control conditions: restricted sleep opportunity (RSO, n = 17) or uninterrupted sleep (US, n = 24). Setting: The study was set in an inpatient clinical research suite. Participants: Healthy, good-sleeping men and women were included. Measurement and Results: Polysomnography was used to measure sleep architecture, and mood was assessed via self-report each day. Compared to restricted sleep opportunity controls, forced awakenings subjects had significantly less slow wave sleep (P < 0.05) after the first night of sleep deprivation, and significantly lower positive mood (P < 0.05) after the second night of sleep deprivation. The differential change in slow wave sleep statistically mediated the observed group differences in positive mood (P = 0.002). Conclusions: To our knowledge, this is the first human experimental study to demonstrate that, despite comparable reductions in total sleep time, partial sleep loss from sleep continuity disruption is more detrimental to positive mood than partial sleep loss from delaying bedtime, even when controlling for concomitant increases in negative mood. With these findings, we provide temporal evidence in support of a putative biologic mechanism (slow wave sleep deficit) that could help explain the strong comorbidity between insomnia and depression. Citation: Finan PH, Quartana PJ, Smith MT. The effects of sleep continuity disruption on positive mood and sleep architecture in healthy adults. SLEEP 2015;38(11):1735–1742. PMID:26085289

Intrauterine growth restriction decreases nuclear factor-kappa B signaling in fetal pulmonary artery endothelial cells of fetal sheep.

PubMed

Dodson, R Blair; Powers, Kyle N; Gien, Jason; Rozance, Paul J; Seedorf, Gregory J; Astling, David; Jones, Kenneth Lloyd; Crombleholme, Timothy M; Abman, Steven H; Alvira, Cristina M

2018-05-03

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis, however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The nuclear factor-kappa-B (NFκB) pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NFκB-regulated pro-angiogenic targets in fetal PAEC. PAECs were isolated from lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NFκB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4α1 and laminin α4, components of the basement membrane and putative NFκB targets. In comparison with controls: (i) immunostaining of active NFκB complexes; (ii) NFκB-DNA binding; (iii) baseline expression of NFκB subunits, p65 and p50; and (iv) LPS-mediated inducible activation of NFκB signaling were decreased in IUGR PAEC. Although pharmacologic NFκB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NFκB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NFκB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NFκB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR.

Quenching and disruption of lunar KREEP lava flows by impacts

NASA Technical Reports Server (NTRS)

Ryder, Graham

1988-01-01

The results of a reexamination of petrography of the Apollo 15 KREEP basalts are reported. Several of the basalts contain yellow residual glasses which cross-cut the crystallized phases; some show more extreme disruption. The features of the glasses appear to be compatible only with impact disruption, ejection, and quenching from actively crystallizing flows, indicating a high impact flux immediately after the impact that formed the Imbrium basin. No other example of impacts into active lava flows is known in the solar system.

Statistical mechanics of unsupervised feature learning in a restricted Boltzmann machine with binary synapses

NASA Astrophysics Data System (ADS)

Huang, Haiping

2017-05-01

Revealing hidden features in unlabeled data is called unsupervised feature learning, which plays an important role in pretraining a deep neural network. Here we provide a statistical mechanics analysis of the unsupervised learning in a restricted Boltzmann machine with binary synapses. A message passing equation to infer the hidden feature is derived, and furthermore, variants of this equation are analyzed. A statistical analysis by replica theory describes the thermodynamic properties of the model. Our analysis confirms an entropy crisis preceding the non-convergence of the message passing equation, suggesting a discontinuous phase transition as a key characteristic of the restricted Boltzmann machine. Continuous phase transition is also confirmed depending on the embedded feature strength in the data. The mean-field result under the replica symmetric assumption agrees with that obtained by running message passing algorithms on single instances of finite sizes. Interestingly, in an approximate Hopfield model, the entropy crisis is absent, and a continuous phase transition is observed instead. We also develop an iterative equation to infer the hyper-parameter (temperature) hidden in the data, which in physics corresponds to iteratively imposing Nishimori condition. Our study provides insights towards understanding the thermodynamic properties of the restricted Boltzmann machine learning, and moreover important theoretical basis to build simplified deep networks.

Characterizing Caregiver Responses to Restricted and Repetitive Behaviors in Toddlers with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Harrop, Clare; Gulsrud, Amanda; Shih, Wendy; Hovsepyan, Lilit; Kasari, Connie

2016-01-01

Restricted and repetitive behaviors are a core feature of autism spectrum disorder. This descriptive study documented the presence of restricted and repetitive behaviors in 85 toddlers with autism spectrum disorder as they interacted with their caregiver in a play interaction. For each child restricted and repetitive behavior, a caregiver…

Control of Visually Guided Saccades in Multiple Sclerosis: Disruption to Higher-Order Processes

ERIC Educational Resources Information Center

Fielding, Joanne; Kilpatrick, Trevor; Millist, Lynette; White, Owen

2009-01-01

Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with more salient deficits reflecting tissue damage within brainstem and cerebellar circuits. However, MS may also result in disruption to higher level or cognitive control processes governing eye movement, including attentional processes that enhance the neural processing…

Orientation-sensitivity to facial features explains the Thatcher illusion.

PubMed

Psalta, Lilia; Young, Andrew W; Thompson, Peter; Andrews, Timothy J

2014-10-09

The Thatcher illusion provides a compelling example of the perceptual cost of face inversion. The Thatcher illusion is often thought to result from a disruption to the processing of spatial relations between face features. Here, we show the limitations of this account and instead demonstrate that the effect of inversion in the Thatcher illusion is better explained by a disruption to the processing of purely local facial features. Using a matching task, we found that participants were able to discriminate normal and Thatcherized versions of the same face when they were presented in an upright orientation, but not when the images were inverted. Next, we showed that the effect of inversion was also apparent when only the eye region or only the mouth region was visible. These results demonstrate that a key component of the Thatcher illusion is to be found in orientation-specific encoding of the expressive features (eyes and mouth) of the face. © 2014 ARVO.

Beliefs About the Causal Structure of the Self-Concept Determine Which Changes Disrupt Personal Identity.

PubMed

Chen, Stephanie Y; Urminsky, Oleg; Bartels, Daniel M

2016-10-01

Personal identity is an important determinant of behavior, yet how people mentally represent their self-concepts and their concepts of other people is not well understood. In the current studies, we examined the age-old question of what makes people who they are. We propose a novel approach to identity that suggests that the answer lies in people's beliefs about how the features of identity (e.g., memories, moral qualities, personality traits) are causally related to each other. We examined the impact of the causal centrality of a feature, a key determinant of the extent to which a feature defines a concept, on judgments of identity continuity. We found support for this approach in three experiments using both measured and manipulated causal centrality. For judgments both of one's self and of others, we found that some features are perceived to be more causally central than others and that changes in such causally central features are believed to be more disruptive to identity.

Gene disruption in Salmonella typhimurim by modified λ Red disruption system.

PubMed

Ahani Azari, A; Zahraei Salehi, T; Nayeri Fasaei, B; Alebouyeh, M

2015-01-01

There are many techniques to knock out directed genes in bacteria, some of which have been described in Salmonella species. In this study, a combination of SOEing PCR method and the λ Red disruption system were used to disrupt phoP gene in wild type and standard strains of Salmonella typhimurium. Three standards PCR and one fusion PCR reactions were performed to construct a linear DNA including upstream and downstream of phoP gene and Kanamycin cassette. As a template plasmid, we used pKD4 which carries kanamycin gene flanked by FRT (FLP recognition target) sites. The resulting construct was electroporated into prepared competent cells of S. typhimurium. The transformants colonies related to the standard strain appeared on the LB-Km-agar plates after incubation, but there was no colony on LB-Km-agar plates corresponding to the wild type strain. The failure in transformation of the wild type strain may be because of inflexibility of the λ Red disruption system in this strain or its unique restriction-modification system. However, by this construct we are able to generate phoP mutant in many of the Salmonella species due to high homology of the phoP gene which exists in different species.

Identification of Chemical Features Linked to Thyroperoxidase ...

EPA Pesticide Factsheets

Disruption of maternal serum thyroid hormone (TH) adversely affects fetal neurodevelopment. Therefore, assay development within the US EPA ToxCast program is ongoing to enable screening for chemicals that may disrupt TH, in support of the Endocrine Disruption Screening Program (EDSP21). The AUR-TPO assay was recently developed to screen >1,000 ToxCast chemicals for potential thyroperoxidase (TPO) inhibition activity. TPO is critical for TH synthesis and is a known target of thyroid-disrupting chemicals. The bioactivity results from the AUR-TPO assay were used to identify chemical substructures associated with in vitro TPO inhibition. Substructure profiles were generated for each chemical in the ToxCast test set using the publicly-available ToxPrint 2.0 chemotypes. Chemotypes enriched among the putative TPO inhibitors were identified using a cumulative hypergeometric probability (p < 0.01). Of the total 729 chemotypes evaluated, 31 were overrepresented among TPO inhibitors. Examination of those 31 chemotypes revealed four basic pharmacophores that accounted for 70% of the ToxCast chemicals active in the AUR-TPO assay: aromatic alcohols, aromatic amines, thiocarbonyls and phosphothioates. Chemico-structural analysis of AUR-TPO screening results enabled the identification of chemical features that likely drive TPO inhibition in the AUR-TPO assay. This highlights the potential to identify thyroid-disrupting chemicals in silico using structural alerts identified by

Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight

NASA Technical Reports Server (NTRS)

Dinges, David F.

1999-01-01

This project is concerned with identifying ways to prevent neurobehavioral and physical deterioration due to inadequate sleep in astronauts during long-duration manned space flight. The performance capability of astronauts during extended-duration space flight depends heavily on achieving recovery through adequate sleep. Even with appropriate circadian alignment, sleep loss can erode fundamental elements of human performance capability including vigilance, cognitive speed and accuracy, working memory, reaction time, and physiological alertness. Adequate sleep is essential during manned space flight not only to ensure high levels of safe and effective human performance, but also as a basic regulatory biology critical to healthy human functioning. There is now extensive objective evidence that astronaut sleep is frequently restricted in space flight to averages between 4 hr and 6.5 hr/day. Chronic sleep restriction during manned space flight can occur in response to endogenous disturbances of sleep (motion sickness, stress, circadian rhythms), environmental disruptions of sleep (noise, temperature, light), and curtailment of sleep due to the work demands and other activities that accompany extended space flight operations. The mechanism through which this risk emerges is the development of cumulative homeostatic pressure for sleep across consecutive days of inadequate sleep. Research has shown that the physiological sleepiness and performance deficits engendered by sleep debt can progressively worsen (i.e., accumulate) over consecutive days of sleep restriction, and that sleep limited to levels commonly experienced by astronauts (i.e., 4 - 6 hr per night) for as little as 1 week, can result in increased lapses of attention, degradation of response times, deficits in complex problem solving, reduced learning, mood disturbance, disruption of essential neuroendocrine, metabolic, and neuroimmune responses, and in some vulnerable persons, the emergence of uncontrolled sleep attacks. The prevention of cumulative performance deficits and neuroendocrine disruption from sleep restriction during extended duration space flight involves finding the most effective ways to obtain sleep in order to maintain the high-level cognitive and physical performance functions required for manned space flight. There is currently a critical deficiency in knowledge of the effects of how variations in sleep duration and timing relate to the most efficient return of performance per unit time invested in sleep during long-duration missions, and how the nature of sleep physiology (i.e., sleep stages, sleep electroencephalographic [EEG] power spectral analyses) change as a function of sleep restriction and performance degradation. The primary aim of this project is to meet these critical deficiencies through utilization of a response surface experimental paradigm, testing in a dose-response manner, varying combinations of sleep duration and timing, for the purpose of establishing how to most effectively limit the cumulative adverse effects on human performance and physiology of chronic sleep restriction in space operations.

Sleep restriction undermines cardiovascular adaptation during stress, contingent on emotional stability.

PubMed

Lü, Wei; Hughes, Brian M; Howard, Siobhán; James, Jack E

2018-02-01

Sleep loss is associated with increased cardiovascular disease, but physiological mechanisms accounting for this relationship are largely unknown. One possible mechanism is that sleep restriction exerts effects on cardiovascular stress responses, and that these effects vary between individuals. Emotional stability (ES) is a personality trait pertinent to sleep restriction and stress responding. However, no study to date has explored how ES and sleep-restriction interactively affect cardiovascular stress responses or processes of adaptation during stress. The present study sought to investigate the association between ES and impact of sleep restriction on cardiovascular function during stress, with particular regard to the trajectory of cardiovascular function change across time. Ninety female university students completed a laboratory vigilance stress task while undergoing continuous cardiovascular (SBP, DBP, HR, SV, CO, TPR) monitoring, after either a night of partial sleep restriction (40% of habitual sleep duration) or a full night's rest. Individuals high in ES showed stable and adaptive cardiovascular (SBP, SV, CO) responses throughout stress exposure, regardless of sleep. In contrast, individuals low in ES exhibited cardiovascular adaptation during stress exposure while rested, but disrupted adaption while sleep-restricted. These findings suggest that sleep-restriction undermines healthful cardiovascular adaptation to stress for individuals low in ES. Copyright © 2017 Elsevier B.V. All rights reserved.

It takes a tissue to make a tumor: epigenetics, cancer and the microenvironment

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

2001-01-01

How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises its ability to suppress carcinogenesis.

Earthquake damage to transportation systems

USGS Publications Warehouse

McCullough, Heather

1994-01-01

Earthquakes represent one of the most destructive natural hazards known to man. A large magnitude earthquake near a populated area can affect residents over thousands of square kilometers and cause billions of dollars in property damage. Such an event can kill or injure thousands of residents and disrupt the socioeconomic environment for months, sometimes years. A serious result of a large-magnitude earthquake is the disruption of transportation systems, which limits post-disaster emergency response. Movement of emergency vehicles, such as police cars, fire trucks and ambulances, is often severely restricted. Damage to transportation systems is categorized below by cause including: ground failure, faulting, vibration damage, and tsunamis.

12 CFR Appendix A to Part 701 - Federal Credit Union Bylaws

Code of Federal Regulations, 2011 CFR

2011-01-01

... union must explain the reasons for the denial in writing. Section 3. Maintenance of membership share... member who is disruptive to credit union operations may be subject to limitations on services and access to credit union facilities. A credit union that wishes to restrict services to members no longer...

48 CFR 52.212-3 - Offeror Representations and Certifications-Commercial Items.

Code of Federal Regulations, 2012 CFR

2012-10-01

...— (i) To restrict the free flow of unbiased information in Iran; or (ii) To disrupt, monitor, or... End Products: Line Item No.: Country of Origin: (List as necessary) (3) The Government will evaluate... will evaluate offers in accordance with the policies and procedures of FAR Part 25. (2) Buy American...

77 FR 67726 - Department of State: State Department Sanctions Information and Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

... information and freedom of expression in Iran and Syria and is cognizant of the vital importance of providing... information in Iran; or (B) to disrupt, monitor, or otherwise restrict speech of the people of Iran.'' Section... of information and freedom of expression over their networks, to track and monitor the communications...

Using Conservation Systems to Alleviate Soil Compaction in a Southeastern United States Ultisol

USDA-ARS?s Scientific Manuscript database

Coastal Plain soils are prone to compaction and tend to form hardpans which restrict root growth and reduce yields. The adoption of non-inversion deep tillage has been recommended to disrupt compacted soil layers and create an adequate medium for crop development. In spite of its efficacy, increased...

Functional Analytic Psychotherapy (FAP) for Cluster B Personality Disorders: Creating Meaning, Mattering, and Skills

ERIC Educational Resources Information Center

Pankey, Julieann

2012-01-01

There are ten identified personality disorders, broken into three clusters: A, B, and C. Individuals with a cluster B diagnosis may demonstrate marked displays of emotional instability, erratic and disruptive patterns around interpersonal relationships, a myopic and restricted range of affect, a pronounced lack of empathy and insight, barriers…

p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus

PubMed Central

Xia, Shuting; Zhou, Zikai; Leung, Celeste; Zhu, Yuehua; Pan, Xingxiu; Qi, Junxia; Morena, Maria; Hill, Matthew N; Xie, Wei; Jia, Zhengping

2016-01-01

PAK1 inhibitors are known to markedly improve social and cognitive function in several animal models of brain disorders, including autism, but the underlying mechanisms remain elusive. We show here that disruption of PAK1 in mice suppresses inhibitory neurotransmission through an increase in tonic, but not phasic, secretion of endocannabinoids (eCB). Consistently, we found elevated levels of anandamide (AEA), but not 2-arachidonoylglycerol (2-AG) following PAK1 disruption. This increased tonic AEA signaling is mediated by reduced cyclooxygenase-2 (COX-2), and COX-2 inhibitors recapitulate the effect of PAK1 deletion on GABAergic transmission in a CB1 receptor-dependent manner. These results establish a novel signaling process whereby PAK1 upregulates COX-2, reduces AEA and restricts tonic eCB-mediated processes. Because PAK1 and eCB are both critically involved in many other organ systems in addition to the brain, our findings may provide a unified mechanism by which PAK1 regulates these systems and their dysfunctions including cancers, inflammations and allergies. DOI: http://dx.doi.org/10.7554/eLife.14653.001 PMID:27296803

GLUT3 gene expression is critical for embryonic growth, brain development and survival.

PubMed

Carayannopoulos, Mary O; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U

2014-04-01

Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly. Copyright © 2014 Elsevier Inc. All rights reserved.

GLUT3 Gene Expression is Critical for Embryonic Growth, Brain Development and Survival

PubMed Central

Carayannopoulos, Mary O.; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U.

2015-01-01

Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly. PMID:24529979

Daily Eating Patterns and Their Impact on Health and Disease.

PubMed

Zarrinpar, Amir; Chaix, Amandine; Panda, Satchidananda

2016-02-01

Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic. Copyright © 2015. Published by Elsevier Ltd.

Daily Eating Patterns and Their Impact on Health and Disease

PubMed Central

Zarrinpar, Amir; Chaix, Amandine; Panda, Satchidananda

2016-01-01

Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic. PMID:26706567

Resilience of Adapting Networks: Results from a Stylized Infrastructure Model.

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

Beyeler, Walter E.; Vugrin, Eric D.; Forden, Geoffrey Ethan

2015-01-01

Adaptation is believed to be a source of resilience in systems. It has been difficult to measure the contribution of adaptation to resilience, unlike other resilience mechanisms such as restoration and recovery. One difficulty comes from treating adaptation as a deus ex machina that is interjected after a disruption. This provides no basis for bounding possible adaptive responses. We can bracket the possible effects of adaptation when we recognize that it occurs continuously, and is in part responsible for the current system’s properties. In this way the dynamics of the system’s pre-disruption structure provides information about post-disruption adaptive reaction. Seenmore » as an ongoing process, adaptation has been argued to produce “robust-yet-fragile” systems. Such systems perform well under historical stresses but become committed to specific features of those stresses in a way that makes them vulnerable to system-level collapse when those features change. In effect adaptation lessens the cost of disruptions within a certain historical range, at the expense of increased cost from disruptions outside that range. Historical adaptive responses leave a signature in the structure of the system. Studies of ecological networks have suggested structural metrics that pick out systemic resilience in the underlying ecosystems. If these metrics are generally reliable indicators of resilience they provide another strategy for gaging adaptive resilience. To progress in understanding how the process of adaptation and the property of resilience interrelate in infrastructure systems, we pose some specific questions: Does adaptation confer resilience?; Does it confer resilience to novel shocks as well, or does it tune the system to fragility?; Can structural features predict resilience to novel shocks?; Are there policies or constraints on the adaptive process that improve resilience?.« less

Tidal Disruptions of Main-sequence Stars of Varying Mass and Age: Inferences from the Composition of the Fallback Material

NASA Astrophysics Data System (ADS)

Gallegos-Garcia, Monica; Law-Smith, Jamie; Ramirez-Ruiz, Enrico

2018-04-01

We use a simple framework to calculate the time evolution of the composition of the fallback material onto a supermassive black hole arising from the tidal disruption of main-sequence stars. We study stars with masses between 0.8 and 3.0 M ⊙, at evolutionary stages from zero-age main sequence to terminal-age main sequence, built using the Modules for Experiments in Stellar Astrophysics code. We show that most stars develop enhancements in nitrogen (14N) and depletions in carbon (12C) and oxygen (16O) over their lifetimes, and that these features are more pronounced for higher mass stars. We find that, in an accretion-powered tidal disruption flare, these features become prominent only after the time of peak of the fallback rate and appear at earlier times for stars of increasing mass. We postulate that no severe compositional changes resulting from the fallback material should be expected near peak for a wide range of stellar masses and, as such, are unable to explain the extreme helium-to-hydrogen line ratios observed in some TDEs. On the other hand, the resulting compositional changes could help explain the presence of nitrogen-rich features, which are currently only detected after peak. When combined with the shape of the light curve, the time evolution of the composition of the fallback material provides a clear method to help constrain the nature of the disrupted star. This will enable a better characterization of the event by helping break the degeneracy between the mass of the star and the mass of the black hole when fitting tidal disruption light curves.

Positive behavioral support planning in the inpatient treatment of severe disruptive behaviors: A description of service features.

PubMed

Hamlett, Nakia M; Carr, Erika R; Hillbrand, Marc

2016-05-01

Positive behavior support (PBS) plans are increasingly used on inpatient units to assess and treat serious and dangerous behaviors displayed by patients with serious psychiatric impairment. A contemporary extension of traditional applied behavior analytic procedures, PBS plans integrate theories from several domains with perspectives on community psychology, positive psychology, and recovery-oriented care. Because there is little evidence to suggest that more invasive, punitive disciplinary strategies lead to long-term positive behavioral change (Parkes, 1996), PBS plans have emerged as an alternative to the use of seclusion and restraint or other forms of restrictive measures typically used on inpatient psychiatric units (Hammer et al., 2011). Moreover, PBS plans are a preferred method of intervention because more invasive interventions often cause more harm than good to all involved (Elliott et al., 2005). This article seeks to provide an integrated framework for the development of positive behavior support plans in inpatient psychiatric settings. In addition to explicating the philosophy and core elements of PBS plans, this work includes discussion of the didactic and pragmatic aspects of training clinical staff in inpatient mental health settings. A case vignette is included for illustration and to highlight the use of PBS plans as a mechanism for helping patients transition to less restrictive settings. This work will add to the scant literature examining the use of positive behavioral support plans in inpatient psychiatric settings. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents.

PubMed

Labruère, Raphaël; Gautier, Benoît; Testud, Marlène; Seguin, Johanne; Lenoir, Christine; Desbène-Finck, Stéphanie; Helissey, Philippe; Garbay, Christiane; Chabot, Guy G; Vidal, Michel; Giorgi-Renault, Sylviane

2010-12-03

We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moieties; in the second series, conformational restriction of the E nucleus was considered. We have identified several new compounds with inhibitory activity toward tubulin polymerization similar to that of CA-4 and colchicine, while displaying low cytotoxic activity against normal and/or cancer cells. An aminologue and a methylenic analogue were shown to disrupt endothelial cell cords on Matrigel at subtoxic concentrations, and an original assay of drug washout allowed us to demonstrate the rapid reversibility of this effect. These two new analogues are promising leads for the development of vascular-disrupting agents in the podophyllotoxin series.

Object Correspondence across Brief Occlusion Is Established on the Basis of both Spatiotemporal and Surface Feature Cues

ERIC Educational Resources Information Center

Hollingworth, Andrew; Franconeri, Steven L.

2009-01-01

The "correspondence problem" is a classic issue in vision and cognition. Frequent perceptual disruptions, such as saccades and brief occlusion, create gaps in perceptual input. How does the visual system establish correspondence between objects visible before and after the disruption? Current theories hold that object correspondence is established…

Age-related alterations in the sarcolemmal environment are attenuated by lifelong caloric restriction and voluntary exercise.

PubMed

Hord, Jeffrey M; Botchlett, Rachel; Lawler, John M

2016-10-01

Age-related loss of skeletal muscle mass and function, referred to as sarcopenia, is mitigated by lifelong calorie restriction as well as exercise. In aged skeletal muscle fibers there is compromised integrity of the cell membrane that may contribute to sarcopenia. The purpose of this study was to determine if lifelong mild (8%) caloric restriction (CR) and lifelong CR+voluntary wheel running (WR) could ameliorate disruption of membrane scaffolding and signaling proteins during the aging process, thus maintaining a favorable, healthy membrane environment in plantaris muscle fibers. Fischer-344 rats were divided into four groups: 24-month old adults fed ad libitum (OAL); 24-month old on 8% caloric restriction (OCR); 24month old 8% caloric restriction+wheel running (OCRWR); and 6-month old sedentary adults fed ad libitum (YAL) were used to determine age-related changes. Aging resulted in discontinuous membrane expression of dystrophin glycoprotein complex (DGC) proteins: dystrophin and α-syntrophin. Older muscle also displayed decreased content of neuronal nitric oxide synthase (nNOS), a key DGC signaling protein. In contrast, OCR and OCRWR provided significant protection against age-related DGC disruption. In conjunction with the age-related decline in membrane DGC patency, key membrane repair proteins (MG53, dysferlin, annexin A6, and annexin A2) were significantly increased in the OAL plantaris. However, lifelong CR and CRWR interventions were effective at maintaining membrane repair proteins near YAL levels of. OAL fibers also displayed reduced protein content of NADPH oxidase isoform 2 (Nox2) subunits (p67phox and p47phox), consistent with a perturbed sarcolemmal environment. Loss of Nox2 subunits was prevented by lifelong CR and CRWR. Our results are therefore consistent with the hypothesis that lifelong CR and WR are effective countermeasures against age-related alterations in the myofiber membrane environment. Copyright © 2016 Elsevier Inc. All rights reserved.

A trans-Dominant Form of Gag Restricts Ty1 Retrotransposition and Mediates Copy Number Control

PubMed Central

Saha, Agniva; Mitchell, Jessica A.; Nishida, Yuri; Hildreth, Jonathan E.; Ariberre, Joshua A.; Gilbert, Wendy V.

2015-01-01

ABSTRACT Saccharomyces cerevisiae and Saccharomyces paradoxus lack the conserved RNA interference pathway and utilize a novel form of copy number control (CNC) to inhibit Ty1 retrotransposition. Although noncoding transcripts have been implicated in CNC, here we present evidence that a truncated form of the Gag capsid protein (p22) or its processed form (p18) is necessary and sufficient for CNC and likely encoded by Ty1 internal transcripts. Coexpression of p22/p18 and Ty1 decreases mobility more than 30,000-fold. p22/p18 cofractionates with Ty1 virus-like particles (VLPs) and affects VLP yield, protein composition, and morphology. Although p22/p18 and Gag colocalize in the cytoplasm, p22/p18 disrupts sites used for VLP assembly. Glutathione S-transferase (GST) affinity pulldowns also suggest that p18 and Gag interact. Therefore, this intrinsic Gag-like restriction factor confers CNC by interfering with VLP assembly and function and expands the strategies used to limit retroelement propagation. IMPORTANCE Retrotransposons dominate the chromosomal landscape in many eukaryotes, can cause mutations by insertion or genome rearrangement, and are evolutionarily related to retroviruses such as HIV. Thus, understanding factors that limit transposition and retroviral replication is fundamentally important. The present work describes a retrotransposon-encoded restriction protein derived from the capsid gene of the yeast Ty1 element that disrupts virus-like particle assembly in a dose-dependent manner. This form of copy number control acts as a molecular rheostat, allowing high levels of retrotransposition when few Ty1 elements are present and inhibiting transposition as copy number increases. Thus, yeast and Ty1 have coevolved a form of copy number control that is beneficial to both “host and parasite.” To our knowledge, this is the first Gag-like retrotransposon restriction factor described in the literature and expands the ways in which restriction proteins modulate retroelement replication. PMID:25609815

High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease.

PubMed

Vaziri, Nosratola D; Liu, Shu-Man; Lau, Wei Ling; Khazaeli, Mahyar; Nazertehrani, Sohrab; Farzaneh, Seyed H; Kieffer, Dorothy A; Adams, Sean H; Martin, Roy J

2014-01-01

Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control) or high fermentable fiber (amylose maize resistant starch, HAM-RS2) for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.

High Amylose Resistant Starch Diet Ameliorates Oxidative Stress, Inflammation, and Progression of Chronic Kidney Disease

PubMed Central

Vaziri, Nosratola D.; Liu, Shu-Man; Lau, Wei Ling; Khazaeli, Mahyar; Nazertehrani, Sohrab; Farzaneh, Seyed H.; Kieffer, Dorothy A.; Adams, Sean H.; Martin, Roy J.

2014-01-01

Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control) or high fermentable fiber (amylose maize resistant starch, HAM-RS2) for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients. PMID:25490712

Induction of Cytoprotective Pathways Is Central to the Extension of Lifespan Conferred by Multiple Longevity Pathways

PubMed Central

Shore, David E.; Carr, Christopher E.; Ruvkun, Gary

2012-01-01

Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60), the ER UPR (hsp-4), ROS response (sod-3, gst-4), and xenobiotic detoxification (gst-4). We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors. PMID:22829775

Development of a high-throughput microscale cell disruption platform for Pichia pastoris in rapid bioprocess design.

PubMed

Bláha, Benjamin A F; Morris, Stephen A; Ogonah, Olotu W; Maucourant, Sophie; Crescente, Vincenzo; Rosenberg, William; Mukhopadhyay, Tarit K

2018-01-01

The time and cost benefits of miniaturized fermentation platforms can only be gained by employing complementary techniques facilitating high-throughput at small sample volumes. Microbial cell disruption is a major bottleneck in experimental throughput and is often restricted to large processing volumes. Moreover, for rigid yeast species, such as Pichia pastoris, no effective high-throughput disruption methods exist. The development of an automated, miniaturized, high-throughput, noncontact, scalable platform based on adaptive focused acoustics (AFA) to disrupt P. pastoris and recover intracellular heterologous protein is described. Augmented modes of AFA were established by investigating vessel designs and a novel enzymatic pretreatment step. Three different modes of AFA were studied and compared to the performance high-pressure homogenization. For each of these modes of cell disruption, response models were developed to account for five different performance criteria. Using multiple responses not only demonstrated that different operating parameters are required for different response optima, with highest product purity requiring suboptimal values for other criteria, but also allowed for AFA-based methods to mimic large-scale homogenization processes. These results demonstrate that AFA-mediated cell disruption can be used for a wide range of applications including buffer development, strain selection, fermentation process development, and whole bioprocess integration. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:130-140, 2018. © 2017 American Institute of Chemical Engineers.

Effects of work-related sleep restriction on acute physiological and psychological stress responses and their interactions: A review among emergency service personnel.

PubMed

Wolkow, Alexander; Ferguson, Sally; Aisbett, Brad; Main, Luana

2015-01-01

Emergency work can expose personnel to sleep restriction. Inadequate amounts of sleep can negatively affect physiological and psychological stress responses. This review critiqued the emergency service literature (e.g., firefighting, police/law enforcement, defense forces, ambulance/paramedic personnel) that has investigated the effect of sleep restriction on hormonal, inflammatory and psychological responses. Furthermore, it investigated if a psycho-physiological approach can help contextualize the significance of such responses to assist emergency service agencies monitor the health of their personnel. The available literature suggests that sleep restriction across multiple work days can disrupt cytokine and cortisol levels, deteriorate mood and elicit simultaneous physiological and psychological responses. However, research concerning the interaction between such responses is limited and inconclusive. Therefore, it is unknown if a psycho-physiological relationship exists and as a result, it is currently not feasible for agencies to monitor sleep restriction related stress based on psycho- physiological interactions. Sleep restriction does however, appear to be a major stressor contributing to physiological and psychological responses and thus, warrants further investigation. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration

PubMed Central

Paris, Nicole D; Soroka, Andrew; Klose, Alanna; Liu, Wenxuan; Chakkalakal, Joe V

2016-01-01

Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of Smad4, the downstream cofactor for canonical TGFβ superfamily signaling, and the target Id1 in aged SCs and MPs during regeneration. Specific deletion of Smad4 in adult mouse SCs led to increased propensity for terminal myogenic commitment connected to impaired proliferative potential. Furthermore, SC-specific Smad4 disruption compromised adult skeletal muscle regeneration. Finally, loss of Smad4 in aged SCs did not promote aged skeletal muscle regeneration. Therefore, SC-specific reduction of Smad4 is a feature of aged regenerating skeletal muscle and Smad4 is a critical regulator of SC and MP amplification during skeletal muscle regeneration. DOI: http://dx.doi.org/10.7554/eLife.19484.001 PMID:27855784

The mammalian Doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells

PubMed Central

Matson, Clinton K.; Murphy, Mark W.; Griswold, Michael D.; Yoshida, Shosei; Bardwell, Vivian J.; Zarkower, David

2010-01-01

Summary The switch from mitosis to meiosis is a unique feature of germ cell development. In mammals, meiotic initiation requires retinoic acid (RA), which activates meiotic inducers including Stra8, but how the switch to meiosis is controlled in male germ cells (spermatogonia) remains poorly understood. Here we examine the role of the Doublesex-related transcription factor DMRT1 in adult spermatogenesis using conditional gene targeting in the mouse. Loss of Dmrt1 causes spermatogonia to precociously exit the spermatogonial program and enter meiosis. Dmrt1 therefore determines whether male germ cells undergo mitosis and spermatogonial differentiation or meiosis. Loss of Dmrt1 in spermatogonia also disrupts cyclical gene expression in Sertoli cells. DMRT1 acts in spermatogonia to restrict RA responsiveness, directly repress Stra8 transcription, and activate transcription of the spermatogonial differentiation factor Sohlh1, thereby preventing meiosis and promoting spermatogonial development. By coordinating spermatogonial development and mitotic amplification with meiosis, DMRT1 allows abundant, continuous production of sperm. PMID:20951351

Potential for stable flies and house flies (Diptera: Muscidae) to transmit Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF), a disease of ruminants and humans, has been responsible for large outbreaks in Africa that have resulted in hundreds of thousands of human infections and major economic disruption due to loss of livestock and to trade restrictions. As indicated by the rapid spread of West N...

Disagreeing over Dress: Can Schools Restrict Student Expression because It Conflicts with the Values They Want To Instill?

ERIC Educational Resources Information Center

Dowling-Sendor, Benjamin

2001-01-01

In a Sixth Circuit Court decision, Judge Harry Welford concluded that the First Amendment did not prohibit an Ohio school district from banning Marilyn Manson T-shirts under the district's constitutional authority to regulate student speech (disruptive behavior) that conflicts with its basic educational mission. (MLH)

Protein Synthesis Underlies Post-Retrieval Memory Consolidation to a Restricted Degree Only when Updated Information Is Obtained

ERIC Educational Resources Information Center

Rodriguez-Ortiz, Carlos J.; De la Cruz, Vanesa; Gutierrez, Ranier; Bermudez-Rattoni, Federico

2005-01-01

Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here…

Social jetlag, obesity and metabolic disorder: investigation in a cohort study.

PubMed

Parsons, M J; Moffitt, T E; Gregory, A M; Goldman-Mellor, S; Nolan, P M; Poulton, R; Caspi, A

2015-05-01

Obesity is one of the leading causes of preventable death worldwide. Circadian rhythms are known to control both sleep timing and energy homeostasis, and disruptions in circadian rhythms have been linked with metabolic dysfunction and obesity-associated disease. In previous research, social jetlag, a measure of chronic circadian disruption caused by the discrepancy between our internal versus social clocks, was associated with elevated self-reported body mass index, possibly indicative of a more generalized association with obesity and metabolic dysfunction. We studied participants from the population-representative Dunedin Longitudinal Study (N=1037) to determine whether social jetlag was associated with clinically assessed measurements of metabolic phenotypes and disease indicators for obesity-related disease, specifically, indicators of inflammation and diabetes. Our analysis was restricted to N=815 non-shift workers in our cohort. Among these participants, we found that social jetlag was associated with numerous clinically assessed measures of metabolic dysfunction and obesity. We distinguished between obese individuals who were metabolically healthy versus unhealthy, and found higher social jetlag levels in metabolically unhealthy obese individuals. Among metabolically unhealthy obese individuals, social jetlag was additionally associated with elevated glycated hemoglobin and an indicator of inflammation. The findings are consistent with the possibility that 'living against our internal clock' may contribute to metabolic dysfunction and its consequences. Further research aimed at understanding that the physiology and social features of social jetlag may inform obesity prevention and have ramifications for policies and practices that contribute to increased social jetlag, such as work schedules and daylight savings time.

Endocannabinoid signaling and memory dynamics: A synaptic perspective.

PubMed

Drumond, Ana; Madeira, Natália; Fonseca, Rosalina

2017-02-01

Memory acquisition is a key brain feature in which our human nature relies on. Memories evolve over time. Initially after learning, memories are labile and sensitive to disruption by the interference of concurrent events. Later on, after consolidation, memories are resistant to disruption. However, reactivation of previously consolidated memories renders them again in an unstable state and therefore susceptible to perturbation. Additionally, and depending on the characteristics of the stimuli, a parallel process may be initiated which ultimately leads to the extinction of the previously acquired response. This dynamic aspect of memory maintenance opens the possibility for an updating of previously acquired memories but it also creates several conceptual challenges. What is the time window for memory updating? What determines whether reconsolidation or extinction is triggered? In this review, we tried to re-examine the relationship between consolidation, reconsolidation and extinction, aiming for a unifying view of memory dynamics. Since cellular models of memory share common principles, we present the evidence that similar rules apply to the maintenance of synaptic plasticity. Recently, a new function of the endocannabinoid (eCB) signaling system has been described for associative forms of synaptic plasticity in amygdala synapses. The eCB system has emerged as a key modulator of memory dynamics by adjusting the outcome to stimuli intensity. We propose a key function of eCB in discriminative forms of learning by restricting associative plasticity in amygdala synapses. Since many neuropsychiatric disorders are associated with a dysregulation in memory dynamics, understanding the rules underlying memory maintenance paves the path to better clinical interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Increasing Susceptibility of the Global Network of Food Trade to Climate Disturbances

NASA Astrophysics Data System (ADS)

Puma, M. J.; Bose, S.; Chon, S.; Cook, B.

2013-12-01

Globalization of agriculture through trade liberalization has led to a dramatic transformation of the global network of food trade. The many benefits of this globalization include greater and more efficient global agricultural production, reduced variability of regional and global food supplies, and savings in global water resources. However, a potential hidden cost is an increasingly fragile network that is more susceptible to shocks or disruptions. Recent studies suggest that complex systems, like the global food trade network, may have architectural features typically associated with the existence of tipping points and susceptibility to collapse. Here we present evidence that this global agricultural network is increasingly connected, homogeneous, and in a state where network nodes (here countries) can flip between alternate states. We use production and trade data from 1986 to 2009 to identify shifts in national self sufficiency and to quantify changes in connectivity and homogeneity of the wheat, maize and rice trade. We then simulate the possible impacts of climate and crop-disease disruptions, which could potentially trigger a global food crisis through an export-restriction-induced domino effect. Changes in self-sufficiency ratio (SSR) over time for various country groups. The SSR is computed based on production and trade of cereals and starchy roots. (Top row) Time series of SSR for the Group of Eight + Five (G8+5) countries. The '+ Five' refers to the five leading emerging economies in the world. (Bottom row) Boxplots of average SSR over two periods (1986-1990 and 2005-2009) for countries designated as 'Annex I' and 'Least Developed Countries' (LDC) by the United Nations.

Studies of the DIII-D disruption database using Machine Learning algorithms

NASA Astrophysics Data System (ADS)

Rea, Cristina; Granetz, Robert; Meneghini, Orso

2017-10-01

A Random Forests Machine Learning algorithm, trained on a large database of both disruptive and non-disruptive DIII-D discharges, predicts disruptive behavior in DIII-D with about 90% of accuracy. Several algorithms have been tested and Random Forests was found superior in performances for this particular task. Over 40 plasma parameters are included in the database, with data for each of the parameters taken from 500k time slices. We focused on a subset of non-dimensional plasma parameters, deemed to be good predictors based on physics considerations. Both binary (disruptive/non-disruptive) and multi-label (label based on the elapsed time before disruption) classification problems are investigated. The Random Forests algorithm provides insight on the available dataset by ranking the relative importance of the input features. It is found that q95 and Greenwald density fraction (n/nG) are the most relevant parameters for discriminating between DIII-D disruptive and non-disruptive discharges. A comparison with the Gradient Boosted Trees algorithm is shown and the first results coming from the application of regression algorithms are presented. Work supported by the US Department of Energy under DE-FC02-04ER54698, DE-SC0014264 and DE-FG02-95ER54309.

It takes a tissue to make a tumor: Epigenetics, cancer and the microenvironment

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

Barcellos-Hoff, Mary Helen

How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises itsmore » ability to suppress carcinogenesis.« less

Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms

PubMed Central

Schimizzi, Gregory V.; Maher, Meghan T.; Loza, Andrew J.; Longmore, Gregory D.

2016-01-01

The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin. PMID:27454609

Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms.

PubMed

Schimizzi, Gregory V; Maher, Meghan T; Loza, Andrew J; Longmore, Gregory D

2016-01-01

The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin.

Disruption to radiation therapy sessions due to anxiety among patients receiving radiation therapy to the head and neck area can be predicted using patient self-report measures.

PubMed

Clover, Kerrie; Oultram, Sharon; Adams, Catherine; Cross, Laraine; Findlay, Naomi; Ponman, Leah

2011-12-01

This analysis sought to determine whether patient self-report measures were associated with disruption to radiation therapy sessions due to anxiety among cancer patients undergoing radiation therapy to the head and neck region. A cohort of patients undergoing radiation therapy to the head and neck region at a major regional radiation oncology treatment centre (ROTC) in Australia completed self-report measures of anxiety, history of panic and fears relevant to use of an immobilising mask. The treating Radiation Therapist (RT) rated the level of session disruption due to patient anxiety during the Computerised Tomography/Simulation (CT/Sim) (baseline) session and first treatment session. Complete data were obtained for 90 patients. RTs rated 11 and 24% of patients as having some level of session disruption session due to anxiety at baseline and Treatment 1, respectively. Five factors were significantly associated with session disruption at baseline in bivariate analyses: currently taking psycho-active medication (p=0.008); fear of enclosed spaces (p=0.006); fear of face being covered up (p=0.006); fear of movement restriction (p=0.041) and ever had an anxiety attack (p=0.034). Sensitivity ranged from 0.57 to 0.75 and specificity ranged from 0.68 to 0.90. Only session disruption at baseline predicted disruption at Treatment 1 (p<0.01). This study offers some preliminary insights into the prevalence of patient anxiety severe enough to cause session disruption and patient self-report measures which might be used to flag patients for prophylactic treatment. Further development and replication in a larger sample is warranted before introduction of these measures into routine practice. Copyright © 2010 John Wiley & Sons, Ltd.

Mating Disruption as a Suppression Tactic in Programs Targeting Regulated Lepidopteran Pests in US.

PubMed

Lance, David R; Leonard, Donna S; Mastro, Victor C; Walters, Michelle L

2016-07-01

Mating disruption, the broadcast application of sex-attractant pheromone to reduce the ability of insects to locate mates, has proven to be an effective method for suppressing populations of numerous moth pests. Since the conception of mating disruption, the species-specificity and low toxicity of pheromone applications has led to their consideration for use in area-wide programs to manage invasive moths. Case histories are presented for four such programs where the tactic was used in the United States: Pectinophora gossypiella (pink bollworm), Lymantria dispar (gypsy moth), Epiphyas postvittana (light brown apple moth), and Lobesia botrana (European grapevine moth). Use of mating disruption against P. gossypiella and L. botrana was restricted primarily to agricultural areas and relied in part (P. gossypiella) or wholly (L. botrana) on hand-applied dispensers. In those programs, mating disruption was integrated with other suppression tactics and considered an important component of overall efforts that are leading toward eradication of the invasive pests from North America. By contrast, L. dispar and E. postvittana are polyphagous pests, where pheromone formulations have been applied aerially as stand-alone treatments across broad areas, including residential neighborhoods. For L. dispar, mating disruption has been a key component in the program to slow the spread of the infestation of this pest, and the applications generally have been well tolerated by the public. For E. postvittana, public outcry halted the use of aerially applied mating disruption after an initial series of treatments, effectively thwarting an attempt to eradicate this pest from California. Reasons for the discrepancies between these two programs are not entirely clear.

Diagnostic features of feline restrictive orbital myofibroblastic sarcoma.

PubMed

Bell, C M; Schwarz, T; Dubielzig, R R

2011-05-01

A progressive debilitating disease of the orbit and adjacent connective tissues of cats has historically been called feline orbital pseudotumor. The authors reviewed clinical, histopathologic, and diagnostic imaging features of this disease in 12 cases from the Comparative Ocular Pathology Laboratory of Wisconsin. The cats' ages ranged from 7 to 16 years (mean, 10.8 years). All cats had a history of severely restricted mobility of the globe and eyelids with secondary corneal disease. Eleven cats (92%) had concurrent involvement of the contralateral eye and/or the oral cavity. Diffuse scleral or episcleral thickening was seen with computed tomography in all clinically affected eyes. Histologically, an insidious infiltration of neoplastic spindle cells in the orbit, eyelids, and periorbital skin and soft tissues, with collagen deposition and a few perivascular lymphocytes, led to entrapment and restricted mobility of the eyelids and orbital tissues. The tumor failed to form a discrete mass, and it spread along fascial planes to the contralateral orbit and eyelids and/or the lips and oral cavity. In all tested cases (n = 10), neoplastic cells were immunohistochemically positive for vimentin, S100 protein, and smooth muscle actin. The authors adopted the term feline restrictive orbital myofibroblastic sarcoma to reflect the restricted mobility of the eyelids and globe and the imaging and histologic features of an invasive yet low-grade myofibroblastic sarcoma.

Deep Restricted Kernel Machines Using Conjugate Feature Duality.

PubMed

Suykens, Johan A K

2017-08-01

The aim of this letter is to propose a theory of deep restricted kernel machines offering new foundations for deep learning with kernel machines. From the viewpoint of deep learning, it is partially related to restricted Boltzmann machines, which are characterized by visible and hidden units in a bipartite graph without hidden-to-hidden connections and deep learning extensions as deep belief networks and deep Boltzmann machines. From the viewpoint of kernel machines, it includes least squares support vector machines for classification and regression, kernel principal component analysis (PCA), matrix singular value decomposition, and Parzen-type models. A key element is to first characterize these kernel machines in terms of so-called conjugate feature duality, yielding a representation with visible and hidden units. It is shown how this is related to the energy form in restricted Boltzmann machines, with continuous variables in a nonprobabilistic setting. In this new framework of so-called restricted kernel machine (RKM) representations, the dual variables correspond to hidden features. Deep RKM are obtained by coupling the RKMs. The method is illustrated for deep RKM, consisting of three levels with a least squares support vector machine regression level and two kernel PCA levels. In its primal form also deep feedforward neural networks can be trained within this framework.

The Changing Face of the Novel

ERIC Educational Resources Information Center

Serafini, Frank; Blasingame, James

2012-01-01

This article uses Dresang's dimensions of radical change to call attention to the evolving structures and features of novels for young readers being published today. The controversial topics and elaborate design features contained in contemporary novels, for example, the expansion of dystopic fiction, the disruption of traditional narrative…

The Trouble with Boys: Social Influences and the Gender Gap in Disruptive Behavior. NBER Working Paper No. 17541

ERIC Educational Resources Information Center

Bertrand, Marianne; Pan, Jessica

2011-01-01

This paper explores the importance of the home and school environments in explaining the gender gap in disruptive behavior. We document large differences in the gender gap across key features of the home environment--boys do especially poorly in broken families. In contrast, we find little impact of the early school environment on non-cognitive…

Background instrumental music and serial recall.

PubMed

Nittono, H

1997-06-01

Although speech and vocal music are consistently shown to impair serial recall for visually presented items, instrumental music does not always produce a significant disruption. This study investigated the features of instrumental music that would modulate the disruption in serial recall. 24 students were presented sequences of nine digits and required to recall the digits in order of presentation. Instrumental music as played either forward or backward during the task. Forward music caused significantly more disruption than did silence, whereas the reversed music did not. Some higher-order factor may be at work in the effect of background music on serial recall.

Strategic response by providers to specialty hospitals, ambulatory surgery centers, and retail clinics.

PubMed

Burns, Lawton R; David, Guy; Helmchen, Lorens A

2011-04-01

Radical innovation and disruptive technologies are frequently heralded as a solution to delivering higher quality, lower cost health care. According to the literature on disruption, local hospitals and physicians (incumbent providers) may be unable to competitively respond to such "creative destruction" and alter their business models for a host of reasons, thus threatening their future survival. However, strategic management theory and research suggest that, under certain conditions, incumbent providers may be able to weather the discontinuities posed by the disrupters. This article analyzes 3 disruptive innovations in service delivery: single-specialty hospitals, ambulatory surgical centers, and retail clinics. We first discuss the features of these innovations to assess how disruptive they are. We then draw on the literature on strategic adaptation to suggest how incumbents develop competitive responses to these disruptive innovations that assure their continued survival. These arguments are then evaluated in a field study of several urban markets based on interviews with both incumbents and entrants. The interviews indicate that entrants have failed to disrupt incumbent providers primarily as a result of strategies pursued by the incumbents. The findings cast doubt on the prospects for these disruptive innovations to transform health care.

Repeating patterns of sleep restriction and recovery: Do we get used to it?

PubMed

Simpson, Norah S; Diolombi, Moussa; Scott-Sutherland, Jennifer; Yang, Huan; Bhatt, Vrushank; Gautam, Shiva; Mullington, Janet; Haack, Monika

2016-11-01

Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and 'catching up' on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4h followed by two nights of 8-h recovery sleep. In an intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p<0.05) and week 3 (p<0.09). Serum cortisol showed a significantly dysregulated 24h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Network Disruption in the Degenerative Dementias

PubMed Central

Pievani, Michela; de Haan, Willem; Wu, Tao; Seeley, William W; Frisoni, Giovanni B

2011-01-01

Despite considerable advances toward understanding the molecular pathophysiology of the neurodegenerative dementias, the mechanisms linking molecular changes to neuropathology and the latter to clinical symptoms remain largely obscure. Connectivity is a distinctive feature of the brain and the integrity of functional network dynamics is critical for normal functioning. A better understanding of network disruption in the neurodegenerative dementias may help bridge the gap between molecular changes, pathology and symptoms. Recent findings on functional network disruption as assessed with “resting-state” or intrinsic connectivity fMRI and EEG/MEG have shown distinct patterns of network disruption across the major neurodegenerative diseases. These network abnormalities are relatively specific to the clinical syndromes, and in Alzheimer's disease and frontotemporal dementia network disruption tracks the pattern of pathological changes. These findings may have a practical impact on diagnostic accuracy, allowing earlier detection of neurodegenerative diseases even at the pre-symptomatic stage, and tracking of disease progression. PMID:21778116

Safe enough to sleep: sleep disruptions associated with trauma, posttraumatic stress, and anxiety in children and adolescents.

PubMed

Charuvastra, Anthony; Cloitre, Marylene

2009-10-01

Sleep disturbance is an essential symptom of posttraumatic stress disorder, and recent evidence suggests that disrupted sleep may play an important role in the development of posttraumatic stress disorder following traumatic stress. The authors review several aspects of sleep as it relates to posttraumatic stress disorder. First, there is an association between traumatic stress and different components of disrupted sleep in children and adolescents. Second, sleep disruption appears to be a core feature of other pediatric anxiety disorders, and the authors consider if this preexisting sleep vulnerability may explain in part why preexisting anxiety disorders are a risk factor for developing posttraumatic stress disorder following a traumatic event. Third, the authors consider attachment theory and the social context of trauma and sleep disruption. This article concludes with a consideration of the therapeutic implications of these findings.

Cercosporin-deficient mutants by plasmid tagging in the asexual fungus Cercospora nicotianae.

PubMed

Chung, K-R; Ehrenshaft, M; Wetzel, D K; Daub, M E

2003-11-01

We have successfully adapted plasmid insertion and restriction enzyme-mediated integration (REMI) to produce cercosporin toxin-deficient mutants in the asexual phytopathogenic fungus Cercospora nicotianae. The use of pre-linearized plasmid or restriction enzymes in the transformation procedure significantly decreased the transformation frequency, but promoted a complicated and undefined mode of plasmid integration that leads to mutations in the C. nicotianae genome. Vector DNA generally integrated in multiple copies, and no increase in single-copy insertion was observed when enzymes were added to the transformation mixture. Out of 1873 transformants tested, 39 putative cercosporin toxin biosynthesis ( ctb) mutants were recovered that showed altered levels of cercosporin production. Seven ctb mutants were recovered using pre-linearized plasmids without the addition of enzymes, and these were considered to be non-REMI mutants. The correlation between a specific insertion and a mutant phenotype was confirmed using rescued plasmids as gene disruption vectors in the wild-type strain. Six out of fifteen rescued plasmids tested yielded cercosporin-deficient transformants when re-introduced into the wild-type strain, suggesting a link between the insertion site and the cercosporin-deficient phenotype. Sequence analysis of a fragment flanking the insert site recovered from one insertion mutant showed it to be disrupted in sequences with high homology to the acyl transferase domain of polyketide synthases from other fungi. Disruption of this polyketide synthase gene ( CTB1) using a rescued plasmid resulted in mutants that were defective in cercosporin production. Thus, we provide the first molecular evidence that cercosporin is synthesized via a polyketide pathway as previously hypothesized.

The Effects of Sleep Continuity Disruption on Positive Mood and Sleep Architecture in Healthy Adults.

PubMed

Finan, Patrick H; Quartana, Phillip J; Smith, Michael T

2015-11-01

The purpose of this study was to test an experimental model of the effects of sleep continuity disturbance on sleep architecture and positive mood in order to better understand the mechanisms linking insomnia and depression. Participants were randomized to receive 3 consecutive nights of sleep continuity disruption via forced nocturnal awakenings (FA, n = 21), or one of two control conditions: restricted sleep opportunity (RSO, n = 17) or uninterrupted sleep (US, n = 24). The study was set in an inpatient clinical research suite. Healthy, good-sleeping men and women were included. Polysomnography was used to measure sleep architecture, and mood was assessed via self-report each day. Compared to restricted sleep opportunity controls, forced awakenings subjects had significantly less slow wave sleep (P < 0.05) after the first night of sleep deprivation, and significantly lower positive mood (P < 0.05) after the second night of sleep deprivation. The differential change in slow wave sleep statistically mediated the observed group differences in positive mood (P = 0.002). To our knowledge, this is the first human experimental study to demonstrate that, despite comparable reductions in total sleep time, partial sleep loss from sleep continuity disruption is more detrimental to positive mood than partial sleep loss from delaying bedtime, even when controlling for concomitant increases in negative mood. With these findings, we provide temporal evidence in support of a putative biologic mechanism (slow wave sleep deficit) that could help explain the strong comorbidity between insomnia and depression. © 2015 Associated Professional Sleep Societies, LLC.

Which interventions against the sale of tobacco to minors can be expected to reduce smoking?

PubMed

DiFranza, Joseph R

2012-07-01

Signatories of the Framework Convention on Tobacco Control have committed themselves to prohibiting the sale of tobacco to minors. The tobacco industry has a long history of legal challenges to such restrictions claiming that they cannot be expected to reduce youth smoking. The object of this study was to determine if disrupting the sale of tobacco to minors can be expected to reduce tobacco use by youths. A comprehensive literature search was conducted for studies that evaluated the impact on youth tobacco use of efforts to disrupt the sale of tobacco to youths. There was little evidence that merely enacting a law without sufficient enforcement had any impact on youth tobacco use. There was no evidence that merchant education programmes had any impact on youth older than 12 years of age. There was no evidence that enforcement efforts that failed to reduce the sale of tobacco to minors had any beneficial impact. All enforcement programmes that disrupted the sale of tobacco to minors reduced smoking among youth. Government officials can expect that enforcement programmes that disrupt the sale of tobacco to minors will reduce adolescent smoking.

Biomechanics, diagnosis, and treatment outcome in inflammatory myopathy presenting as oropharyngeal dysphagia

PubMed Central

Williams, R B; Grehan, M J; Hersch, M; Andre, J; Cook, I J

2003-01-01

Aims: In patients with inflammatory myopathy and dysphagia, our aims were to determine: (1) the diagnostic utility of clinical and laboratory indicators; (2) the biomechanical properties of the pharyngo-oesophageal segment; (3) the usefulness of pharyngeal videomanometry in distinguishing neuropathic from myopathic dysphagia; and (4) clinical outcome. Methods: Clinical, laboratory, and videomanometric assessment was performed in 13 patients with myositis and dysphagia, in 17 disease controls with dysphagia (due to proven CNS disease), and in 22 healthy age matched controls. The diagnostic accuracy of creatine kinase (CPK), erythrocyte sedimentation rate, antinuclear antibody, and electromyography (EMG) were compared with the gold standard muscle biopsy. The biomechanical properties of the pharyngo-oesophageal segment were assessed by videomanometry. Results: Mean time from dysphagia onset to the diagnosis of myositis was 55 months (range 1–180). One third had no extrapharyngeal muscle weakness; 25% had normal CPK, and EMG was unhelpful in 28%. Compared with neurogenic controls, myositis patients had more prevalent cricopharyngeal restrictive disorders (69% v 14%; p=0.0003), reduced upper oesophageal sphincter (UOS) opening (p=0.01), and elevated hypopharyngeal intrabolus pressures (p=0.001). Videomanometric features favouring a myopathic over a neuropathic aetiology were: preserved pharyngeal swallow response, complete UOS relaxation, and normal swallow coordination. The 12 month mortality was 31%. Conclusions: The notable lack of supportive clinical signs and significant false negative rates for laboratory tests contribute to the marked delay in diagnosis. The myopathic process is strongly associated with restricted sphincter opening suggesting that cricopharyngeal disruption is a useful adjunct to immunosuppressive therapy. The condition has a poor prognosis. PMID:12631653

Clinical phenotype of ASD-associated DYRK1A haploinsufficiency.

PubMed

Earl, Rachel K; Turner, Tychele N; Mefford, Heather C; Hudac, Caitlin M; Gerdts, Jennifer; Eichler, Evan E; Bernier, Raphael A

2017-01-01

DYRK1A is a gene recurrently disrupted in 0.1-0.5% of the ASD population. A growing number of case reports with DYRK1A haploinsufficiency exhibit common phenotypic features including microcephaly, intellectual disability, speech delay, and facial dysmorphisms. Phenotypic information from previously published DYRK1A cases ( n  = 51) and participants in an ongoing study at the University of Washington (UW, n  = 10) were compiled. Frequencies of recurrent phenotypic features in this population were compared to features observed in a large sample with idiopathic ASD from the Simons Simplex Collection ( n  = 1981). UW DYRK1A cases were further characterized quantitatively and compared to a randomly subsampled set of idiopathic ASD cases matched on age and gender ( n  = 10) and to cases with an ASD-associated disruptive mutation to CHD8 ( n  = 12). Contribution of familial genetic background to clinical heterogeneity was assessed by comparing head circumference, IQ, and ASD-related symptoms of UW DYRK1A cases to their unaffected parents. DYRK1A haploinsufficiency results in a common phenotypic profile including intellectual disability, speech and motor difficulties, microcephaly, feeding difficulties, and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD presented with a constellation of five or more of these symptoms. When compared quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive functioning compared to idiopathic cases and significantly smaller head size compared to both idiopathic and CHD8 cases. Phenotypic variability in parental head circumference, IQ, and ASD-related symptoms corresponded to observed variability in affected child phenotype. Results confirm a core clinical phenotype for DYRK1A disruptions, with a combination of features that is distinct from idiopathic ASD. Cases with DYRK1A mutations are also distinguishable from disruptive mutations to CHD8 by head size. Measurable, quantitative characterization of DYRK1A haploinsufficiency illuminates clinical variability, which may be, in part, due to familial genetic background.

Low Frequency Vibrations Disrupt Left-Right Patterning in the Xenopus Embryo

PubMed Central

Vandenberg, Laura N.; Pennarola, Brian W.; Levin, Michael

2011-01-01

The development of consistent left-right (LR) asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia). Investigating one frequency (7 Hz), we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs. PMID:21826245

Synthesis and structure-activity relationships of constrained heterocyclic analogues of combretastatin A4.

PubMed

Arthuis, Martin; Pontikis, Renée; Chabot, Guy G; Seguin, Johanne; Quentin, Lionel; Bourg, Stéphane; Morin-Allory, Luc; Florent, Jean-Claude

2011-09-05

A series of combretastatin A4 (CA4) analogues with a lactam or lactone ring fused to the trimethoxyphenyl or the B-phenyl moiety were synthesized in an efficient and stereoselective manner by using a domino Heck-Suzuki-Miyaura coupling reaction. The vascular-disrupting potential of these conformationally restricted CA4 analogues was assessed by various in vitro assays: inhibition of tubulin polymerization, modification of endothelial cell morphology, and disruption of endothelial cell cords. Compounds were also evaluated for their growth inhibitory effects against murine and human tumor cells. B-ring-constrained derivatives that contain an oxindole ring (in contrast to compounds with a benzofuranone ring) as well as analogues bearing a six-membered lactone core fused to the trimethoxyphenyl ring are endowed with significant biological activity. The most potent compound of this series (oxindole 9 b) is of particular interest, as it combines chemical stability and a biological activity profile characteristic of a vascular-disrupting agent. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HopW1 from Pseudomonas syringae disrupts the actin cytoskeleton to promote virulence in Arabidopsis.

PubMed

Kang, Yongsung; Jelenska, Joanna; Cecchini, Nicolas M; Li, Yujie; Lee, Min Woo; Kovar, David R; Greenberg, Jean T

2014-06-01

A central mechanism of virulence of extracellular bacterial pathogens is the injection into host cells of effector proteins that modify host cellular functions. HopW1 is an effector injected by the type III secretion system that increases the growth of the plant pathogen Pseudomonas syringae on the Columbia accession of Arabidopsis. When delivered by P. syringae into plant cells, HopW1 causes a reduction in the filamentous actin (F-actin) network and the inhibition of endocytosis, a known actin-dependent process. When directly produced in plants, HopW1 forms complexes with actin, disrupts the actin cytoskeleton and inhibits endocytosis as well as the trafficking of certain proteins to vacuoles. The C-terminal region of HopW1 can reduce the length of actin filaments and therefore solubilize F-actin in vitro. Thus, HopW1 acts by disrupting the actin cytoskeleton and the cell biological processes that depend on actin, which in turn are needed for restricting P. syringae growth in Arabidopsis.

Effects of Context on Eye Movements When Reading About Possible and Impossible Events

PubMed Central

Warren, Tessa; McConnell, Kerry; Rayner, Keith

2009-01-01

Plausibility violations resulting in impossible scenarios lead to earlier and longer lasting eye movement disruption than violations resulting in highly unlikely scenarios (K. Rayner, T. Warren, B. J. Juhasz, & S. P. Liversedge, 2004; T. Warren & K. McConnell, 2007). This could reflect either differences in the timing of availability of different kinds of information (e.g., selectional restrictions, world knowledge, and context) or differences in their relative power to guide semantic interpretation. The authors investigated eye movements to possible and impossible events in real-world and fantasy contexts to determine when contextual information influences detection of impossibility cued by a semantic mismatch between a verb and an argument. Gaze durations on a target word were longer to impossible events independent of context. However, a measure of the time elapsed from first fixating the target word to moving past it showed disruption only in the real-world context. These results suggest that contextual information did not eliminate initial disruption but moderated it quickly thereafter. PMID:18605885

Application of climatic indices to analyse viticultural suitability in Extremadura, south-western Spain

NASA Astrophysics Data System (ADS)

Moral, Francisco J.; Rebollo, Francisco J.; Paniagua, Luis L.; García, Abelardo; de Salazar, Enrique Martínez

2016-01-01

Although climate is recognised as one of the main drivers of viticulture success, its main features have not been sufficiently described in many viticultural regions, including Extremadura, which contains one of the largest grapevine-growing areas in Europe. Using climatic data from 80 weather stations located throughout Extremadura, seven bioclimatic indices were calculated to estimate heat accumulation and potential water balance during the growing season and the thermal regime during the ripening of grapes. Differences in some climatic indices were found, and after a multivariate geographic analysis, four groups were delimited containing weather stations with similar climatic features, with variability between groups explained by heat accumulation and tempearture and thermal amplitude during the ripening season. Suitability for cultivation of grapevines without thermal restriction and temperate nights during the ripening period are the main characteristics of the weather stations studied, but spatial variability found in climatic potential denotes the importance of differentiating locations to properly relate the viticultural climate to grape quality factors and the style of wines produced. The climatic features of the four groups are very similar to those described in other viticultural regions, including those in close proximity to Extremadura and others worldwide, but few studies have used broad and updated temporal climate data for computing bioclimatic indices as in this case study. Finally, trends in climate indices were analysed. Results revealed that all groups have experienced warmer growing seasons, driven mainly by changes in minimum temperatures. This fact has numerous potential impacts, including changes in grapevine phenological timing, disruption of balanced composition in grapes (ultimately affecting wine characteristics), alterations in varieties grown and spatial changes in viable winegrape-growing zones.

Detecting opinion spams through supervised boosting approach.

PubMed

Hazim, Mohamad; Anuar, Nor Badrul; Ab Razak, Mohd Faizal; Abdullah, Nor Aniza

2018-01-01

Product reviews are the individual's opinions, judgement or belief about a certain product or service provided by certain companies. Such reviews serve as guides for these companies to plan and monitor their business ventures in terms of increasing productivity or enhancing their product/service qualities. Product reviews can also increase business profits by convincing future customers about the products which they have interest in. In the mobile application marketplace such as Google Playstore, reviews and star ratings are used as indicators of the application quality. However, among all these reviews, hereby also known as opinions, spams also exist, to disrupt the online business balance. Previous studies used the time series and neural network approach (which require a lot of computational power) to detect these opinion spams. However, the detection performance can be restricted in terms of accuracy because the approach focusses on basic, discrete and document level features only thereby, projecting little statistical relationships. Aiming to improve the detection of opinion spams in mobile application marketplace, this study proposes using statistical based features that are modelled through the supervised boosting approach such as the Extreme Gradient Boost (XGBoost) and the Generalized Boosted Regression Model (GBM) to evaluate two multilingual datasets (i.e. English and Malay language). From the evaluation done, it was found that the XGBoost is most suitable for detecting opinion spams in the English dataset while the GBM Gaussian is most suitable for the Malay dataset. The comparative analysis also indicates that the implementation of the proposed statistical based features had achieved a detection accuracy rate of 87.43 per cent on the English dataset and 86.13 per cent on the Malay dataset.

Early dietary sodium restriction disrupts the peripheral anatomical development of the gustatory system.

PubMed

Krimm, R F; Hill, D L

1999-05-01

Dietary sodium restriction has profound effects on the development of peripheral taste function and central taste system anatomy. This study examined whether early dietary sodium restriction also affects innervation of taste buds. The number of geniculate ganglion cells that innervate single fungiform taste buds were quantified for the midregion of the tongue in two groups of rats: those fed either a low-sodium diet and those fed a sodium replete diet (control rats) from early prenatal development through adulthood. The same mean number of ganglion cells in developmentally sodium-restricted and control adult rats innervated taste buds on the midregion of the tongue. However, the characteristic relationship of the larger the taste bud, the more neurons that innervate it did not develop in sodium-restricted rats. The failure to form such a relationship in experimental rats was likely due to a substantially smaller mean taste bud volume than controls and probably not to changes in innervation. Further experiments demonstrated that the altered association between number of innervating neurons and taste bud size in restricted rats was reversible. Feeding developmentally sodium-restricted rats a sodium replete diet at adulthood resulted in an increase in taste bud size. Accordingly, the high correlation between taste bud volume and innervation was established in sodium-replete rats. Findings from the current study reveal that early dietary manipulations influence neuron-target interactions; however, the effects of dietary sodium restriction on peripheral gustatory anatomy can be completely restored, even in adult animals.

Collisional and dynamical history of Gaspra

NASA Technical Reports Server (NTRS)

Greenberg, R.; Nolan, M. C.; Bottke, W. F., Jr.; Kolvoord, R. A.

1993-01-01

Interpretation of the impact record on Gaspra requires understanding of the effects of collisions on a target body of Gaspra's size and shape, recognition of impact features that may have different morphologies from craters on larger planets, and models of the geological processes that erase and modify impact features. Crater counts on the 140 sq km of Gaspra imaged at highest resolution by the Galileo spacecraft show a steep size-frequency distribution (cumulative power-law index near -3.5) from the smallest resolvable size (150 m diameter) up through the large feature (1.5 km diameter crater) of familiar crater-like morphology. In addition, there appear to be as many as eight roughly circular concavities with diameters greater than 3 km visible on the asteroid. If we restrict our crater counts to features with traditionally recognized crater morphologies, these concavities would not be included. However, if we define craters to include any concave structures that may represent local or regional damage at an impact size, then the larger features on Gaspra are candidates for consideration. Acceptance of the multi-km features as craters has been cautious for several reasons. First, scaling laws (the physically plausible algorithms for extrapolating from experimental data) indicate that Gaspra could not have sustained such large-crater-forming impacts without being disrupted; second, aside from concavity, the larger structures have no other features (e.g. rims) that can be identified with known impact craters; and third, extrapolation of the power-law size distribution for smaller craters predicts no craters larger than 3 km over the entire surface. On the other hand, recent hydrocode modeling of impacts shows that for given impact (albeit into a sphere), the crater size is much larger than given by scaling laws. Gaspra-size bodies can sustain formation of up to 8-km craters without disruption. Besides allowing larger impact craters, this result doubles the lifetime since the last catastrophic fragmentation event up to one billion years. Events that create multi-km craters also globally damage the material structure, such that regolith is produced, whether or not Gaspra 'initially' had a regolith, contrary to other models in which initial regolith is required in order to allow current regolith. Because the globally destructive shock wave precedes basin formation, crater size is closer to the large size extrapolated from gravity-scaling rather than the strength-scaling that had earlier been assumed for such small bodies. This mechanism may also help explain the existence of Stickney on Phobos. Moreover, rejection of the large concavities as craters based on unfamiliar morphology would be premature, because (aside from Stickney) we have no other data on such large impact structures on such a small, irregular body. The eight candidate concavities cover an area greater than that counted for smaller craters, because they are most apparent where small craters cannot be seen: on low resolution images and at the limb on high resolution images. We estimate that there are at least two with diameter greater than 4 km per 140 sq km, which would have to be accounted for in any model that claims these are impact craters.

Septic disruption of lactiferous ducts with heterogeneous carcinoma of the breast in a lactating woman.

PubMed

Naim, Mohammed; John, Vanesa T; Gaur, Kavita; Anees, Afzal

2010-08-06

This report documents the diagnostic histopathological features of heterogeneous breast carcinoma following sepsis and disruption of the lactiferous ducts in a lactating woman and discusses the pathogenesis. Sections from the nipple revealed disrupted collecting lactiferous ducts presenting with intraduct precarcinoma and carcinoma of the epidermoid type, and attached reparative sprouts lined by lactiferous cells. Breast lobules showed generalised benign adenotic change with various foci of carcinoma microscopically identifiable as intraduct primitive lactiferal ectodermal carcinoma, lactating carcinoma, primitive neuroendocrine carcinoma and myoepithelioid granulomatous carcinoma. The findings led to the conclusion that the lactiferous ducts are susceptible to sepsis and disruption, which may predispose a patient to breast carcinoma. The pattern of carcinoma suggested that lactiferous epithelial cells behaved colonially, with different metaplastic changes, precarcinoma and carcinoma.

Exploitation of insect vibrational signals reveals a new method of pest management.

PubMed

Eriksson, Anna; Anfora, Gianfranco; Lucchi, Andrea; Lanzo, Francesco; Virant-Doberlet, Meta; Mazzoni, Valerio

2012-01-01

Food production is considered to be the main source of human impact on the environment and the concerns about detrimental effects of pesticides on biodiversity and human health are likely to lead to an increasingly restricted use of chemicals in agriculture. Since the first successful field trial, pheromone based mating disruption enabled sustainable insect control, which resulted in reduced levels of pesticide use. Organic farming is one of the fastest growing segments of agriculture and with the continuously growing public concern about use of pesticides, the main remaining challenge in increasing the safety of the global food production is to identify appropriate alternative mating disruption approaches for the numerous insect pests that do not rely on chemical communication. In the present study, we show for the first time that effective mating disruption based on substrate-borne vibrational signals can be achieved in the field. When disruptive vibrational signals were applied to grapevine plants through a supporting wire, mating frequency of the leafhopper pest Scaphoideus titanus dropped to 9 % in semi-field conditions and to 4 % in a mature vineyard. The underlying mechanism of this environmentally friendly pest-control tactic is a masking of the vibrational signals used in mate recognition and location. Because vibrational communication is widespread in insects, mating disruption using substrate vibrations can transform many open field and greenhouse based farming systems.

Dietary fat and corticosterone levels are contributing factors to meal anticipation.

PubMed

Namvar, Sara; Gyte, Amy; Denn, Mark; Leighton, Brendan; Piggins, Hugh D

2016-04-15

Daily restricted access to food leads to the development of food anticipatory activity and metabolism, which depends upon an as yet unidentified food-entrainable oscillator(s). A premeal anticipatory peak in circulating hormones, including corticosterone is also elicited by daily restricted feeding. High-fat feeding is associated with elevated levels of corticosterone with disrupted circadian rhythms and a failure to develop robust meal anticipation. It is not clear whether the disrupted corticosterone rhythm, resulting from high-fat feeding contributes to attenuated meal anticipation in high-fat fed rats. Our aim was to better characterize meal anticipation in rats fed a low- or high-fat diet, and to better understand the role of corticosterone in this process. To this end, we utilized behavioral observations, hypothalamic c-Fos expression, and indirect calorimetry to assess meal entrainment. We also used the glucocorticoid receptor antagonist, RU486, to dissect out the role of corticosterone in meal anticipation in rats given daily access to a meal with different fat content. Restricted access to a low-fat diet led to robust meal anticipation, as well as entrainment of hypothalamic c-Fos expression, metabolism, and circulating corticosterone. These measures were significantly attenuated in response to a high-fat diet, and animals on this diet exhibited a postanticipatory rise in corticosterone. Interestingly, antagonism of glucocorticoid activity using RU486 attenuated meal anticipation in low-fat fed rats, but promoted meal anticipation in high-fat-fed rats. These findings suggest an important role for corticosterone in the regulation of meal anticipation in a manner dependent upon dietary fat content. Copyright © 2016 the American Physiological Society.

Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring

PubMed Central

Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Barella, Luiz Felipe; Malta, Ananda; Martins, Isabela Peixoto; Franco, Claudinéia Conationi da Silva; Pavanello, Audrei; Torrezan, Rosana; Natali, Maria Raquel Marçal; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar

2016-01-01

Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID:27007071

The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function.

PubMed

Wan, Lixin; Chen, Ming; Cao, Juxiang; Dai, Xiangpeng; Yin, Qing; Zhang, Jinfang; Song, Su-Jung; Lu, Ying; Liu, Jing; Inuzuka, Hiroyuki; Katon, Jesse M; Berry, Kelsey; Fung, Jacqueline; Ng, Christopher; Liu, Pengda; Song, Min Sup; Xue, Lian; Bronson, Roderick T; Kirschner, Marc W; Cui, Rutao; Pandolfi, Pier Paolo; Wei, Wenyi

2017-04-01

BRAF drives tumorigenesis by coordinating the activation of the RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. Here, we report that in primary cells with active APC FZR1 , APC FZR1 earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases. Phosphorylation of FZR1 inhibits APC FZR1 , leading to elevation of a cohort of oncogenic APC FZR1 substrates to facilitate melanomagenesis. Importantly, CDK4 and/or BRAF/MEK inhibitors restore APC FZR1 E3 ligase activity, which might be critical for their clinical effects. Furthermore, FZR1 depletion cooperates with AKT hyperactivation to transform primary melanocytes, whereas genetic ablation of Fzr1 synergizes with Pten loss, leading to aberrant coactivation of BRAF/ERK and AKT signaling in mice. Our findings therefore reveal a reciprocal suppression mechanism between FZR1 and BRAF in controlling tumorigenesis. Significance: FZR1 inhibits BRAF oncogenic functions via both APC-dependent proteolysis and APC-independent disruption of BRAF dimers, whereas hyperactivated ERK and CDK4 reciprocally suppress APC FZR1 E3 ligase activity. Aberrancies in this newly defined signaling network might account for BRAF hyperactivation in human cancers, suggesting that targeting CYCLIN D1/CDK4, alone or in combination with BRAF/MEK inhibition, can be an effective anti-melanoma therapy. Cancer Discov; 7(4); 424-41. ©2017 AACR. See related commentary by Zhang and Bollag, p. 356 This article is highlighted in the In This Issue feature, p. 339 . ©2017 American Association for Cancer Research.

A Tidal Disruption Event in Arp299B

NASA Image and Video Library

2018-06-15

An image of the galaxy Arp299B, which is undergoing a merging process with Arp299A (the galaxy to the left), captured by NASA's Hubble space telescope. The inset features an artist's illustration of a tidal disruption event (TDE), which occurs when a star passes fatally close to a supermassive black hole. A TDE was recently observed near the center of Arp299B. https://photojournal.jpl.nasa.gov/catalog/PIA22356

Disruptive and Sustaining Technology Development Approaches in Defense Acquisition

DTIC Science & Technology

2014-04-30

feature for the emerging personal computer market. Disruptive innovation also operates on the scale of an entire market. The story of Eastman Kodak ...quality pictures, it was only available to those with expertise in, and desire to, chemically process the film. The Kodak box camera took lower quality...into a niche market. A century later the scenario repeated itself in amateur photography. Kodak had become locked into their century-old business

PLASMAP: an interactive computational tool for storage, retrieval and device-independent graphic display of conventional restriction maps.

PubMed Central

Stone, B N; Griesinger, G L; Modelevsky, J L

1984-01-01

We describe an interactive computational tool, PLASMAP, which allows the user to electronically store, retrieve, and display circular restriction maps. PLASMAP permits users to construct libraries of plasmid restriction maps as a set of files which may be edited in the laboratory at any time. The display feature of PLASMAP quickly generates device-independent, artist-quality, full-color or monochrome, hard copies or CRT screens of complex, conventional circular restriction maps. PMID:6320096

The effect of sleep restriction on snacking behaviour during a week of simulated shiftwork.

PubMed

Heath, Georgina; Roach, Gregory D; Dorrian, Jillian; Ferguson, Sally A; Darwent, David; Sargent, Charli

2012-03-01

Due to irregular working hours shiftworkers experience circadian disruption and sleep restriction. There is some evidence to indicate that these factors adversely affect health through changes in snacking behaviour. The aim of this study was to investigate the impact of sleep restriction, prior wake and circadian phase on snacking behaviour during a week of simulated shiftwork. Twenty-four healthy males (age: 22.0 ± 3.6 years, mean ± SD) lived in a sleep laboratory for 12 consecutive days. Participants were assigned to one of two schedules: a moderate sleep restriction condition (n=10) equivalent to a 6-h sleep opportunity per 24h or a severe sleep restriction condition (n=14) equivalent to a 4-h sleep opportunity per 24h. In both conditions, sleep/wake episodes occurred 4h later each day to simulate a rotating shiftwork pattern. While living in the laboratory, participants were served three meals and were provided with either five (moderate sleep restriction condition) or six (severe sleep restriction condition) snack opportunities daily. Snack choice was recorded at each opportunity and assigned to a category (sweet, savoury or healthy) based on the content of the snack. Data were analysed using a Generalised Estimating Equations approach. Analyses show a significant effect of sleep restriction condition on overall and sweet snack consumption. The odds of consuming a snack were significantly greater in the severe sleep restriction condition (P<0.05) compared to the moderate sleep restriction condition. In particular, the odds of choosing a sweet snack were significantly increased in the severe sleep restriction condition (P<0.05). Shiftworkers who are severely sleep restricted may be at risk of obesity and related health disorders due to elevated snack consumption and unhealthy snack choice. To further understand the impact of sleep restriction on snacking behaviour, future studies should examine physiological, psychological and environmental motivators. Copyright © 2011 Elsevier Ltd. All rights reserved.

Origin of bistability underlying mammalian cell cycle entry

PubMed Central

Yao, Guang; Tan, Cheemeng; West, Mike; Nevins, Joseph R; You, Lingchong

2011-01-01

Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb–E2F signaling pathway. Our recent work has further demonstrated that this regulation is mediated by a bistable switch mechanism. Nevertheless, the essential regulatory features in the Rb–E2F pathway that create this switching property have not been defined. Here we analyzed a library of gene circuits comprising all possible link combinations in a simplified Rb–E2F network. We identified a minimal circuit that is able to generate robust, resettable bistability. This minimal circuit contains a feed-forward loop coupled with a mutual-inhibition feedback loop, which forms an AND-gate control of the E2F activation. Underscoring its importance, experimental disruption of this circuit abolishes maintenance of the activated E2F state, supporting its importance for the bistability of the Rb–E2F system. Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point. PMID:21525871

Epigenetic regulation of neuroblastoma development.

PubMed

Durinck, Kaat; Speleman, Frank

2018-05-01

In recent years, technological advances have enabled a detailed landscaping of the epigenome and the mechanisms of epigenetic regulation that drive normal cell function, development and cancer. Rather than merely a structural entity to support genome compaction, we now look at chromatin as a very dynamic and essential constellation that is actively participating in the tight orchestration of transcriptional regulation as well as DNA replication and repair. The unique feature of chromatin flexibility enabling fast switches towards more or less restricted epigenetic cellular states is, not surprisingly, intimately connected to cancer development and treatment resistance, and the central role of epigenetic alterations in cancer is illustrated by the finding that up to 50% of all mutations across cancer entities affect proteins controlling the chromatin status. We summarize recent insights into epigenetic rewiring underlying neuroblastoma (NB) tumor formation ranging from changes in DNA methylation patterns and mutations in epigenetic regulators to global effects on transcriptional regulatory circuits that involve key players in NB oncogenesis. Insights into the disruption of the homeostatic epigenetic balance contributing to developmental arrest of sympathetic progenitor cells and subsequent NB oncogenesis are rapidly growing and will be exploited towards the development of novel therapeutic strategies to increase current survival rates of patients with high-risk NB.

Expression of Mutant Human DISC1 in Mice Supports Abnormalities in Differentiation of Oligodendrocytes

PubMed Central

Katsel, Pavel; Tan, Weilun; Abazyan, Bagrat; Davis, Kenneth L; Ross, Christopher; Pletnikov, Mikhail V; Haroutunian, Vahram

2011-01-01

Abnormalities in oligodendrocyte (OLG) differentiation and OLG gene expression deficit have been described in schizophrenia (SZ). Recent studies revealed a critical requirement for Disrupted-in-Schizophrenia 1 (DISC1) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (ΔhDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of ΔhDISC1 may influence the development of OLGs in this mouse model. OLG- and cell cycle-associated gene and protein expression were characterized in the forebrain of ΔhDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood. The results suggest that the expression of ΔhDISC1 exerts a significant influence on oligodendrocyte differentiation and function, evidenced by premature OLG differentiation and increased proliferation of their progenitors. Additional findings showed that neuregulin 1 and its receptors may be contributing factors to the observed upregulation of OLG genes. Thus, OLG function may be perturbed by mutant hDISC1 in a model system that provides new avenues for studying aspects of the pathogenesis of SZ. PMID:21605958

METABOLIC SYNDROME AND THE ROLE OF DIETARY LIFESTYLES IN ALZHEIMER’S DISEASE

PubMed Central

Pasinetti, Giulio Maria; Eberstein, Jacqueline A.

2008-01-01

Since Alzheimer’s disease (AD) has no cure or preventive treatment, an urgent need exists to find a means of preventing, delaying the onset, or reversing the course of the disease. Clinical and epidemiological evidence suggests that lifestyle factors, especially nutrition, may be crucial in controlling AD. Unhealthy lifestyle choices lead to an increasing incidence of obesity, dyslipidemia and hypertension — components of the metabolic syndrome. These disorders can also be linked to AD. Recent research supports the hypothesis that calorie intake, among other nongenetic factors, can influence the risk of clinical dementia. In animal studies, high calorie intake in the form of saturated fat promoted AD-type amyloidosis, while calorie restriction via reduced carbohydrate intake prevented it. Pending further study, it is prudent to recommend to those at risk for AD — e.g., with a family history or features of metabolic syndrome, such as obesity, insulin insensitivity, etc. — to avoid foods and beverages with added sugars; to eat whole, unrefined foods with natural fats, especially fish, nuts and seeds, olives and olive oil; and to minimize foods that disrupt insulin and blood sugar balance. PMID:18466323

Effects of fear of falling and activity restriction on normal and dual task walking in community dwelling older adults.

PubMed

Donoghue, Orna A; Cronin, Hilary; Savva, George M; O'Regan, Claire; Kenny, Rose Anne

2013-05-01

Fear of falling (FOF) is associated with poor physical and psychosocial health and can have debilitating consequences especially when it leads to activity restriction. This study examined whether normal and dual task gait disruptions were independently associated with FOF and activity restriction or if they were fully explained by impaired health status. Data was obtained from The Irish Longitudinal Study on Ageing (TILDA). Community dwelling adults ≥65 years, with a Mini-Mental State Examination score ≥18 and who completed a gait assessment (n=1307) were divided into three groups: no FOF, FOF but no activity restriction (FOF-NAR), FOF with activity restriction (FOF-AR). Physical, psychosocial and cognitive measures were obtained and gait characteristics were assessed using a GAITRite(®) mat during normal and dual task (cognitive) walking. After adjusting for sociodemographics, physical, mental and cognitive health, FOF was associated with reduced gait speed and stride length and increased double support phase and step width in normal and dual task conditions; these changes were most pronounced in those who restrict activities as a result of FOF. These gait changes may be associated with an increased fall risk, however some changes especially increased step width may also reflect positive, compensatory adaptations to FOF. The results also highlight the importance of treating underlying health impairments and preventing the transition from FOF to activity restriction. Copyright © 2012 Elsevier B.V. All rights reserved.

Measuring aging rates of mice subjected to caloric restriction and genetic disruption of growth hormone signaling

PubMed Central

Koopman, Jacob J.E.; van Heemst, Diana; van Bodegom, David; Bonkowski, Michael S.; Sun, Liou Y.; Bartke, Andrzej

2016-01-01

Caloric restriction and genetic disruption of growth hormone signaling have been shown to counteract aging in mice. The effects of these interventions on aging are examined through age-dependent survival or through the increase in age-dependent mortality rates on a logarithmic scale fitted to the Gompertz model. However, these methods have limitations that impede a fully comprehensive disclosure of these effects. Here we examine the effects of these interventions on murine aging through the increase in age-dependent mortality rates on a linear scale without fitting them to a model like the Gompertz model. Whereas these interventions negligibly and non-consistently affected the aging rates when examined through the age-dependent mortality rates on a logarithmic scale, they caused the aging rates to increase at higher ages and to higher levels when examined through the age-dependent mortality rates on a linear scale. These results add to the debate whether these interventions postpone or slow aging and to the understanding of the mechanisms by which they affect aging. Since different methods yield different results, it is worthwhile to compare their results in future research to obtain further insights into the effects of dietary, genetic, and other interventions on the aging of mice and other species. PMID:26959761

Measuring aging rates of mice subjected to caloric restriction and genetic disruption of growth hormone signaling.

PubMed

Koopman, Jacob J E; van Heemst, Diana; van Bodegom, David; Bonkowski, Michael S; Sun, Liou Y; Bartke, Andrzej

2016-03-01

Caloric restriction and genetic disruption of growth hormone signaling have been shown to counteract aging in mice. The effects of these interventions on aging are examined through age-dependent survival or through the increase in age-dependent mortality rates on a logarithmic scale fitted to the Gompertz model. However, these methods have limitations that impede a fully comprehensive disclosure of these effects. Here we examine the effects of these interventions on murine aging through the increase in age-dependent mortality rates on a linear scale without fitting them to a model like the Gompertz model. Whereas these interventions negligibly and non-consistently affected the aging rates when examined through the age-dependent mortality rates on a logarithmic scale, they caused the aging rates to increase at higher ages and to higher levels when examined through the age-dependent mortality rates on a linear scale. These results add to the debate whether these interventions postpone or slow aging and to the understanding of the mechanisms by which they affect aging. Since different methods yield different results, it is worthwhile to compare their results in future research to obtain further insights into the effects of dietary, genetic, and other interventions on the aging of mice and other species.

Different modes of retrovirus restriction by human APOBEC3A and APOBEC3G in vivo.

PubMed

Stavrou, Spyridon; Crawford, Daniel; Blouch, Kristin; Browne, Edward P; Kohli, Rahul M; Ross, Susan R

2014-05-01

The apolipoprotein B editing complex 3 (A3) cytidine deaminases are among the most highly evolutionarily selected retroviral restriction factors, both in terms of gene copy number and sequence diversity. Primate genomes encode seven A3 genes, and while A3F and 3G are widely recognized as important in the restriction of HIV, the role of the other genes, particularly A3A, is not as clear. Indeed, since human cells can express multiple A3 genes, and because of the lack of an experimentally tractable model, it is difficult to dissect the individual contribution of each gene to virus restriction in vivo. To overcome this problem, we generated human A3A and A3G transgenic mice on a mouse A3 knockout background. Using these mice, we demonstrate that both A3A and A3G restrict infection by murine retroviruses but by different mechanisms: A3G was packaged into virions and caused extensive deamination of the retrovirus genomes while A3A was not packaged and instead restricted infection when expressed in target cells. Additionally, we show that a murine leukemia virus engineered to express HIV Vif overcame the A3G-mediated restriction, thereby creating a novel model for studying the interaction between these proteins. We have thus developed an in vivo system for understanding how human A3 proteins use different modes of restriction, as well as a means for testing therapies that disrupt HIV Vif-A3G interactions.

Severe Craniofacial Involvement due to Amniotic Band Sequence.

PubMed

Becerra-Solano, Luis Eduardo; Castañeda-Cisneros, Gema; Corona-Rivera, Jorge Roman; Díaz-Rodríguez, Manuel; Figuera, Luis Eduardo; López-Muñoz, Eunice; Nastasi-Catanese, José Antonio; Toscano-Flores, José Jesús; Ramírez-Dueñas, María de Lourdes; García-Ortíz, José Elias

2018-02-01

Disruptive amniotic band sequence (DABS) is a sporadic, non-familial disorder with unclear etiology. Diagnosis is based on clinical features because there is currently no reliable laboratory diagnostic tests. We describe six cases of DABS with severe craniofacial deformations, three with and three without classical constrictive limb deformation. The craniofacial deformities were delimited by peripheral sharply demarcated scarring. When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS should be considered despite the absence of constrictive limb scarring.

Precision disablement aiming system

DOEpatents

Monda, Mark J.; Hobart, Clinton G.; Gladwell, Thomas Scott

2016-02-16

A disrupter to a target may be precisely aimed by positioning a radiation source to direct radiation towards the target, and a detector is positioned to detect radiation that passes through the target. An aiming device is positioned between the radiation source and the target, wherein a mechanical feature of the aiming device is superimposed on the target in a captured radiographic image. The location of the aiming device in the radiographic image is used to aim a disrupter towards the target.

Hiro and Evans currents in Vertical Disruption Event

NASA Astrophysics Data System (ADS)

Zakharov, Leonid; Xujing Li Team; Sergei Galkin Team

2014-10-01

The notion of Tokamak Magneto-Hydrodynamics (TMHD), which explicitly reflects the anisotropy of a high temperature tokamak plasma is introduced. The set of TMHD equations is formulated for simulations of macroscopic plasma dynamics and disruptions in tokamaks. Free from the Courant restriction on the time step, this set of equations is appropriate for high performance plasmas and does not require any extension of the MHD plasma model. At the same time, TMHD requires the use of magnetic field aligned numerical grids. The TMHD model was used for creation of theory of the Wall Touching Kink and Vertical Modes (WTKM and WTVM), prediction of Hiro and Evans currents, design of an innovative diagnostics for Hiro current measurements, installed on EAST device. While Hiro currents have explained the toroidal asymmetry in the plasma current measurements in JET disruptions, the Evans currents explain the tile current measurements in tokamaks. The recently developed Vertical Disruption Code (VDE) have demonstrated 5 regimes of VDE and confirmed the generation of both Hiro and Evans currents. The results challenge the 24 years long misinterpretation of the tile currents in tokamaks as ``halo'' currents, which were a product of misuse of equilibrium reconstruction for VDE. This work is supported by US DoE Contract No. DE-AC02-09-CH1146.

Near-infrared detection of potential evidence for microscopic organisms on Europa

NASA Technical Reports Server (NTRS)

Dalton, J. Brad; Mogul, Rakesh; Kagawa, Hiromi K.; Chan, Suzanne L.; Jamieson, Corey S.

2003-01-01

The possibility of an ocean within the icy shell of Jupiter's moon Europa has established that world as a primary candidate in the search for extraterrestrial life within our Solar System. This paper evaluates the potential to detect evidence for microbial life by comparing laboratory studies of terrestrial microorganisms with measurements from the Galileo Near Infrared Imaging Spectrometer (NIMS). If the interior of Europa at one time harbored life, some evidence may remain in the surface materials. Examination of laboratory spectra of terrestrial extremophiles measured at cryogenic temperatures reveals distorted, asymmetric nearinfrared absorption features due to water of hydration. The band centers, widths, and shapes of these features closely match those observed in the Europa spectra. These features are strongest in reddish-brown, disrupted terrains such as linea and chaos regions. Narrow spectral features due to amide bonds in the microbe proteins provide a means of constraining the abundances of such materials using the NIMS data. The NIMS data of disrupted terrains exhibit distorted, asymmetric near-infrared absorption features consistent with the presence of water ice, sulfuric acid octahydrate, hydrated salts, and possibly as much as 0.2 mg cm(-3) of carbonaceous material that could be of biological origin. However, inherent noise in the observations and limitations of spectral sampling must be taken into account when discussing these findings.

Near-infrared detection of potential evidence for microscopic organisms on Europa.

PubMed

Dalton, J Brad; Mogul, Rakesh; Kagawa, Hiromi K; Chan, Suzanne L; Jamieson, Corey S

2003-01-01

The possibility of an ocean within the icy shell of Jupiter's moon Europa has established that world as a primary candidate in the search for extraterrestrial life within our Solar System. This paper evaluates the potential to detect evidence for microbial life by comparing laboratory studies of terrestrial microorganisms with measurements from the Galileo Near Infrared Imaging Spectrometer (NIMS). If the interior of Europa at one time harbored life, some evidence may remain in the surface materials. Examination of laboratory spectra of terrestrial extremophiles measured at cryogenic temperatures reveals distorted, asymmetric nearinfrared absorption features due to water of hydration. The band centers, widths, and shapes of these features closely match those observed in the Europa spectra. These features are strongest in reddish-brown, disrupted terrains such as linea and chaos regions. Narrow spectral features due to amide bonds in the microbe proteins provide a means of constraining the abundances of such materials using the NIMS data. The NIMS data of disrupted terrains exhibit distorted, asymmetric near-infrared absorption features consistent with the presence of water ice, sulfuric acid octahydrate, hydrated salts, and possibly as much as 0.2 mg cm(-3) of carbonaceous material that could be of biological origin. However, inherent noise in the observations and limitations of spectral sampling must be taken into account when discussing these findings.

Toward a Best-Practice Protocol for Assessment of Sensory Features in ASD

ERIC Educational Resources Information Center

Schaaf, Roseann C.; Lane, Alison E.

2015-01-01

Sensory difficulties are a commonly occurring feature of autism spectrum disorders and are now included as one manifestation of the "restricted, repetitive patterns of behavior, interests, or activities" diagnostic criteria of the DSM5 necessitating guidelines for comprehensive assessment of these features. To facilitate the development…

CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity.

PubMed

Pereira, Catia S; Macedo, M Fatima

2016-01-01

Lipid-specific T cells comprise a group of T cells that recognize lipids bound to the MHC class I-like CD1 molecules. There are four isoforms of CD1 that are expressed at the surface of antigen presenting cells and therefore capable of presenting lipid antigens: CD1a, CD1b, CD1c, and CD1d. Each one of these isoforms has distinct structural features and cellular localizations, which promotes binding to a broad range of different types of lipids. Lipid antigens originate from either self-tissues or foreign sources, such as bacteria, fungus, or plants and their recognition by CD1-restricted T cells has important implications in infection but also in cancer and autoimmunity. In this review, we describe the characteristics of CD1 molecules and CD1-restricted lipid-specific T cells, highlighting the innate-like and adaptive-like features of different CD1-restricted T cell subtypes.

Is an Appreciation of Isomerism the Key to Unlocking the Mysteries of the Cardiac Findings in Heterotaxy?

PubMed

Anderson, Robert H; Spicer, Diane E; Loomba, Rohit

2018-02-06

Pediatric cardiologists treating patients with severe congenital cardiac defects define "visceral heterotaxy" on the basis of isomerism of the atrial appendages. The isomeric features represent an obvious manifestation of disruption of left-right asymmetry during embryonic development. Thus, there are two subsets of individuals within the overall syndrome, with features of either right or left isomerism. Within the heart, it is only the atrial appendages that are truly isomeric. The remainder of the cardiac components shows variable morphology, as does the arrangement of the remaining body organs. Order is provided in this potentially chaotic arrangement simply by describing the specific features of each of the systems. These features as defined by clinicians, however, seem less well recognized by those investigating the developmental origins of the disruption of symmetry. Developmental biologists place much greater emphasis on ventricular looping. Although the direction of the loop can certainly be interpreted as representing an example of asymmetry, it is not comparable to the isomeric features that underscore the clinical syndromes. This is because, thus far, there is no evidence of ventricular isomerism, with the ventricles distinguished one from the other on the basis of their disparate anatomical features. In similar fashion, some consider transposition to represent abnormal lateralization, but again, clinical diagnosis depends on recognition of the lateralized features. In this review, therefore, we discuss the key questions that currently underscore the mismatch in the approaches to "lateralization" as taken by clinicians and developmental biologists.

Liposome Disruption Assay to Examine Lytic Properties of Biomolecules.

PubMed

Jimah, John R; Schlesinger, Paul H; Tolia, Niraj H

2017-08-05

Proteins may have three dimensional structural or amino acid features that suggest a role in targeting and disrupting lipids within cell membranes. It is often necessary to experimentally investigate if these proteins and biomolecules are able to disrupt membranes in order to conclusively characterize the function of these biomolecules. Here, we describe an in vitro assay to evaluate the membrane lytic properties of proteins and biomolecules. Large unilamellar vesicles (liposomes) containing carboxyfluorescein at fluorescence-quenching concentrations are treated with the biomolecule of interest. A resulting increase in fluorescence due to leakage of the dye from liposomes and subsequent dilution in the buffer demonstrates that the biomolecule is sufficient for disrupting liposomes and membranes. Additionally, since liposome disruption may occur via pore-formation or via general solubilization of lipids similar to detergents, we provide a method to distinguish between these two mechanisms. Pore-formation can be identified and evaluated by examining the blockade of carboxyfluorescein release with dextran molecules that fit the pore. The methods described here were used to determine that the malaria vaccine candidate CelTOS and proapoptotic Bax disrupt liposomes by pore formation (Saito et al. , 2000; Jimah et al. , 2016). Since membrane lipid binding by a biomolecule precedes membrane disruption, we recommend the companion protocol: Jimah et al. , 2017.

Characteristics of Low-q(a) Disruptions in the Compact Toroidal Hybrid

NASA Astrophysics Data System (ADS)

Pandya, M. D.; Archmiller, M. C.; Ennis, D. A.; Hartwell, G. J.; Maurer, D. A.

2014-10-01

Tokamak disruptions are dramatic events that lead to a sudden loss of plasma confinement. Disruptions that occur at low edge safety-factor, q (a) , limit the operation of tokamaks to q (a) >= 2 . The Compact Toroidal Hybrid (CTH) is a torsatron-tokamak hybrid with a helical field coil and vertical field coils to establish a stellartor equilibrium, while an ohmic coil induces plasma current. A feature of the CTH device is the ability to adjust the vacuum rotational transform, tvac (t =1/q ), by varying the ratio of current in the helical and toroidal field coils. The value of edge tvac can be varied from about 0.02 to 0.3 (qvac (a) ~ 50 to 3.3). Plasma discharges in CTH are routinely observed to operate with q (a) < 2 , and in some cases as low as q (a) ~ 1 . 1 . In CTH, low-q(a) disruptions are observed with a dominant m/n=3/2 precursor. The disruptivity of plasma discharges is over 80% when tvac (a) < 0 . 04 (qvac (a) < 25) and as tvac (a) is increased further, the disruptivity of the plasma discharges decreases. The disruptions are completely suppressed for tvac (a) > 0 . 07 (qvac (a) ~ 14) . This work is supported by US Department of Energy Grant No. DE-FG02-00ER54610.

Neuroimmunomodulation in unipolar depression: a focus on chronobiology and chronotherapeutics.

PubMed

Eyre, Harris; Baune, Bernhard T

2012-10-01

The rising burden of unipolar depression along with its often related sleep disturbances, as well as increasing rates of sleep restriction in modern society, make the search for an extended understanding of the aetiology and pathophysiology of depression necessary. Accumulating evidence suggests an important role for the immune system in mediating disrupted neurobiological and chronobiological processes in depression. This review aims to provide an overview of the neuroimmunomodulatory processes involved with depression and antidepressant treatments with a special focus on chronobiology, chronotherapeutics and the emerging field of immune-circadian bi-directional crosstalk. Increasing evidence suggests that chronobiological disruption can mediate immune changes in depression, and likewise, immune processes can mediate chronobiological disruption. This may suggest a bi-directional relationship in immune-circadian crosstalk. Furthermore, given the immunomodulatory effects of antidepressants and chronotherapeutics, as well as their associated beneficial effects on circadian disturbance, we--and others--suggest that these therapeutic agents may exert their chronobiotic effects partially via the neuroimmune system. Further research is required to better elucidate the mechanisms of immune involvement in the chronobiology of depression.

Altering the selection capabilities of common cloning vectors via restriction enzyme mediated gene disruption

PubMed Central

2013-01-01

Background The cloning of gene sequences forms the basis for many molecular biological studies. One important step in the cloning process is the isolation of bacterial transformants carrying vector DNA. This involves a vector-encoded selectable marker gene, which in most cases, confers resistance to an antibiotic. However, there are a number of circumstances in which a different selectable marker is required or may be preferable. Such situations can include restrictions to host strain choice, two phase cloning experiments and mutagenesis experiments, issues that result in additional unnecessary cloning steps, in which the DNA needs to be subcloned into a vector with a suitable selectable marker. Results We have used restriction enzyme mediated gene disruption to modify the selectable marker gene of a given vector by cloning a different selectable marker gene into the original marker present in that vector. Cloning a new selectable marker into a pre-existing marker was found to change the selection phenotype conferred by that vector, which we were able to demonstrate using multiple commonly used vectors and multiple resistance markers. This methodology was also successfully applied not only to cloning vectors, but also to expression vectors while keeping the expression characteristics of the vector unaltered. Conclusions Changing the selectable marker of a given vector has a number of advantages and applications. This rapid and efficient method could be used for co-expression of recombinant proteins, optimisation of two phase cloning procedures, as well as multiple genetic manipulations within the same host strain without the need to remove a pre-existing selectable marker in a previously genetically modified strain. PMID:23497512

Targets of small interfering RNA restriction during human immunodeficiency virus type 1 replication.

PubMed

Gao, Yong; Lobritz, Michael A; Roth, Justin; Abreha, Measho; Nelson, Kenneth N; Nankya, Immaculate; Moore-Dudley, Dawn M; Abraha, Awet; Gerson, Stanton L; Arts, Eric J

2008-03-01

Small interfering RNAs (siRNAs) have been shown to effectively inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro. The mechanism(s) for this inhibition is poorly understood, as siRNAs may interact with multiple HIV-1 RNA species during different steps of the retroviral life cycle. To define susceptible HIV-1 RNA species, siRNAs were first designed to specifically inhibit two divergent primary HIV-1 isolates via env and gag gene targets. A self-inactivating lentiviral vector harboring these target sequences confirmed that siRNA cannot degrade incoming genomic RNA. Disruption of the incoming core structure by rhesus macaque TRIM5alpha did, however, provide siRNA-RNA-induced silencing complex access to HIV-1 genomic RNA and promoted degradation. In the absence of accelerated core disruption, only newly transcribed HIV-1 mRNA in the cytoplasm is sensitive to siRNA degradation. Inhibitors of HIV-1 mRNA nuclear export, such as leptomycin B and camptothecin, blocked siRNA restriction. All HIV-1 RNA regions and transcripts found 5' of the target sequence, including multiply spliced HIV-1 RNA, were degraded by unidirectional 3'-to-5' siRNA amplification and spreading. In contrast, HIV-1 RNA 3' of the target sequence was not susceptible to siRNA. Even in the presence of siRNA, full-length HIV-1 RNA is still encapsidated into newly assembled viruses. These findings suggest that siRNA can target only a relatively "naked" cytoplasmic HIV-1 RNA despite the involvement of viral RNA at nearly every step in the retroviral life cycle. Protection of HIV-1 RNA within the core following virus entry, during encapsidation/virus assembly, or within the nucleus may reflect virus evolution in response to siRNA, TRIM5alpha, or other host restriction factors.

Expressive inhibition in response to stress: implications for emotional processing following trauma.

PubMed

Clapp, Joshua D; Patton, Samantha C; Beck, J Gayle

2015-01-01

Expressive inhibition--the willful restriction of expressed emotion--is documented in individuals reporting trauma-related distress, but its impact on global affective functioning remains unclear. Theoretical models propose that chronic activation of negative emotion and deliberate restriction of affect operate synergistically to produce trauma-related emotional deficits. The current project examined the impact of these factors on subjective experience and physiological activation following exposure to an analog trauma. University students (N=192; Mage=20, 57% female, 42% White/Non-Hispanic) viewed a graphic film depicting scenes of a televised suicide. Participants then viewed either a sadness- or humor-eliciting film under instructions to inhibit [nsadness=45, nhumor=52] or naturally express emotion [nsadness=48, nhumor=47]. Expressive inhibition was associated with restricted amusement specifically among participants viewing the humor film. Inhibition also produced attenuated sympathetic and parasympathetic recovery, irrespective of film assignment. Evidence of disruptions in emotional processing supports models identifying inhibition as a possible mechanism in post-trauma affect dysregulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Unusual target site disruption by the rare-cutting HNH restriction endonuclease PacI

PubMed Central

Shen, Betty; Heiter, Daniel F.; Chan, Siu-Hong; Wang, Hua; Xu, Shuang-Yong; Morgan, Richard D.; Wilson, Geoffrey G.; Stoddard, Barry L.

2010-01-01

The crystal structure of the rare-cutting HNH restriction endonuclease PacI in complex with its eight base pair target recognition sequence 5'-TTAATTAA-3' has been determined to 1.9 Å resolution. The enzyme forms an extended homodimer, with each subunit containing two zinc-bound motifs surrounding a ββα-metal catalytic site. The latter is unusual in that a tyrosine residue likely initiates strand-cleavage. PacI dramatically distorts its target sequence from Watson-Crick duplex DNA basepairing, with every base separated from its original partner. Two bases on each strand are unpaired, four are engaged in non-canonical A:A and T:T base pairs, and the remaining two bases are matched with new Watson-Crick partners. This represents a highly unusual DNA binding mechanism for a restriction endonuclease, and implies that initial recognition of the target site might involve significantly different contacts from those visualized in the DNA-bound cocrystal structures. PMID:20541511

Expressive inhibition in response to stress: Implications for emotional processing following trauma

PubMed Central

Clapp, Joshua D.; Patton, Samantha C.; Beck, J. Gayle

2015-01-01

Expressive inhibition - the willful restriction of expressed emotion - is documented in individuals reporting trauma-related distress, but its impact on global affective functioning remains unclear. Theoretical models propose that chronic activation of negative emotion and deliberate restriction of affect operate synergistically to produce trauma-related emotional deficits. The current project examined the impact of these factors on subjective experience and physiological activation following exposure to an analog trauma. University students (N = 192; Mage = 20, 57% female, 42% White/Non-Hispanic) viewed a graphic film depicting scenes of a televised suicide. Participants then viewed either a sadness- or humor-eliciting film under instructions to inhibit [nsadness = 45, nhumor = 52] or naturally express emotion [nsadness = 48, nhumor = 47]. Expressive inhibition was associated with restricted amusement specifically among participants viewing the humor film. Inhibition also produced attenuated sympathetic and parasympathetic recovery, irrespective of film assignment. Evidence of disruptions in emotional processing supports models identifying inhibition as a possible mechanism in post-trauma affect dysregulation. PMID:25576773

Active site remodeling switches HIV specificity of antiretroviral TRIMCyp

PubMed Central

Price, Amanda J; Marzetta, Flavia; Lammers, Michael; Ylinen, Laura M J; Schaller, Torsten; Wilson, Sam J; Towers, Greg J; James, Leo C

2011-01-01

TRIMCyps are primate antiretroviral proteins that potently inhibit HIV replication. Here we describe how rhesus macaque TRIMCyp (RhTC) has evolved to target and restrict HIV-2. We show that the ancestral cyclophilin A (CypA) domain of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in RhTC by two mutations (D66N and R69H) at the expense of HIV-1 binding. These mutations disrupt a constraining intramolecular interaction in CypA, triggering the complete restructuring (>16 Å) of an active site loop. This new configuration discriminates between divergent HIV-1 and HIV-2 loop conformations mediated by capsid residue 88. Viral sensitivity to RhTC restriction can be conferred or abolished by mutating position 88. Furthermore, position 88 determines the susceptibility of naturally occurring HIV-1 sequences to restriction. Our results reveal the complex molecular, structural and thermodynamic changes that underlie the ongoing evolutionary race between virus and host. PMID:19767750

Contextual Risk Factors as Predictors of Disruptive Behavior Disorder Trajectories in Girls: The Moderating Effect of Callous-Unemotional Features

ERIC Educational Resources Information Center

Kroneman, Leoniek M.; Hipwell, Alison E.; Loeber, Rolf; Koot, Hans M.; Pardini, Dustin A.

2011-01-01

Background: The presence of callous-unemotional (CU) features may delineate a severe and persistent form of conduct problems in children with unique developmental origins. Contextual risk factors such as poor parenting, delinquent peers, or neighborhood risk are believed to influence the development of conduct problems primarily in children with…

Observing Behavior and Atypically Restricted Stimulus Control

ERIC Educational Resources Information Center

Dube, William V.; Dickson, Chata A.; Balsamo, Lyn M.; O'Donnell, Kristin Lombard; Tomanari, Gerson Y.; Farren, Kevin M.; Wheeler, Emily E.; McIlvane, William J.

2010-01-01

Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded…

Reduced amygdala response in youths with disruptive behavior disorders and psychopathic traits: decreased emotional response versus increased top-down attention to nonemotional features.

PubMed

White, Stuart F; Marsh, Abigail A; Fowler, Katherine A; Schechter, Julia C; Adalio, Christopher; Pope, Kayla; Sinclair, Stephen; Pine, Daniel S; Blair, R James R

2012-07-01

Amygdala dysfunction has been reported to exist in youths and adults with psychopathic traits. However, there has been disagreement as to whether this dysfunction reflects a primary emotional deficit or is secondary to atypical attentional control. The authors examined the validity of the contrasting predictions. Participants were 15 children and adolescents (ages 10–17 years) with both disruptive behavior disorders and psychopathic traits and 17 healthy comparison youths. Functional MRI was used to assess the response of the amygdala and regions implicated in top-down attentional control (the dorsomedial and lateral frontal cortices) to emotional expression under conditions of high and low attentional load. Relative to youths with disruptive behavior disorders and psychopathic traits, healthy comparison subjects showed a significantly greater increase in the typical amygdala response to fearful expressions under low relative to high attentional load conditions. There was also a selective inverse relationship between the response to fearful expressions under low attentional load and the callous-unemotional component (but not the narcissism or impulsivity component) of psychopathic traits. In contrast, the two groups did not differ in the significant recruitment of the dorsomedial and lateral frontal cortices as a function of attentional load. Youths with disruptive behavior disorders and psychopathic traits showed reduced amygdala responses to fearful expressions under low attentional load but no indications of increased recruitment of regions implicated in top-down attentional control. These findings suggest that the emotional deficit observed in youths with disruptive behavior disorders and psychopathic traits is primary and not secondary to increased top-down attention to nonemotional stimulus features.

Impact of a child's cancer disease on parents' everyday life: a longitudinal study from Sweden.

PubMed

Hovén, Emma; Grönqvist, Helena; Pöder, Ulrika; von Essen, Louise; Lindahl Norberg, Annika

2017-01-01

A child's cancer disease may disrupt the daily life of the affected family for a long period. The aim was to describe restrictions on parents' leisure activities and work/studies during and after the child's treatment. This study used data from a cohort of mothers and fathers (n = 246) of children diagnosed with cancer. Data was collected five times from two months after diagnosis to one year after end of treatment. Reports of restrictions were evaluated over time, between mothers and fathers, and in relation to parent-reported child symptom burden (The Memorial Symptom Assessment Scale) and partial post-traumatic stress disorder (PTSD) (The PTSD Checklist-Civilian Version). Two (51%) and four (45%) months after diagnosis, about half reported that their leisure activities were restricted at least some of the time. Corresponding percentages for restrictions on work/studies were 84% and 77%. One year after end of treatment, the great majority reported that their leisure activities (91%) and/or work/studies (76%) were never/seldom restricted. During treatment, more mothers than fathers reported restrictions on work/studies all/most of the time. After end of treatment, gender was only related to reports of restrictions among parents not reporting partial PTSD. More parents who reported being restricted all/most of the time also reported partial PTSD and/or a greater symptom burden for the child. Parents report frequent restrictions on everyday life during treatment. One year after end of treatment, parents report only a limited impact of the child's cancer on their leisure activities and work/studies. More parents who report restrictions also report partial PTSD and/or a greater child symptom burden. The effect of gender on restrictions varies depending on reports of partial PTSD. Future studies of gender differences regarding the impact of a child's cancer on parents' everyday life should thus consider mothers' and fathers' level of psychological distress.

Disrupting Somali Piracy via Trust and Influence Operations

DTIC Science & Technology

2009-06-01

cigarettes, and other provisions for future missions, 30 percent in bribes to government officials” (Associated Press, 2009a). Once a group of pirates...incentive – there is a lack of incentive for the crewmembers to be proactive since in most cases pirates pose little threat to the crew; legal and... ethical issues – shipping companies are hesitant to arm their crews due to the dangers associated with firearms onboard ship, insurance restrictions

Sleep disorders in the elderly

MedlinePlus

... this page: //medlineplus.gov/ency/article/000064.htm Sleep disorders in older adults To use the sharing features on this page, please enable JavaScript. Sleep disorders in older adults involve any disrupted sleep ...

The Importance of Chaos and Lenticulae on Europa for the JIMO Mission

NASA Technical Reports Server (NTRS)

Spaun, Nicole A.

2003-01-01

The Galileo Solid State Imaging (SSI) experiment provided high-resolution images of Europa's surface allowing identification of surface features barely distinguishable at Voyager's resolution. SSI revealed the visible pitting on Europa's surface to be due to large disrupted features, chaos, and smaller sub-circular patches, lenticulae. Chaos features contain a hummocky matrix material and commonly contain dislocated blocks of ridged plains. Lenticulae are morphologically interrelated and can be divided into three classes: domes, spots, and micro-chaos. Domes are broad, upwarped features that generally do not disrupt the texture of the ridged plains. Spots are areas of low albedo that are generally smooth in texture compared to other units. Micro-chaos are disrupted features with a hummocky matrix material, resembling that observed within chaos regions. Chaos and lenticulae are ubiquitous in the SSI regional map observations, which average approximately 200 meters per pixel (m/pxl) in resolution, and appear in several of the ultra-high resolution, i.e., better than 50 m/pxl, images of Europa as well. SSI also provided a number of multi-spectral observations of chaos and lenticulae. Using this dataset we have undertaken a thorough study of the morphology, size, spacing, stratigraphy, and color of chaos and lenticulae to determine their properties and evaluate models of their formation. Geological mapping indicates that chaos and micro-chaos have a similar internal morphology of in-situ degradation suggesting that a similar process was operating during their formation. The size distribution denotes a dominant size of 4-8 km in diameter for features containing hummocky material (i.e., chaos and micro-chaos). Results indicate a dominant spacing of 15 - 36 km apart. Chaos and lenticulae are generally among the youngest features stratigraphically observed on the surface, suggesting a recent change in resurfacing style. Also, the reddish non-icy materials on Europa's surface have high concentrations in many chaos and lenticulae features. Nonetheless, a complete global map of the distribution of chaos and lenticulae is not possible with the SSI dataset. Only <20% of the surface has been imaged at 200 m/pxl or better resolution, mostly of the near-equatorial regions. Color and ultra-high-res images have much less surface coverage. Thus we suggest that full global imaging of Europa at 200 m/pxl or better resolution, preferably in multi-spectral wavelengths, should be a high priority for the JIMO mission.

NGH: A Dynamic Factor in Deep Water Sediments & the Geological Record

NASA Astrophysics Data System (ADS)

Max, M. D.; Johnson, A. H.

2012-12-01

Prior to identification of natural gas hydrate (NGH) in marine sediments, gravity and tectonic forces were the recognized dynamic forces that could cause disruption in deep marine sediments. NGH introduces a new dynamic factor into continental slope and rise sediments as well as sediments in the deeper parts of some continental shelves. Two critical elements interplay to provide for a slow acting, long-term NGH-dynamic cyclical system. First, NGH forms spontaneously from dissolved natural gas generally in a passive manner without causing any other than very subtle alterations to the megascopic sediment structure. When NGH forms in either dispersed form in muddy sediments or in concentrated form in veins or nodules or in porosity in sandy sediments, it increases overall mechanical strength. Second, when it dissociates, mechanical strength weakens to the point where shear strengths can approach zero. Because the chemical reaction of NGH is highly reversible, changes in sea level that affect pressure, and changes in seafloor temperature can alter rapidly the tendency of NGH to either crystallize or dissociate, with consequent structural and morphological effects. The cyclicity of the Earth's climate introduces a mechanism for periodically injecting overpressured gas into marine sediments as the gas hydrate stability zones (GHSZ) undergoes changes to its thickness and depth. Natural climate change has the potential to produce overpressured natural gas converted from NGH in marine sediments periodically. In-place disruption would consist of disrupted sandy beds, chaotic textures on all scales, intrusion effects, limited mass flow features, dramatic sediment mixing not related to large scale movement and sediment redeposition from fluidized beds. Mobilization would involve larger scale sediment mass flow effects that would be indistinguishable from olistostromic melanges postulated to be initiated by tectonic or gravitational forces. The earliest interpretation of this fluidization type of large scale sediment disruption in the later part of the 1900s identified them as tectonic in origin. Subsequently, in the 1970s, it was recognized that the features were more likely a product of soft sediment deformation whose initiator might be gravity or tectonic forces, of 'tectonosedimentary' origin. The action of the NGH cycle to initiate sedimentary disruption may more readily explain many of these features in the geological record. Drill core taken across seismic reflection sediment redeposition features that otherwise show no tectonic activity related movement in abandoned GHSZ could provide important evidence for the long-term geological action of the NGH cycle.

Perceived Community Environmental Factors and Risk of Five-Year Participation Restriction Among Older Adults With or at Risk of Knee Osteoarthritis.

PubMed

Vaughan, Molly W; Felson, David T; LaValley, Michael P; Orsmond, Gael I; Niu, Jingbo; Lewis, Cora E; Segal, Neil A; Nevitt, Michael C; Keysor, Julie J

2017-07-01

Older adults with knee osteoarthritis (OA) who live in environments with mobility barriers may be at greater risk of developing participation restrictions, defined as difficulties in engagement in life situations. We investigated the risk of participation restriction over 5 years due to self-reported environmental features among older adults with knee OA. Participants from the Multicenter Osteoarthritis (MOST) Study self-reported participation at baseline, 30 months, and 60 months using the instrumental role subscale of the Late Life Disability Index (LLDI). Data on self-reported environmental features were from the Home and Community Environment questionnaire administered in the MOST Knee Pain and Disability study, an ancillary study of MOST. The relative risks (RRs) of developing participation restriction at 60 months, indicated by an LLDI score <67.6 out of a possible 100, due to reported high community mobility barriers and high transportation facilitators, were calculated using robust Poisson regression, adjusting for covariates. Sixty-nine of the 322 participants (27%) developed participation restriction by 60 months. Participants reporting high community mobility barriers at baseline had 1.8 times the risk (95% confidence interval [95% CI] 1.2-2.7) of participation restriction at 60 months, after adjusting for covariates. Self-report of high transportation facilitators at baseline resulted in a reduced but statistically nonsignificant risk of participation restriction at 60 months (RR 0.7, 95% CI 0.4-1.1). Higher perceived environmental barriers impact the risk of long-term participation restriction among older adults with or at risk of knee OA. Approaches aimed at reducing the development of participation restrictions in this population should consider decreasing environmental barriers. © 2017, American College of Rheumatology.

FATS: Feature Analysis for Time Series

NASA Astrophysics Data System (ADS)

Nun, Isadora; Protopapas, Pavlos; Sim, Brandon; Zhu, Ming; Dave, Rahul; Castro, Nicolas; Pichara, Karim

2017-11-01

FATS facilitates and standardizes feature extraction for time series data; it quickly and efficiently calculates a compilation of many existing light curve features. Users can characterize or analyze an astronomical photometric database, though this library is not necessarily restricted to the astronomical domain and can also be applied to any kind of time series data.

Amphipathic Alpha-Helical Peptide Compositions as Antiviral Agents

NASA Technical Reports Server (NTRS)

Frank, Curtis W. (Inventor); Cheong, Kwang Ho (Inventor); Glenn, Jeffrey (Inventor); Cho, Nam-Joon (Inventor)

2014-01-01

The invention features methods and compositions that exploit the ability of amphipathic alpha-helical (AH) peptides to cause disruption of lipid-containing vesicles, such as enveloped viruses, in a size-dependent manner.

Genetics Home Reference: atelosteogenesis type 3

MedlinePlus

... in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet. 2004 Apr; ... Celebrates Its 15th Anniversary Genetic Information Non-Discrimination Act (GINA) Turns 10 All Bulletins Features What is ...

Genetics Home Reference: boomerang dysplasia

MedlinePlus

... in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet. 2004 Apr; ... Celebrates Its 15th Anniversary Genetic Information Non-Discrimination Act (GINA) Turns 10 All Bulletins Features What is ...

Genetics Home Reference: atelosteogenesis type 1

MedlinePlus

... in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet. 2004 Apr; ... Celebrates Its 15th Anniversary Genetic Information Non-Discrimination Act (GINA) Turns 10 All Bulletins Features What is ...

Genetics Home Reference: adenosine deaminase 2 deficiency

MedlinePlus

... not fully understand how a loss of this enzyme's function leads to the features of ADA2 deficiency. They speculate that a lack of this enzyme may disrupt the balance between pro-inflammatory and ...

Europa Ice

NASA Image and Video Library

1998-05-08

This image of Jupiter icy satellite Europa shows surface features such as domes and ridges, as well as a region of disrupted terrain including crustal plates which are thought to have broken apart and rafted into new positions.

Some novel features in 2D non-Abelian theory: BRST approach

NASA Astrophysics Data System (ADS)

Srinivas, N.; Kumar, S.; Kureel, B. K.; Malik, R. P.

2017-08-01

Within the framework of Becchi-Rouet-Stora-Tyutin (BRST) formalism, we discuss some novel features of a two (1+1)-dimensional (2D) non-Abelian 1-form gauge theory (without any interaction with matter fields). Besides the usual off-shell nilpotent and absolutely anticommutating (anti-)BRST symmetry transformations, we discuss the off-shell nilpotent and absolutely anticommutating (anti-)co-BRST symmetry transformations. Particularly, we lay emphasis on the existence of the coupled (but equivalent) Lagrangian densities of the 2D non-Abelian theory in view of the presence of (anti-)co-BRST symmetry transformations where we pin-point some novel features associated with the Curci-Ferrari (CF-)type restrictions. We demonstrate that these CF-type restrictions can be incorporated into the (anti-)co-BRST invariant Lagrangian densities through the fermionic Lagrange multipliers which carry specific ghost numbers. The modified versions of the Lagrangian densities (where we get rid of the new CF-type restrictions) respect some precise symmetries as well as a couple of symmetries with CF-type constraints. These observations are completely novel as far as the BRST formalism, with proper (anti-)co-BRST symmetries, is concerned.

Structural deformation at the Flynn Creek impact crater, Tennessee - A preliminary report on deep drilling

NASA Technical Reports Server (NTRS)

Roddy, D. J.

1979-01-01

The geologic and core drilling studies described in the present paper show that the Flynn Creek crater has such distinctive morphological features as a broad flat hummocky floor; large central peak; locally terraced crater walls; uplifted, as well as flat-lying rim segments; and a surrounding ejecta blanket. The major structural features include a shallow depth of total brecciation and excavation as compared with apparent crater diameter; a thin breccia lens underlain by a thin zone of disrupted strata; concentric ring fault zones in inner rim, beneath crater wall, and outer crater floor regions; a large central uplift underlain by a narrow dipping zone of deeply disrupted strata; faulted, folded, brecciated, and fractured rim strata; and uplifted rim strata, which dip away from the crater, and flat-lying rim strata, which terminate as inward dipping rocks.

The fragmented self: imbalance between intrinsic and extrinsic self-networks in psychotic disorders.

PubMed

Ebisch, Sjoerd J H; Aleman, André

2016-08-01

Self-disturbances are among the core features of schizophrenia and related psychotic disorders. The basic structure of the self could depend on the balance between intrinsic and extrinsic self-processing. We discuss studies on self-related processing in psychotic disorders that provide converging evidence for disrupted communication between neural networks subserving the so-called intrinsic self and extrinsic self. This disruption might be mainly caused by impaired integrity of key brain hubs. The intrinsic self has been associated with cortical midline structures involved in self-referential processing, autobiographical memory, and emotional evaluation. Additionally, we highlight central aspects of the extrinsic self in its interaction with the environment using sensorimotor networks, including self-experience in sensation and actions. A deficient relationship between these self-aspects because of disrupted between-network interactions offers a framework to explain core clinical features of psychotic disorders. In particular, we show how relative isolation and reduced modularity of networks subserving intrinsic and extrinsic self-processing might trigger the emergence of hallucinations and delusions, and why patients with psychosis typically have difficulties with self-other relationships and do not recognise mental problems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

DOE PAGES

Blundon, Jay A.; Roy, Noah C.; Teubner, Brett J. W.; ...

2017-06-30

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. We show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5'-nucleotidase–dependent adenosine production or A1–adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement ofmore » tone-discrimination abilities. We determined that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.« less

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

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

Blundon, Jay A.; Roy, Noah C.; Teubner, Brett J. W.

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. We show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5'-nucleotidase–dependent adenosine production or A1–adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement ofmore » tone-discrimination abilities. We determined that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.« less

Inhibition of microtubules and dynein rescues human immunodeficiency virus type 1 from owl monkey TRIMCyp-mediated restriction in a cellular context-specific fashion.

PubMed

Pawlica, Paulina; Dufour, Caroline; Berthoux, Lionel

2015-04-01

IFN-induced restriction factors can significantly affect the replicative capacity of retroviruses in mammals. TRIM5α (tripartite motif protein 5, isoform α) is a restriction factor that acts at early stages of the virus life cycle by intercepting and destabilizing incoming retroviral cores. Sensitivity to TRIM5α maps to the N-terminal domain of the retroviral capsid proteins. In several New World and Old World monkey species, independent events of retrotransposon-mediated insertion of the cyclophilin A (CypA)-coding sequence in the trim5 gene have given rise to TRIMCyp (also called TRIM5-CypA), a hybrid protein that is active against some lentiviruses in a species-specific fashion. In particular, TRIMCyp from the owl monkey (omkTRIMCyp) very efficiently inhibits human immunodeficiency virus type 1 (HIV-1). Previously, we showed that disrupting the integrity of microtubules (MTs) and of cytoplasmic dynein complexes partially rescued replication of retroviruses, including HIV-1, from restriction mediated by TRIM5α. Here, we showed that efficient restriction of HIV-1 by omkTRIMCyp was similarly dependent on the MT network and on dynein complexes, but in a context-dependent fashion. When omkTRIMCyp was expressed in human HeLa cells, restriction was partially counteracted by pharmacological agents targeting MTs or by small interfering RNA-mediated inhibition of dynein. The same drugs (nocodazole and paclitaxel) also rescued HIV-1 from restriction in cat CRFK cells, although to a lesser extent. Strikingly, neither nocodazole, paclitaxel nor depletion of the dynein heavy chain had a significant effect on the restriction of HIV-1 in an owl monkey cell line. These results suggested the existence of cell-specific functional interactions between MTs/dynein and TRIMCyp. © 2015 The Authors.

Imaging flow cytometry for the screening of compounds that disrupt the Plasmodium falciparum digestive vacuole.

PubMed

Chia, Wan Ni; Lee, Yan Quan; Tan, Kevin Shyong-Wei

2017-01-01

Malaria, despite being one of the world's oldest infectious diseases, remains difficult to eradicate because the parasite is rapidly developing resistance to frontline chemotherapies. Previous studies have shown that the parasite exhibits features resembling programmed cell death upon treatment with drugs that disrupt its digestive vacuole (DV), providing a phenotypic readout that can be detected using the imaging flow cytometer. Large compound collections can thus be screened to identify drugs that are able to disrupt the DV of the malaria parasite using this high-content high-throughput screening platform. As a proof-of-concept, 4440 compounds were screened using this platform in 4months and 254 hits (5.7% hit rate) were obtained. Additionally, 25 compounds (0.6% top hit rate) were observed to retain potent DV disruption activity that was comparable to the canonical DV disruptive drug chloroquine when tested at a ten-fold lower concentration from the original screen. This pilot study demonstrates the robustness and high-throughput capability of the imaging flow cytometer and we report herein the methodology of this screening assay. Copyright © 2016 Elsevier Inc. All rights reserved.

Surgical management of haemangiopericytoma involving the biceps femoris muscle in four dogs.

PubMed

Connery, N A; Bellenger, C R

2002-11-01

Four dogs with haemangiopericytoma of the subcutaneous tissue overlying and infiltrating the biceps femoris muscle were successfully managed using complete resection of the involved muscle with 2 to 3 cm skin margins. Postoperatively, no local recurrence was noted in any of the dogs in a follow-up period of four to 33 months (mean 22 months). Wound dehiscence, attributed to increased tension and inadequate exercise restriction, occurred in two of the four cases. Closure of the large cutaneous deficit in the craniolateral thigh and stifle was achieved by rotation of a flank-fold skin flap in one case. Strict exercise restriction and the use of a Robert Jones dressing may prevent muscle suture disruption. These measures should enable primary wound healing in the region to progress without complication.

Analysis and Design of a Double-Divert Spiral Groove Seal

NASA Technical Reports Server (NTRS)

Zheng, Xiaoqing; Berard, Gerald

2007-01-01

This viewgraph presentation describes the design and analysis of a double spiral groove seal. The contents include: 1) Double Spiral Design Features; 2) Double Spiral Operational Features; 3) Mating Ring/Rotor Assembly; 4) Seal Ring Assembly; 5) Insert Segment Joints; 6) Rotor Assembly Completed Prototype Parts; 7) Seal Assembly Completed Prototype Parts; 8) Finite Element Analysis; 9) Computational Fluid Dynamics (CFD) Analysis; 10) Restrictive Orifice Design; 11) Orifice CFD Model; 12) Orifice Results; 13) Restrictive Orifice; 14) Seal Face Coning; 15) Permanent Magnet Analysis; 16) Magnetic Repulsive Force; 17) Magnetic Repulsive Test Results; 18) Spin Testing; and 19) Testing and Validation.

Identifying product order with restricted Boltzmann machines

NASA Astrophysics Data System (ADS)

Rao, Wen-Jia; Li, Zhenyu; Zhu, Qiong; Luo, Mingxing; Wan, Xin

2018-03-01

Unsupervised machine learning via a restricted Boltzmann machine is a useful tool in distinguishing an ordered phase from a disordered phase. Here we study its application on the two-dimensional Ashkin-Teller model, which features a partially ordered product phase. We train the neural network with spin configuration data generated by Monte Carlo simulations and show that distinct features of the product phase can be learned from nonergodic samples resulting from symmetry breaking. Careful analysis of the weight matrices inspires us to define a nontrivial machine-learning motivated quantity of the product form, which resembles the conventional product order parameter.

Disruption of 3D MCF-12A Breast Cell Cultures by Estrogens – An In Vitro Model for ER-Mediated Changes Indicative of Hormonal Carcinogenesis

PubMed Central

Marchese, Stephanie; Silva, Elisabete

2012-01-01

Introduction Estrogens regulate the proliferation of normal and neoplastic breast epithelium. Although the intracellular mechanisms of estrogens in the breast are largely understood, little is known about how they induce changes in the structure of the mammary epithelium, which are characteristic of breast cancer. In vitro three dimensional (3D) cultures of immortalised breast epithelial cells recapitulate features of the breast epithelium in vivo, including formation of growth arrested acini with hollow lumen and basement membrane. This model can also reproduce features of malignant transformation and breast cancer, such as increased cellular proliferation and filling of the lumen. However, a system where a connection between estrogen receptor (ER) activation and disruption of acini formation can be studied to elucidate the role of estrogens is still missing. Methods/Principal Findings We describe an in vitro 3D model for breast glandular structure development, using breast epithelial MCF-12A cells cultured in a reconstituted basement membrane matrix. These cells are estrogen receptor (ER)α, ERβ and G-protein coupled estrogen receptor 1 (GPER) competent, allowing the investigation of the effects of estrogens on mammary gland formation and disruption. Under normal conditions, MCF-12A cells formed organised acini, with deposition of basement membrane and hollow lumen. However, treatment with 17β-estradiol, and the exogenous estrogens bisphenol A and propylparaben resulted in deformed acini and filling of the acinar lumen. When these chemicals were combined with ER and GPER inhibitors (ICI 182,780 and G-15, respectively), the deformed acini recovered normal features, such as a spheroid shape, proliferative arrest and luminal clearing, suggesting a role for the ER and GPER in the estrogenic disruption of acinar formation. Conclusion This new model offers the opportunity to better understand the role of the ER and GPER in the morphogenesis of breast glandular structure as well as the events implicated in breast cancer initiation and progression. PMID:23056216

The ultraviolet-bright, slowly declining transient PS1-11af as a partial tidal disruption event

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

Chornock, R.; Berger, E.; Zauderer, B. A.

2014-01-01

We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of knownmore » types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only ∼0.002 M {sub ☉}, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.« less

External and internal facial features modulate processing of vertical but not horizontal spatial relations.

PubMed

Meinhardt, Günter; Kurbel, David; Meinhardt-Injac, Bozana; Persike, Malte

2018-03-22

Some years ago an asymmetry was reported for the inversion effect for horizontal (H) and vertical (V) relational face manipulations (Goffaux & Rossion, 2007). Subsequent research examined whether a specific disruption of long-range relations underlies the H/V inversion asymmetry (Sekunova & Barton, 2008). Here, we tested how detection of changes in interocular distance (H) and eye height (V) depends on cardinal internal features and external feature surround. Results replicated the H/V inversion asymmetry. Moreover, we found very different face cue dependencies for both change types. Performance and inversion effects did not depend on the presence of other face cues for detecting H changes. In contrast, accuracy for detecting V changes strongly depended on internal and external features, showing cumulative improvement when more cues were added. Inversion effects were generally large, and larger with external feature surround. The cue independence in detecting H relational changes indicates specialized local processing tightly tuned to the eyes region, while the strong cue dependency in detecting V relational changes indicates a global mechanism of cue integration across different face regions. These findings suggest that the H/V asymmetry of the inversion effect rests on an H/V anisotropy of face cue dependency, since only the global V mechanism suffers from disruption of cue integration as the major effect of face inversion. Copyright © 2018. Published by Elsevier Ltd.

The I-Tribe Community Pharmacy Practice Model: professional pharmacy unshackled.

PubMed

Alston, Greg L; Waitzman, Jennifer A

2013-01-01

To describe a mechanism by which pharmacists could create a disruptive innovation to provide professional primary care services via a Web-based delivery model. Several obstacles have prevented pharmacists from using available technology to develop business models that capitalize on their clinical skills in primary care. Community practice has experienced multiple sustaining innovations that have improved dispensing productivity but have not stimulated sufficient demand for pharmacy services to disrupt the marketplace and provide new opportunities for pharmacists. Pharmacists are in a unique position to bridge the gap between demand for basic primary medical care and access to a competent medical professional. Building on the historic strengths of community pharmacy practice, modern pharmacists could provide a disruptive innovation in the marketplace for primary care by taking advantage of new technology and implementing the I-Tribe Community Pharmacy Practice Model (I-Tribe). This model would directly connect pharmacists to patients through an interactive, secure Web presence that would liberate the relationship from geographic restrictions. The I-Tribe is a disruptive innovation that could become the foundation for a vibrant market in pharmacist professional service offerings. The I-Tribe model could benefit society by expanding access to primary medical care while simultaneously providing a new source of revenue for community practice pharmacists. Entrepreneurial innovation through I-Tribe pharmacy would free pharmacists to become the care providers envisioned by the profession's thought leaders.

Disruption of root carbon transport into forest humus stimulates fungal opportunists at the expense of mycorrhizal fungi.

PubMed

Lindahl, Björn D; de Boer, Wietse; Finlay, Roger D

2010-07-01

Ectomycorrhizal fungi dominate the humus layers of boreal forests. They depend on carbohydrates that are translocated through roots, via fungal mycelium to microsites in the soil, wherein they forage for nutrients. Mycorrhizal fungi are therefore sensitive to disruptive disturbances that may restrict their carbon supply. By disrupting root connections, we induced a sudden decline in mycorrhizal mycelial abundance and studied the consequent effects on growth and activity of free living, saprotrophic fungi and bacteria in pine forest humus, using molecular community analyses in combination with enzyme activity measurements. Ectomycorrhizal fungi had decreased in abundance 14 days after root severing, but the abundance of certain free-living ascomycetes was three times higher within 5 days of the disturbance compared with undisturbed controls. Root disruption also increased laccase production by an order of magnitude and cellulase production by a factor of 5. In contrast, bacterial populations seemed little affected. The results indicate that access to an external carbon source enables mycorrhizal fungi to monopolise the humus, but disturbances may induce rapid growth of opportunistic saprotrophic fungi that presumably use the dying mycorrhizal mycelium. Studies of such functional shifts in fungal communities, induced by disturbance, may shed light on mechanisms behind nutrient retention and release in boreal forests. The results also highlight the fundamental problems associated with methods that study microbial processes in soil samples that have been isolated from living roots.

Respiratory Sinus Arrhythmia Predicts Restricted Repetitive Behavior Severity

ERIC Educational Resources Information Center

Condy, Emma E.; Scarpa, Angela; Friedman, Bruce H.

2017-01-01

In addition to social communication deficits, restricted repetitive behaviors (RRBs) are a key diagnostic feature of autism spectrum disorder (ASD). Dysfunction of the autonomic nervous system (ANS) in ASD has been posited as a mechanism of RRBs; however, most studies investigating ANS activity in ASD have focused on its relation to social…

Early-onset restrictive eating disturbances in primary school boys and girls.

PubMed

Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

2015-07-01

This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). A total of 1,444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. 46 children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study's findings.

Edge enhancement improves disruptive camouflage by emphasising false edges and creating pictorial relief

PubMed Central

Egan, John; Sharman, Rebecca J.; Scott-Brown, Kenneth C.; Lovell, Paul George

2016-01-01

Disruptive colouration is a visual camouflage composed of false edges and boundaries. Many disruptively camouflaged animals feature enhanced edges; light patches are surrounded by a lighter outline and/or a dark patches are surrounded by a darker outline. This camouflage is particularly common in amphibians, reptiles and lepidopterans. We explored the role that this pattern has in creating effective camouflage. In a visual search task utilising an ultra-large display area mimicking search tasks that might be found in nature, edge enhanced disruptive camouflage increases crypsis, even on substrates that do not provide an obvious visual match. Specifically, edge enhanced camouflage is effective on backgrounds both with and without shadows; i.e. this is not solely due to background matching of the dark edge enhancement element with the shadows. Furthermore, when the dark component of the edge enhancement is omitted the camouflage still provided better crypsis than control patterns without edge enhancement. This kind of edge enhancement improved camouflage on all background types. Lastly, we show that edge enhancement can create a perception of multiple surfaces. We conclude that edge enhancement increases the effectiveness of disruptive camouflage through mechanisms that may include the improved disruption of the object outline by implying pictorial relief. PMID:27922058

Edge enhancement improves disruptive camouflage by emphasising false edges and creating pictorial relief.

PubMed

Egan, John; Sharman, Rebecca J; Scott-Brown, Kenneth C; Lovell, Paul George

2016-12-06

Disruptive colouration is a visual camouflage composed of false edges and boundaries. Many disruptively camouflaged animals feature enhanced edges; light patches are surrounded by a lighter outline and/or a dark patches are surrounded by a darker outline. This camouflage is particularly common in amphibians, reptiles and lepidopterans. We explored the role that this pattern has in creating effective camouflage. In a visual search task utilising an ultra-large display area mimicking search tasks that might be found in nature, edge enhanced disruptive camouflage increases crypsis, even on substrates that do not provide an obvious visual match. Specifically, edge enhanced camouflage is effective on backgrounds both with and without shadows; i.e. this is not solely due to background matching of the dark edge enhancement element with the shadows. Furthermore, when the dark component of the edge enhancement is omitted the camouflage still provided better crypsis than control patterns without edge enhancement. This kind of edge enhancement improved camouflage on all background types. Lastly, we show that edge enhancement can create a perception of multiple surfaces. We conclude that edge enhancement increases the effectiveness of disruptive camouflage through mechanisms that may include the improved disruption of the object outline by implying pictorial relief.

Autism: Oxytocin, serotonin, and social reward.

PubMed

Dölen, Gül

2015-01-01

Over 70 years since the first description of the disease, disrupted social behavior remains a core clinical feature of autistic spectrum disorder. The complex etiology of the disorder portends the need for a better understanding of the brain mechanisms that enable social behaviors, particularly those that are relevant to autism which is characterized by a failure to develop peer relationships, difficulty with emotional reciprocity and imitative play, and disrupted language and communication skills. Toward this end, the current review will examine recent progress that has been made toward understanding the neural mechanisms underlying consociate social attachments.

The use of the coping power program to treat a 10-year-old girl with disruptive behaviors.

PubMed

Lochman, John E; Boxmeyer, Caroline; Powell, Nicole; Wojnaroski, Mary; Yaros, Anna

2007-01-01

This article describes the successful application of the Coping Power program by school-based clinicians to address a 10-year-old girl's disruptive behavior symptoms. Coping Power is an empirically supported cognitive-behavioral program for children at risk for serious conduct problems and their parents. The following case study illustrates the core features of the Coping Power child and parent components while describing the use of assessment data and clinical decision making during the implementation of a manualized intervention.

Initiation of Martian Outflow Channels: Related to the Dissociation of Gas Hydrate?

NASA Technical Reports Server (NTRS)

Max, Michael D.; Clifford, Stephen M.

2001-01-01

We propose that the disruption of subpermafrost aquifers on Mars by the thermal- or pressure-induced dissociation of methane hydrate may have been a frequent trigger for initiating outflow channel activity. This possibility is raised by recent work that suggests that significant amounts of methane and gas hydrate may have been produced within and beneath the planet's cryosphere. On Earth, the build-up of overpressured water and gas by the decomposition of hydrate deposits has been implicated in the formation of large blowout features on the ocean floor. These features display a remarkable resemblance (in both morphology and scale) to the chaotic terrain found at the source of many Martian channels. The destabilization of hydrate can generate pressures sufficient to disrupt aquifers confined by up to 5 kilometers of frozen ground, while smaller discharges may result from the water produced by the decomposition of near-surface hydrate alone.

Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

PubMed Central

Jiang, Xi; Hu, Haiyang; Guijarro, Patricia; Mitchell, Amanda; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Pääbo, Svante; Akbarian, Schahram; Khaitovich, Philipp

2016-01-01

Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID:27685936

Gain-of-function mutations in SMAD4 cause a distinctive repertoire of cardiovascular phenotypes in patients with Myhre syndrome.

PubMed

Lin, Angela E; Michot, Caroline; Cormier-Daire, Valerie; L'Ecuyer, Thomas J; Matherne, G Paul; Barnes, Barrett H; Humberson, Jennifer B; Edmondson, Andrew C; Zackai, Elaine; O'Connor, Matthew J; Kaplan, Julie D; Ebeid, Makram R; Krier, Joel; Krieg, Elizabeth; Ghoshhajra, Brian; Lindsay, Mark E

2016-10-01

Myhre syndrome is a rare, distinctive syndrome due to specific gain-of-function mutations in SMAD4. The characteristic phenotype includes short stature, dysmorphic facial features, hearing loss, laryngotracheal anomalies, arthropathy, radiographic defects, intellectual disability, and a more recently appreciated spectrum of cardiovascular defects with a striking fibroproliferative response to surgical intervention. We report four newly described patients with typical features of Myhre syndrome who had (i) a mildly narrow descending aorta and restrictive cardiomyopathy; (ii) recurrent pericardial and pleural effusions; (iii) a large persistent ductus arteriosus with juxtaductal aortic coarctation; and (iv) restrictive pericardial disease requiring pericardiectomy. Additional information is provided about a fifth previously reported patient with fatal pericardial disease. A literature review of the cardiovascular features of Myhre syndrome was performed on 54 total patients, all with a SMAD4 mutation. Seventy percent had a cardiovascular abnormality including congenital heart defects (63%), pericardial disease (17%), restrictive cardiomyopathy (9%), and systemic hypertension (15%). Pericarditis and restrictive cardiomyopathy are associated with high mortality (three patients each among 10 deaths); one patient with restrictive cardiomyopathy also had epicarditis. Cardiomyopathy and pericardial abnormalities distinguish Myhre syndrome from other disorders caused by mutations in the TGF-β signaling cascade (Marfan, Loeys-Dietz, or Shprintzen-Goldberg syndromes). We hypothesize that the expanded spectrum of cardiovascular abnormalities relates to the ability of the SMAD4 protein to integrate diverse signaling pathways, including canonical TGF-β, BMP, and Activin signaling. The co-occurrence of congenital and acquired phenotypes demonstrates that the gene product of SMAD4 is required for both developmental and postnatal cardiovascular homeostasis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification

NASA Astrophysics Data System (ADS)

Tessarz, Peter; Santos-Rosa, Helena; Robson, Sam C.; Sylvestersen, Kathrine B.; Nelson, Christopher J.; Nielsen, Michael L.; Kouzarides, Tony

2014-01-01

Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes. Here we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that fibrillarin is the orthologue enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows that this modification is exclusively enriched over the 35S ribosomal DNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (facilitator of chromatin transcription) complex. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and increased transcription at the ribosomal DNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.

Retrieval from long-term memory reduces working memory representations for visual features and their bindings.

PubMed

van Lamsweerde, Amanda E; Beck, Melissa R; Elliott, Emily M

2015-02-01

The ability to remember feature bindings is an important measure of the ability to maintain objects in working memory (WM). In this study, we investigated whether both object- and feature-based representations are maintained in WM. Specifically, we tested the hypotheses that retaining a greater number of feature representations (i.e., both as individual features and bound representations) results in a more robust representation of individual features than of feature bindings, and that retrieving information from long-term memory (LTM) into WM would cause a greater disruption to feature bindings. In four experiments, we examined the effects of retrieving a word from LTM on shape and color-shape binding change detection performance. We found that binding changes were more difficult to detect than individual-feature changes overall, but that the cost of retrieving a word from LTM was the same for both individual-feature and binding changes.

Molecular, mesoscopic and microscopic structure evolution during amylase digestion of maize starch granules.

PubMed

Shrestha, Ashok K; Blazek, Jaroslav; Flanagan, Bernadine M; Dhital, Sushil; Larroque, Oscar; Morell, Matthew K; Gilbert, Elliot P; Gidley, Michael J

2012-09-01

Cereal starch granules with high (>50%) amylose content are a promising source of nutritionally desirable resistant starch, i.e. starch that escapes digestion in the small intestine, but the structural features responsible are not fully understood. We report the effects of partial enzyme digestion of maize starch granules on amylopectin branch length profiles, double and single helix contents, gelatinisation properties, crystallinity and lamellar periodicity. Comparing results for three maize starches (27, 57, and 84% amylose) that differ in both structural features and amylase-sensitivity allows conclusions to be drawn concerning the rate-determining features operating under the digestion conditions used. All starches are found to be digested by a side-by-side mechanism in which there is no major preference during enzyme attack for amylopectin branch lengths, helix form, crystallinity or lamellar organisation. We conclude that the major factor controlling enzyme susceptibility is granule architecture, with shorter length scales not playing a major role as inferred from the largely invariant nature of numerous structural measures during the digestion process (XRD, NMR, SAXS, DSC, FACE). Results are consistent with digestion rates being controlled by restricted diffusion of enzymes within densely packed granular structures, with an effective surface area for enzyme attack determined by external dimensions (57 or 84% amylose - relatively slow) or internal channels and pores (27% amylose - relatively fast). Although the process of granule digestion is to a first approximation non-discriminatory with respect to structure at molecular and mesoscopic length scales, secondary effects noted include (i) partial crystallisation of V-type helices during digestion of 27% amylose starch, (ii) preferential hydrolysis of long amylopectin branches during the early stage hydrolysis of 27% and 57% but not 84% amylose starches, linked with disruption of lamellar repeating structure and (iii) partial B-type recrystallisation after prolonged enzyme incubation for 57% and 84% amylose starches but not 27% amylose starch. Copyright © 2012 Elsevier Ltd. All rights reserved.

Identification of a two-component signal transduction system involved in fimbriation of Porphyromonas gingivalis.

PubMed

Hayashi, J; Nishikawa, K; Hirano, R; Noguchi, T; Yoshimura, F

2000-01-01

Porphyromonas gingivalis, a periodontopathogen, is an oral anaerobic gram-negative bacterium with numerous fimbriae on the cell surface. Fimbriae have been considered to be an important virulence factor in this organism. We analyzed the genomic DNA of transposon-induced, fimbria-deficient mutants derived from ATCC 33277 and found that seven independent mutants had transposon insertions within the same restriction fragment. Cloning and sequencing of the disrupted region from one of the mutants revealed two adjacent open reading frames (ORFs) which seemed to encode a two-component signal transduction system. We also found that six of the mutants had insertions in a gene, fimS, a homologue of the genes encoding sensor kinase, and that the insertion in the remaining one disrupted the gene immediately downstream, fimR, a homologue of the response regulator genes in other bacteria. These findings suggest that this two-component regulatory system is involved in fimbriation of P. gingivalis.

Virtual reality for freely moving animals.

PubMed

Stowers, John R; Hofbauer, Maximilian; Bastien, Renaud; Griessner, Johannes; Higgins, Peter; Farooqui, Sarfarazhussain; Fischer, Ruth M; Nowikovsky, Karin; Haubensak, Wulf; Couzin, Iain D; Tessmar-Raible, Kristin; Straw, Andrew D

2017-10-01

Standard animal behavior paradigms incompletely mimic nature and thus limit our understanding of behavior and brain function. Virtual reality (VR) can help, but it poses challenges. Typical VR systems require movement restrictions but disrupt sensorimotor experience, causing neuronal and behavioral alterations. We report the development of FreemoVR, a VR system for freely moving animals. We validate immersive VR for mice, flies, and zebrafish. FreemoVR allows instant, disruption-free environmental reconfigurations and interactions between real organisms and computer-controlled agents. Using the FreemoVR platform, we established a height-aversion assay in mice and studied visuomotor effects in Drosophila and zebrafish. Furthermore, by photorealistically mimicking zebrafish we discovered that effective social influence depends on a prospective leader balancing its internally preferred directional choice with social interaction. FreemoVR technology facilitates detailed investigations into neural function and behavior through the precise manipulation of sensorimotor feedback loops in unrestrained animals.

Circadian physiology of metabolism.

PubMed

Panda, Satchidananda

2016-11-25

A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

Foveal damage in habitual poppers users.

PubMed

Audo, Isabelle; El Sanharawi, Mohamed; Vignal-Clermont, Catherine; Villa, Antoine; Morin, Annie; Conrath, John; Fompeydie, Dominique; Sahel, José-Alain; Gocho-Nakashima, Kiyoko; Goureau, Olivier; Paques, Michel

2011-06-01

To describe foveal damage in habitual use of poppers, a popular recreational drug. Retrospective observational case series. Six patients with bilateral vision loss after chronic popper inhalation were seen in 4 university-based ophthalmology departments. Symptoms, medical history, ophthalmic examination, and functional and morphological tests are described. All patients experienced progressive bilateral vision loss, with central photopsia in 2 cases. Initial visual acuities ranged from 20/50 to 20/25. In all patients, a bilateral yellow foveal spot was present that, by optical coherence tomography, was associated with disruption of the outer segments of foveal cones. Functional and anatomical damage was restricted to the fovea. The poppers involved were identified as isopropyl nitrite in 3 cases. Four patients showed anatomical and/or functional improvement over several months after discontinuing popper inhalation. Repeated inhalation of poppers may be associated with prolonged bilateral vision loss due to the disruption of foveal cone outer segments. Retinal damage may progressively improve following drug discontinuation.

Limits on the location of planetesimal formation in self-gravitating protostellar discs

NASA Astrophysics Data System (ADS)

Clarke, C. J.; Lodato, G.

2009-09-01

In this Letter, we show that if planetesimals form in spiral features in self-gravitating discs, as previously suggested by the idealized simulations of Rice et al., then in realistic protostellar discs, this process will be restricted to the outer regions of the disc (i.e. at radii in excess of several tens of au). This restriction relates to the requirement that dust has to be concentrated in spiral features on a time-scale that is less than the (roughly dynamical) lifetime of such features, and that such rapid accumulation requires spiral features whose fractional amplitude is not much less than unity. This in turn requires that the cooling time-scale of the gas is relatively short, which restricts the process to the outer disc. We point out that the efficient conversion of a large fraction of the primordial dust in the disc into planetesimals could rescue this material from the well-known problem of rapid inward migration at an approximate metre-size scale and that in principle the collisional evolution of these objects could help to resupply small dust to the protostellar disc. We also point out the possible implications of this scenario for the location of planetesimal belts inferred in debris discs around main sequence stars, but stress that further dynamical studies are required in order to establish whether the disc retains a memory of the initial site of planetesimal creation.

Alaska OCS (outer continental shelf) social and economic studies program. Technical report number 90. Effects of renewable-resource harvest disruptions on socioeconomic and sociocultural systems impact analysis, Unalakleet, Norton Sound. Final technical report

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

Jorgensen, J.G.; Maxwell, J.A.; Katchatag, V.

1984-01-01

Part I of this report briefly analyzes the history, culture, and environment of Unalakeet, the ways in which it is used by the natives. The political economy of dependency that overlays the local subsistence economy, the relation between subsistence and the commercial fishery (and the naturally occurring, renewable resources on which both are based), the local and regional social structures (formal and informal), and the wide networks of kinship and friendship which link Unalakleet villagers to persons and families in distant locales. This report contains a brief summary of the field investigations as Part II. Part III explicates the methodologymore » employed to collect and analyze village level and family level data on which the first and fourth parts of the report are based. It also specifies the restrictions and constraints placed on the investigation by the funding agency as well as the impacts analysis. Part IV is conventionally an impacts analysis defines and rationalizes harvest disruptions of increasing severity--low, medium and high--and offers concluding hypotheses about the probable consequences of disruptions at each level.« less

Rupture of the gastrocnemius muscle in six foals.

PubMed

Jesty, Sophy A; Palmer, Jonathan E; Parente, Eric J; Schaer, Thomas P; Wilkins, Pamela A

2005-12-15

Rupture of the gastrocnemius muscle and subsequent disruption of the reciprocal mechanism of the hind limb was diagnosed in 6 foals examined at 7 hours to 3 weeks of age. In 2 foals, the musculoskeletal injury was detected as an ancillary finding to clinical signs of neurologic dysfunction ascribed to hypoxic ischemic insult during delivery, whereas in the other 4 foals, musculoskeletal injury, manifested as inability to rise or stand unsupported, was the chief complaint at admission. Five foals had a history of dystocia and assisted delivery. Common clinical signs were inability to rise, disruption of the reciprocal mechanism, swelling in the caudal aspect of the thigh, instability of the stifle joint, and stifle joint effusion. For mild gastrocnemius injury, exercise restriction via forced recumbency, with minimal or no bandaging, may be sufficient treatment. For more severe disruption of the muscle, limb stabilization via splinting and intensive nursing and monitoring are necessary. Four foals had important concurrent problems, including musculoskeletal deformations (joint contractures), hypoxic ischemic disease, and failure of passive transfer and associated problems (ie, sepsis, polyarthritis, and pneumonia). Moderate to severe gastrocnemius muscle injury is difficult to treat successfully, and the long-term prognosis for athletic function should be regarded as guarded.

The cis decoy against the estrogen response element suppresses breast cancer cells via target disrupting c-fos not mitogen-activated protein kinase activity.

PubMed

Wang, Li Hua; Yang, Xiao Yi; Zhang, Xiaohu; Mihalic, Kelly; Xiao, Weihua; Farrar, William L

2003-05-01

Breast cancer, the most common malignancy in women, has been demonstrated to be associated with the steroid hormone estrogen and its receptor (ER), a ligand-activated transcription factor. Therefore, we developed a phosphorothiolate cis-element decoy against the estrogen response element (ERE decoy) to target disruption of ER DNA binding and transcriptional activity. Here, we showed that the ERE decoy potently ablated the 17beta-estrogen-inducible cell proliferation and induced apoptosis of human breast carcinoma cells by functionally affecting expression of c-fos gene and AP-1 luciferase gene reporter activity. Specificity of the decoy was demonstrated by its ability to directly block ER binding to a cis-element probe and transactivation. Moreover, the decoy failed to inhibit ER-mediated mitogen-activated protein kinase signaling pathways and cell growth of ER-negative breast cancer cells. Taken together, these data suggest that estrogen-mediated cell growth of breast cancer cells can be preferentially restricted via targeted disruption of ER at the level of DNA binding by a novel and specific decoy strategy applied to steroid nuclear receptors.

A Drastic Change in Background Luminance or Motion Degrades the Preview Benefit.

PubMed

Osugi, Takayuki; Murakami, Ikuya

2017-01-01

When some distractors (old items) precede some others (new items) in an inefficient visual search task, the search is restricted to new items, and yields a phenomenon termed the preview benefit. It has recently been demonstrated that, in this preview search task, the onset of repetitive changes in the background disrupts the preview benefit, whereas a single transient change in the background does not. In the present study, we explored this effect with dynamic background changes occurring in the context of realistic scenes, to examine the robustness and usefulness of visual marking. We examined whether preview benefit in a preview search task survived through task-irrelevant changes in the scene, namely a luminance change and the initiation of coherent motion, both occurring in the background. Luminance change of the background disrupted preview benefit if it was synchronized with the onset of the search display. Furthermore, although the presence of coherent background motion per se did not affect preview benefit, its synchronized initiation with the onset of the search display did disrupt preview benefit if the motion speed was sufficiently high. These results suggest that visual marking can be destroyed by a transient event in the scene if that event is sufficiently drastic.

RNA viruses can hijack vertebrate microRNAs to suppress innate immunity

NASA Astrophysics Data System (ADS)

Trobaugh, Derek W.; Gardner, Christina L.; Sun, Chengqun; Haddow, Andrew D.; Wang, Eryu; Chapnik, Elik; Mildner, Alexander; Weaver, Scott C.; Ryman, Kate D.; Klimstra, William B.

2014-02-01

Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses. This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs. Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3' non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.

Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

PubMed Central

Burkhard, Silja Barbara

2018-01-01

Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions. PMID:29400650

Restricted and Repetitive Behaviors in Autism Spectrum Disorders: A Review of Research in the Last Decade

ERIC Educational Resources Information Center

Leekam, Susan R.; Prior, Margot R.; Uljarevic, Mirko

2011-01-01

Restricted and repetitive behaviors (RRBs) are a core feature of autism spectrum disorders. They constitute a major barrier to learning and social adaptation, but research on their definition, cause, and capacity for change has been relatively neglected. The last decade of research has brought new measurement techniques that have improved the…

Functional Analysis and Treatment of Arranging and Ordering by Individuals with an Autism Spectrum Disorder

ERIC Educational Resources Information Center

Rodriguez, Nicole M.; Thompson, Rachel H.; Schlichenmeyer, Kevin; Stocco, Corey S.

2012-01-01

Of the diagnostic features of autism, relatively little research has been devoted to restricted and repetitive behavior, particularly topographically complex forms of restricted and repetitive behavior such as rigidity in routines or compulsive-like behavior (e.g., arranging objects in patterns or rows). Like vocal or motor stereotypy,…

Misconceptions on Missing Data in RAD-seq Phylogenetics with a Deep-scale Example from Flowering Plants.

PubMed

Eaton, Deren A R; Spriggs, Elizabeth L; Park, Brian; Donoghue, Michael J

2017-05-01

Restriction-site associated DNA (RAD) sequencing and related methods rely on the conservation of enzyme recognition sites to isolate homologous DNA fragments for sequencing, with the consequence that mutations disrupting these sites lead to missing information. There is thus a clear expectation for how missing data should be distributed, with fewer loci recovered between more distantly related samples. This observation has led to a related expectation: that RAD-seq data are insufficiently informative for resolving deeper scale phylogenetic relationships. Here we investigate the relationship between missing information among samples at the tips of a tree and information at edges within it. We re-analyze and review the distribution of missing data across ten RAD-seq data sets and carry out simulations to determine expected patterns of missing information. We also present new empirical results for the angiosperm clade Viburnum (Adoxaceae, with a crown age >50 Ma) for which we examine phylogenetic information at different depths in the tree and with varied sequencing effort. The total number of loci, the proportion that are shared, and phylogenetic informativeness varied dramatically across the examined RAD-seq data sets. Insufficient or uneven sequencing coverage accounted for similar proportions of missing data as dropout from mutation-disruption. Simulations reveal that mutation-disruption, which results in phylogenetically distributed missing data, can be distinguished from the more stochastic patterns of missing data caused by low sequencing coverage. In Viburnum, doubling sequencing coverage nearly doubled the number of parsimony informative sites, and increased by >10X the number of loci with data shared across >40 taxa. Our analysis leads to a set of practical recommendations for maximizing phylogenetic information in RAD-seq studies. [hierarchical redundancy; phylogenetic informativeness; quartet informativeness; Restriction-site associated DNA (RAD) sequencing; sequencing coverage; Viburnum.]. © The authors 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Differential Responses to Wnt and PCP Disruption Predict Expression and Developmental Function of Conserved and Novel Genes in a Cnidarian

PubMed Central

Lapébie, Pascal; Ruggiero, Antonella; Barreau, Carine; Chevalier, Sandra; Chang, Patrick; Dru, Philippe; Houliston, Evelyn; Momose, Tsuyoshi

2014-01-01

We have used Digital Gene Expression analysis to identify, without bilaterian bias, regulators of cnidarian embryonic patterning. Transcriptome comparison between un-manipulated Clytia early gastrula embryos and ones in which the key polarity regulator Wnt3 was inhibited using morpholino antisense oligonucleotides (Wnt3-MO) identified a set of significantly over and under-expressed transcripts. These code for candidate Wnt signaling modulators, orthologs of other transcription factors, secreted and transmembrane proteins known as developmental regulators in bilaterian models or previously uncharacterized, and also many cnidarian-restricted proteins. Comparisons between embryos injected with morpholinos targeting Wnt3 and its receptor Fz1 defined four transcript classes showing remarkable correlation with spatiotemporal expression profiles. Class 1 and 3 transcripts tended to show sustained expression at “oral” and “aboral” poles respectively of the developing planula larva, class 2 transcripts in cells ingressing into the endodermal region during gastrulation, while class 4 gene expression was repressed at the early gastrula stage. The preferential effect of Fz1-MO on expression of class 2 and 4 transcripts can be attributed to Planar Cell Polarity (PCP) disruption, since it was closely matched by morpholino knockdown of the specific PCP protein Strabismus. We conclude that endoderm and post gastrula-specific gene expression is particularly sensitive to PCP disruption while Wnt-/β-catenin signaling dominates gene regulation along the oral-aboral axis. Phenotype analysis using morpholinos targeting a subset of transcripts indicated developmental roles consistent with expression profiles for both conserved and cnidarian-restricted genes. Overall our unbiased screen allowed systematic identification of regionally expressed genes and provided functional support for a shared eumetazoan developmental regulatory gene set with both predicted and previously unexplored members, but also demonstrated that fundamental developmental processes including axial patterning and endoderm formation in cnidarians can involve newly evolved (or highly diverged) genes. PMID:25233086

Differential responses to Wnt and PCP disruption predict expression and developmental function of conserved and novel genes in a cnidarian.

PubMed

Lapébie, Pascal; Ruggiero, Antonella; Barreau, Carine; Chevalier, Sandra; Chang, Patrick; Dru, Philippe; Houliston, Evelyn; Momose, Tsuyoshi

2014-09-01

We have used Digital Gene Expression analysis to identify, without bilaterian bias, regulators of cnidarian embryonic patterning. Transcriptome comparison between un-manipulated Clytia early gastrula embryos and ones in which the key polarity regulator Wnt3 was inhibited using morpholino antisense oligonucleotides (Wnt3-MO) identified a set of significantly over and under-expressed transcripts. These code for candidate Wnt signaling modulators, orthologs of other transcription factors, secreted and transmembrane proteins known as developmental regulators in bilaterian models or previously uncharacterized, and also many cnidarian-restricted proteins. Comparisons between embryos injected with morpholinos targeting Wnt3 and its receptor Fz1 defined four transcript classes showing remarkable correlation with spatiotemporal expression profiles. Class 1 and 3 transcripts tended to show sustained expression at "oral" and "aboral" poles respectively of the developing planula larva, class 2 transcripts in cells ingressing into the endodermal region during gastrulation, while class 4 gene expression was repressed at the early gastrula stage. The preferential effect of Fz1-MO on expression of class 2 and 4 transcripts can be attributed to Planar Cell Polarity (PCP) disruption, since it was closely matched by morpholino knockdown of the specific PCP protein Strabismus. We conclude that endoderm and post gastrula-specific gene expression is particularly sensitive to PCP disruption while Wnt-/β-catenin signaling dominates gene regulation along the oral-aboral axis. Phenotype analysis using morpholinos targeting a subset of transcripts indicated developmental roles consistent with expression profiles for both conserved and cnidarian-restricted genes. Overall our unbiased screen allowed systematic identification of regionally expressed genes and provided functional support for a shared eumetazoan developmental regulatory gene set with both predicted and previously unexplored members, but also demonstrated that fundamental developmental processes including axial patterning and endoderm formation in cnidarians can involve newly evolved (or highly diverged) genes.

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

Koch, Andreas; Burkert, Andreas; Rich, R. Michael

We report on the discovery of strong tidal features around a dwarf spheroidal galaxy in the Hydra I galaxy cluster, indicating its ongoing tidal disruption. This very low surface brightness object, HCC-087, was originally classified as an early-type dwarf in the Hydra Cluster Catalogue (HCC), but our re-analysis of the ESO-VLT/FORS images of the HCC unearthed a clear indication of an S-shaped morphology and a large spatial extent. Its shape, luminosity (M{sub V} = -11.6 mag), and physical size (at a half-light radius of 3.1 kpc and a full length of {approx}5.9 kpc) are comparable to the recently discovered NGCmore » 4449B and the Sagittarius dwarf spheroidal, all of which are undergoing clear tidal disruption. Aided by N-body simulations we argue that HCC-087 is currently at its first apocenter, at 150 kpc, around the cluster center and that it is being tidally disrupted by the galaxy cluster's potential itself. An interaction with the nearby (50 kpc) S0 cluster galaxy HCC-005, at M{sub *} {approx} 3 Multiplication-Sign 10{sup 10} M{sub Sun} is rather unlikely, as this constellation requires a significant amount of dynamical friction and thus low relative velocities. The S-shaped morphology and large spatial extent of the satellite would, however, also appear if HCC-087 would orbit the cluster center. These features appear to be characteristic properties of satellites that are seen in the process of being tidally disrupted, independent of the environment of the destruction. An important finding of our simulations is an orientation of the tidal tails perpendicular to the orbit.« less

Disruption of River Networks in Nature and Models

NASA Astrophysics Data System (ADS)

Perron, J. T.; Black, B. A.; Stokes, M.; McCoy, S. W.; Goldberg, S. L.

2017-12-01

Many natural systems display especially informative behavior as they respond to perturbations. Landscapes are no exception. For example, longitudinal elevation profiles of rivers responding to changes in uplift rate can reveal differences among erosional mechanisms that are obscured while the profiles are in equilibrium. The responses of erosional river networks to perturbations, including disruption of their network structure by diversion, truncation, resurfacing, or river capture, may be equally revealing. In this presentation, we draw attention to features of disrupted erosional river networks that a general model of landscape evolution should be able to reproduce, including the consequences of different styles of planetary tectonics and the response to heterogeneous bedrock structure and deformation. A comparison of global drainage directions with long-wavelength topography on Earth, Mars, and Saturn's moon Titan reveals the extent to which persistent and relatively rapid crustal deformation has disrupted river networks on Earth. Motivated by this example and others, we ask whether current models of river network evolution adequately capture the disruption of river networks by tectonic, lithologic, or climatic perturbations. In some cases the answer appears to be no, and we suggest some processes that models may be missing.

Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function.

PubMed

Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; de Boer, Sietse F; Koolhaas, Jaap M; Meerlo, Peter

2017-02-01

Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly the performance in a differential reinforcement of low rate responding (DRL) task, which is highly dependent upon an intact prefrontal cortex. Animals were trained to withhold a lever press until an imposed delay of 30 s after the last press had passed in order to achieve a food reward. Once the animals had mastered the task, they were sleep-restricted for 7 days with 20 h of sleep deprivation per day. At the end of each daily sleep deprivation session, performance on the DRL task was assessed. The results show that sleep-restricted animals were less able to time their responses correctly, started pressing the lever more randomly and showed signs of behavioural disinhibition, the latter possibly reflecting enhanced impulsivity. Our data support the hypothesis that a sleep debt has disruptive consequences for the functioning of the prefrontal cortex. This model offers possibilities for future studies investigating the underlying biochemical and molecular mechanisms of this relationship. © 2016 European Sleep Research Society.

Live fate-mapping of joint-associated fibroblasts visualizes expansion of cell contributions during zebrafish fin regeneration.

PubMed

Tornini, Valerie A; Thompson, John D; Allen, Raymond L; Poss, Kenneth D

2017-08-15

The blastema is a mass of progenitor cells responsible for regeneration of amputated salamander limbs and fish fins. Previous studies have indicated that resident cell sources producing the blastema contribute lineage-restricted progeny to regenerating tissue. However, these studies have labeled general cell types rather than granular cell subpopulations, and they do not explain the developmental transitions that must occur for distal structures to arise from cells with proximal identities in the appendage stump. Here, we find that regulatory sequences of tph1b , which encodes an enzyme that synthesizes serotonin, mark a subpopulation of fibroblast-like cells restricted to the joints of uninjured adult zebrafish fins. Amputation stimulates serotonin production in regenerating fin fibroblasts, yet targeted tph1b mutations abrogating this response do not disrupt fin regeneration. In uninjured animals, tph1b -expressing cells contribute fibroblast progeny that remain restricted to joints throughout life. By contrast, upon amputation, tph1b + joint cells give rise to fibroblasts that distribute across the entire lengths of regenerating fin rays. Our experiments visualize and quantify how incorporation into an appendage blastema broadens the progeny contributions of a cellular subpopulation that normally has proximodistal restrictions. © 2017. Published by The Company of Biologists Ltd.

IS THE LARGE CRATER ON THE ASTEROID (2867) STEINS REALLY AN IMPACT CRATER?

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

Morris, A. J. W.; Price, M. C.; Burchell, M. J., E-mail: m.j.burchell@kent.ac.uk

The large crater on the asteroid (2867) Steins attracted much attention when it was first observed by the Rosetta spacecraft in 2008. Initially, it was widely thought to be unusually large compared to the size of the asteroid. It was quickly realized that this was not the case and there are other examples of similar (or larger) craters on small bodies in the same size range; however, it is still widely accepted that it is a crater arising from an impact onto the body which occurred after its formation. The asteroid (2867) Steins also has an equatorial bulge, usually consideredmore » to have arisen from redistribution of mass due to spin-up of the body caused by the YORP effect. Conversely, it is shown here that, based on catastrophic disruption experiments in laboratory impact studies, a similarly shaped body to the asteroid Steins can arise from the break-up of a parent in a catastrophic disruption event; this includes the presence of a large crater-like feature and equatorial bulge. This suggests that the large crater-like feature on Steins may not be a crater from a subsequent impact, but may have arisen directly from the fragmentation process of a larger, catastrophically disrupted parent.« less

Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors.

PubMed

Gasparre, Giuseppe; Porcelli, Anna Maria; Bonora, Elena; Pennisi, Lucia Fiammetta; Toller, Matteo; Iommarini, Luisa; Ghelli, Anna; Moretti, Massimo; Betts, Christine M; Martinelli, Giuseppe Nicola; Ceroni, Alberto Rinaldi; Curcio, Francesco; Carelli, Valerio; Rugolo, Michela; Tallini, Giovanni; Romeo, Giovanni

2007-05-22

Oncocytic tumors are a distinctive class of proliferative lesions composed of cells with a striking degree of mitochondrial hyperplasia that are particularly frequent in the thyroid gland. To understand whether specific mitochondrial DNA (mtDNA) mutations are associated with the accumulation of mitochondria, we sequenced the entire mtDNA in 50 oncocytic lesions (45 thyroid tumors of epithelial cell derivation and 5 mitochondrion-rich breast tumors) and 52 control cases (21 nononcocytic thyroid tumors, 15 breast carcinomas, and 16 gliomas) by using recently developed technology that allows specific and reliable amplification of the whole mtDNA with quick mutation scanning. Thirteen oncocytic lesions (26%) presented disruptive mutations (nonsense or frameshift), whereas only two samples (3.8%) presented such mutations in the nononcocytic control group. In one case with multiple thyroid nodules analyzed separately, a disruptive mutation was found in the only nodule with oncocytic features. In one of the five mitochondrion-rich breast tumors, a disruptive mutation was identified. All disruptive mutations were found in complex I subunit genes, and the association between these mutations and the oncocytic phenotype was statistically significant (P=0.001). To study the pathogenicity of these mitochondrial mutations, primary cultures from oncocytic tumors and corresponding normal tissues were established. Electron microscopy and biochemical and molecular analyses showed that primary cultures derived from tumors bearing disruptive mutations failed to maintain the mutations and the oncocytic phenotype. We conclude that disruptive mutations in complex I subunits are markers of thyroid oncocytic tumors.

Automated selective disruption of slow wave sleep.

PubMed

Ooms, Sharon J; Zempel, John M; Holtzman, David M; Ju, Yo-El S

2017-04-01

Slow wave sleep (SWS) plays an important role in neurophysiologic restoration. Experimentally testing the effect of SWS disruption previously required highly time-intensive and subjective methods. Our goal was to develop an automated and objective protocol to reduce SWS without affecting sleep architecture. We developed a custom Matlab™ protocol to calculate electroencephalogram spectral power every 10s live during a polysomnogram, exclude artifact, and, if measurements met criteria for SWS, deliver increasingly louder tones through earphones. Middle-aged healthy volunteers (n=10) each underwent 2 polysomnograms, one with the SWS disruption protocol and one with sham condition. The SWS disruption protocol reduced SWS compared to sham condition, as measured by spectral power in the delta (0.5-4Hz) band, particularly in the 0.5-2Hz range (mean 20% decrease). A compensatory increase in the proportion of total spectral power in the theta (4-8Hz) and alpha (8-12Hz) bands was seen, but otherwise normal sleep features were preserved. N3 sleep decreased from 20±34 to 3±6min, otherwise there were no significant changes in total sleep time, sleep efficiency, or other macrostructural sleep characteristics. This novel SWS disruption protocol produces specific reductions in delta band power similar to existing methods, but has the advantage of being automated, such that SWS disruption can be performed easily in a highly standardized and operator-independent manner. This automated SWS disruption protocol effectively reduces SWS without impacting overall sleep architecture. Copyright © 2017 Elsevier B.V. All rights reserved.

Circadian rhythms, sleep, and performance in space.

PubMed

Mallis, M M; DeRoshia, C W

2005-06-01

Maintaining optimal alertness and neurobehavioral functioning during space operations is critical to enable the National Aeronautics and Space Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars and beyond" to become a reality. Field data have demonstrated that sleep times and performance of crewmembers can be compromised by extended duty days, irregular work schedules, high workload, and varying environmental factors. This paper documents evidence of significant sleep loss and disruption of circadian rhythms in astronauts and associated performance decrements during several space missions, which demonstrates the need to develop effective countermeasures. Both sleep and circadian disruptions have been identified in the Behavioral Health and Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews, thus reducing the safety margin and increasing the chances of an accident or incident. These decrements oftentimes can be difficult to detect and counter effectively in restrictive operational environments. NASA is focusing research on the development of optimal sleep/wake schedules and countermeasure timing and application to help mitigate the cumulative effects of sleep and circadian disruption and enhance operational performance. Investing research in humans is one of NASA's building blocks that will allow for both short- and long-duration space missions and help NASA in developing approaches to manage and overcome the human limitations of space travel. In addition to reviewing the current state of knowledge concerning sleep and circadian disruptions during space operations, this paper provides an overview of NASA's broad research goals. Also, NASA-funded research, designed to evaluate the relationships between sleep quality, circadian rhythm stability, and performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed.

Circadian rhythms, sleep, and performance in space

NASA Technical Reports Server (NTRS)

Mallis, M. M.; DeRoshia, C. W.

2005-01-01

Maintaining optimal alertness and neurobehavioral functioning during space operations is critical to enable the National Aeronautics and Space Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars and beyond" to become a reality. Field data have demonstrated that sleep times and performance of crewmembers can be compromised by extended duty days, irregular work schedules, high workload, and varying environmental factors. This paper documents evidence of significant sleep loss and disruption of circadian rhythms in astronauts and associated performance decrements during several space missions, which demonstrates the need to develop effective countermeasures. Both sleep and circadian disruptions have been identified in the Behavioral Health and Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews, thus reducing the safety margin and increasing the chances of an accident or incident. These decrements oftentimes can be difficult to detect and counter effectively in restrictive operational environments. NASA is focusing research on the development of optimal sleep/wake schedules and countermeasure timing and application to help mitigate the cumulative effects of sleep and circadian disruption and enhance operational performance. Investing research in humans is one of NASA's building blocks that will allow for both short- and long-duration space missions and help NASA in developing approaches to manage and overcome the human limitations of space travel. In addition to reviewing the current state of knowledge concerning sleep and circadian disruptions during space operations, this paper provides an overview of NASA's broad research goals. Also, NASA-funded research, designed to evaluate the relationships between sleep quality, circadian rhythm stability, and performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed.

[In Process Citation

PubMed

Ackermann; Mathiak

1999-11-01

Pure word deafness (auditory verbal agnosia) is characterized by an impairment of auditory comprehension, repetition of verbal material and writing to dictation whereas spontaneous speech production and reading largely remain unaffected. Sometimes, this syndrome is preceded by complete deafness (cortical deafness) of varying duration. Perception of vowels and suprasegmental features of verbal utterances (e.g., intonation contours) seems to be less disrupted than the processing of consonants and, therefore, might mediate residual auditory functions. Often, lip reading and/or slowing of speaking rate allow within some limits to compensate for speech comprehension deficits. Apart from a few exceptions, the available reports of pure word deafness documented a bilateral temporal lesion. In these instances, as a rule, identification of nonverbal (environmental) sounds, perception of music, temporal resolution of sequential auditory cues and/or spatial localization of acoustic events were compromised as well. The observed variable constellation of auditory signs and symptoms in central hearing disorders following bilateral temporal disorders, most probably, reflects the multitude of functional maps at the level of the auditory cortices subserving, as documented in a variety of non-human species, the encoding of specific stimulus parameters each. Thus, verbal/nonverbal auditory agnosia may be considered a paradigm of distorted "auditory scene analysis" (Bregman 1990) affecting both primitive and schema-based perceptual processes. It cannot be excluded, however, that disconnection of the Wernicke-area from auditory input (Geschwind 1965) and/or an impairment of suggested "phonetic module" (Liberman 1996) contribute to the observed deficits as well. Conceivably, these latter mechanisms underly the rare cases of pure word deafness following a lesion restricted to the dominant hemisphere. Only few instances of a rather isolated disruption of the discrimination/identification of nonverbal sound sources, in the presence of uncompromised speech comprehension, have been reported so far (nonverbal auditory agnosia). As a rule, unilateral right-sided damage has been found to be the relevant lesion.

Comment on 'The Global Resurfacing of Venus' by R. G. Strom, G.G. Schaber, and D.D. Dawson

NASA Technical Reports Server (NTRS)

Herrick, Robert R.; Izenberg, Noam; Phillips, Roger J.

1995-01-01

The distribution of impact craters on Venus has been the subject of a great deal of analysis since the return of Magellan data. Phillips el al. (1992) performed Monte Carlo two-dimensional (2-D) modeling of the areal distribution of craters, and the results of that exercise allowed a restricted, but still quite large, range of possible planetary resurfacing histories, including the possibility that the crater, were emplaced on a geologically inactive planet. However, the nonrandom distribution of embayed and deformed craters (Phillips el al., 1992), the hypsometric distribution of craters (Herrick and Phillips, 1994), the varied degradation states of craters (Izenberg et al., 1994), their nonrandom distribution with different geologic terrain types (Namiki and Solomon, 1994; Price et al, 1994), and three-dimensional resurfacing modeling (Bullock el al., 1993) all seem to argue against that particular possibility. In contrast, Strom el al. (1994) have collected a refined and more comprehensive data set of impact features, and they input these data into more sophisticated 2-D Monte Carlo modeling and statistical analyses of the areal distribution of craters, the hypsometric distribution of craters, and the number of embayed craters. They concluded that 'Venus experienced a global resurfacing event about 300 m.y. ago followed by a dramatic reduction of volcanism and tectonism. This global resurfacing event ended abruptly (less than 10 m.y.). The present crater population has accumulated since then and remains largely intact . . . only about 4%-6% of the planet has been volcanically resurfaced since the global event . . .' If these conclusions are well-founded, this work certainly represents a significant advancement in restricting tile number of plausible resurfacing histories for the planet. If Strom et al. (1994) are correct, it would also mean that all of the other aforementioned works are in error to various degrees, or at least represent overzealous interpretation of the data. However, we have identified apparent flaws in the observations, modeling, and interpretations presented by Strom el al. (1994) that lead us to question whether their conclusions are warranted. We limit our comments to three areas of their analysis: (1) observations pertaining to the number and area of disrupted and pristine craters and crater-related features, (2) modeling of the areal and elevation distribution of craters, and (3) interpretations of resurfacing models.

Disruption Warning Database Development and Exploratory Machine Learning Studies on Alcator C-Mod

NASA Astrophysics Data System (ADS)

Montes, Kevin; Rea, Cristina; Granetz, Robert

2017-10-01

A database of about 1800 shots from the 2015 campaign on the Alcator C-Mod tokamak is assembled, including disruptive and non-disruptive discharges. The database consists of 40 relevant plasma parameters with data taken from 160k time slices. In order to investigate the possibility of developing a robust disruption prediction algorithm that is tokamak-independent, we focused machine learning studies on a subset of dimensionless parameters such as βp, n /nG , etc. The Random Forests machine learning algorithm provides insight on the available data set by ranking the relative importance of the input features. Its application on the C-Mod database, however, reveals that virtually no one parameter has more importance than any other, and that its classification algorithm has a low rate of successfully predicted samples, as well as poor false positive and false negative rates. Comparing the analysis of this algorithm on the C-Mod database with its application to a similar database on DIII-D, we conclude that disruption prediction may not be feasible on C-Mod. This conclusion is supported by empirical observations that most C-Mod disruptions are caused by radiative collapse due to molybdenum from the first wall, which happens on just a 1-2ms timescale. Supported by the US Dept. of Energy under DE-FC02-99ER54512 and DE-FC02-04ER54698.

Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

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

Wang, Xiang; Zhao, Fang

Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit themore » expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.« less

Dome shaped features on Europa's surface

NASA Technical Reports Server (NTRS)

1997-01-01

The Solid State Imaging system aboard the spacecraft Galileo took this image of the surface of Europa on February 20, 1997 during its sixth orbit around Jupiter. The image is located near 16 North, 268 West; illumination is from the lower-right. The area covered is approximately 48 miles (80 kilometers) by 56 miles (95 kilometers) across. North is toward the top of the image.

This image reveals that the icy surface of Europa has been disrupted by ridges and faults numerous times during its past. These ridges have themselves been disrupted by the localized formation of domes and other features that may be indicative of thermal upwelling of water from beneath the crust. These features provide strong evidence for the presence of subsurface liquid during Europa's recent past.

The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.

This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

40 CFR 31.36 - Procurement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... procurements, contain features which unduly restrict competition. The description may include a statement of... requirements of a procurement. The specific features of the named brand which must be met by offerors shall be...) Construction grants awarded under Title II of the Clean Water Act are subject to the following “Buy American...

40 CFR 31.36 - Procurement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... procurements, contain features which unduly restrict competition. The description may include a statement of... requirements of a procurement. The specific features of the named brand which must be met by offerors shall be...) Construction grants awarded under Title II of the Clean Water Act are subject to the following “Buy American...

40 CFR 31.36 - Procurement.

Code of Federal Regulations, 2014 CFR

2014-07-01

... procurements, contain features which unduly restrict competition. The description may include a statement of... requirements of a procurement. The specific features of the named brand which must be met by offerors shall be...) Construction grants awarded under Title II of the Clean Water Act are subject to the following “Buy American...

Mapping Surface Features Produced by an Active Landslide

NASA Astrophysics Data System (ADS)

Parise, Mario; Gueguen, Erwan; Vennari, Carmela

2016-10-01

A large landslide reactivated on December 2013, at Montescaglioso, southern Italy, after 56 hours of rainfall. The landslide disrupted over 500 m of a freeway, involved a few warehouses, a supermarket, and private homes. After the event, it has been performed field surveys, aided by visual analysis of terrestrial and helicopter photographs, to compile a map of the surface deformations. The geomorphological features mapped included single fractures, sets of fractures, tension cracks, trenches, and pressure ridges. In this paper we present the methodology used, the map obtained through the intensive field work, and discuss the main surface features produced by the landslide.

Stress within a Restricted Time Window Selectively Affects the Persistence of Long-Term Memory

PubMed Central

Fang, Qin; Chai, Ning; Zhao, Li-Yan; Xue, Yan-Xue; Luo, Yi-Xiao; Jian, Min; Han, Ying; Shi, Hai-Shui; Lu, Lin; Wu, Ping; Wang, Ji-Shi

2013-01-01

The effects of stress on emotional memory are distinct and depend on the stages of memory. Memory undergoes consolidation and reconsolidation after acquisition and retrieval, respectively. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. Previous research on the effects of stress on memory have focused on long-term memory (LTM) formation (tested 24 h later), but the effects of stress on the persistence of LTM (tested at least 1 week later) are unclear. Recent findings indicated that the persistence of LTM requires late-phase protein synthesis in the dorsal hippocampus. The present study investigated the effect of stress (i.e., cold water stress) during the late phase after the acquisition and retrieval of contextual fear memory in rats. We found that stress and corticosterone administration during the late phase (12 h) after acquisition, referred to as late consolidation, selectively enhanced the persistence of LTM, whereas stress during the late phase (12 h) after retrieval, referred to as late reconsolidation, selectively disrupted the restabilized persistence of LTM. Moreover, the effects of stress on the persistence of LTM were blocked by the corticosterone synthesis inhibitor metyrapone, which was administered before stress, suggesting that the glucocorticoid system is involved in the effects of stress on the persistence of LTM. We conclude that stress within a restricted time window after acquisition or retrieval selectively affects the persistence of LTM and depends on the glucocorticoid system. PMID:23544051

Torrance type of lethal neonatal short-limbed platyspondylic dwarfism.

PubMed

Kaibara, N; Yokoyama, K; Nakano, H

1983-01-01

A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity.

A LUMINOUS, FAST RISING UV-TRANSIENT DISCOVERED BY ROTSE: A TIDAL DISRUPTION EVENT?

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

Vinkó, J.; Wheeler, J. C.; Chatzopoulos, E.

2015-01-01

We present follow-up observations of an optical transient (OT) discovered by ROTSE on 2009 January 21. Photometric monitoring was carried out with ROTSE-IIIb in the optical and Swift in the UV up to +70 days after discovery. The light curve showed a fast rise time of ∼10 days followed by a steep decline over the next 60 days, which was much faster than that implied by {sup 56}Ni—{sup 56}Co radioactive decay. The Sloan Digital Sky Survey Data Release 10 database contains a faint, red object at the position of the OT, which appears slightly extended. This and other lines ofmore » evidence suggest that the OT is of extragalactic origin, and this faint object is likely the host galaxy. A sequence of optical spectra obtained with the 9.2 m Hobby-Eberly Telescope between +8 and +45 days after discovery revealed a hot, blue continuum with no visible spectral features. A few weak features that appeared after +30 days probably originated from the underlying host. Fitting synthetic templates to the observed spectrum of the host galaxy revealed a redshift of z = 0.19. At this redshift, the peak magnitude of the OT is close to –22.5, similar to the brightest super-luminous supernovae; however, the lack of identifiable spectral features makes the massive stellar death hypothesis less likely. A more plausible explanation appears to be the tidal disruption of a Sun-like star by the central supermassive black hole. We argue that this transient likely belongs to a class of super-Eddington tidal disruption events.« less

Central and peripheral regulation of feeding and nutrition by the mammalian circadian clock: implications for nutrition during manned space flight

NASA Technical Reports Server (NTRS)

Cassone, Vincent M.; Stephan, Friedrich K.

2002-01-01

Circadian clocks have evolved to predict and coordinate physiologic processes with the rhythmic environment on Earth. Space studies in non-human primates and humans have suggested that this clock persists in its rhythmicity in space but that its function is altered significantly in long-term space flight. Under normal circumstances, the clock is synchronized by the light-dark cycle via the retinohypothalamic tract and the suprachiasmatic nucleus. It is also entrained by restricted feeding regimes via a suprachiasmatic nucleus-independent circadian oscillator. The site of this suboscillator (or oscillators) is not known, but new evidence has suggested that peripheral tissues in the liver and viscera may express circadian clock function when forced to do so by restricted feeding schedules or other homeostatic disruptions. New research on the role of the circadian clock in the control of feeding on Earth and in space is warranted.

Medically indigent women seeking abortion prior to legalization: New York City, 1969-1970.

PubMed

Belsky, J E

1992-01-01

If the efforts now underway to limit access to abortion services in the United States are successful, their greatest impact will be on women who lack the funds to obtain abortions elsewhere. There is little published information, however, about the experience of medically indigent women who sought abortions under the old, restrictive state laws. This article details the psychiatric evaluation of 199 women requesting a therapeutic abortion at a large municipal hospital in New York City under a restrictive abortion law. Thirty-nine percent had tried to abort the pregnancy. Fifty-seven percent had concrete evidence of serious psychiatric disorder. Forty-eight percent had been traumatized by severe family disruption, gross emotional deprivation or abuse during childhood. Seventy-nine percent lacked emotional support from the man responsible for the pregnancy, and the majority were experiencing overwhelming stress from the interplay of multiple problems exacerbated by their unwanted pregnancy.

Two-layer contractive encodings for learning stable nonlinear features.

PubMed

Schulz, Hannes; Cho, Kyunghyun; Raiko, Tapani; Behnke, Sven

2015-04-01

Unsupervised learning of feature hierarchies is often a good strategy to initialize deep architectures for supervised learning. Most existing deep learning methods build these feature hierarchies layer by layer in a greedy fashion using either auto-encoders or restricted Boltzmann machines. Both yield encoders which compute linear projections of input followed by a smooth thresholding function. In this work, we demonstrate that these encoders fail to find stable features when the required computation is in the exclusive-or class. To overcome this limitation, we propose a two-layer encoder which is less restricted in the type of features it can learn. The proposed encoder is regularized by an extension of previous work on contractive regularization. This proposed two-layer contractive encoder potentially poses a more difficult optimization problem, and we further propose to linearly transform hidden neurons of the encoder to make learning easier. We demonstrate the advantages of the two-layer encoders qualitatively on artificially constructed datasets as well as commonly used benchmark datasets. We also conduct experiments on a semi-supervised learning task and show the benefits of the proposed two-layer encoders trained with the linear transformation of perceptrons. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultraviolet Spectroscopy of Tidal Disruption Flares

NASA Astrophysics Data System (ADS)

Cenko, Stephen B.

2017-08-01

When a star passes within the sphere of disruption of a massive black hole, tidal forces will overcome self-gravity and unbind the star. While approximately half of the stellar debris is ejected at high velocities, the remaining material stays bound to the black hole and accretes, resulting in a luminous, long-lived transient known as a tidal disruption flare (TDF). In addition to serving as unique laboratories for accretion physics,TDFs offer the hope of measuring black hole masses in galaxies much too distant for resolved kinematic studies.In order to realize this potential, we must better understand the detailed processes by which the bound debris circularizes and forms an accretion disk. Spectroscopy is critical to this effort, as emission and absorption line diagnostics provide insight into the location and physical state (velocity, density, composition) of the emitting gas (in analogy with quasars). UV spectra are particularly critical, as most strong atomic features fall in this bandpass, and high-redshift TDF discoveries from LSST will sample rest-frame UV wavelengths.Here I present recent attempts to obtain UV spectra of tidal disruption flares. I describe the UV spectrum of ASASSN-14li, in which we detect three classes of features: narrow absorption from the Milky Way (probably a high-velocity cloud), and narrow absorption and broad (2000-8000 km s-1) emission lines at or near the systemic host velocity. The absorption lines are blueshifted with respect to the emission lines by 250-400 km s-1. Due both to this velocity offset and the lack of common low-ionization features (Mg II, Fe II), we argue these arise from the same absorbing material responsible for the low-velocity outflow discovered at X-ray wavelengths. The broad nuclear emission lines display a remarkable abundance pattern: N III], N IV], and He II are quite prominent, while the common quasar emission lines of C III] and Mg II are weak or entirely absent. Detailed modeling of this spectrum will help elucidate fundamental questions regarding the nature of the emission processes at work in TDFs, while future UV spectroscopy of ASASSN-14li would help to confirm (or refute) the previously proposed connection between TDFs and “N-rich” quasars.

Multidisciplinary approach to non-surgical management of inguinal disruption in a professional hockey player treated with platelet-rich plasma, manual therapy and exercise: a case report

PubMed Central

St-Onge, Eric; MacIntyre, Ian G.; Galea, Anthony M.

2015-01-01

Objective: To present the clinical management of inguinal disruption in a professional hockey player and highlight the importance of a multidisciplinary approach to diagnosis and management. Clinical Features: A professional hockey player with recurrent groin pain presented to the clinic after an acute exacerbation of pain while playing hockey. Intervention: The patient received a clinical diagnosis of inguinal disruption. Imaging revealed a tear in the rectus abdominis. Management included two platelet-rich plasma (PRP) injections to the injured tissue, and subsequent manual therapy and exercise. The patient returned to his prior level of performance in 3.5 weeks. Discussion: This case demonstrated the importance of a multidisciplinary team and the need for advanced imaging in athletes with groin pain. Summary: Research quality concerning the non-surgical management of inguinal disruption remains low. This case adds evidence that PRP, with the addition of manual therapy and exercise may serve as a relatively quick and effective non-surgical management strategy. PMID:26816415

Aggregation of endosomal-vacuolar compartments in the Aovps24-deleted strain in the filamentous fungus Aspergillus oryzae

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

Tatsumi, Akinori; Shoji, Jun-ya; Kikuma, Takashi

2007-10-19

Previously, we found that deletion of Aovps24, an ortholog of Saccharomyces cerevisiae VPS24, that encodes an ESCRT (endosomal sorting complex required for transport)-III component required for late endosomal function results in fragmented and aggregated vacuoles. Although defective late endosomal function is likely responsible for this phenotype, critical lack of our knowledge on late endosomes in filamentous fungi prevented us from further characterization. In this study, we identified late endosomes of Aspergillus oryzae, by expressing a series of fusion proteins of fluorescent proteins with orthologs of late endosomal proteins. Using these fusion proteins as markers, we observed late endosomes in themore » wild type strain and the Aovps24 disruptant and demonstrated that late endosomes are aberrantly aggregated in the Aovps24 disruptant. Moreover, we revealed that the aggregated late endosomes have features of vacuoles as well. As deletion of another ESCRT-III component-encoding gene, Aovps2, resulted in similar phenotypes to that in the Aovps24 disruptant, phenotypes of the Aovps24 disruptant are probably due to defective late endosomal function.« less

Automated selective disruption of slow wave sleep

PubMed Central

Ooms, Sharon J.; Zempel, John M.; Holtzman, David M.; Ju, Yo-El S.

2017-01-01

Background Slow wave sleep (SWS) plays an important role in neurophysiologic restoration. Experimentally testing the effect of SWS disruption previously required highly time-intensive and subjective methods. Our goal was to develop an automated and objective protocol to reduce SWS without affecting sleep architecture. New Method We developed a custom Matlab™ protocol to calculate electroencephalogram spectral power every 10 seconds live during a polysomnogram, exclude artifact, and, if measurements met criteria for SWS, deliver increasingly louder tones through earphones. Middle-aged healthy volunteers (n=10) each underwent 2 polysomnograms, one with the SWS disruption protocol and one with sham condition. Results The SWS disruption protocol reduced SWS compared to sham condition, as measured by spectral power in the delta (0.5–4 Hz) band, particularly in the 0.5–2 Hz range (mean 20% decrease). A compensatory increase in the proportion of total spectral power in the theta (4–8 Hz) and alpha (8–12 Hz) bands was seen, but otherwise normal sleep features were preserved. N3 sleep decreased from 20±34 to 3±6 minutes, otherwise there were no significant changes in total sleep time, sleep efficiency, or other macrostructural sleep characteristics. Comparison with existing method This novel SWS disruption protocol produces specific reductions in delta band power similar to existing methods, but has the advantage of being automated, such that SWS disruption can be performed easily in a highly standardized and operator-independent manner. Conclusion This automated SWS disruption protocol effectively reduces SWS without impacting overall sleep architecture. PMID:28238859

Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options.

PubMed

Gallmeier, Eike; Calhoun, Eric S; Rago, Carlo; Brody, Jonathan R; Cunningham, Steven C; Hucl, Tomas; Gorospe, Myriam; Kohli, Manu; Lengauer, Christoph; Kern, Scott E

2006-06-01

How specifically to treat pancreatic and other cancers harboring Fanconi anemia gene mutations has raised great interest recently, yet preclinical studies have been hampered by the lack of well-controlled human cancer models. We endogenously disrupted FANCC and FANCG in a human adenocarcinoma cell line and determined the impact of these genes on drug sensitivity, irradiation sensitivity, and genome maintenance. FANCC and FANCG disruption abrogated FANCD2 monoubiquitination, confirming an impaired Fanconi anemia pathway function. On treatment with DNA interstrand-cross-linking agents, FANCC and FANCG disruption caused increased clastogenic damage, G2/M arrest, and decreased proliferation. The extent of hypersensitivity varied among agents, with ratios of inhibitory concentration 50% ranging from 2-fold for oxaliplatin to 14-fold for melphalan, a drug infrequently used in solid tumors. No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, NU1025, or hydrogen peroxide. FANCC and FANCG disruption also resulted in increased clastogenic damage on irradiation, but only FANCG disruption caused a subsequent decrease in relative survival. Finally, FANCC and FANCG disruption increased spontaneous chromosomal breakage, supporting the role of these genes in genome maintenance and likely explaining why they are mutated in sporadic cancer. Our human cancer cell model provides optimal controls to elucidate fundamental biologic features of individual Fanconi anemia gene defects and facilitates preclinical studies of therapeutic options. The impact of Fanconi gene defects on drug and irradiation sensitivity renders these genes promising targets for a specific, genotype-based therapy for individual cancer patients, providing a strong rationale for clinical trials.

The Sleep/Wake Cycle is Directly Modulated by Changes in Energy Balance.

PubMed

Collet, Tinh-Hai; van der Klaauw, Agatha A; Henning, Elana; Keogh, Julia M; Suddaby, Diane; Dachi, Sekesai V; Dunbar, Síle; Kelway, Sarah; Dickson, Suzanne L; Farooqi, I Sadaf; Schmid, Sebastian M

2016-09-01

The rise in obesity has been paralleled by a decline in sleep duration in epidemiological studies. However, the potential mechanisms linking energy balance and the sleep/wake cycle are not well understood. We aimed to examine the effects of manipulating energy balance on the sleep/wake cycle. Twelve healthy normal weight men were housed in a clinical research facility and studied at three time points: baseline, after energy balance was disrupted by 2 days of caloric restriction to 10% of energy requirements, and after energy balance was restored by 2 days of ad libitum/free feeding. Sleep architecture, duration of sleep stages, and sleep-associated respiratory parameters were measured by polysomnography. Two days of caloric restriction significantly increased the duration of deep (stage 4) sleep (16.8% to 21.7% of total sleep time; P = 0.03); an effect which was entirely reversed upon free feeding (P = 0.01). Although the apnea-hypopnea index stayed within the reference range (< 5 events per hour), it decreased significantly from caloric restriction to free feeding (P = 0.03). Caloric restriction was associated with a marked fall in leptin (P < 0.001) and insulin levels (P = 0.002). The fall in orexin levels from baseline to caloric restriction correlated positively with duration of stage 4 sleep (Spearman rho = 0.83, P = 0.01) and negatively with the number of awakenings in caloric restriction (Spearman rho = -0.79, P = 0.01). We demonstrate that changes in energy homeostasis directly and reversibly impact on the sleep/wake cycle. These findings provide a mechanistic framework for investigating the association between sleep duration and obesity risk. © 2016 Associated Professional Sleep Societies, LLC.

Disruptive behaviour disorders and DSM-5.

PubMed

Hawes, David J

2014-10-01

This article provides an overview of the revisions to the diagnoses of oppositional defiant disorder (ODD) and conduct disorder (CD) in DSM-5, and examines the key issues they raise. Particular attention is given to these changes in light of current treatment outcome evidence, including that published since the development of DSM-5. For both ODD and CD, DSM-5 retains the core features that previously defined the phenotypes for these diagnoses. DSM-5 nonetheless introduces a number of revisions pertaining to the guidelines for the application of these criteria, and markers for key individual differences in presentations of these disorders. These revisions reflect small but significant steps towards the perspective that children with disruptive behaviour problems are a highly heterogeneous population, and best characterised on the basis of both behavioural and emotional features. Importantly, there is growing evidence that the newly introduced changes to these diagnoses in DSM-5 may be better able to inform predictions regarding treatment response than previous diagnostic criteria. Copyright © 2014 Elsevier B.V. All rights reserved.

Predicting traffic volumes and estimating the effects of shocks in massive transportation systems.

PubMed

Silva, Ricardo; Kang, Soong Moon; Airoldi, Edoardo M

2015-05-05

Public transportation systems are an essential component of major cities. The widespread use of smart cards for automated fare collection in these systems offers a unique opportunity to understand passenger behavior at a massive scale. In this study, we use network-wide data obtained from smart cards in the London transport system to predict future traffic volumes, and to estimate the effects of disruptions due to unplanned closures of stations or lines. Disruptions, or shocks, force passengers to make different decisions concerning which stations to enter or exit. We describe how these changes in passenger behavior lead to possible overcrowding and model how stations will be affected by given disruptions. This information can then be used to mitigate the effects of these shocks because transport authorities may prepare in advance alternative solutions such as additional buses near the most affected stations. We describe statistical methods that leverage the large amount of smart-card data collected under the natural state of the system, where no shocks take place, as variables that are indicative of behavior under disruptions. We find that features extracted from the natural regime data can be successfully exploited to describe different disruption regimes, and that our framework can be used as a general tool for any similar complex transportation system.

Predicting traffic volumes and estimating the effects of shocks in massive transportation systems

PubMed Central

Silva, Ricardo; Kang, Soong Moon; Airoldi, Edoardo M.

2015-01-01

Public transportation systems are an essential component of major cities. The widespread use of smart cards for automated fare collection in these systems offers a unique opportunity to understand passenger behavior at a massive scale. In this study, we use network-wide data obtained from smart cards in the London transport system to predict future traffic volumes, and to estimate the effects of disruptions due to unplanned closures of stations or lines. Disruptions, or shocks, force passengers to make different decisions concerning which stations to enter or exit. We describe how these changes in passenger behavior lead to possible overcrowding and model how stations will be affected by given disruptions. This information can then be used to mitigate the effects of these shocks because transport authorities may prepare in advance alternative solutions such as additional buses near the most affected stations. We describe statistical methods that leverage the large amount of smart-card data collected under the natural state of the system, where no shocks take place, as variables that are indicative of behavior under disruptions. We find that features extracted from the natural regime data can be successfully exploited to describe different disruption regimes, and that our framework can be used as a general tool for any similar complex transportation system. PMID:25902504

Two visual systems in monitoring of dynamic traffic: effects of visual disruption.

PubMed

Zheng, Xianjun Sam; McConkie, George W

2010-05-01

Studies from neurophysiology and neuropsychology provide support for two separate object- and location-based visual systems, ventral and dorsal. In the driving context, a study was conducted using a change detection paradigm to explore drivers' ability to monitor the dynamic traffic flow, and the effects of visual disruption on these two visual systems. While driving, a discrete change, such as vehicle location, color, or identity, was occasionally made in one of the vehicles on the road ahead of the driver. Experiment results show that without visual disruption, all changes were detected very well; yet, these equally perceivable changes were disrupted differently by a brief blank display (150 ms): the detection of location changes was especially reduced. The disruption effects were also bigger for the parked vehicle compared to the moving ones. The findings support the different roles for two visual systems in monitoring the dynamic traffic: the "where", dorsal system, tracks vehicle spatiotemporal information on perceptual level, encoding information in a coarse and transient manner; whereas the "what", ventral system, monitors vehicles' featural information, encoding information more accurately and robustly. Both systems work together contributing to the driver's situation awareness of traffic. Benefits and limitations of using the driving simulation are also discussed. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Emotion Dysregulation and the Core Features of Autism Spectrum Disorder

ERIC Educational Resources Information Center

Samson, Andrea C.; Phillips, Jennifer M.; Parker, Karen J.; Shah, Shweta; Gross, James J.; Hardan, Antonio Y.

2014-01-01

The aim of this study was to examine the relationship between emotion dysregulation and the core features of Autism Spectrum Disorder (ASD), which include social/communication deficits, restricted/repetitive behaviors, and sensory abnormalities. An 18-item Emotion Dysregulation Index was developed on the basis of expert ratings of the Child…

Multiscale Feature Analysis of Salivary Gland Branching Morphogenesis

PubMed Central

Baydil, Banu; Daley, William P.; Larsen, Melinda; Yener, Bülent

2012-01-01

Pattern formation in developing tissues involves dynamic spatio-temporal changes in cellular organization and subsequent evolution of functional adult structures. Branching morphogenesis is a developmental mechanism by which patterns are generated in many developing organs, which is controlled by underlying molecular pathways. Understanding the relationship between molecular signaling, cellular behavior and resulting morphological change requires quantification and categorization of the cellular behavior. In this study, tissue-level and cellular changes in developing salivary gland in response to disruption of ROCK-mediated signaling by are modeled by building cell-graphs to compute mathematical features capturing structural properties at multiple scales. These features were used to generate multiscale cell-graph signatures of untreated and ROCK signaling disrupted salivary gland organ explants. From confocal images of mouse submandibular salivary gland organ explants in which epithelial and mesenchymal nuclei were marked, a multiscale feature set capturing global structural properties, local structural properties, spectral, and morphological properties of the tissues was derived. Six feature selection algorithms and multiway modeling of the data was performed to identify distinct subsets of cell graph features that can uniquely classify and differentiate between different cell populations. Multiscale cell-graph analysis was most effective in classification of the tissue state. Cellular and tissue organization, as defined by a multiscale subset of cell-graph features, are both quantitatively distinct in epithelial and mesenchymal cell types both in the presence and absence of ROCK inhibitors. Whereas tensor analysis demonstrate that epithelial tissue was affected the most by inhibition of ROCK signaling, significant multiscale changes in mesenchymal tissue organization were identified with this analysis that were not identified in previous biological studies. We here show how to define and calculate a multiscale feature set as an effective computational approach to identify and quantify changes at multiple biological scales and to distinguish between different states in developing tissues. PMID:22403724

Spatio-temporal texture (SpTeT) for distinguishing vulnerable from stable atherosclerotic plaque on dynamic contrast enhancement (DCE) MRI in a rabbit model

PubMed Central

Wan, Tao; Madabhushi, Anant; Phinikaridou, Alkystis; Hamilton, James A.; Hua, Ning; Pham, Tuan; Danagoulian, Jovanna; Kleiman, Ross; Buckler, Andrew J.

2014-01-01

Purpose: To develop a new spatio-temporal texture (SpTeT) based method for distinguishing vulnerable versus stable atherosclerotic plaques on DCE-MRI using a rabbit model of atherothrombosis. Methods: Aortic atherosclerosis was induced in 20 New Zealand White rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell's-viper-venom and histamine. Of the 30 vascular targets (segments) under histology analysis, 16 contained thrombus (vulnerable) and 14 did not (stable). A total of 352 voxel-wise computerized SpTeT features, including 192 Gabor, 36 Kirsch, 12 Sobel, 52 Haralick, and 60 first-order textural features, were extracted on DCE-MRI to capture subtle texture changes in the plaques over the course of contrast uptake. Different combinations of SpTeT feature sets, in which the features were ranked by a minimum-redundancy-maximum-relevance feature selection technique, were evaluated via a random forest classifier. A 500 iterative 2-fold cross validation was performed for discriminating the vulnerable atherosclerotic plaque and stable atherosclerotic plaque on per voxel basis. Four quantitative metrics were utilized to measure the classification results in separating between vulnerable and stable plaques. Results: The quantitative results show that the combination of five classes of SpTeT features can distinguish between vulnerable (disrupted plaques with an overlying thrombus) and stable plaques with the best AUC values of 0.9631 ± 0.0088, accuracy of 89.98% ± 0.57%, sensitivity of 83.71% ± 1.71%, and specificity of 94.55% ± 0.48%. Conclusions: Vulnerable and stable plaque can be distinguished by SpTeT based features. The SpTeT features, following validation on larger datasets, could be established as effective and reliable imaging biomarkers for noninvasively assessing atherosclerotic risk. PMID:24694153

Misinterpretations in agreement and agreement attraction.

PubMed

Patson, Nikole D; Husband, E Matthew

2016-01-01

It has been well established that subject-verb number agreement can be disrupted by local noun phrases that differ in number from the subject head noun phrase. In sentence production, mismatches in the grammatical number of the head and local noun phrases lead to agreement errors on the verb as in: the key to the cabinets are. Similarly, although ungrammaticality typically causes disruption in measures of sentence comprehension, the disruption is reduced when the local noun phrase has a plural feature. Using a forced-choice comprehension question method, we report two experiments that provide evidence that comprehenders were likely to misinterpret the number information on the head noun phrase when morphosyntactic number markings on the local noun phrase and verb did not match the head. These results are consistent with a growing body of research that suggests that comprehenders often arrive at a final interpretation of a sentence that is not faithful to the linguistic input.

Irrelevant learned reward associations disrupt voluntary spatial attention.

PubMed

MacLean, Mary H; Diaz, Gisella K; Giesbrecht, Barry

2016-10-01

Attention can be guided involuntarily by physical salience and by non-salient, previously learned reward associations that are currently task-irrelevant. Attention can be guided voluntarily by current goals and expectations. The current study examined, in two experiments, whether irrelevant reward associations could disrupt current, goal-driven, voluntary attention. In a letter-search task, attention was directed voluntarily (i.e., cued) on half the trials by a cue stimulus indicating the hemifield in which the target letter would appear with 100 % accuracy. On the other half of the trials, a cue stimulus was presented, but it did not provide information about the target hemifield (i.e., uncued). On both cued and uncued trials, attention could be involuntarily captured by the presence of a task-irrelevant, and physically non-salient, color, either within the cued or the uncued hemifield. Importantly, one week prior to the letter search task, the irrelevant color had served as a target feature that was predictive of reward in a separate training task. Target identification accuracy was better on cued compared to uncued trials. However, this effect was reduced when the irrelevant, and physically non-salient, reward-associated feature was present in the uncued hemifield. This effect was not observed in a second, control experiment in which the irrelevant color was not predictive of reward during training. Our results indicate that involuntary, value-driven capture can disrupt the voluntary control of spatial attention.

International trade inoperability input-output model (IT-IIM): theory and application.

PubMed

Jung, Jeesang; Santos, Joost R; Haimes, Yacov Y

2009-01-01

The inoperability input-output model (IIM) has been used for analyzing disruptions due to man-made or natural disasters that can adversely affect the operation of economic systems or critical infrastructures. Taking economic perturbation for each sector as inputs, the IIM provides the degree of economic production impacts on all industry sectors as the outputs for the model. The current version of the IIM does not provide a separate analysis for the international trade component of the inoperability. If an important port of entry (e.g., Port of Los Angeles) is disrupted, then international trade inoperability becomes a highly relevant subject for analysis. To complement the current IIM, this article develops the International Trade-IIM (IT-IIM). The IT-IIM investigates the resulting international trade inoperability for all industry sectors resulting from disruptions to a major port of entry. Similar to traditional IIM analysis, the inoperability metrics that the IT-IIM provides can be used to prioritize economic sectors based on the losses they could potentially incur. The IT-IIM is used to analyze two types of direct perturbations: (1) the reduced capacity of ports of entry, including harbors and airports (e.g., a shutdown of any port of entry); and (2) restrictions on commercial goods that foreign countries trade with the base nation (e.g., embargo).

Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing

PubMed Central

Crain, D. Andrew; Janssen, Sarah J.; Edwards, Thea M.; Heindel, Jerrold; Ho, Shuk-mei; Hunt, Patricia; Iguchi, Taisen; Juul, Anders; McLachlan, John A.; Schwartz, Jackie; Skakkebaek, Niels; Soto, Ana M.; Swan, Shanna; Walker, Cheryl; Woodruff, Teresa K.; Woodruff, Tracey J.; Giudice, Linda C.; Guillette, Louis J.

2014-01-01

Objective To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. Design Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. Conclusion(s) The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which women’s health can be improved. PMID:18929049

Defensive and pathological functions of the gastrointestinal NK3 receptor.

PubMed

Sanger, Gareth J; Tuladhar, Bishwa R; Bueno, Lionel; Furness, John B

2006-10-01

In general, normal gut functions are unaffected by selective NK(3) receptor antagonists such as talnetant (SB-223412), osanetant (SR 142901) or SB-235375. However, NK(3) receptors may mediate certain defensive or pathological intestinal processes. The precise mechanisms, by which this role is achieved, are not fully understood. In summary, intense stimulation of the intrinsic primary afferent neurones (IPANs) of the enteric nervous system is thought to release tachykinins from these neurones, to induce slow excitation (slow EPSPs) of connecting IPANs. This is hypothesised to cause hypersensitivity and disrupt intestinal motility, at least partly explaining why NK(3) receptor antagonism can reduce the level of disruption caused by supramaximal distension pressures in vitro. Tachykinin release from IPANs may also increase C-fibre sensitivity, directly or indirectly. Thus, NK(3) receptor antagonists can inhibit nociception associated with intestinal distension, in normal animals or after pre-sensitisation by restraint stress. Importantly, such inhibition has been found with SB-235375, a peripherally restricted antagonist. SB-235375 can also reduce a visceromotor response to brief colorectal distension without affecting similar responses to skin pinch, providing additional evidence for intestinal-specific activity. NK(3) receptor biology is, therefore, revealing a novel pathway by which disruptions in intestinal motility and nociception can be induced.

Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier.

PubMed

Bowie, Rachel V; Donatello, Simona; Lyes, Clíona; Owens, Mark B; Babina, Irina S; Hudson, Lance; Walsh, Shaun V; O'Donoghue, Diarmuid P; Amu, Sylvie; Barry, Sean P; Fallon, Padraic G; Hopkins, Ann M

2012-04-15

Intestinal epithelial barrier disruption is a feature of inflammatory bowel disease (IBD), but whether barrier disruption precedes or merely accompanies inflammation remains controversial. Tight junction (TJ) adhesion complexes control epithelial barrier integrity. Since some TJ proteins reside in cholesterol-enriched regions of the cell membrane termed lipid rafts, we sought to elucidate the relationship between rafts and intestinal epithelial barrier function. Lipid rafts were isolated from Caco-2 intestinal epithelial cells primed with the proinflammatory cytokine interferon-γ (IFN-γ) or treated with methyl-β-cyclodextrin as a positive control for raft disruption. Rafts were also isolated from the ilea of mice in which colitis had been induced in conjunction with in vivo intestinal permeability measurements, and lastly from intestinal biopsies of ulcerative colitis (UC) patients with predominantly mild or quiescent disease. Raft distribution was analyzed by measuring activity of the raft-associated enzyme alkaline phosphatase and by performing Western blot analysis for flotillin-1. Epithelial barrier integrity was estimated by measuring transepithelial resistance in cytokine-treated cells or in vivo permeability to fluorescent dextran in colitic mice. Raft and nonraft fractions were analyzed by Western blotting for the TJ proteins occludin and zonula occludens-1 (ZO-1). Our results revealed that lipid rafts were disrupted in IFN-γ-treated cells, in the ilea of mice with subclinical colitis, and in UC patients with quiescent inflammation. This was not associated with a clear pattern of occludin or ZO-1 relocalization from raft to nonraft fractions. Significantly, a time-course study in colitic mice revealed that disruption of lipid rafts preceded the onset of increased intestinal permeability. Our data suggest for the first time that lipid raft disruption occurs early in the inflammatory cascade in murine and human colitis and, we speculate, may contribute to subsequent disruption of epithelial barrier function.

PML nuclear bodies: regulation, function and therapeutic perspectives.

PubMed

Sahin, Umut; Lallemand-Breitenbach, Valérie; de Thé, Hugues

2014-11-01

PML nuclear bodies (NBs) were first described by electron microscopy and rediscovered through their treatment-reversible disruption in a rare leukaemia. They recruit multiple partner proteins and now emerge as interferon- and oxidative stress-responsive sumoylation factories. NBs mediate interferon-induced viral restriction, enhance proteolysis, finely tune metabolism and enforce stress-induced senescence. Apart from being markers of cellular stress, PML NBs could be harnessed pharmacologically in a number of conditions, including cancer, viral infection or neurodegenerative diseases. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Diet Coke or Not?

PubMed

Ralph-Edwards; Deitel; Deitel

1992-08-01

Many obese patients are attempting to diet. Furthermore, many gastric restrictive procedures permit the ready flow of liquids, and the individual may want to be assured that the liquid is in the "non-calorie" form. Many obese patients have diabetes, and an incorrect or misrepresented beverage can result in elevated plasma glucose with a disruption in glycemic control. The studies below have been extended for orange-flavored carbonated beverages (Orange Crush, Fanta Orange, etc.) with the same findings-no color change with the diet drink and immediate brown color change with the regular drink on the Diastix.

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

Adam, C.; Romanczukiewicz, T.; Wereszczynski, A.

A restriction of the baby Skyrme model consisting of the quartic and potential terms only is investigated in detail for a wide range of potentials. Further, its properties are compared with those of the corresponding full baby Skyrme models. We find that topological (charge) as well as geometrical (nucleus/shell shape) features of baby Skyrmions are captured already by the soliton solutions of the restricted model. Further, we find a coincidence between the compact or noncompact nature of solitons in the restricted model, on the one hand, and the existence or nonexistence of multi-Skyrmions in the full baby Skyrme model, onmore » the other hand.« less

A Putative Type III Secretion System Effector Encoded by the MA20_12780 Gene in Bradyrhizobium japonicum Is-34 Causes Incompatibility with Rj4 Genotype Soybeans

PubMed Central

Hashimoto, Syougo; Okizaki, Kouhei; Kanesaki, Yu; Yoshikawa, Hirofumi; Yamakawa, Takeo

2015-01-01

The nodulation of Bradyrhizobium japonicum Is-34 is restricted by Rj4 genotype soybeans (Glycine max). To identify the genes responsible for this incompatibility, Tn5 mutants of B. japonicum Is-34 that were able to overcome this nodulation restriction were obtained. Analysis of the Tn5 mutants revealed that Tn5 was inserted into a region containing the MA20_12780 gene. In addition, direct disruption of this gene using marker exchange overcame the nodulation restriction by Rj4 genotype soybeans. The MA20_12780 gene has a tts box motif in its upstream region, indicating a possibility that this gene encodes a type III secretion system (T3SS) effector protein. Bioinformatic characterization revealed that the MA20_12780 protein contains the small ubiquitin-like modifier (SUMO) protease domain of the C48 peptidase (ubiquitin-like protease 1 [Ulp1]) family. The results of the present study indicate that a putative T3SS effector encoded by the MA20_12780 gene causes the incompatibility with Rj4 genotype soybeans, and they suggest the possibility that the nodulation restriction of B. japonicum Is-34 may be due to Rj4 genotype soybeans recognizing the putative T3SS effector (MA20_12780 protein) as a virulence factor. PMID:26092458

A Putative Type III Secretion System Effector Encoded by the MA20_12780 Gene in Bradyrhizobium japonicum Is-34 Causes Incompatibility with Rj4 Genotype Soybeans.

PubMed

Tsurumaru, Hirohito; Hashimoto, Syougo; Okizaki, Kouhei; Kanesaki, Yu; Yoshikawa, Hirofumi; Yamakawa, Takeo

2015-09-01

The nodulation of Bradyrhizobium japonicum Is-34 is restricted by Rj4 genotype soybeans (Glycine max). To identify the genes responsible for this incompatibility, Tn5 mutants of B. japonicum Is-34 that were able to overcome this nodulation restriction were obtained. Analysis of the Tn5 mutants revealed that Tn5 was inserted into a region containing the MA20_12780 gene. In addition, direct disruption of this gene using marker exchange overcame the nodulation restriction by Rj4 genotype soybeans. The MA20_12780 gene has a tts box motif in its upstream region, indicating a possibility that this gene encodes a type III secretion system (T3SS) effector protein. Bioinformatic characterization revealed that the MA20_12780 protein contains the small ubiquitin-like modifier (SUMO) protease domain of the C48 peptidase (ubiquitin-like protease 1 [Ulp1]) family. The results of the present study indicate that a putative T3SS effector encoded by the MA20_12780 gene causes the incompatibility with Rj4 genotype soybeans, and they suggest the possibility that the nodulation restriction of B. japonicum Is-34 may be due to Rj4 genotype soybeans recognizing the putative T3SS effector (MA20_12780 protein) as a virulence factor. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Effects of Sleep on Emotional Target Detection Performance: A Novel iPad-Based Pediatric Game

PubMed Central

Colonna, Annalisa; Smith, Anna B.; Smith, Stuart; VanDenEshof, Kirandeep; Orgill, Jane; Gringras, Paul; Pal, Deb K.

2018-01-01

Background: Consolidation of learning occurs during sleep but when it is disturbed there may be an adverse impact upon these functions. While research has focused upon how sleep affects cognition in adulthood, the effects of disrupted sleep are likely to impact more heavily on learning among children and adolescents. We aimed to investigate whether a night’s sleep impacts upon executive function compared with an equivalent wakefulness period. We also wanted to know whether restricting sleep would reduce these effects on performance. To investigate this issue in children, we adapted existing research methods to make them more suitable for this population. Methods: Using a cross-over trial design, 22 children aged 7–14 completed an updated but previously validated, continuous performance task (CPT) designed to be appealing to children, containing emotional and neutral targets and presented on an iPad. We measured omission and commission errors, mean and variability of reaction times (RTs) immediately and after a delay spent in the following three ways: 11-h intervals of unrestricted and restricted sleep in the style of a ‘sleepover’ and daytime wakefulness. We examined differences in immediate and delayed testing for each dependent variable. Both sleep nights were spent in a specialist sleep lab where polysomnography data were recorded. Results: While there were no significant main effects of sleep condition, as expected we observed significantly faster and more accurate performance in delayed compared with immediate testing across all conditions for omission errors, RT and variability of RT. Importantly, we saw a significant interaction for commission errors to emotional targets (p = 0.034): while they were comparable across all conditions during immediate testing, for delayed testing there were significantly more errors after wakefulness compared with unrestricted sleep (p = 0.019) and at a trend level for restricted sleep (p = 0.063). Performance improvement after restricted sleep was inversely correlated with sleep opportunity time (p = 0.03), total sleep time (p = 0.01) and total non-REM time (p = 0.005). Conclusion: This tool, designed to be simple to use and appealing to children, revealed a preserving effect of typical and disrupted sleep periods on performance during an emotionally themed target detection task compared with an equivalent wakefulness period. PMID:29563887

Empirical tests of the role of disruptive coloration in reducing detectability

PubMed Central

Fraser, Stewart; Callahan, Alison; Klassen, Dana; Sherratt, Thomas N

2007-01-01

Disruptive patterning is a potentially universal camouflage technique that is thought to enhance concealment by rendering the detection of body shapes more difficult. In a recent series of field experiments, artificial moths with markings that extended to the edges of their ‘wings’ survived at higher rates than moths with the same edge patterns inwardly displaced. While this result seemingly indicates a benefit to obscuring edges, it is possible that the higher density markings of the inwardly displaced patterns concomitantly reduced their extent of background matching. Likewise, it has been suggested that the mealworm baits placed on the artificial moths could have created differential contrasts with different moth patterns. To address these concerns, we conducted controlled trials in which human subjects searched for computer-generated moth images presented against images of oak trees. Moths with edge-extended disruptive markings survived at higher rates, and took longer to find, than all other moth types, whether presented sequentially or simultaneously. However, moths with no edge markings and reduced interior pattern density survived better than their high-density counterparts, indicating that background matching may have played a so-far unrecognized role in the earlier experiments. Our disruptively patterned non-background-matching moths also had the lowest overall survivorship, indicating that disruptive coloration alone may not provide significant protection from predators. Collectively, our results provide independent support for the survival value of disruptive markings and demonstrate that there are common features in human and avian perception of camouflage. PMID:17360282

T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium

PubMed Central

Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

2016-01-01

An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an “inverse” configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this migration pathway to neuroinflammatory and neuroinfectious disorders which are typified by elevated chemokine levels in CSF. PMID:26942913

T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium.

PubMed

Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

2016-01-01

An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an "inverse" configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this migration pathway to neuroinflammatory and neuroinfectious disorders which are typified by elevated chemokine levels in CSF.

Fabricating Expert Knowledge of the Behaviour of Problematic Students

ERIC Educational Resources Information Center

Koskela, Anne; Lanas, Maija

2016-01-01

This article examines what constitutes students' disruptive and good behaviour, as described and defined by teachers. Teachers are viewed as professional experts who produce official information regarding their students. The present study analysed the overarching features of behaviour descriptions provided by teachers in official statements…

Sleep restriction may lead to disruption in physiological attention and reaction time.

PubMed

Choudhary, Arbind Kumar; Kishanrao, Sadawarte Sahebrao; Dadarao Dhanvijay, Anup Kumar; Alam, Tanwir

2016-01-01

Sleepiness is the condition where for some reason fails to go into a sleep state and will have difficulty in remaining awake even while carrying out activities. Sleep restriction occurs when an individual fails to get enough sleep due to high work demands. The mechanism between sleep restriction and underlying brain physiology deficits is not well assumed. The objective of the present study was to investigate the mental attention (P300) and reaction time [visual (VRT) and auditory (ART)] among night watchmen, at subsequent; first (1st) day, fourth (4th) day and seventh (7th) day of restricted sleep period. After exclusion and inclusion criteria, the study was performed among 50 watchmen (age=18-35 years) (n=50) after providing written informed consent and divided into two group. Group I-(Normal sleep) (n=28) working in day time and used to have normal sleep in night (≥8 h); Group II-(Restricted sleep) (n=22) - working in night time and used to have less sleep in night (≤3 h). Statistical significance between the different groups was determined by the independent student ' t ' test and the significance level was fixed at p≤0.05. We observed that among all normal and restricted sleep watchmen there was not any significant variation in Karolinska Sleepiness Scale (KSS) score, VRT and ART, along with latency and amplitude of P300 on 1st day of restricted sleep. However at subsequent on 4th day and 7th day of restricted sleep, there was significant increase in (KSS)score, and prolongation of VRT and ART as well as alteration in latency and amplitude of P300 wave in restricted sleep watchmen when compare to normal sleep watchmen. The present finding concludes that loss of sleep has major impact in dynamic change in mental attention and reaction time among watchmen employed in night shift. Professional regulations and work schedules should integrate sleep schedules before and during the work period as an essential dimension for their healthy life.

"Free butterflies will come out of these deep wounds": A grounded theory of how endometriosis affects women's psychological health.

PubMed

Facchin, Federica; Saita, Emanuela; Barbara, Giussy; Dridi, Dhouha; Vercellini, Paolo

2018-03-01

This study aimed to develop a grounded theory of how endometriosis affects psychological health. Open interviews were conducted with 74 patients. The Hospital Anxiety and Depression Scale was administered to all women, who were divided into distressed versus non-distressed. At the core of our grounded theory was the notion of disruption due to the common features of living with endometriosis. Experiencing disruption (vs restoring continuity) involved higher distress and was associated with a long pathway to diagnosis, bad doctor-patient relationships, poor physical health, lack of support, negative sense of female identity, and identification of life with endometriosis.

Successful treatment of severe disruptive disorder featuring symptoms of the Klüver-Bucy Syndrome following a massive right temporal-parietal hemorrhage.

PubMed

De Benedictis, Luigi; Dumais, Alexandre; Landry, Pierre

2013-01-01

We know little about effective treatment for patients suffering from partial or complete Klüver-Bucy Syndrome (KBS) and other disruptive behaviors following a stroke. Reported cases have shown that certain medication, given alone or combined, can be partially effective. In this specific case study, we will try to demonstrate the effectiveness of a combination of carbamazepine, clonidine, quetiapine and methylphenidate in the alleviating of these symptoms. The wide range of symptoms found in KBS led us to use several kinds of psychotropic medication in spite of the inherent risks associated to polypharmacy.

Restriction Endonucleases from Invasive Neisseria gonorrhoeae Cause Double-Strand Breaks and Distort Mitosis in Epithelial Cells during Infection

PubMed Central

Weyler, Linda; Engelbrecht, Mattias; Mata Forsberg, Manuel; Brehwens, Karl; Vare, Daniel; Vielfort, Katarina; Wojcik, Andrzej; Aro, Helena

2014-01-01

The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies. PMID:25460012

Restriction endonucleases from invasive Neisseria gonorrhoeae cause double-strand breaks and distort mitosis in epithelial cells during infection.

PubMed

Weyler, Linda; Engelbrecht, Mattias; Mata Forsberg, Manuel; Brehwens, Karl; Vare, Daniel; Vielfort, Katarina; Wojcik, Andrzej; Aro, Helena

2014-01-01

The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies.

Shank3 mutant mice display autistic-like behaviours and striatal dysfunction

PubMed Central

Peça, João; Feliciano, Cátia; Ting, Jonathan T.; Wang, Wenting; Wells, Michael F.; Venkatraman, Talaignair N.; Lascola, Christopher D.; Fu, Zhanyan; Feng, Guoping

2011-01-01

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. Shank3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for development of 22q13 deletion syndrome (Phelan-McDermid Syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for Shank3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic like-behaviours in mice. PMID:21423165

The Genomic Landscape of Balanced Cytogenetic Abnormalities Associated with Human Congenital Anomalies

PubMed Central

Redin, Claire; Brand, Harrison; Collins, Ryan L.; Kammin, Tammy; Mitchell, Elyse; Hodge, Jennelle C.; Hanscom, Carrie; Pillalamarri, Vamsee; Seabra, Catarina M.; Abbott, Mary-Alice; Abdul-Rahman, Omar A.; Aberg, Erika; Adley, Rhett; Alcaraz-Estrada, Sofia L.; Alkuraya, Fowzan S.; An, Yu; Anderson, Mary-Anne; Antolik, Caroline; Anyane-Yeboa, Kwame; Atkin, Joan F.; Bartell, Tina; Bernstein, Jonathan A.; Beyer, Elizabeth; Blumenthal, Ian; Bongers, Ernie M.H.F.; Brilstra, Eva H.; Brown, Chester W.; Brüggenwirth, Hennie T.; Callewaert, Bert; Chiang, Colby; Corning, Ken; Cox, Helen; Cuppen, Edwin; Currall, Benjamin B.; Cushing, Tom; David, Dezso; Deardorff, Matthew A.; Dheedene, Annelies; D’Hooghe, Marc; de Vries, Bert B.A.; Earl, Dawn L.; Ferguson, Heather L.; Fisher, Heather; FitzPatrick, David R.; Gerrol, Pamela; Giachino, Daniela; Glessner, Joseph T.; Gliem, Troy; Grady, Margo; Graham, Brett H.; Griffis, Cristin; Gripp, Karen W.; Gropman, Andrea L.; Hanson-Kahn, Andrea; Harris, David J.; Hayden, Mark A.; Hill, Rosamund; Hochstenbach, Ron; Hoffman, Jodi D.; Hopkin, Robert J.; Hubshman, Monika W.; Innes, A. Micheil; Irons, Mira; Irving, Melita; Jacobsen, Jessie C.; Janssens, Sandra; Jewett, Tamison; Johnson, John P.; Jongmans, Marjolijn C.; Kahler, Stephen G.; Koolen, David A.; Korzelius, Jerome; Kroisel, Peter M.; Lacassie, Yves; Lawless, William; Lemyre, Emmanuelle; Leppig, Kathleen; Levin, Alex V.; Li, Haibo; Li, Hong; Liao, Eric C.; Lim, Cynthia; Lose, Edward J.; Lucente, Diane; Macera, Michael J.; Manavalan, Poornima; Mandrile, Giorgia; Marcelis, Carlo L.; Margolin, Lauren; Mason, Tamara; Masser-Frye, Diane; McClellan, Michael W.; Zepeda Mendoza, Cinthya J.; Menten, Björn; Middelkamp, Sjors; Mikami, Liya R.; Moe, Emily; Mohammed, Shehla; Mononen, Tarja; Mortenson, Megan E.; Moya, Graciela; Nieuwint, Aggie W.; Ordulu, Zehra; Parkash, Sandhya; Pauker, Susan P.; Pereira, Shahrin; Perrin, Danielle; Phelan, Katy; Piña Aguilar, Raul E.; Poddighe, Pino J.; Pregno, Giulia; Raskin, Salmo; Reis, Linda; Rhead, William; Rita, Debra; Renkens, Ivo; Roelens, Filip; Ruliera, Jayla; Rump, Patrick; Schilit, Samantha L.P.; Shaheen, Ranad; Sparkes, Rebecca; Spiegel, Erica; Stevens, Blair; Stone, Matthew R.; Tagoe, Julia; Thakuria, Joseph V.; van Bon, Bregje W.; van de Kamp, Jiddeke; van Der Burgt, Ineke; van Essen, Ton; van Ravenswaaij-Arts, Conny M.; van Roosmalen, Markus J.; Vergult, Sarah; Volker-Touw, Catharina M.L.; Warburton, Dorothy P.; Waterman, Matthew J.; Wiley, Susan; Wilson, Anna; Yerena-de Vega, Maria de la Concepcion A.; Zori, Roberto T.; Levy, Brynn; Brunner, Han G.; de Leeuw, Nicole; Kloosterman, Wigard P.; Thorland, Erik C.; Morton, Cynthia C.; Gusella, James F.; Talkowski, Michael E.

2017-01-01

Despite their clinical significance, characterization of balanced chromosomal abnormalities (BCAs) has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and revealed complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. This study proposes that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements, and provides insight into novel pathogenic mechanisms such as altered regulation due to changes in chromosome topology. PMID:27841880

Evolutionary genomics and HIV restriction factors.

PubMed

Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

2015-03-01

To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

The Rac-GAP alpha2-chimaerin regulates hippocampal dendrite and spine morphogenesis.

PubMed

Valdez, Chris M; Murphy, Geoffrey G; Beg, Asim A

2016-09-01

Dendritic spines are fine neuronal processes where spatially restricted input can induce activity-dependent changes in one spine, while leaving neighboring spines unmodified. Morphological spine plasticity is critical for synaptic transmission and is thought to underlie processes like learning and memory. Significantly, defects in dendritic spine stability and morphology are common pathogenic features found in several neurodevelopmental and neuropsychiatric disorders. The remodeling of spines relies on proteins that modulate the underlying cytoskeleton, which is primarily composed of filamentous (F)-actin. The Rho-GTPase Rac1 is a major regulator of F-actin and is essential for the development and plasticity of dendrites and spines. However, the key molecules and mechanisms that regulate Rac1-dependent pathways at spines and synapses are not well understood. We have identified the Rac1-GTPase activating protein, α2-chimaerin, as a critical negative regulator of Rac1 in hippocampal neurons. The loss of α2-chimaerin significantly increases the levels of active Rac1 and induces the formation of aberrant polymorphic dendritic spines. Further, disruption of α2-chimaerin signaling simplifies dendritic arbor complexity and increases the presence of dendritic spines that appear poly-innervated. Our data suggests that α2-chimaerin serves as a "brake" to constrain Rac1-dependent signaling to ensure that the mature morphology of spines is maintained in response to network activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Docker Container Manager: A Simple Toolkit for Isolated Work with Shared Computational, Storage, and Network Resources

NASA Astrophysics Data System (ADS)

Polyakov, S. P.; Kryukov, A. P.; Demichev, A. P.

2018-01-01

We present a simple set of command line interface tools called Docker Container Manager (DCM) that allow users to create and manage Docker containers with preconfigured SSH access while keeping the users isolated from each other and restricting their access to the Docker features that could potentially disrupt the work of the server. Users can access DCM server via SSH and are automatically redirected to DCM interface tool. From there, they can create new containers, stop, restart, pause, unpause, and remove containers and view the status of the existing containers. By default, the containers are also accessible via SSH using the same private key(s) but through different server ports. Additional publicly available ports can be mapped to the respective ports of a container, allowing for some network services to be run within it. The containers are started from read-only filesystem images. Some initial images must be provided by the DCM server administrators, and after containers are configured to meet one’s needs, the changes can be saved as new images. Users can see the available images and remove their own images. DCM server administrators are provided with commands to create and delete users. All commands were implemented as Python scripts. The tools allow to deploy and debug medium-sized distributed systems for simulation in different fields on one or several local computers.

Humus depths under cut and uncut northern hardwood forests

Treesearch

George Hart

1960-01-01

Harvesting timber on lands devoted primarily to watershed management may alter, for better or worse, many features of a forested watershed. One such feature is forest humus. The beneficial role of forest humus in watershed management is widely recognized. A protective mantle of humus serves to cushion the impact of rain, to impede surface runoff, to restrict soil...

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle.

PubMed

Rader, Erik P; Turk, Rolf; Willer, Tobias; Beltrán, Daniel; Inamori, Kei-Ichiro; Peterson, Taylor A; Engle, Jeffrey; Prouty, Sally; Matsumura, Kiichiro; Saito, Fumiaki; Anderson, Mary E; Campbell, Kevin P

2016-09-27

Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contraction-induced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contraction-induced injury was not accompanied by increased necrosis, excitation-contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions.

Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities

PubMed Central

Hodge, Jennelle C.; Mitchell, Elyse; Pillalamarri, Vamsee; Toler, Tomi L.; Bartel, Frank; Kearney, Hutton M.; Zou, Ying S.; Tan, Wen-Hann; Hanscom, Carrie; Kirmani, Salman; Hanson, Rae R.; Skinner, Steven A.; Rogers, Curtis; Everman, David B.; Boyd, Ellen; Mullegama, Sureni V.; Keelean-Fuller, Debra; Powell, Cynthia M.; Elsea, Sarah H.; Morton, Cynthia C.; Gusella, James F.; DuPont, Barbara; Chaubey, Alka; Lin, Angela E.; Talkowski, Michael E.

2016-01-01

Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 contribute to a spectrum of neurodevelopmental phenotypes, however the impact of this locus in human psychopathology has not been described. To characterize the structural variation landscape of MBD5 disruptions and the associated psychopathology, 22 individuals with genomic disruption of MBD5 (translocation, point mutation, and deletion) were identified through whole-genome sequencing or cytogenomic microarray at 11 molecular diagnostic centers. The genomic impact ranged from a single base pair to 5.4 Mb. Parents were available for 11 cases, all of which confirmed the rearrangement arose de novo. Phenotypes were largely indistinguishable between patients with full-segment 2q23.1 deletions and those with intragenic MBD5 rearrangements, including alterations confined entirely to the 5′UTR, confirming the critical impact of non-coding sequence at this locus. We found heterogeneous, multi-system pathogenic effects of MBD5 disruption and characterized the associated spectrum of psychopathology, which includes sensory integration disorder, anxiety, self-hugging, bipolar disorder and others. Importantly, unique features of the oldest assessed patient were early-onset dementia and behavioral regression. Analyses also revealed phenotypes that distinguish MBD5 disruptions from seven well-established syndromes with significant diagnostic overlap. This study indicates that haploinsufficiency of MBD5 causes diverse phenotypes, yields insight into the spectrum of resulting neurodevelopmental and behavioral psychopathology, and provides clinical context for interpretation of MBD5 structural variations. Empirical evidence also suggests that disruption of non-coding MBD5 regulatory regions is sufficient for clinical manifestation, highlighting the limitations of exon-focused assessments. These results suggest an ongoing perturbation of neurological function throughout the lifespan, including risks for neurobehavioral regression and early-onset dementia. PMID:23587880

Development of an efficient genetic manipulation strategy for sequential gene disruption and expression of different heterologous GFP genes in Candida tropicalis.

PubMed

Zhang, Lihua; Chen, Xianzhong; Chen, Zhen; Wang, Zezheng; Jiang, Shan; Li, Li; Pötter, Markus; Shen, Wei; Fan, You

2016-11-01

The diploid yeast Candida tropicalis, which can utilize n-alkane as a carbon and energy source, is an attractive strain for both physiological studies and practical applications. However, it presents some characteristics, such as rare codon usage, difficulty in sequential gene disruption, and inefficiency in foreign gene expression, that hamper strain improvement through genetic engineering. In this work, we present a simple and effective method for sequential gene disruption in C. tropicalis based on the use of an auxotrophic mutant host defective in orotidine monophosphate decarboxylase (URA3). The disruption cassette, which consists of a functional yeast URA3 gene flanked by a 0.3 kb gene disruption auxiliary sequence (gda) direct repeat derived from downstream or upstream of the URA3 gene and of homologous arms of the target gene, was constructed and introduced into the yeast genome by integrative transformation. Stable integrants were isolated by selection for Ura + and identified by PCR and sequencing. The important feature of this construct, which makes it very attractive, is that recombination between the flanking direct gda repeats occurs at a high frequency (10 -8 ) during mitosis. After excision of the URA3 marker, only one copy of the gda sequence remains at the recombinant locus. Thus, the resulting ura3 strain can be used again to disrupt a second allelic gene in a similar manner. In addition to this effective sequential gene disruption method, a codon-optimized green fluorescent protein-encoding gene (GFP) was functionally expressed in C. tropicalis. Thus, we propose a simple and reliable method to improve C. tropicalis by genetic manipulation.

Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice.

PubMed

Bentzon, Jacob F; Sondergaard, Claus S; Kassem, Moustapha; Falk, Erling

2007-10-30

Signs of preceding episodes of plaque rupture and smooth muscle cell (SMC)-mediated healing are common in atherosclerotic plaques, but the source of the healing SMCs is unknown. Recent studies suggest that activated platelets adhering to sites of injury recruit neointimal SMCs from circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice. To determine the origin of SMCs after spontaneous plaque disruption, irradiated 18-month-old apoE-/- mice were reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE-/- mice and examined when they died up to 9 months later. Plaque hemorrhage, indicating previous plaque disruption, was widely present, but no bone marrow-derived eGFP+ SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE-/- mice. Mechanical plaque disruption was produced in irradiated apoE-/- mice reconstituted with eGFP+ apoE-/- bone marrow cells and in carotid bifurcations cross-grafted between apoE-/- and eGFP+ apoE-/- mice. Apart from few non-graft-derived SMCs near the anastomosis site in 1 transplanted carotid bifurcation, no SMCs originating from outside the local arterial segment were detected in healed plaques. Healing SMCs after atherosclerotic plaque disruption are derived entirely from the local arterial wall and not circulating progenitor cells in apoE-/- mice.

Adolescent Disruptive Behavior and Borderline Personality Disorder Symptoms in Young Adult Men

ERIC Educational Resources Information Center

Burke, Jeffrey D.; Stepp, Stephanie D.

2012-01-01

Very few studies have prospective information, especially regarding males, on the prediction of Borderline Personality Disorder (BPD) in adulthood from psychiatric disorders in childhood. Certain childhood disorders, however, have notably similar features in common with BPD. In particular, the affective dysfunction, hostility and interpersonal…

Interference Effects from Grammatically Unavailable Constituents during Sentence Processing

ERIC Educational Resources Information Center

Van Dyke, Julie A.

2007-01-01

Evidence from 3 experiments reveals interference effects from structural relationships that are inconsistent with any grammatical parse of the perceived input. Processing disruption was observed when items occurring between a head and a dependent overlapped with either (or both) syntactic or semantic features of the dependent. Effects of syntactic…

Abnormal Functional Activation and Connectivity in the Working Memory Network in Early-Onset Schizophrenia

ERIC Educational Resources Information Center

Kyriakopoulos, Marinos; Dima, Danai; Roiser, Jonathan P.; Corrigall, Richard; Barker, Gareth J.; Frangou, Sophia

2012-01-01

Objective: Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related…

Formation of Mesosiderites: Fragmentation and Reaccretion of a Large Differentiated Asteroid

NASA Technical Reports Server (NTRS)

Scott, Edward R. D.; Haack, Henning; Love, Stanley G.

2001-01-01

We propose that these stony-iron meteorites formed when a 50-150 km diameter projectile disrupted a 200-400 km diameter asteroid with a molten core. Several mineralogical features of mesosiderites need reinterpreting if our model is correct. Additional information is contained in the original extended abstract.

In vivo placental MRI shape and textural features predict fetal growth restriction and postnatal outcome.

PubMed

Dahdouh, Sonia; Andescavage, Nickie; Yewale, Sayali; Yarish, Alexa; Lanham, Diane; Bulas, Dorothy; du Plessis, Adre J; Limperopoulos, Catherine

2018-02-01

To investigate the ability of three-dimensional (3D) MRI placental shape and textural features to predict fetal growth restriction (FGR) and birth weight (BW) for both healthy and FGR fetuses. We recruited two groups of pregnant volunteers between 18 and 39 weeks of gestation; 46 healthy subjects and 34 FGR. Both groups underwent fetal MR imaging on a 1.5 Tesla GE scanner using an eight-channel receiver coil. We acquired T2-weighted images on either the coronal or the axial plane to obtain MR volumes with a slice thickness of either 4 or 8 mm covering the full placenta. Placental shape features (volume, thickness, elongation) were combined with textural features; first order textural features (mean, variance, kurtosis, and skewness of placental gray levels), as well as, textural features computed on the gray level co-occurrence and run-length matrices characterizing placental homogeneity, symmetry, and coarseness. The features were used in two machine learning frameworks to predict FGR and BW. The proposed machine-learning based method using shape and textural features identified FGR pregnancies with 86% accuracy, 77% precision and 86% recall. BW estimations were 0.3 ± 13.4% (mean percentage error ± standard error) for healthy fetuses and -2.6 ± 15.9% for FGR. The proposed FGR identification and BW estimation methods using in utero placental shape and textural features computed on 3D MR images demonstrated high accuracy in our healthy and high-risk cohorts. Future studies to assess the evolution of each feature with regard to placental development are currently underway. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:449-458. © 2017 International Society for Magnetic Resonance in Medicine.

Autonomous learning in gesture recognition by using lobe component analysis

NASA Astrophysics Data System (ADS)

Lu, Jian; Weng, Juyang

2007-02-01

Gesture recognition is a new human-machine interface method implemented by pattern recognition(PR).In order to assure robot safety when gesture is used in robot control, it is required to implement the interface reliably and accurately. Similar with other PR applications, 1) feature selection (or model establishment) and 2) training from samples, affect the performance of gesture recognition largely. For 1), a simple model with 6 feature points at shoulders, elbows, and hands, is established. The gestures to be recognized are restricted to still arm gestures, and the movement of arms is not considered. These restrictions are to reduce the misrecognition, but are not so unreasonable. For 2), a new biological network method, called lobe component analysis(LCA), is used in unsupervised learning. Lobe components, corresponding to high-concentrations in probability of the neuronal input, are orientation selective cells follow Hebbian rule and lateral inhibition. Due to the advantage of LCA method for balanced learning between global and local features, large amount of samples can be used in learning efficiently.

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.

PubMed

Fung, Camille M; White, Jessica R; Brown, Ashley S; Gong, Huiyu; Weitkamp, Jörn-Hendrik; Frey, Mark R; McElroy, Steven J

2016-01-01

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.

Sensitivity of MJO propagation to a robust positive Indian Ocean dipole event in the superparameterized CAM

DOE PAGES

Benedict, James J.; Pritchard, Michael S.; Collins, William D.

2015-11-23

The superparameterized Community Atmosphere Model (SPCAM) is used to investigate the impact and geographic sensitivity of positive Indian Ocean Dipole (+IOD) sea-surface temperatures (SSTs) on Madden-Julian oscillation (MJO) propagation. The goal is to clarify potentially appreciable +IOD effects on MJO dynamics detected in prior studies by using a global model with explicit convection representation. Prescribed climatological October SSTs and variants of the SST distribution from October 2006, a +IOD event, force the model. Modest MJO convection weakening over the Maritime Continent occurs when either climatological SSTs, or +IOD SST anomalies restricted to the Indian Ocean, are applied. However, severe MJOmore » weakening occurs when either +IOD SST anomalies are applied globally or restricted to the equatorial Pacific. MJO disruption is associated with time-mean changes in the zonal wind profile and lower moist static energy (MSE) in subsiding air masses imported from the Subtropics by Rossby-like gyres. On intraseasonal scales, MJO disruption arises from significantly smaller MSE accumulation, weaker meridional advective moistening, and overactive submonthly eddies that mix drier subtropical air into the path of MJO convection. These results (1) demonstrate that SPCAM reproduces observed time-mean and intraseasonal changes during +IOD episodes, (2) reaffirm the role that submonthly eddies play in MJO propagation and show that such multiscale interactions are sensitive to interannual SST states, and (3) suggest that boreal fall +IOD SSTs local to the Indian Ocean have a significantly smaller impact on Maritime Continent MJO propagation compared to contemporaneous Pacific SST anomalies which, for October 2006, resemble El Ninõ-like conditions.« less

Altered decorin leads to disrupted endothelial cell function: a possible mechanism in the pathogenesis of fetal growth restriction?

PubMed

Chui, A; Murthi, P; Gunatillake, T; Brennecke, S P; Ignjatovic, V; Monagle, P T; Whitelock, J M; Said, J M

2014-08-01

Fetal growth restriction (FGR) is a key cause of adverse pregnancy outcome where maternal and fetal factors are identified as contributing to this condition. Idiopathic FGR is associated with altered vascular endothelial cell functions. Decorin (DCN) has important roles in the regulation of endothelial cell functions in vascular environments. DCN expression is reduced in FGR. The objectives were to determine the functional consequences of reduced DCN in a human microvascular endothelial cell line model (HMVEC), and to determine downstream targets of DCN and their expression in primary placental microvascular endothelial cells (PLECs) from control and FGR-affected placentae. Short-interference RNA was used to reduce DCN expression in HMVECs and the effect on proliferation, angiogenesis and thrombin generation was determined. A Growth Factor PCR Array was used to identify downstream targets of DCN. The expression of target genes in control and FGR PLECs was performed. DCN reduction decreased proliferation and angiogenesis but increased thrombin generation with no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18 and MSTN. Validation of target genes confirmed decreased expression of VEGFA, MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies. Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sensitivity of MJO propagation to a robust positive Indian Ocean dipole event in the superparameterized CAM

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

Benedict, James J.; Pritchard, Michael S.; Collins, William D.

The superparameterized Community Atmosphere Model (SPCAM) is used to investigate the impact and geographic sensitivity of positive Indian Ocean Dipole (+IOD) sea-surface temperatures (SSTs) on Madden-Julian oscillation (MJO) propagation. The goal is to clarify potentially appreciable +IOD effects on MJO dynamics detected in prior studies by using a global model with explicit convection representation. Prescribed climatological October SSTs and variants of the SST distribution from October 2006, a +IOD event, force the model. Modest MJO convection weakening over the Maritime Continent occurs when either climatological SSTs, or +IOD SST anomalies restricted to the Indian Ocean, are applied. However, severe MJOmore » weakening occurs when either +IOD SST anomalies are applied globally or restricted to the equatorial Pacific. MJO disruption is associated with time-mean changes in the zonal wind profile and lower moist static energy (MSE) in subsiding air masses imported from the Subtropics by Rossby-like gyres. On intraseasonal scales, MJO disruption arises from significantly smaller MSE accumulation, weaker meridional advective moistening, and overactive submonthly eddies that mix drier subtropical air into the path of MJO convection. These results (1) demonstrate that SPCAM reproduces observed time-mean and intraseasonal changes during +IOD episodes, (2) reaffirm the role that submonthly eddies play in MJO propagation and show that such multiscale interactions are sensitive to interannual SST states, and (3) suggest that boreal fall +IOD SSTs local to the Indian Ocean have a significantly smaller impact on Maritime Continent MJO propagation compared to contemporaneous Pacific SST anomalies which, for October 2006, resemble El Ninõ-like conditions.« less

Investigations into Hypoxia and Oxidative Stress at the Optic Nerve Head in a Rat Model of Glaucoma

PubMed Central

Chidlow, Glyn; Wood, John P. M.; Casson, Robert J.

2017-01-01

The vascular hypothesis of glaucoma proposes that retinal ganglion cell axons traversing the optic nerve head (ONH) undergo oxygen and nutrient insufficiency as a result of compromised local blood flow, ultimately leading to their degeneration. To date, evidence for the hypothesis is largely circumstantial. Herein, we made use of an induced rat model of glaucoma that features reproducible and widespread axonal transport disruption at the ONH following chronic elevation of intraocular pressure. If vascular insufficiency plays a role in the observed axonal transport failure, there should exist a physical signature at this time point. Using a range of immunohistochemical and molecular tools, we looked for cellular events indicative of vascular insufficiency, including the presence of hypoxia, upregulation of hypoxia-inducible, or antioxidant-response genes, alterations to antioxidant enzymes, increased formation of superoxide, and the presence of oxidative stress. Our data show that ocular hypertension caused selective hypoxia within the laminar ONH in 11/13 eyes graded as either medium or high for axonal transport disruption. Hypoxia was always present in areas featuring injured axons, and, the greater the abundance of axonal transport disruption, the greater the likelihood of a larger hypoxic region. Nevertheless, hypoxic regions were typically focal and were not necessarily evident in sections taken deeper within the same ONH, while disrupted axonal transport was frequently encountered without any discernible hypoxia. Ocular hypertension caused upregulation of heme oxygenase-1—an hypoxia-inducible and redox-sensitive enzyme—in ONH astrocytes. The distribution and abundance of heme oxygenase-1 closely matched that of axonal transport disruption, and encompassed hypoxic regions and their immediate penumbra. Ocular hypertension also caused upregulations in the iron-regulating protein ceruloplasmin, the anaerobic glycolytic enzyme lactate dehydrogenase, and the transcription factors cFos and p-cJun. Moreover, ocular hypertension increased the generation of superoxide radicals in the retina and ONH, as well as upregulating the active subunit of the superoxide-generating enzyme NADPH oxidase, and invoking modest alterations to antioxidant-response enzymes. The results of this study provide further indirect support for the hypothesis that reduced blood flow to the ONH contributes to axonal injury in glaucoma. PMID:28883787

Constraints on cosmic strings due to black holes formed from collapsed cosmic string loops

NASA Technical Reports Server (NTRS)

Caldwell, R. R.; Gates, Evalyn

1993-01-01

The cosmological features of primordial black holes formed from collapsed cosmic string loops are studied. Observational restrictions on a population of primordial black holes are used to restrict f, the fraction of cosmic string loops which collapse to form black holes, and mu, the cosmic string mass-per-unit length. Using a realistic model of cosmic strings, we find the strongest restriction on the parameters f and mu is due to the energy density in 100MeV photons radiated by the black holes. We also find that inert black hole remnants cannot serve as the dark matter. If earlier, crude estimates of f are reliable, our results severely restrict mu, and therefore limit the viability of the cosmic string large-scale structure scenario.

Defining Tolerance: Impacts of Delay and Disruption when Managing Challenged Networks

NASA Technical Reports Server (NTRS)

Birrane, Edward J. III; Burleigh, Scott C.; Cerf, Vint

2011-01-01

Challenged networks exhibit irregularities in their communication performance stemming from node mobility, power constraints, and impacts from the operating environment. These irregularities manifest as high signal propagation delay and frequent link disruption. Understanding those limits of link disruption and propagation delay beyond which core networking features fail is an ongoing area of research. Various wireless networking communities propose tools and techniques that address these phenomena. Emerging standardization activities within the Internet Research Task Force (IRTF) and the Consultative Committee for Space Data Systems (CCSDS) look to build upon both this experience and scalability analysis. Successful research in this area is predicated upon identifying enablers for common communication functions (notably node discovery, duplex communication, state caching, and link negotiation) and how increased disruptions and delays affect their feasibility within the network. Networks that make fewer assumptions relating to these enablers provide more universal service. Specifically, reliance on node discovery and link negotiation results in network-specific operational concepts rather than scalable technical solutions. Fundamental to this debate are the definitions, assumptions, operational concepts, and anticipated scaling of these networks. This paper presents the commonalities and differences between delay and disruption tolerance, including support protocols and critical enablers. We present where and how these tolerances differ. We propose a set of use cases that must be accommodated by any standardized delay-tolerant network and discuss the implication of these on existing tool development.

Macroeconomics and oil-supply disruptions

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

Hubbard, R.G.; Fry, R.C. Jr.

1981-04-01

Energy-economy interactions and domestic linkages have been used in a system of models. Domestic economic aggregates are linked with a model of the world oil market by a core macroeconomic model with real and financial sectors. The model can be used to examine the policy ramifications of various short-run scenarios. Demand factors are not taken as exogenous to the world oil market, nor are oil prices taken as exogenous to the US economy. Simulations of the model have generated endogenous cycles in the world oil market; which then affect the US economy primarily through output and inflation channels. Policy simulationmore » was centered around the short-run imposition of a disruption tariff. The disruption tariff exhibited at least some of the desirable features noted by its proponents, though it did not function as a shield against the short-run output loss forced by the disruption. One might also simulate the rebate of tariff revenues as a reduction in the social security payroll tax. Other possible simulations include the use of any of the fiscal and monetary instruments included in the model. The effectiveness of these other policy instruments will be examined in a later paper.« less

Cations as Switches of Amyloid-Mediated Membrane Disruption Mechanisms: Calcium and IAPP

PubMed Central

Sciacca, Michele F.M.; Milardi, Danilo; Messina, Grazia M.L.; Marletta, Giovanni; Brender, Jeffrey R.; Ramamoorthy, Ayyalusamy; La Rosa, Carmelo

2013-01-01

Disruption of the integrity of the plasma membrane by amyloidogenic proteins is linked to the pathogenesis of a number of common age-related diseases. Although accumulating evidence suggests that adverse environmental stressors such as unbalanced levels of metal ions may trigger amyloid-mediated membrane damage, many features of the molecular mechanisms underlying these events are unknown. Using human islet amyloid polypeptide (hIAPP, aka amylin), an amyloidogenic peptide associated with β-cell death in type 2 diabetes, we demonstrate that the presence of Ca2+ ions inhibits membrane damage occurring immediately after the interaction of freshly dissolved hIAPP with the membrane, but significantly enhances fiber-dependent membrane disruption. In particular, dye leakage, quartz crystal microbalance, atomic force microscopy, and NMR experiments show that Ca2+ ions promote a shallow membrane insertion of hIAPP, which leads to the removal of lipids from the bilayer through a detergent-like mechanism triggered by fiber growth. Because both types of membrane-damage mechanisms are common to amyloid toxicity by most amyloidogenic proteins, it is likely that unregulated ion homeostasis, amyloid aggregation, and membrane disruption are all parts of a self-perpetuating cycle that fuels amyloid cytotoxicity. PMID:23332070

Coincident disruptive coloration

PubMed Central

Cuthill, Innes C.; Székely, Aron

2008-01-01

Even if an animal matches its surroundings perfectly in colour and texture, any mismatch between the spatial phase of its pattern and that of the background, or shadow created by its three-dimensional relief, is potentially revealing. Nevertheless, for camouflage to be fully broken, the shape must be recognizable. Disruptive coloration acts against object recognition by the use of high-contrast internal colour boundaries to break up shape and form. As well as the general outline, characteristic features such as eyes and limbs must also be concealed; this can be achieved by having the colour patterns on different, but adjacent, body parts aligned to match each other (i.e. in phase). Such ‘coincident disruptive coloration’ ensures that there is no phase disjunction where body parts meet, and causes different sections of the body to blend perceptually. We tested this theory using field experiments with predation by wild birds on artificial moth-like targets, whose wings and (edible pastry) bodies had colour patterns that were variously coincident or not. We also carried out an experiment with humans searching for analogous targets on a computer screen. Both experiments show that coincident disruptive coloration is an effective mechanism for concealing an otherwise revealing body form. PMID:18990668

ECETOC Florence workshop on risk assessment of endocrine substances, including the potency concept.

PubMed

Fegert, Ivana

2013-12-16

The European regulation on plant protection products (1107/2009) and the Biocidal Products Regulation (EC Regulation 528/2012) only support the marketing and use of chemicals if they do not cause endocrine disruption in humans or wildlife species. Also, substances with endocrine properties are subject to authorization under the European regulation on the registration, evaluation, authorization and restriction of chemicals (REACH; 1907/2006). Therefore, the regulatory consequences of identifying a substance as an endocrine disrupting chemical are severe. In contrast to that, basic scientific criteria, necessary to define endocrine disrupting properties, are not described in any of these legislative documents. Thus, the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) established a task force to provide scientific criteria for the identification and assessment of chemicals with endocrine disrupting properties that may be used within the context of these three legislative texts (ECETOC, 2009a). In 2009, ECETOC introduced a scientific framework as a possible concept for identifying endocrine disrupting properties within a regulatory context (ECETOC, 2009b; Bars et al., 2011a,b). The proposed scientific criteria integrated, in a weight of evidence approach, information from regulatory (eco)toxicity studies and mechanistic/screening studies by combining evidence for adverse effects detected in apical whole-organism studies with an understanding of the mode of action (MoA) of endocrine toxicity. However, since not all chemicals with endocrine disrupting properties are of equal hazard, an adequate concept should also be able to differentiate between chemicals with endocrine properties of low concern from those of higher concern (for regulatory purposes). For this purpose, the task force refined this part of their concept. Following an investigation of the key factors at a second workshop of invited regulatory, academic and industry scientists, the guidance was advanced further. For human health assessments it is based on the relevance to humans of the endocrine mechanism of toxicity, the specificity of the endocrine effects with respect to other toxic effects, the potency of the chemical to induce endocrine toxicity and consideration of exposure levels. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Nature of Covariation between Autistic Traits and Clumsiness: A Twin Study in a General Population Sample

ERIC Educational Resources Information Center

Moruzzi, Sara; Ogliari, Anna; Ronald, Angelica; Happe, Francesca; Battaglia, Marco

2011-01-01

While social impairment, difficulties with communication, and restricted repetitive behaviors are central features of Autism Spectrum Disorders, physical clumsiness is a commonly co-occurring feature. In a sample of 398 twin pairs (aged 8-17 years) from the Italian Twin Registry we investigated the nature of the co-variation between a psychometric…

Memory of Gender and Gait Direction from Biological Motion: Gender Fades Away but Directions Stay

ERIC Educational Resources Information Center

Poom, Leo

2012-01-01

The delayed discrimination methodology has been used to demonstrate a high-fidelity nondecaying visual short-term memory (VSTM) for so-called preattentive basic features. In the current Study, I show that the nondecaying high VSTM precision is not restricted to basic features by using the same method to measure memory precision for gait direction…

STUDIES IN EDUCATIONAL CLOSED-CIRCUIT TELEVISION.

ERIC Educational Resources Information Center

MARTIN, JOHN R.; AND OTHERS

THE 3 MOST OBJECTED-TO FEATURES OF INSTRUCTIONAL TV ARE (1) RESTRICTIONS IMPOSED BY THE USE OF A SPECIAL STUDIO, (2) LOSS OF TEACHER-STUDENT CONTACT, (3) THE LIMITED VIEWING AREA OF TV SCREENS. THIS STUDY INVESTIGATED 4 CLOSED-CIRCUIT TV COURSES IN AN ATTEMPT TO MINIMIZE FEATURES (1) AND (2). OVER THE ACADEMIC YEAR 1957-58 AT THE CASE INSTITUTE,…

Recent Asteroid Disruptions in the WISE Dataset - Constraining Asteroid Surface Properties Using Solar System Dust Bands

NASA Astrophysics Data System (ADS)

Kehoe, A. E.; Shaw, C.; Kehoe, T. J. J.

2017-12-01

Zodiacal dust bands are a fine-structure feature of the mid-IR emission profile of the zodiacal cloud. The dust bands have been studied for many years dating back to the InfraRed Astronomical Satellite (IRAS) data of the 1980's. The recent discovery and modeling (Espy et al., 2009; 2010; Espy Kehoe et al., 2015) of a very young, still-forming dust band structure has shown that, in the early stages following an asteroid disruption, much information on the dust parameters of the original disruption is retained in the band. Partial dust bands allow a never-before-seen observational look at the size distribution and cross-sectional area of dust produced in an asteroidal disruption, before it has been lost or significantly altered by orbital and collisional decay. The study of these partial band structures reveals information on the way asteroids disrupt and allow us to reconstruct the surface properties of the parent asteroid, including the depth of the surface regolith and the size distribution of particles composing the regolith. Using the greatly increased sensitivity of the Wide-field Infrared Survey Explorer (WISE), we can now detect much fainter (and thus younger) dust bands. The WISE data also reveals much better longitudinal resolution of the bands, allowing a better constraint on the source and age of the disruption. We will present our newest results from the WISE dataset, including detection of faint partial dust bands, improved models of more prominent bands, and our constraints on the asteroid surface properties from modeling these structures.

Rapid Actions of Xenoestrogens Disrupt Normal Estrogenic Signaling

PubMed Central

Watson, Cheryl S.; Hu, Guangzhen; Paulucci-Holthauzen, Adriana A.

2014-01-01

Some chemicals used in consumer products or manufacturing (eg. plastics, surfactants, pesticides, resins) have estrogenic activities; these xenoestrogens (XEs) chemically resemble physiological estrogens and are one of the major categories of synthesized compounds that disrupt endocrine actions. Potent rapid actions of XEs via nongenomic mechanisms contribute significantly to their disruptive effects on functional endpoints (eg. cell proliferation/death, transport, peptide release). Membrane-initiated hormonal signaling in our pituitary cell model is predominantly driven by mERα with mERβ and GPR30 participation. We visualized ERα on plasma membranes using many techniques in the past (impeded ligands, antibodies to ERα ) and now add observations of epitope proximity with other membrane signaling proteins. We have demonstrated a range of rapid signals/protein activations by XEs including: calcium channels, cAMP/PKA, MAPKs, G proteins, caspases, and transcription factors. XEs can cause disruptions of the oscillating temporal patterns of nongenomic signaling elicited by endogenous estrogens. Concentration effects of XEs are nonmonotonic (a trait shared with natural hormones), making it difficult to design efficient (single concentration) toxicology tests to monitor their harmful effects. A plastics monomer, Bisphenol A, modified by waste treatment (chlorination) and other processes causes dephosphorylation of extracellular-regulated kinases, in contrast to having no effects as it does in genomic signaling. Mixtures of XEs, commonly found in contaminated environments, disrupt the signaling actions of physiological estrogens even more severely than do single XEs. Understanding the features of XEs that drive these disruptive mechanisms will allow us to redesign useful chemicals that exclude estrogenic or anti-estrogenic activities. PMID:24269739

Controlling direct contact force for wet adhesion with different wedged film stabilities

NASA Astrophysics Data System (ADS)

Li, Meng; Xie, Jun; Shi, Liping; Huang, Wei; Wang, Xiaolei

2018-04-01

In solid–liquid–solid adhesive systems, wedged films often feature instability at microscopic thicknesses, which can easily disrupt the adhesive strength of their remarkable direct contact force. Here, sodium dodecyl sulfate (SDS) was employed to tune the instability of adhesion in wedged glass–water–rubber films, achieving controllable direct contact. Experimental results showed that the supplement of SDS molecules significantly weakened the direct contact force for wet adhesion and eliminated it at high concentrations. The underlying reason was suggested to be the repulsive double-layer force caused by SDS molecules, which lowers the instability of the wedged film and balances the preload, disrupting the direct contact in wet adhesion.

Disruption of vertical motility by shear triggers formation of thin phytoplankton layers.

PubMed

Durham, William M; Kessler, John O; Stocker, Roman

2009-02-20

Thin layers of phytoplankton are important hotspots of ecological activity that are found in the coastal ocean, meters beneath the surface, and contain cell concentrations up to two orders of magnitude above ambient concentrations. Current interpretations of their formation favor abiotic processes, yet many phytoplankton species found in these layers are motile. We demonstrated that layers formed when the vertical migration of phytoplankton was disrupted by hydrodynamic shear. This mechanism, which we call gyrotactic trapping, can be responsible for the thin layers of phytoplankton commonly observed in the ocean. These results reveal that the coupling between active microorganism motility and ambient fluid motion can shape the macroscopic features of the marine ecological landscape.

Cerebral organization of oral and signed language responses: case study evidence from amytal and cortical stimulation studies.

PubMed

Mateer, C A; Rapport, R L; Kettrick, C

1984-01-01

A normally hearing left-handed patient familiar with American Sign Language (ASL) was assessed under sodium amytal conditions and with left cortical stimulation in both oral speech and signed English. Lateralization was mixed but complementary in each language mode: the right hemisphere perfusion severely disrupted motoric aspects of both types of language expression, the left hemisphere perfusion specifically disrupted features of grammatical and semantic usage in each mode of expression. Both semantic and syntactic aspects of oral and signed responses were altered during left posterior temporal-parietal stimulation. Findings are discussed in terms of the neurological organization of ASL and linguistic organization in cases of early left hemisphere damage.

Can high quality overcome consumer resistance to restricted provider access? Evidence from a health plan choice experiment.

PubMed

Harris, Katherine M

2002-06-01

To investigate the impact of quality information on the willingness of consumers to enroll in health plans that restrict provider access. A survey administered to respondents between the ages of 25 and 64 in the West Los Angeles area with private health insurance. An experimental approach is used to measure the effect of variation in provider network features and information about the quality of network physicians on hypothetical plan choices. Conditional logit models are used to analyze the experimental choice data. Next, choice model parameter estimates are used to simulate the impact of changes in plan features on the market shares of competing health plans and to calculate the quality level required to make consumers indifferent to changes in provider access. The presence of quality information reduced the importance of provider network features in plan choices as hypothesized. However, there were not statistically meaningful differences by type of quality measure (i.e., consumer assessed versus expert assessed). The results imply that large quality differences are required to make consumers indifferent to changes in provider access. The impact of quality on plan choices depended more on the particular measure and less on the type of measure. Quality ratings based on the proportion of survey respondents "extremely satisfied with results of care" had the greatest impact on plan choice while the proportion of network doctors "affiliated with university medical centers" had the least. Other consumer and expert assessed measures had more comparable effects. Overall the results provide empirical evidence that consumers are willing to trade high quality for restrictions on provider access. This willingness to trade implies that relatively small plans that place restrictions on provider access can successfully compete against less restrictive plans when they can demonstrate high quality. However, the results of this study suggest that in many cases, the level of quality required for consumers to accept access restrictions may be so high as to be unattainable. The results provide empirical support for the current focus of decision support efforts on consumer assessed quality measures. At the same time, however, the results suggest that consumers would also value quality measures based on expert assessments. This finding is relevant given the lack of comparative quality information based on expert judgment and research suggesting that consumers have apprehensions about their ability to meaningfully interpret performance-based quality measures.

Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity.

PubMed

Speer, Colenso M; Sun, Chao; Liets, Lauren C; Stafford, Ben K; Chapman, Barbara; Cheng, Hwai-Jong

2014-11-07

Spontaneous retinal activity (SRA) is important during eye-specific segregation within the dorsal lateral geniculate nucleus (dLGN), but the feature(s) of activity critical for retinogeniculate refinement are controversial. Pharmacologically or genetically manipulating cholinergic signaling during SRA perturbs correlated retinal ganglion cell (RGC) spiking and disrupts eye-specific retinofugal refinement in vivo, consistent with an instructive role for SRA during visual system development. Paradoxically, ablating the starburst amacrine cells (SACs) that generate cholinergic spontaneous activity disrupts correlated RGC firing without impacting retinal activity levels or eye-specific segregation in the dLGN. Such experiments suggest that patterned SRA during retinal waves is not critical for eye-specific refinement and instead, normal activity levels are permissive for retinogeniculate development. Here we revisit the effects of ablating the cholinergic network during eye-specific segregation and show that SAC ablation disrupts, but does not eliminate, retinal waves with no concomitant impact on normal eye-specific segregation in the dLGN. We induced SAC ablation in postnatal ferret pups beginning at birth by intraocular injection of a novel immunotoxin selective for the ferret vesicular acetylcholine transporter (Ferret VAChT-Sap). Through dual-patch whole-cell and multi-electrode array recording we found that SAC ablation altered SRA patterns and led to significantly smaller retinal waves compared with controls. Despite these defects, eye-specific segregation was normal. Further, interocular competition for target territory in the dLGN proceeded in cases where SAC ablation was asymmetric in the two eyes. Our data demonstrate normal eye-specific retinogeniculate development despite significant abnormalities in patterned SRA. Comparing our current results with earlier studies suggests that defects in retinal wave size, absolute levels of SRA, correlations between RGC pairs, RGC burst frequency, high frequency RGC firing during bursts, and the number of spikes per RGC burst are each uncorrelated with abnormalities in eye-specific segregation in the dLGN. An increase in the fraction of asynchronous spikes occurring outside of bursts and waves correlates with eye-specific segregation defects in studies reported to date. These findings highlight the relative importance of different features of SRA while providing additional constraints for computational models of Hebbian plasticity mechanisms in the developing visual system.

Dissociation in Response to Methylphenidate on Response Variability in a Group of Medication Naive Children with ADHD

ERIC Educational Resources Information Center

Johnson, Katherine A.; Barry, Edwina; Bellgrove, Mark A.; Cox, Marie; Kelly, Simon P.; Daibhis, Aoife; Daly, Michael; Keavey, Michelle; Watchorn, Amy; Fitzgerald, Michael; McNicholas, Fiona; Kirley, Aiveen; Robertson, Ian H.; Gill, Michael

2008-01-01

Increased variability in reaction time (RT) has been proposed as a cardinal feature of attention deficit hyperactivity disorder (ADHD). Increased variability during sustained attention tasks may reflect inefficient fronto-striatal and fronto-parietal circuitry; activity within these circuits is modulated by the catecholamines. A disruption to…

A resistant starch fiber diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)

USDA-ARS?s Scientific Manuscript database

Inflammation is a constant feature and a major mediator of CKD progression. It is, in part, driven by altered gut microbiome and disruption of intestinal epithelial barrier, events which are primarily caused by: 1- urea influx in the intestine resulting in dominance of urease-possessing bacteria; 2-...

Olfactocentric Paralimbic Cortex Morphology in Adolescents with Bipolar Disorder

ERIC Educational Resources Information Center

Wang, Fei; Kalmar, Jessica H.; Womer, Fay Y.; Edmiston, Erin E.; Chepenik, Lara G.; Chen, Rachel; Spencer, Linda; Blumberg, Hilary P.

2011-01-01

The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together,…

The Impact of Salient Advertisements on Reading and Attention on Web Pages

ERIC Educational Resources Information Center

Simola, Jaana; Kuisma, Jarmo; Oorni, Anssi; Uusitalo, Liisa; Hyona, Jukka

2011-01-01

Human vision is sensitive to salient features such as motion. Therefore, animation and onset of advertisements on Websites may attract visual attention and disrupt reading. We conducted three eye tracking experiments with authentic Web pages to assess whether (a) ads are efficiently ignored, (b) ads attract overt visual attention and disrupt…

Positive Behavior Support Strategies for Young Children with Severe Disruptive Behavior

ERIC Educational Resources Information Center

Sharma, Raj Narayan; Singh, Shobra; Geromette, Jason

2008-01-01

Positive Behavior Support (PBS) has emerged as a behavioral support that focuses on ecological relevance and meaningful outcome in the form of lifestyle change. PBS is a strategy that attempts to reduce or eliminate inappropriate behavior utilizing a multi-component behavior plan. The plan has two features: functional behavior assessment and a…

Canavan Disease: A White Matter Disorder

ERIC Educational Resources Information Center

Kumar, Shalini; Mattan, Natalia S.; de Vellis, Jean

2006-01-01

Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as the loss of myelin, results in axonal dysfunction and hence a disruption of information processing between brain regions. The major feature of leukodystrophies is the lack of proper myelin formation during early development or the onset of myelin loss late in life.…

Characteristics of patients with symbrachydactyly.

PubMed

De Smet, L; Fabry, G

1998-04-01

The clinical and radiologic spectrum of symbrachydactyly has been extended, on the basis of experimental embryology, into four categories: typical symbrachydactyly, atypical cleft hand, monodactyly, and adactyly. The origin of this embryologic failure is probably a vascular disruption. A series of 64 hands and 3 feet are reported, indicating associated anomalies and possible etiologic features.

Faculty Agency in Striving University Contexts: Mundane yet Powerful Acts of Agency

ERIC Educational Resources Information Center

Gonzales, Leslie D.

2015-01-01

Drawing from Archer's critical realist theory of agency, this paper has two specific aims. First, the cultural and structural features of one "striving" institution are outlined. Then, I illustrate how faculty members asserted agency inside their striving university in ways intended to disrupt the structures and cultures that striving…

On Applications of Disruption Tolerant Networking to Optical Networking in Space

NASA Technical Reports Server (NTRS)

Hylton, Alan Guy; Raible, Daniel E.; Juergens, Jeffrey; Iannicca, Dennis

2012-01-01

The integration of optical communication links into space networks via Disruption Tolerant Networking (DTN) is a largely unexplored area of research. Building on successful foundational work accomplished at JPL, we discuss a multi-hop multi-path network featuring optical links. The experimental test bed is constructed at the NASA Glenn Research Center featuring multiple Ethernet-to-fiber converters coupled with free space optical (FSO) communication channels. The test bed architecture models communication paths from deployed Mars assets to the deep space network (DSN) and finally to the mission operations center (MOC). Reliable versus unreliable communication methods are investigated and discussed; including reliable transport protocols, custody transfer, and fragmentation. Potential commercial applications may include an optical communications infrastructure deployment to support developing nations and remote areas, which are unburdened with supporting an existing heritage means of telecommunications. Narrow laser beam widths and control of polarization states offer inherent physical layer security benefits with optical communications over RF solutions. This paper explores whether or not DTN is appropriate for space-based optical networks, optimal payload sizes, reliability, and a discussion on security.

Nance-Horan syndrome in females due to a balanced X;1 translocation that disrupts the NHS gene: Familial case report and review of the literature.

PubMed

Gómez-Laguna, Laura; Martínez-Herrera, Alejandro; Reyes-de la Rosa, Alejandra Del Pilar; García-Delgado, Constanza; Nieto-Martínez, Karem; Fernández-Ramírez, Fernando; Valderrama-Atayupanqui, Tania Yanet; Morales-Jiménez, Ariadna Berenice; Villa-Morales, Judith; Kofman, Susana; Cervantes, Alicia; Morán-Barroso, Verónica Fabiola

2018-01-01

The Nance-Horan syndrome is an X-linked disorder characterized by congenital cataract, facial features, microcornea, microphthalmia, and dental anomalies; most of the cases are due to NHS gene mutations on Xp22.13. Heterozygous carrier females generally present less severe features, and up to 30% of the affected males have intellectual disability. We describe two patients, mother and daughter, manifesting Nance-Horan syndrome. The cytogenetic and molecular analyses demonstrated a 46,X,t(X;1)(p22.13;q22) karyotype in each of them. No copy-number genomic imbalances were detected by high-density microarray analysis. The mother had a preferential inactivation of the normal X chromosome; expression analysis did not detect any mRNA isoform of NHS. This is the first report of Nance-Horan syndrome due to a skewed X chromosome inactivation resulting from a balanced translocation t(X;1) that disrupts the NHS gene expression, with important implications for clinical presentation and genetic counseling.

Artificial sweetener saccharin disrupts intestinal epithelial cells' barrier function in vitro.

PubMed

Santos, P S; Caria, C R P; Gotardo, E M F; Ribeiro, M L; Pedrazzoli, J; Gambero, A

2018-06-25

Consumption of non-nutritive sweeteners (NNS) is a dietary practice used by those who wish to lose weight or by patients on a sugar-restricted diet such as those with DM2. Although these substances are safe, possible biological interactions with the digestive tract, particularly in relation to intestinal permeability, have not been studied. Thus, the current work sought to investigate the action of different NNS on intestinal permeability using an in vitro Caco-2 cell model. Caco-2 cells were incubated with acesulfame K, aspartame, saccharin, or sucralose at equimolar concentrations. Acesulfame K, aspartame, and sucralose did not disrupt monolayer integrity in the cells. However, saccharin increased paracellular permeability and decreased transepithelial electrical resistance (TEER) via a non-cytotoxic mechanism. The levels of the tight junction protein claudin-1 were reduced in Caco-2 cells that had previously been exposed to saccharin. The inhibition of nuclear factor-κB (NF-κB) was able to prevent the reduction in TEER induced by saccharin treatment. Thalidomide, as an inhibitor of ubiquitin ligase, was able to prevent the decrease in claudin-1 protein expression and the TEER reduction in Caco-2 cells. Saccharin disrupts monolayer integrity and alters paracellular permeability in a Caco-2 cell monolayer model, via a mechanism involving NF-κB activation, resulting in the ubiquitination of the tight junction protein claudin-1. Saccharin consumption may potentially alter the intestinal integrity in humans.

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

Liu, Ying, E-mail: yingliu@doheny.org; Sun Yet-sen University, Zhongshan Ophthalmic Center, State Key Ophthalmic Laboratory, Guangzhou 510060; Kawai, Kirio

Research highlights: {yields} Inactivation of Smad4 caused disruption in the development of the anterior segment. {yields} Inactivation of Smad4 failed to disrupt early lens development. {yields} Smad4 controlled lens cell cycle and cell death processes. {yields} Smad4 may regulate actin stress fiber assembly and eyelid epithelial movement. -- Abstract: Purpose: Signaling by members of the TGF{beta} superfamily of molecules is essential for embryonic development and homeostasis. Smad4, a key intracellular mediator in TGF{beta} signaling, forms transcriptional activator complexes with Activin-, BMP-, and TGF{beta}-restricted Smad proteins. However, the functional role of Smad4 in controlling different visual system compartments has not beenmore » fully investigated. Methods: Using the Pax6 promoter-driven Cre transgenic, smad4 was conditionally inactivated in the lens, cornea and ectoderm of the eyelids. Standard histological and molecular analytical approaches were employed to reveal morphological and cellular changes. Results: Inactivation of Smad4 in the lens led to microphthalmia and cataract formation in addition to the persistent adhesion of the retina to the lens and the iris to the cornea. Inactivation of Smad4 from the ectoderm of the eyelid and cornea caused disruption to eyelid fusion and proper development of the corneal epithelium and corneal stroma. Conclusions: Smad4 is required for the development and maintenance of the lens in addition to the proper development of the cornea, eyelids, and retina.« less

The grammar of visual narrative: Neural evidence for constituent structure in sequential image comprehension.

PubMed

Cohn, Neil; Jackendoff, Ray; Holcomb, Phillip J; Kuperberg, Gina R

2014-11-01

Constituent structure has long been established as a central feature of human language. Analogous to how syntax organizes words in sentences, a narrative grammar organizes sequential images into hierarchic constituents. Here we show that the brain draws upon this constituent structure to comprehend wordless visual narratives. We recorded neural responses as participants viewed sequences of visual images (comics strips) in which blank images either disrupted individual narrative constituents or fell at natural constituent boundaries. A disruption of either the first or the second narrative constituent produced a left-lateralized anterior negativity effect between 500 and 700ms. Disruption of the second constituent also elicited a posteriorly-distributed positivity (P600) effect. These neural responses are similar to those associated with structural violations in language and music. These findings provide evidence that comprehenders use a narrative structure to comprehend visual sequences and that the brain engages similar neurocognitive mechanisms to build structure across multiple domains. Copyright © 2014 Elsevier Ltd. All rights reserved.

The grammar of visual narrative: Neural evidence for constituent structure in sequential image comprehension

PubMed Central

Cohn, Neil; Jackendoff, Ray; Holcomb, Phillip J.; Kuperberg, Gina R.

2014-01-01

Constituent structure has long been established as a central feature of human language. Analogous to how syntax organizes words in sentences, a narrative grammar organizes sequential images into hierarchic constituents. Here we show that the brain draws upon this constituent structure to comprehend wordless visual narratives. We recorded neural responses as participants viewed sequences of visual images (comics strips) in which blank images either disrupted individual narrative constituents or fell at natural constituent boundaries. A disruption of either the first or the second narrative constituent produced a left-lateralized anterior negativity effect between 500-700ms. Disruption of the second constituent also elicited a posteriorly-distributed positivity (P600) effect. These neural responses are similar to those associated with structural violations in language and music. These findings provide evidence that comprehenders use a narrative structure to comprehend visual sequences and that the brain engages similar neurocognitive mechanisms to build structure across multiple domains. PMID:25241329

Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina.

PubMed

Leach, Natalie R; Roller, Richard J

2010-10-10

The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus. However, specific inhibition of either conventional PKCs or PKC delta does not inhibit viral growth. Second, we show hyperphosphorylation of emerin by viral and cellular kinases is required for its disassociation from the lamina. These data support hypothesis that phosphorylation of lamina components mediates lamina disruption during HSV nuclear egress. Copyright © 2010 Elsevier Inc. All rights reserved.

A Rapid and Quantitative Flow Cytometry Method for the Analysis of Membrane Disruptive Antimicrobial Activity.

PubMed

O'Brien-Simpson, Neil M; Pantarat, Namfon; Attard, Troy J; Walsh, Katrina A; Reynolds, Eric C

2016-01-01

We describe a microbial flow cytometry method that quantifies within 3 hours antimicrobial peptide (AMP) activity, termed Minimum Membrane Disruptive Concentration (MDC). Increasing peptide concentration positively correlates with the extent of bacterial membrane disruption and the calculated MDC is equivalent to its MBC. The activity of AMPs representing three different membranolytic modes of action could be determined for a range of Gram positive and negative bacteria, including the ESKAPE pathogens, E. coli and MRSA. By using the MDC50 concentration of the parent AMP, the method provides high-throughput, quantitative screening of AMP analogues. A unique feature of the MDC assay is that it directly measures peptide/bacteria interactions and lysed cell numbers rather than bacteria survival as with MIC and MBC assays. With the threat of multi-drug resistant bacteria, this high-throughput MDC assay has the potential to aid in the development of novel antimicrobials that target bacteria with improved efficacy.

Compactness of viral genomes: effect of disperse and localized random mutations

NASA Astrophysics Data System (ADS)

Lošdorfer Božič, Anže; Micheletti, Cristian; Podgornik, Rudolf; Tubiana, Luca

2018-02-01

Genomes of single-stranded RNA viruses have evolved to optimize several concurrent properties. One of them is the architecture of their genomic folds, which must not only feature precise structural elements at specific positions, but also allow for overall spatial compactness. The latter was shown to be disrupted by random synonymous mutations, a disruption which can consequently negatively affect genome encapsidation. In this study, we use three mutation schemes with different degrees of locality to mutate the genomes of phage MS2 and Brome Mosaic virus in order to understand the observed sensitivity of the global compactness of their folds. We find that mutating local stretches of their genomes’ sequence or structure is less disruptive to their compactness compared to inducing randomly-distributed mutations. Our findings are indicative of a mechanism for the conservation of compactness acting on a global scale of the genomes, and have several implications for understanding the interplay between local and global architecture of viral RNA genomes.

Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina

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

Leach, Natalie R.; Roller, Richard J., E-mail: richard-roller@uiowa.ed

2010-10-10

The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus. However, specific inhibition of eithermore » conventional PKCs or PKC delta does not inhibit viral growth. Second, we show hyperphosphorylation of emerin by viral and cellular kinases is required for its disassociation from the lamina. These data support hypothesis that phosphorylation of lamina components mediates lamina disruption during HSV nuclear egress.« less

Disruption of DNA methylation-dependent long gene repression in Rett syndrome

PubMed Central

Gabel, Harrison W.; Kinde, Benyam Z.; Stroud, Hume; Gilbert, Caitlin S.; Harmin, David A.; Kastan, Nathaniel R.; Hemberg, Martin; Ebert, Daniel H.; Greenberg, Michael E.

2015-01-01

Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism1. MECP2 encodes a methyl-DNA-binding protein2 that has been proposed to function as a transcriptional repressor, but despite numerous studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 regulates transcription3–9. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain. PMID:25762136

Shapes and features of the primordial bispectrum

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

Gong, Jinn-Ouk; Palma, Gonzalo A.; Sypsas, Spyros, E-mail: jinn-ouk.gong@apctp.org, E-mail: gpalmaquilod@ing.uchile.cl, E-mail: s.sypsas@gmail.com

If time-dependent disruptions from slow-roll occur during inflation, the correlation functions of the primordial curvature perturbation should have scale-dependent features, a case which is marginally supported from the cosmic microwave background (CMB) data. We offer a new approach to analyze the appearance of such features in the primordial bispectrum that yields new consistency relations and justifies the search of oscillating patterns modulated by orthogonal and local templates. Under the assumption of sharp features, we find that the cubic couplings of the curvature perturbation can be expressed in terms of the bispectrum in two specific momentum configurations, for example local andmore » equilateral. This allows us to derive consistency relations among different bispectrum shapes, which in principle could be tested in future CMB surveys. Furthermore, based on the form of the consistency relations, we construct new two-parameter templates for features that include all the known shapes.« less

Conflict, camps and coercion: the ongoing livelihoods crisis in Darfur.

PubMed

Buchanan-Smith, Margie; Jaspars, Susanne

2007-03-01

This paper presents the findings of a study commissioned by World Food Programme (WFP) in early 2006 to enhance understanding of how the conflict in Darfur has affected livelihoods and markets, and of the effects of food aid. The livelihoods of many in Darfur were devastated early on in the conflict, principally through the widespread looting or destruction of assets and highly restricted population movements, which struck at the heart of pre-conflict livelihoods. Livelihood strategies for most people are now restricted, poorly remunerated and often associated with high risk of attack. Patterns of coercion and exploitation have also become entrenched; and markets and trade, the lifeblood of Da fur's economy pre-conflict, severely disrupted. Against this backdrop the impact of food aid on livelihoods in Darfur has been overwhelmingly positive. The paper proposes a number of preconditions for investment in recovery in Darfur, and recommends ways in which livelihoods can be supported in the current context of ongoing conflict.

Constraining movement alters the recruitment of motor processes in mental rotation.

PubMed

Moreau, David

2013-02-01

Does mental rotation depend on the readiness to act? Recent evidence indicates that the involvement of motor processes in mental rotation is experience-dependent, suggesting that different levels of expertise in sensorimotor interactions lead to different strategies to solve mental rotation problems. Specifically, experts in motor activities perceive spatial material as objects that can be acted upon, triggering covert simulation of rotations. Because action simulation depends on the readiness to act, movement restriction should therefore disrupt mental rotation performance in individuals favoring motor processes. In this experiment, wrestlers and non-athletes judged whether pairs of three-dimensional stimuli were identical or different, with their hands either constrained or unconstrained. Wrestlers showed higher performance than controls in the rotation of geometric stimuli, but this difference disappeared when their hands were constrained. However, movement restriction had similar consequences for both groups in the rotation of hands. These findings suggest that expert's advantage in mental rotation of abstract objects is based on the readiness to act, even when physical manipulation is impossible.

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease.

PubMed

Neves, Joana; Leitz, Dominik; Kraut, Simone; Brandenberger, Christina; Agrawal, Raman; Weissmann, Norbert; Mühlfeld, Christian; Mall, Marcus A; Altamura, Sandro; Muckenthaler, Martina U

2017-06-01

Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s) involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1 C326S ), increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1 C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Brain–blood amino acid correlates following protein restriction in murine maple syrup urine disease

PubMed Central

2014-01-01

Background Conventional therapy for patients with maple syrup urine disease (MSUD) entails restriction of protein intake to maintain acceptable levels of the branched chain amino acid, leucine (LEU), monitored in blood. However, no data exists on the correlation between brain and blood LEU with protein restriction, and whether correction in blood is reflected in brain. Methods To address this question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein, with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for quantitative amino acid analyses. Results LEU and valine (VAL) levels in all brain regions improved on average 28% when shifting from 19% to 6% protein, whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in brain regions did not improve, while the SE level improved 24% with low-protein consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE)) were 362-434 μM, consistent with human values considered within control. Nonetheless, numerous amino acids in brain regions remained abnormal despite protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU), gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine (SER). To assess the specificity of these anomalies, we piloted preliminary studies in hyperphenylalaninemic mice, modeling another large neutral aminoacidopathy. Employing an identical dietary regimen, we found remarkably consistent abnormalities in GLN, ASP, and GLU. Conclusions Our results suggest that blood amino acid analysis may be a poor surrogate for assessing the outcomes of protein restriction in the large neutral amino acidopathies, and further indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may contribute to long-term neurocognitive dysfunction in these disorders. PMID:24886632

Brain-blood amino acid correlates following protein restriction in murine maple syrup urine disease.

PubMed

Vogel, Kara R; Arning, Erland; Wasek, Brandi L; McPherson, Sterling; Bottiglieri, Teodoro; Gibson, K Michael

2014-05-08

Conventional therapy for patients with maple syrup urine disease (MSUD) entails restriction of protein intake to maintain acceptable levels of the branched chain amino acid, leucine (LEU), monitored in blood. However, no data exists on the correlation between brain and blood LEU with protein restriction, and whether correction in blood is reflected in brain. To address this question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein, with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for quantitative amino acid analyses. LEU and valine (VAL) levels in all brain regions improved on average 28% when shifting from 19% to 6% protein, whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in brain regions did not improve, while the SE level improved 24% with low-protein consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE)) were 362-434 μM, consistent with human values considered within control. Nonetheless, numerous amino acids in brain regions remained abnormal despite protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU), gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine (SER). To assess the specificity of these anomalies, we piloted preliminary studies in hyperphenylalaninemic mice, modeling another large neutral aminoacidopathy. Employing an identical dietary regimen, we found remarkably consistent abnormalities in GLN, ASP, and GLU. Our results suggest that blood amino acid analysis may be a poor surrogate for assessing the outcomes of protein restriction in the large neutral amino acidopathies, and further indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may contribute to long-term neurocognitive dysfunction in these disorders.

Distraction by smartphone use during clinical practice and opinions about smartphone restriction policies: A cross-sectional descriptive study of nursing students.

PubMed

Cho, Sumi; Lee, Eunjoo

2016-05-01

Smartphone use in healthcare settings may distract healthcare providers and disrupt patient care. Moreover, it may lead to adverse events, thereby threatening patient safety. This study assessed nursing students' smartphone use as a source of distraction in clinical practice and identified their opinions about policies restricting smartphone use during patient care. A cross-sectional descriptive design was used with convenience sampling. Third-year nursing students (n=312) from two nursing schools in the Republic of Korea completed the survey in 2012. A self-report questionnaire-based on addiction theories for problem behaviors and literature on the distraction caused by cellular phone use-was used to assess smartphone use, experiences of distraction caused by smartphone use, and opinions about restriction policies on smartphone use during clinical practice. Nearly half (46.2%) of the nursing students used smartphones at least sometimes during clinical practice and about a quarter of the respondents (24.7%) were at least sometimes distracted by smartphones during clinical practice. The majority of the respondents (83.7%) had witnessed nurses using smartphones at least sometimes during their work. A few respondents (15.7%) agreed or strongly agreed with the policy for restricting smartphone use in hospitals. Students who used smartphones more often tended to disagree with restriction policies for smartphone use in hospitals. Awareness about the risks of smartphone use, especially regarding patient safety, is necessary for nursing students in school and hospital settings. Educators and faculty of nursing schools need to develop policies that encourage intelligent and safe use of smartphones during clinical practice. Copyright © 2016. Published by Elsevier Ltd.

Occurrence of endocrine-disrupting chemicals in indoor dust

PubMed Central

Hwang, Hyun-Min; Park, Eun-Kee; Young, Thomas M.; Hammock, Bruce D.

2010-01-01

Human exposure to indoor dust enriched with endocrine-disrupting chemicals released from numerous indoor sources has been a focus of increasing concern. Longer residence times and elevated contaminant concentrations in the indoor environment may increase chances of exposure to these contaminants by 1000-fold compared to outdoor exposure. To investigate the occurrence of semi-volatile endocrine-disrupting chemicals, including PBDEs (polybrominated diphenyl ethers), PCBs (polychlorinated biphenyls), phthalates, pyrethroids, DDT (dichlorodiphenyltrichloroethane) and its metabolites, and chlordanes, indoor dust samples were collected from household vacuum cleaner bags provided by 10 apartments and 1 community hall in Davis, California, USA. Chemical analyses show that all indoor dust samples are highly contaminated by target analytes measured in the present study. Di-(2-ethylhexyl)phthalate was the most abundant (104–7630 μg/g) in all samples and higher than other target analytes by 2 to 6 orders of magnitude. PBDEs were also found at high concentrations (1780–25,200 ng/g). Although the use of PCBs has been banned or restricted for decades, some samples had PCBs at levels that are considered to be concerns for human health, indicating that the potential risk posed by PCBs still remains high in the indoor environment, probably due to a lack of dissipation processes and continuous release from the sources. Although the use of some PBDEs is being phased out in some parts of the U.S., this trend may apply to PBDEs as well. We can anticipate that exposure to PBDEs will continue as long as the general public keeps using existing household items such as sofas, mattresses, and carpets that contain PBDEs. This study provides additional information that indoor dust is highly contaminated by persistent and endocrine-disrupting chemicals. PMID:18632138

Study of physical and biological factors involved in the disruption of E. coli by hydrodynamic cavitation.

PubMed

Balasundaram, B; Harrison, S T L

2006-01-01

Hydrodynamic cavitation results in flow restriction in a flow system causing rapid pressure fluctuations and significant fluid forces. These can be harnessed to mediate microbial cell damage. Hydrodynamic cavitation was studied for the partial disruption of E. coli and selective release of specific proteins relative to the total soluble protein. The effects of the cavitation number, the number of passes, and the specific growth rate of E. coli on the release of periplasmic and cytoplasmic proteins were studied. At the optimum cavitation number of 0.17 for this experimental configuration, 48% of the total soluble protein, 88% of acid phosphatase, and 67% of beta-galactosidase were released by hydrodynamic cavitation in comparison with the maximum release attained using multiple passes through the French Press. The higher release of the acid phosphatase over the total soluble protein suggested preferred release of periplasmic compounds. This was supported by SDS-PAGE analysis. The absence of micronization of cell material resulting in the potential for ease of solid-liquid separation downstream of the cell disruption operation was confirmed by TEM microscopy. E. coli cells cultivated at a higher specific growth rate (0.36 h(-1)) were more easily disrupted than slower grown cells (0.11 h(-1)). The specific activity of the enzyme of interest released by hydrodynamic cavitation, defined as the units of enzyme in solution per milligram of total soluble protein, was greater than that obtained on release by the French Press, high-pressure homogenization, osmotic shock, and EDTA treatment. The selectivity offered indicates the potential of enzyme release by hydrodynamic cavitation to ease the purification in the subsequent downstream processing.

Disruption of Thiamine Uptake and Growth of Cells by Feline Leukemia Virus Subgroup A

PubMed Central

Mendoza, Ramon; Miller, A. Dusty

2013-01-01

Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection. PMID:23269813

Disruption of thiamine uptake and growth of cells by feline leukemia virus subgroup A.

PubMed

Mendoza, Ramon; Miller, A Dusty; Overbaugh, Julie

2013-03-01

Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection.

Developmental Programming: Exposure to Testosterone Excess Disrupts Steroidal and Metabolic Environment in Pregnant Sheep

PubMed Central

Abi Salloum, B.; Veiga-Lopez, A.; Abbott, D. H.; Burant, C. F.

2015-01-01

Gestational exposure to excess T leads to intrauterine growth restriction, low birth weight, and adult metabolic/reproductive disorders in female sheep. We hypothesized that as early mediators of such disruptions, gestational T disrupts steroidal and metabolic homeostasis in both the mother and fetus by both androgenic and metabolic pathways. Maternal blood samples were measured weekly for levels of insulin, glucose, and progesterone from four groups of animals: control; gestational T (twice weekly im injections of 100 mg of T propionate from d 30 to d 90 of gestation); T plus an androgen antagonist, flutamide (15 mg/kg·d oral; T-Flutamide); and T plus the insulin sensitizer, rosiglitazone (0.11 mg/kg·d oral; T-Rosi) (n = 10–12/group). On day 90 of gestation, maternal and umbilical cord samples were collected after a 48-hour fast from a subset (n = 6/group) for the measurement of steroids, free fatty acids, amino acids, and acylcarnitines. Gestational T decreased maternal progesterone levels by 36.5% (P < .05), which was prevented by flutamide showing direct androgenic mediation. Gestational T also augmented maternal insulin levels and decreased medium chained acylcarnitines, suggesting increased mitochondrial fatty acid oxidation. These changes were prevented by rosiglitazone, suggesting alterations in maternal fuel use. Gestational T-induced increases in fetal estradiol were not prevented by either cotreatment. Gestational T disrupted associations of steroids with metabolites and progesterone with acylcarnitines, which was prevented either by androgen antagonist or insulin sensitizer cotreatment. These findings suggest a future combination of these treatments might be required to prevent alteration in maternal/fetal steroidal and metabolic milieu(s). PMID:25763641

Developmental programming: exposure to testosterone excess disrupts steroidal and metabolic environment in pregnant sheep.

PubMed

Abi Salloum, B; Veiga-Lopez, A; Abbott, D H; Burant, C F; Padmanabhan, V

2015-06-01

Gestational exposure to excess T leads to intrauterine growth restriction, low birth weight, and adult metabolic/reproductive disorders in female sheep. We hypothesized that as early mediators of such disruptions, gestational T disrupts steroidal and metabolic homeostasis in both the mother and fetus by both androgenic and metabolic pathways. Maternal blood samples were measured weekly for levels of insulin, glucose, and progesterone from four groups of animals: control; gestational T (twice weekly im injections of 100 mg of T propionate from d 30 to d 90 of gestation); T plus an androgen antagonist, flutamide (15 mg/kg·d oral; T-Flutamide); and T plus the insulin sensitizer, rosiglitazone (0.11 mg/kg·d oral; T-Rosi) (n = 10-12/group). On day 90 of gestation, maternal and umbilical cord samples were collected after a 48-hour fast from a subset (n = 6/group) for the measurement of steroids, free fatty acids, amino acids, and acylcarnitines. Gestational T decreased maternal progesterone levels by 36.5% (P < .05), which was prevented by flutamide showing direct androgenic mediation. Gestational T also augmented maternal insulin levels and decreased medium chained acylcarnitines, suggesting increased mitochondrial fatty acid oxidation. These changes were prevented by rosiglitazone, suggesting alterations in maternal fuel use. Gestational T-induced increases in fetal estradiol were not prevented by either cotreatment. Gestational T disrupted associations of steroids with metabolites and progesterone with acylcarnitines, which was prevented either by androgen antagonist or insulin sensitizer cotreatment. These findings suggest a future combination of these treatments might be required to prevent alteration in maternal/fetal steroidal and metabolic milieu(s).

Impact of sleep restriction on local immune response and skin barrier restoration with and without "multinutrient" nutrition intervention.

PubMed

Smith, Tracey J; Wilson, Marques A; Karl, J Philip; Orr, Jeb; Smith, Carl D; Cooper, Adam D; Heaton, Kristin J; Young, Andrew J; Montain, Scott J

2018-01-01

Systemic immune function is impaired by sleep restriction. However, the impact of sleep restriction on local immune responses and to what extent any impairment can be mitigated by nutritional supplementation is unknown. We assessed the effect of 72-h sleep restriction (2-h nightly sleep) on local immune function and skin barrier restoration of an experimental wound, and determined the influence of habitual protein intake (1.5 g·kg -1 ·day -1 ) supplemented with arginine, glutamine, zinc sulfate, vitamin C, vitamin D3, and omega-3 fatty acids compared with lower protein intake (0.8 g·kg -1 ·day -1 ) without supplemental nutrients on these outcomes. Wounds were created in healthy adults by removing the top layer of less than or equal to eight forearm blisters induced via suction, after adequate sleep (AS) or 48 h of a 72-h sleep restriction period (SR; 2-h nightly sleep). A subset of participants undergoing sleep restriction received supplemental nutrients during and after sleep restriction (SR+). Wound fluid was serially sampled 48 h postblistering to assess local cytokine responses. The IL-8 response of wound fluid was higher for AS compared with SR [area-under-the-curve (log 10 ), 5.1 ± 0.2 and 4.9 ± 0.2 pg/ml, respectively; P = 0.03]; and both IL-6 and IL-8 concentrations were higher for SR+ compared with SR ( P < 0.0001), suggestive of a potentially enhanced early wound healing response. Skin barrier recovery was shorter for AS (4.2 ± 0.9 days) compared with SR (5.0 ± 0.9 days) ( P = 0.02) but did not differ between SR and SR+ ( P = 0.18). Relatively modest sleep disruption delays wound healing. Supplemental nutrition may mitigate some decrements in local immune responses, without detectable effects on wound healing rate. NEW & NOTEWORTHY The data herein characterizes immune function in response to sleep restriction in healthy volunteers with and without nutrition supplementation. We used a unique skin wound model to show that sleep restriction delays skin barrier recovery, and nutrition supplementation attenuates decrements in local immune responses produced by sleep restriction. These findings support the beneficial effects of adequate sleep on immune function. Additional studies are necessary to characterize practical implications for populations where sleep restriction is unavoidable.

Attentional bias in restrictive eating disorders. Stronger attentional avoidance of high-fat food compared to healthy controls?

PubMed

Veenstra, Esther M; de Jong, Peter J

2012-02-01

A striking feature of the restricting subtype of anorexia nervosa (AN) is that these patients are extremely successful in restricting their food intake. Possibly, they are highly efficient in avoiding attentional engagement of food cues, thereby preventing more elaborate processing of food cues and thus subsequent craving. This study examined whether patients diagnosed with restrictive eating disorders ('restricting AN-like patients'; N=88) indeed show stronger attentional avoidance of visual food stimuli than healthy controls (N=76). Attentional engagement and disengagement were assessed by means of a pictorial exogenous cueing task, and (food and neutral) pictures were presented for 300, 500, or 1000 ms. In the 500 ms condition, both restricting AN-like patients and healthy controls demonstrated attentional avoidance of high-fat food as indexed by a negative cue-validity effect and impaired attentional engagement with high-fat food, whereas no evidence was found for facilitated disengagement from high-fat food. Within the group of restricting AN-like patients, patients with relatively severe eating pathology showed relatively strong attentional engagement with low-fat food. There was no evidence for attentional bias in the 300 and 1000 ms condition. The pattern of findings indicate that attentional avoidance of high-fat food is a common phenomenon that may become counterproductive in restricting AN-like patients, as it could facilitate their restricted food intake. Copyright © 2011 Elsevier Ltd. All rights reserved.

Restriction of Retrotransposon Mobilization in Schizosaccharomyces pombe by Transcriptional Silencing and Higher-Order Chromatin Organization

PubMed Central

Murton, Heather E.; Grady, Patrick J. R.; Chan, Tsun Ho; Cam, Hugh P.; Whitehall, Simon K.

2016-01-01

Uncontrolled propagation of retrotransposons is potentially detrimental to host genome integrity. Therefore, cells have evolved surveillance mechanisms to restrict the mobility of these elements. In Schizosaccharomyces pombe the Tf2 LTR retrotransposons are transcriptionally silenced and are also clustered in the nucleus into structures termed Tf bodies. Here we describe the impact of silencing and clustering on the mobility of an endogenous Tf2 element. Deletion of genes such as set1+ (histone H3 lysine 4 methyltransferase) or abp1+ (CENP-B homolog) that both alleviate silencing and clustering, result in a corresponding increase in mobilization. Furthermore, expression of constitutively active Sre1, a transcriptional activator of Tf2 elements, also alleviates clustering and induces mobilization. In contrast, clustering is not disrupted by loss of the HIRA histone chaperone, despite high levels of expression, and in this background, mobilization frequency is only marginally increased. Thus, mutations that compromise transcriptional silencing but not Tf bodies are insufficient to drive mobilization. Furthermore, analyses of mutant alleles that separate the transcriptional repression and clustering functions of Set1 are consistent with control of Tf2 propagation via a combination of silencing and spatial organization. Our results indicate that host surveillance mechanisms operate at multiple levels to restrict Tf2 retrotransposon mobilization. PMID:27343236

HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism

PubMed Central

Conrad, E; Polonio-Vallon, T; Meister, M; Matt, S; Bitomsky, N; Herbel, C; Liebl, M; Greiner, V; Kriznik, B; Schumacher, S; Krieghoff-Henning, E; Hofmann, T G

2016-01-01

Upon severe DNA damage a cellular signalling network initiates a cell death response through activating tumour suppressor p53 in association with promyelocytic leukaemia (PML) nuclear bodies. The deacetylase Sirtuin 1 (SIRT1) suppresses cell death after DNA damage by antagonizing p53 acetylation. To facilitate efficient p53 acetylation, SIRT1 function needs to be restricted. How SIRT1 activity is regulated under these conditions remains largely unclear. Here we provide evidence that SIRT1 activity is limited upon severe DNA damage through phosphorylation by the DNA damage-responsive kinase HIPK2. We found that DNA damage provokes interaction of SIRT1 and HIPK2, which phosphorylates SIRT1 at Serine 682 upon lethal damage. Furthermore, upon DNA damage SIRT1 and HIPK2 colocalize at PML nuclear bodies, and PML depletion abrogates DNA damage-induced SIRT1 Ser682 phosphorylation. We show that Ser682 phosphorylation inhibits SIRT1 activity and impacts on p53 acetylation, apoptotic p53 target gene expression and cell death. Mechanistically, we found that DNA damage-induced SIRT1 Ser682 phosphorylation provokes disruption of the complex between SIRT1 and its activator AROS. Our findings indicate that phosphorylation-dependent restriction of SIRT1 activity by HIPK2 shapes the p53 response. PMID:26113041

Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach.

PubMed

Cui, Zaixu; Xia, Zhichao; Su, Mengmeng; Shu, Hua; Gong, Gaolang

2016-04-01

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white-matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school-aged dyslexic children with 33 age-matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well-recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. © 2016 Wiley Periodicals, Inc.

Attention-Based Recurrent Temporal Restricted Boltzmann Machine for Radar High Resolution Range Profile Sequence Recognition.

PubMed

Zhang, Yifan; Gao, Xunzhang; Peng, Xuan; Ye, Jiaqi; Li, Xiang

2018-05-16

The High Resolution Range Profile (HRRP) recognition has attracted great concern in the field of Radar Automatic Target Recognition (RATR). However, traditional HRRP recognition methods failed to model high dimensional sequential data efficiently and have a poor anti-noise ability. To deal with these problems, a novel stochastic neural network model named Attention-based Recurrent Temporal Restricted Boltzmann Machine (ARTRBM) is proposed in this paper. RTRBM is utilized to extract discriminative features and the attention mechanism is adopted to select major features. RTRBM is efficient to model high dimensional HRRP sequences because it can extract the information of temporal and spatial correlation between adjacent HRRPs. The attention mechanism is used in sequential data recognition tasks including machine translation and relation classification, which makes the model pay more attention to the major features of recognition. Therefore, the combination of RTRBM and the attention mechanism makes our model effective for extracting more internal related features and choose the important parts of the extracted features. Additionally, the model performs well with the noise corrupted HRRP data. Experimental results on the Moving and Stationary Target Acquisition and Recognition (MSTAR) dataset show that our proposed model outperforms other traditional methods, which indicates that ARTRBM extracts, selects, and utilizes the correlation information between adjacent HRRPs effectively and is suitable for high dimensional data or noise corrupted data.

Litho-kinematic facies model for large landslide deposits in arid settings

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

Yarnold, J.C.; Lombard, J.P.

1989-04-01

Reconnaissance field studies of six large landslide deposits in the S. Basin and Range suggest that a set of characteristic features is common to the deposits of large landslides in an arid setting. These include a coarse boulder cap, an upper massive zone, a lower disrupted zone, and a mixed zone overlying disturbed substrate. The upper massive zone is dominated by crackel breccia. This grades downward into a lower disrupted zone composed of a more matrix-rich breccia that is internally sheared, intruded by clastic dikes, and often contains a cataclasite layer at its base. An underlying discontinuous mixed zone ismore » composed of material from the overlying breccia mixed with material entrained from the underlying substrate. Bedding in the substrate sometimes displays folding and contortion that die out downward. The authors work suggests a spatial zonation of these characteristic features within many landslide deposits. In general, clastic dikes, the basal cataclasite, and folding in the substrate are observed mainly in distal parts of landslides. In most cases, total thickness, thickness of the basal disturbed and mixed zones, and the degree of internal shearing increase distally, whereas maximum clast size commonly decreases distally. Zonation of these features is interpreted to result from kinematics of emplacement that cause generally increased deformation in the distal regions of the landslide.« less

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa.

PubMed

Chowdhury, Tara Gunkali; Chen, Yi-Wen; Aoki, Chiye

2015-10-22

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive - running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals' wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

PubMed Central

Chowdhury, Tara Gunkali; Chen, Yi-Wen; Aoki, Chiye

2015-01-01

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive – running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals’ wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity. PMID:26555618

The Sleep/Wake Cycle is Directly Modulated by Changes in Energy Balance

PubMed Central

Collet, Tinh-Hai; van der Klaauw, Agatha A.; Henning, Elana; Keogh, Julia M.; Suddaby, Diane; Dachi, Sekesai V.; Dunbar, Síle; Kelway, Sarah; Dickson, Suzanne L.; Farooqi, I. Sadaf; Schmid, Sebastian M.

2016-01-01

Study Objectives: The rise in obesity has been paralleled by a decline in sleep duration in epidemiological studies. However, the potential mechanisms linking energy balance and the sleep/wake cycle are not well understood. We aimed to examine the effects of manipulating energy balance on the sleep/wake cycle. Methods: Twelve healthy normal weight men were housed in a clinical research facility and studied at three time points: baseline, after energy balance was disrupted by 2 days of caloric restriction to 10% of energy requirements, and after energy balance was restored by 2 days of ad libitum/free feeding. Sleep architecture, duration of sleep stages, and sleep-associated respiratory parameters were measured by polysomnography. Results: Two days of caloric restriction significantly increased the duration of deep (stage 4) sleep (16.8% to 21.7% of total sleep time; P = 0.03); an effect which was entirely reversed upon free feeding (P = 0.01). Although the apnea-hypopnea index stayed within the reference range (< 5 events per hour), it decreased significantly from caloric restriction to free feeding (P = 0.03). Caloric restriction was associated with a marked fall in leptin (P < 0.001) and insulin levels (P = 0.002). The fall in orexin levels from baseline to caloric restriction correlated positively with duration of stage 4 sleep (Spearman rho = 0.83, P = 0.01) and negatively with the number of awakenings in caloric restriction (Spearman rho = -0.79, P = 0.01). Conclusions: We demonstrate that changes in energy homeostasis directly and reversibly impact on the sleep/wake cycle. These findings provide a mechanistic framework for investigating the association between sleep duration and obesity risk. Citation: Collet TH, van der Klaauw AA, Henning E, Keogh JM, Suddaby D, Dachi SV, Dunbar S, Kelway S, Dickson SL, Farooqi IS, Schmid SM. The sleep/ wake cycle is directly modulated by changes in energy balance. SLEEP 2016;39(9):1691–1700. PMID:27306267

Transformation of Infrastructure Projects for the Sustainable Development of the Transport Complex

NASA Astrophysics Data System (ADS)

Polyakova, Irina; Vasilyeva, Elena; Vorontsova, Natalya

2017-10-01

The article contains actual data on the review of the performance of the transport infrastructure in Russia. The problems and restrictions, affecting its sustainable development, are identified; their interaction and interrelations are traced. The authors argue that the majority of the revealed restrictions are of internal character and mainly is the feature of the state contract scheme. According to the authors, the scheme of public-and-private partnership is an effective mechanism, which can be suggested for the existing problems solution.

The relationship between sleep disorders and testosterone in men

PubMed Central

Wittert, Gary

2014-01-01

Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH) secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin (SHBG), or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea (OSA) appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure (CPAP) does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture. PMID:24435056

A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression.

PubMed

Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J; Schmidt, Kristina H

2016-12-01

In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks.

Sleep Characteristics and Daytime Cortisol Levels in Older Adults.

PubMed

Morgan, Ethan; Schumm, L Philip; McClintock, Martha; Waite, Linda; Lauderdale, Diane S

2017-05-01

Older adults frequently report sleep problems and are at increased risk of cardiometabolic disruption. Experimental sleep restriction of younger adults has suggested that cortisol may be on the pathway between sleep restriction and cardiometabolic disease. We investigated whether the natural variation in sleep among older adults is associated with daytime cortisol level. Salivary cortisol samples and actigraphy sleep data were collected from a random subsample of participants in the National Social Life, Health and Aging Project, a nationally representative probability sample of adults aged 62-90 (N = 672). Salivary cortisol was measured with 3 timed samples at the beginning, middle, and end of a 2-hr in-home interview. Sleep characteristics were derived from wrist actigraphy (fragmentation, wake after sleep onset [WASO], and duration) and from survey responses about usual sleep duration and sleep problems. For each individual, a single summary daytime cortisol level was estimated by fitting a marginal longitudinal model for the 3 time-stamped cortisol samples. The resulting estimates were then regressed on each sleep measure, adjusting for sociodemographics, health behaviors, and comorbidities. From actigraphy, both higher fragmentation score (β = 0.02; 95% confidence interval [CI] = 0.00 to 0.03) and longer WASO (β = 0.27; 95% CI = 0.04 to 0.51) were significantly associated with higher daytime cortisol; sleep duration was not. Self-reported sleep duration and sleep problems were also not associated with cortisol. Actigraph measures of sleep disturbance are associated with higher daytime cortisol among older adults. However, cross-sectional data cannot distinguish causal direction or whether cortisol and sleep disruption have a common cause. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

PubMed Central

Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J.; Schmidt, Kristina H.

2016-01-01

In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks. PMID:27923055

Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease.

PubMed

Zinnanti, William J; Lazovic, Jelena; Griffin, Kathleen; Skvorak, Kristen J; Paul, Harbhajan S; Homanics, Gregg E; Bewley, Maria C; Cheng, Keith C; Lanoue, Kathryn F; Flanagan, John M

2009-04-01

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with life-threatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branched-chain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress.

Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex123

PubMed Central

Billeh, Yazan N.; Bernard, Amy; de Vivo, Luisa; Honjoh, Sakiko; Mihalas, Stefan; Ng, Lydia; Koch, Christof

2016-01-01

Abstract Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25–P30, ≥50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments. PMID:27351022

Disrupting vagal feedback affects birdsong motor control.

PubMed

Méndez, Jorge M; Dall'asén, Analía G; Goller, Franz

2010-12-15

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback.

Disrupting vagal feedback affects birdsong motor control

PubMed Central

Méndez, Jorge M.; Dall'Asén, Analía G.; Goller, Franz

2010-01-01

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback. PMID:21113000

Modeling the Structure and Dynamics of Dwarf Spheroidal Galaxies with Dark Matter and Tides

NASA Astrophysics Data System (ADS)

Muñoz, Ricardo R.; Majewski, Steven R.; Johnston, Kathryn V.

2008-05-01

We report the results of N-body simulations of disrupting satellites aimed at exploring whether the observed features of dSphs can be accounted for with simple, mass-follows-light (MFL) models including tidal disruption. As a test case, we focus on the Carina dwarf spheroidal (dSph), which presently is the dSph system with the most extensive data at large radius. We find that previous N-body, MFL simulations of dSphs did not sufficiently explore the parameter space of satellite mass, density, and orbital shape to find adequate matches to Galactic dSph systems, whereas with a systematic survey of parameter space we are able to find tidally disrupting, MFL satellite models that rather faithfully reproduce Carina's velocity profile, velocity dispersion profile, and projected density distribution over its entire sampled radius. The successful MFL model satellites have very eccentric orbits, currently favored by CDM models, and central velocity dispersions that still yield an accurate representation of the bound mass and observed central M/L ~ 40 of Carina, despite inflation of the velocity dispersion outside the dSph core by unbound debris. Our survey of parameter space also allows us to address a number of commonly held misperceptions of tidal disruption and its observable effects on dSph structure and dynamics. The simulations suggest that even modest tidal disruption can have a profound effect on the observed dynamics of dSph stars at large radii. Satellites that are well described by tidally disrupting MFL models could still be fully compatible with ΛCDM if, for example, they represent a later stage in the evolution of luminous subhalos.

AN ELDERLY PATIENT WITH ACUTE TRANSIENT OUTER RETINAL DISRUPTION RESEMBLING BILATERAL MULTIPLE EVANESCENT WHITE DOT SYNDROME.

PubMed

Golshani, Cyrus; Gal-Or, Orly; Giovinazzo, Vincent; Freund, K Bailey

2017-11-07

To report an unusual case of an elderly patient with transient outer retinal disruption resembling bilateral multiple evanescent white dot syndrome. Observational case report. Fundus photographs, fluorescein angiography, standard and ultra-widefield fundus autofluorescence, and cross-sectional and en face optical coherence tomography were used to characterize and describe the clinical findings. A 67-year-old woman presented with decreased vision and floaters in her left eye. Best-corrected visual acuity was 20/20-3 in the right eye and 20/80-2 in the left eye. Funduscopic examination showed small deep white dots and foveal granularity of the left eye corresponding to hyperautofluorescent spots on fundus autofluorescence and ellipsoid zone disruption on spectral domain optical coherence tomography. The asymptomatic right eye had evidence of subretinal deposits on spectral domain optical coherence tomography but was otherwise unremarkable. At 4-week follow-up, the patient noted resolution of her symptoms in the left eye but had developed floaters and blurry vision in her right eye. The left eye showed resolving white spots and ellipsoid zone disruption. However, the right eye had new evidence of white spots corresponding to hyperautofluorescent spots on fundus autofluorescence. Spectral domain optical coherence tomography demonstrated subretinal deposits overlying areas of ellipsoid zone disruption. At 8-week follow-up, the patient was asymptomatic in both eyes with best-corrected visual acuity of 20/20 in both eyes. The hyperautofluorescent spots on ultra-widefield fundus autofluorescence had faded with restoration of ellipsoid zone disruption in both eyes and disappearance of subretinal deposits. Our case demonstrates multimodal retinal imaging findings resembling multiple evanescent white dot syndrome in an elderly patient. The bilateral presentation, presence of subretinal deposits before symptom onset, and older age of the patient were atypical features for this entity.

The long-term evolution of multilocus traits under frequency-dependent disruptive selection.

PubMed

van Doorn, G Sander; Dieckmann, Ulf

2006-11-01

Frequency-dependent disruptive selection is widely recognized as an important source of genetic variation. Its evolutionary consequences have been extensively studied using phenotypic evolutionary models, based on quantitative genetics, game theory, or adaptive dynamics. However, the genetic assumptions underlying these approaches are highly idealized and, even worse, predict different consequences of frequency-dependent disruptive selection. Population genetic models, by contrast, enable genotypic evolutionary models, but traditionally assume constant fitness values. Only a minority of these models thus addresses frequency-dependent selection, and only a few of these do so in a multilocus context. An inherent limitation of these remaining studies is that they only investigate the short-term maintenance of genetic variation. Consequently, the long-term evolution of multilocus characters under frequency-dependent disruptive selection remains poorly understood. We aim to bridge this gap between phenotypic and genotypic models by studying a multilocus version of Levene's soft-selection model. Individual-based simulations and deterministic approximations based on adaptive dynamics theory provide insights into the underlying evolutionary dynamics. Our analysis uncovers a general pattern of polymorphism formation and collapse, likely to apply to a wide variety of genetic systems: after convergence to a fitness minimum and the subsequent establishment of genetic polymorphism at multiple loci, genetic variation becomes increasingly concentrated on a few loci, until eventually only a single polymorphic locus remains. This evolutionary process combines features observed in quantitative genetics and adaptive dynamics models, and it can be explained as a consequence of changes in the selection regime that are inherent to frequency-dependent disruptive selection. Our findings demonstrate that the potential of frequency-dependent disruptive selection to maintain polygenic variation is considerably smaller than previously expected.

Illumination-invariant and deformation-tolerant inner knuckle print recognition using portable devices.

PubMed

Xu, Xuemiao; Jin, Qiang; Zhou, Le; Qin, Jing; Wong, Tien-Tsin; Han, Guoqiang

2015-02-12

We propose a novel biometric recognition method that identifies the inner knuckle print (IKP). It is robust enough to confront uncontrolled lighting conditions, pose variations and low imaging quality. Such robustness is crucial for its application on portable devices equipped with consumer-level cameras. We achieve this robustness by two means. First, we propose a novel feature extraction scheme that highlights the salient structure and suppresses incorrect and/or unwanted features. The extracted IKP features retain simple geometry and morphology and reduce the interference of illumination. Second, to counteract the deformation induced by different hand orientations, we propose a novel structure-context descriptor based on local statistics. To our best knowledge, we are the first to simultaneously consider the illumination invariance and deformation tolerance for appearance-based low-resolution hand biometrics. Settings in previous works are more restrictive. They made strong assumptions either about the illumination condition or the restrictive hand orientation. Extensive experiments demonstrate that our method outperforms the state-of-the-art methods in terms of recognition accuracy, especially under uncontrolled lighting conditions and the flexible hand orientation requirement.

Illumination-Invariant and Deformation-Tolerant Inner Knuckle Print Recognition Using Portable Devices

PubMed Central

Xu, Xuemiao; Jin, Qiang; Zhou, Le; Qin, Jing; Wong, Tien-Tsin; Han, Guoqiang

2015-01-01

We propose a novel biometric recognition method that identifies the inner knuckle print (IKP). It is robust enough to confront uncontrolled lighting conditions, pose variations and low imaging quality. Such robustness is crucial for its application on portable devices equipped with consumer-level cameras. We achieve this robustness by two means. First, we propose a novel feature extraction scheme that highlights the salient structure and suppresses incorrect and/or unwanted features. The extracted IKP features retain simple geometry and morphology and reduce the interference of illumination. Second, to counteract the deformation induced by different hand orientations, we propose a novel structure-context descriptor based on local statistics. To our best knowledge, we are the first to simultaneously consider the illumination invariance and deformation tolerance for appearance-based low-resolution hand biometrics. Settings in previous works are more restrictive. They made strong assumptions either about the illumination condition or the restrictive hand orientation. Extensive experiments demonstrate that our method outperforms the state-of-the-art methods in terms of recognition accuracy, especially under uncontrolled lighting conditions and the flexible hand orientation requirement. PMID:25686317

Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome)

PubMed Central

Drake-Pérez, Marta; de Lucas, Enrique Marco; Lyo, John; Fernández-Torre, José L.

2017-01-01

Purpose To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). Methods We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. Results Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%. Conclusions SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical-subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions. PMID:27391464

Disrupting the Education Monopoly: A Conversation with Reed Hastings

ERIC Educational Resources Information Center

Jacobs, Joanne

2015-01-01

This article features an interview with Netflix CEO, Reed Hastings. In this interview, Hastings relates that he told the "Wall Street Journal" in 2008 that he started looking at education--trying to figure out why our education is lagging when our technology is increasing at great rates and there's great innovation in so many other areas…

Geographies of Social Exclusion: Education Access in the Philippines

ERIC Educational Resources Information Center

Symaco, Lorraine Pe

2013-01-01

Despite the massive education sector of the country, the Philippines--being located in the Pacific Ring of Fire and the typhoon belt--is home to a number of natural instabilities that frequently disrupt the school calendar. Conflict areas in selected parts of the island of Mindanao and the remote geographic features of the country also pose…

Disrupting the Forrest Gump Effect: Countering Suggestibility in the Social Studies Classroom through the Use of Actual Footage

ERIC Educational Resources Information Center

Nathan, Judith Raizy

2017-01-01

Film is a tool used in the social studies classroom, even if it contradicts documented history. Suggestibility, the incorporation of misinformation from historical feature film, is commonplace, and some social studies instructional methods exacerbate inaccurate memories. Existing research indicates that attempts to counter suggestibility have met…

Increasing Emotional Regulation for Youths in Residential Care: Phases of Change

ERIC Educational Resources Information Center

Cimmarusti, Rocco A.

2011-01-01

Youths in residential care have likely experienced trauma as they have had atypical and disruptive events occur in their lives that has contributed to their out-of-home placement. For people who have been traumatized, the regulation of emotions is an important feature of their recovery. This article presents a model that traces phases from…

Safe and Autonomous Drones for Urban Flight

NASA Technical Reports Server (NTRS)

Krishnakumar, Kalmanje

2016-01-01

Autonomous vehicles are no longer futuristic technology; in fact, there are already cars with self-driving features on the road. Over the next five years, the connected vehicles will disrupt the entire automotive and UAS ecosystems. The industry will undergo fundamental change as semi-autonomous driving and flying emerges, followed by an eventual shift to full autonomy.

Visual Processing of Faces in Individuals with Fragile X Syndrome: An Eye Tracking Study

ERIC Educational Resources Information Center

Farzin, Faraz; Rivera, Susan M.; Hessl, David

2009-01-01

Gaze avoidance is a hallmark behavioral feature of fragile X syndrome (FXS), but little is known about whether abnormalities in the visual processing of faces, including disrupted autonomic reactivity, may underlie this behavior. Eye tracking was used to record fixations and pupil diameter while adolescents and young adults with FXS and sex- and…

Cell Phones in the Classroom: Teachers' Perspectives of Inclusion, Benefits, and Barriers

ERIC Educational Resources Information Center

Thomas, Kevin M.; O'Bannon, Blanche W.; Bolton, Natalie

2013-01-01

Historically viewed as a disruption by teachers, cell phones have been banned from 69% of classrooms (Common Sense Media, 2009). The increased ubiquity and instructional features of cell phones have prompted some teachers to re-evaluate the ban and consider the benefits associated with allowing cell phones in the classroom. This study surveyed 79…

Testing for Camouflage Using Virtual Prey and Human "Predators"

ERIC Educational Resources Information Center

Todd, Peter A.

2009-01-01

Camouflage is a prevalent feature of the natural world and as such has a ready appeal to students; however, it is a difficult subject to study using real predators and prey. This paper focuses how one fundamental type of camouflage, disruptive colouration (bold markings that break up the outline of the organism), can be tested using paper…

Framing faces: Frame alignment impacts holistic face perception.

PubMed

Curby, Kim M; Entenman, Robert

2016-11-01

Traditional accounts of face perception emphasise the importance of the prototypical configuration of features within faces. However, here we probe influences of more general perceptual grouping mechanisms on holistic face perception. Participants made part-matching judgments about composite faces presented in intact external oval frames or frames made from misaligned oval parts. This manipulation served to disrupt basic perceptual grouping cues that facilitate the grouping of the two face halves together. This manipulation also produced an external face contour like that in the standard misaligned condition used within the classic composite face task. Notably, by introducing a discontinuity in the external contour, grouping of the face halves into a cohesive unit was discouraged, but face configuration was preserved. Conditions where both the face parts and the frames were misaligned together, as in the typical composite task paradigm, or where just the internal face parts where misaligned, were also included. Disrupting only the face frame similarly disrupted holistic face perception as disrupting both the frame and face configuration. However, misaligned face parts presented in aligned frames also incurred a cost to holistic perception. These findings provide support for the contribution of general-purpose perceptual grouping mechanisms to holistic face perception and are presented and discussed in the context of an enhanced object-based selection account of holistic perception.

Cations as switches of amyloid-mediated membrane disruption mechanisms: calcium and IAPP.

PubMed

Sciacca, Michele F M; Milardi, Danilo; Messina, Grazia M L; Marletta, Giovanni; Brender, Jeffrey R; Ramamoorthy, Ayyalusamy; La Rosa, Carmelo

2013-01-08

Disruption of the integrity of the plasma membrane by amyloidogenic proteins is linked to the pathogenesis of a number of common age-related diseases. Although accumulating evidence suggests that adverse environmental stressors such as unbalanced levels of metal ions may trigger amyloid-mediated membrane damage, many features of the molecular mechanisms underlying these events are unknown. Using human islet amyloid polypeptide (hIAPP, aka amylin), an amyloidogenic peptide associated with β-cell death in type 2 diabetes, we demonstrate that the presence of Ca(2+) ions inhibits membrane damage occurring immediately after the interaction of freshly dissolved hIAPP with the membrane, but significantly enhances fiber-dependent membrane disruption. In particular, dye leakage, quartz crystal microbalance, atomic force microscopy, and NMR experiments show that Ca(2+) ions promote a shallow membrane insertion of hIAPP, which leads to the removal of lipids from the bilayer through a detergent-like mechanism triggered by fiber growth. Because both types of membrane-damage mechanisms are common to amyloid toxicity by most amyloidogenic proteins, it is likely that unregulated ion homeostasis, amyloid aggregation, and membrane disruption are all parts of a self-perpetuating cycle that fuels amyloid cytotoxicity. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Listeriolysin O Membrane Damaging Activity Involves Arc Formation and Lineaction -- Implication for Listeria monocytogenes Escape from Phagocytic Vacuole

PubMed Central

Ruan, Yi; Rezelj, Saša; Bedina Zavec, Apolonija; Anderluh, Gregor; Scheuring, Simon

2016-01-01

Listeriolysin-O (LLO) plays a crucial role during infection by Listeria monocytogenes. It enables escape of bacteria from phagocytic vacuole, which is the basis for its spread to other cells and tissues. It is not clear how LLO acts at phagosomal membranes to allow bacterial escape. The mechanism of action of LLO remains poorly understood, probably due to unavailability of suitable experimental tools that could monitor LLO membrane disruptive activity in real time. Here, we used high-speed atomic force microscopy (HS-AFM) featuring high spatio-temporal resolution on model membranes and optical microscopy on giant unilamellar vesicles (GUVs) to investigate LLO activity. We analyze the assembly kinetics of toxin oligomers, the prepore-to-pore transition dynamics and the membrane disruption in real time. We reveal that LLO toxin efficiency and mode of action as a membrane-disrupting agent varies strongly depending on the membrane cholesterol concentration and the environmental pH. We discovered that LLO is able to form arc pores as well as damage lipid membranes as a lineactant, and this leads to large-scale membrane defects. These results altogether provide a mechanistic basis of how large-scale membrane disruption leads to release of Listeria from the phagocytic vacuole in the cellular context. PMID:27104344

Exogenous attention can be counter-selective: onset cues disrupt sensitivity to color changes.

PubMed

Müller-Plath, Gisela; Klöckner, Nils

2014-03-01

In peripheral spatial cueing paradigms, exogenous attentional capture is commonly observed after salient onset cues or with cues contingent on target characteristics. We proposed that exogenously captured attention disrupts the selectivity to target features. We tested this by experimentally emulating the everyday observation that in a viewing situation in which the observer is monitoring a stationary display fort change to occur, the onset of a salient stimulus (onset cue) or a change in a stationary stimulus similar to the expected one (contingent cue) has a distracting effect. As predicted, we found that both types of cues reduced the target detection sensitivity but enhanced the bias to respond in a go-nogo-paradigm. With the onset cue, the sensitivity loss was more pronounced at the side of the cue, whereas the contingent cue affected both sides likewise. Moreover, the effects of the onset cue interacted with the task difficulty: the more selectivity a task required the more immune it was against disruption, but the more likely was a response. We concluded that onset capture disrupts selective attention by adding noise to the processing of the target location. The effects of contingent capture could be explained with cue-target confounding. Finally, we suggest a new model of attentional capture in which exogenous and endogenous components interact in a dynamic way.

Depression and embodiment: phenomenological reflections on motility, affectivity, and transcendence.

PubMed

Aho, Kevin A

2013-11-01

This paper integrates personal narratives with the methods of phenomenology in order to draw some general conclusions about 'what it means' and 'what it feels like' to be depressed. The analysis has three parts. First, it explores the ways in which depression disrupts everyday experiences of spatial orientation and motility. This disruption makes it difficult for the person to move and perform basic functional tasks, resulting in a collapse or contraction of the life-world. Second, it illustrates how depression creates a situational atmosphere of emotional indifference that reduces the person's ability to qualitatively distinguish what matters in his or her life because nothing stands out as significant or important anymore. In this regard, depression is distinct from other feelings because it is not directed towards particular objects or situations but to the world as a whole. Finally, the paper examines how depression diminishes the possibility for 'self-creation' or 'self-making'. Restricted by the illness, depression becomes something of a destiny, preventing the person from being open and free to access a range of alternative self-interpretations, identities, and possible ways of being-in-the-world.

Neocortical malformation as consequence of nonadaptive regulation of neuronogenetic sequence

NASA Technical Reports Server (NTRS)

Caviness, V. S. Jr; Takahashi, T.; Nowakowski, R. S.

2000-01-01

Variations in the structure of the neocortex induced by single gene mutations may be extreme or subtle. They differ from variations in neocortical structure encountered across and within species in that these "normal" structural variations are adaptive (both structurally and behaviorally), whereas those associated with disorders of development are not. Here we propose that they also differ in principle in that they represent disruptions of molecular mechanisms that are not normally regulatory to variations in the histogenetic sequence. We propose an algorithm for the operation of the neuronogenetic sequence in relation to the overall neocortical histogenetic sequence and highlight the restriction point of the G1 phase of the cell cycle as the master regulatory control point for normal coordinate structural variation across species and importantly within species. From considerations based on the anatomic evidence from neocortical malformation in humans, we illustrate in principle how this overall sequence appears to be disrupted by molecular biological linkages operating principally outside the control mechanisms responsible for the normal structural variation of the neocortex. MRDD Research Reviews 6:22-33, 2000. Copyright 2000 Wiley-Liss, Inc.

Asymmetrical Macromolecular Complex Formation of Lysophosphatidic Acid Receptor 2 (LPA2) Mediates Gradient Sensing in Fibroblasts*

PubMed Central

Ren, Aixia; Moon, Changsuk; Zhang, Weiqiang; Sinha, Chandrima; Yarlagadda, Sunitha; Arora, Kavisha; Wang, Xusheng; Yue, Junming; Parthasarathi, Kaushik; Heil-Chapdelaine, Rick; Tigyi, Gabor; Naren, Anjaparavanda P.

2014-01-01

Chemotactic migration of fibroblasts toward growth factors relies on their capacity to sense minute extracellular gradients and respond to spatially confined receptor-mediated signals. Currently, mechanisms underlying the gradient sensing of fibroblasts remain poorly understood. Using single-particle tracking methodology, we determined that a lysophosphatidic acid (LPA) gradient induces a spatiotemporally restricted decrease in the mobility of LPA receptor 2 (LPA2) on chemotactic fibroblasts. The onset of decreased LPA2 mobility correlates to the spatial recruitment and coupling to LPA2-interacting proteins that anchor the complex to the cytoskeleton. These localized PDZ motif-mediated macromolecular complexes of LPA2 trigger a Ca2+ puff gradient that governs gradient sensing and directional migration in response to LPA. Disruption of the PDZ motif-mediated assembly of the macromolecular complex of LPA2 disorganizes the gradient of Ca2+ puffs, disrupts gradient sensing, and reduces the directional migration of fibroblasts toward LPA. Our findings illustrate that the asymmetric macromolecular complex formation of chemoattractant receptors mediates gradient sensing and provides a new mechanistic basis for models to describe gradient sensing of fibroblasts. PMID:25542932

Large-scale filament formation inhibits the activity of CTP synthetase

PubMed Central

Barry, Rachael M; Bitbol, Anne-Florence; Lorestani, Alexander; Charles, Emeric J; Habrian, Chris H; Hansen, Jesse M; Li, Hsin-Jung; Baldwin, Enoch P; Wingreen, Ned S; Kollman, Justin M; Gitai, Zemer

2014-01-01

CTP Synthetase (CtpS) is a universally conserved and essential metabolic enzyme. While many enzymes form small oligomers, CtpS forms large-scale filamentous structures of unknown function in prokaryotes and eukaryotes. By simultaneously monitoring CtpS polymerization and enzymatic activity, we show that polymerization inhibits activity, and CtpS's product, CTP, induces assembly. To understand how assembly inhibits activity, we used electron microscopy to define the structure of CtpS polymers. This structure suggests that polymerization sterically hinders a conformational change necessary for CtpS activity. Structure-guided mutagenesis and mathematical modeling further indicate that coupling activity to polymerization promotes cooperative catalytic regulation. This previously uncharacterized regulatory mechanism is important for cellular function since a mutant that disrupts CtpS polymerization disrupts E. coli growth and metabolic regulation without reducing CTP levels. We propose that regulation by large-scale polymerization enables ultrasensitive control of enzymatic activity while storing an enzyme subpopulation in a conformationally restricted form that is readily activatable. DOI: http://dx.doi.org/10.7554/eLife.03638.001 PMID:25030911

The cognitive cost of sleep lost

PubMed Central

McCoy, John G.; Strecker, Robert E.

2013-01-01

A substantial body of literature supports the intuitive notion that a good night’s sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances. PMID:21875679

Cell-free fetal DNA concentration in plasma of patients with abnormal uterine artery Doppler waveform and intrauterine growth restriction--a pilot study.

PubMed

Caramelli, Elisabetta; Rizzo, Nicola; Concu, Manuela; Simonazzi, Giuliana; Carinci, Paolo; Bondavalli, Corrado; Bovicelli, Luciano; Farina, Antonio

2003-05-01

To evaluate if an increased amount of fetal DNA concentration can be found in women screened positive for intrauterine growth restriction because of abnormal uterine artery Doppler waveforms. We enrolled eight pregnant women (each bearing a male fetus), with the evidence of abnormal uterine artery Doppler waveforms, and 16 control patients for a case-control study matched for gestational age (1 : 2). Uterine artery Doppler was carried out at 20 to 35 weeks' gestation (median 29). The mean uterine artery resistance index (RI) was subsequently calculated, and a value >0.6 was considered positive for the clinical features of pre-eclampsia. The SRY locus was used to determine the amount of male fetal DNA in the maternal plasma at the time of Doppler analysis. Two controls (normal Doppler) were excluded from the final analysis because they had a pre-term delivery. One case (abnormal Doppler) had evidence of intrauterine growth restriction at the time of enrolment. In four out of eight cases (abnormal Doppler), intrauterine growth restriction was subsequently observed. Multiples of median (MoM) conversion of the fetal DNA values showed an increase of 1.81 times in the cases when compared to the controls. An increase of 2.16 times was instead observed for the cases with a growth-restricted fetus (5 cases out of 8) in comparison with the controls (14 cases). In subjects positive to uterine artery Doppler velocimetry analysis (Doppler analysis for pre-eclampsia screening), the fetal DNA concentration is higher than expected, in the absence of any other clinical feature. Since the increase in fetal DNA seems to be related to the presence or to the future development of intrauterine growth restriction, this paper suggests a possible integration between ultrasound and molecular markers for predicting the disease in some cases. Copyright 2003 John Wiley & Sons, Ltd.

"Retweet to Pass the Blunt": Analyzing Geographic and Content Features of Cannabis-Related Tweeting Across the United States.

PubMed

Daniulaityte, Raminta; Lamy, Francois R; Smith, G Alan; Nahhas, Ramzi W; Carlson, Robert G; Thirunarayan, Krishnaprasad; Martins, Silvia S; Boyer, Edward W; Sheth, Amit

2017-11-01

Twitter data offer new possibilities for tracking health-related communications. This study is among the first to apply advanced information processing to identify geographic and content features of cannabis-related tweeting in the United States. Tweets were collected using streaming Application Programming Interface (March-May 2016) and were processed by eDrugTrends to identify geolocation and classify content by source (personal communication, media, retail) and sentiment (positive, negative, neutral). States were grouped by cannabis legalization policies into "recreational," "medical, less restrictive," "medical, more restrictive," and "illegal." Permutation tests were performed to analyze differences among four groups in adjusted percentages of all tweets, unique users, personal communications only, and positive-to-negative sentiment ratios. About 30% of all 13,233,837 cannabis-related tweets had identifiable state-level geo-information. Among geolocated tweets, 76.2% were personal communications, 21.1% media, and 2.7% retail. About 71% of personal communication tweets expressed positive sentiment toward cannabis; 16% expressed negative sentiment. States in the recreational group had significantly greater average adjusted percentage of cannabis tweets (3.01%) compared with other groups. For personal communication tweets only, the recreational group (2.47%) was significantly greater than the medical, more restrictive (1.84%) and illegal (1.85%) groups. Similarly, the recreational group had significantly greater average positive-to-negative sentiment ratio (4.64) compared with the medical, more restrictive (4.15) and illegal (4.19) groups. Average adjusted percentages of unique users showed similar differences between recreational and other groups. States with less restrictive policies displayed greater cannabis-related tweeting and conveyed more positive sentiment. The study demonstrates the potential of Twitter data to become a valuable indicator of drug-related communications in the context of varying policy environments.

Humans have already increased the risk of major disruption to Pacific rainfall

NASA Astrophysics Data System (ADS)

Power, Scott; Delage, Francois; Chung, Christine; Ye, Harvey; Murphy, Brad

2017-04-01

Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to approximately one year have major impacts on severe weather, agricultural production, ecosystems, and disease within the Pacific, and in many countries beyond. These disruptions are primarily driven by the El Niño/La Niña cycle, which is a naturally occurring phenomenon centered in the tropical Pacific. Recent research concluded that global warming under scenarios with further large increases in global greenhouse gas emissions will increase the frequency of disruptions to Pacific rainfall over the 21st century. Fortunately governments from around the world recently agreed to markedly reduce emissions over coming decades. But will these cuts be sufficient to prevent a human-forced increase in the risk of major disruption? And has the risk (i.e., likelihood) of major disruption driven by year-to-year rainfall variability already increased relative to pre-industrial times? These issues are addressed here (Power et al., Nature Communications, in press). We examined disruption in CMIP5 models under climatic conditions corresponding to the pre-industrial era, the historical period and the remainder of the 21st century under the RCP2.6, RCP4.5 and RCP8.5 scenarios. RCP2.6 results in global warming in the late 21st century that is likely to be in the range of approximately 0.9-2.3°C (relative to the latter half of the 19th century). The equivalent figures for RCP8.5 are 3.2-5.4°C (IPCC 2014). We use a simple measure of disruption or volatility: the time evolving RMS difference in seasonal rainfall over the Pacific relative to a changing climatological value of seasonal rainfall. The CMIP5 models, the observations and an SST-forced AGCM all indicate that while both El Nino and La Nina can cause major disruptions, the largest disruptions occur during El Nino years. We also show that there is a 26% increase in the frequency of major disruptions in the models by the early twentieth century and a 28% increase by the end of the twentieth century, relative to the pre-idustrial value of approximately one major disruption every nine years. Under RCP8.5 there is a 90% increase in the early 21st century and a 126% increase during the late 21st century, again relative to the pre-industrial value. The increase in the frequency of disruption arises from an increase in the frequency of El Niño and La Niña events in some models, and a non-linear boost in precipitation anomalies during El Niño and La Niña events caused by the associated global warming. This boost occurs even if the underlying sea-surface temperature anomalies during El Niño and La Niña events are unchanged from pre-industrial times. The non-linear boost increases the likelihood that a given El Niño or La Niña event will cause major disruption to rainfall. Unfortunately, even the stringent mitigation represented in RCP2.6 does not prevent further increases in the frequency of disruption: there is a 56% increase in the early twenty first century, and a 61% increase in the late 21st century. Four important conclusions can be drawn from these climate model results. First, the risk of major disruption to Pacific rainfall had already increased by the end of the 20th century and the early 21st century. This means, for example, that some of the disruption actually witnessed in the real world might have been partially due to anthropogenic increases in greenhouse gas concentrations that had already occurred by that time. Second, the risk is elevated today relative to pre-industrial times, and will remain elevated over coming years. Third, further increases in the risk of major disruption during the remainder of the 21st century can be strongly moderated if major and sustained cuts to global emissions of GHGs are made, but elevated risk for at least the remainder of the 21st century might arise, even if global action is successful in restricting emissions to RCP2.6 levels.

The investigation and comparison of the underlying needs of common disruptive behaviours in patients with Alzheimer's disease.

PubMed

Wang, Chi-Jane; Pai, Ming-Chyi; Hsiao, Hua-Shan; Wang, Jing-Jy

2015-12-01

Management of the disruptive behaviours is one of the most challenging aspects of caring for patients with Alzheimer's dementia (PwAD). The underlying needs of disruptive behaviours in PwAD had rarely been studied, especially the comparison of the underlying needs of disruptive behaviours in PwAD have never been mentioned. The purpose of this study was to investigate and compare the underlying needs of five common disruptive behaviours including hoarding, aggressive behaviour, repetitive behaviour, altered eating behaviour and delusion in PwAD, as perceived by family caregivers, and to relate these needs from the perspective of Maslow's hierarchy. An exploratory research design with qualitative data collection techniques was employed. Informed consent was obtained from each participant prior to the data collection. A total of 65 pairs of caregiver-patient with Alzheimer's disease participated in the study. A semi-structured interview guide was used during the interview, and the directed content analysis method was conducted to analyse data. Four themes related to the underlying needs of the five selected disruptive behaviours emerged from the data, and these included a desire for comfort (physical and psychological), a desire for security (psychological and economic), a need for a sense of belonging (including a need to connect with the outside world and a need for attention) and a need for self-control. These behaviour features were found closely related to Maslow's hierarchy model of human needs. Although the data were gathered from the caregivers, and the views of the patients were thus not included in the analysis, the findings provide information for health providers that can enable them to better understand the underlying needs of common disruptive behaviours in patients with Alzheimer's disease and thus help develop better patient-centred care plans. © 2015 Nordic College of Caring Science.

Language Design in the Processing of Non-Restrictive Relative Clauses in French as a Second Language

ERIC Educational Resources Information Center

Lorente Lapole, Amandine

2012-01-01

Recent years have witnessed a lively debate on the nature of learners' morphological competence and use. Some argue that a breakdown in acquisition of second-language (L2) is expected whenever features required for the analysis of L2 input are not present in the L1. Others argue that features have the same nature and etiology in first…

Developmental palaeontology in synapsids: the fossil record of ontogeny in mammals and their closest relatives

PubMed Central

Sánchez-Villagra, Marcelo R.

2010-01-01

The study of fossilized ontogenies in mammals is mostly restricted to postnatal and late stages of growth, but nevertheless can deliver great insights into life history and evolutionary mechanisms affecting all aspects of development. Fossils provide evidence of developmental plasticity determined by ecological factors, as when allometric relations are modified in species which invaded a new space with a very different selection regime. This is the case of dwarfing and gigantism evolution in islands. Skeletochronological studies are restricted to the examination of growth marks mostly in the cement and dentine of teeth and can provide absolute age estimates. These, together with dental replacement data considered in a phylogenetic context, provide life-history information such as maturation time and longevity. Palaeohistology and dental replacement data document the more or less gradual but also convergent evolution of mammalian growth features during early synapsid evolution. Adult phenotypes of extinct mammals can inform developmental processes by showing a combination of features or levels of integration unrecorded in living species. Some adult features such as vertebral number, easily recorded in fossils, provide indirect information about somitogenesis and hox-gene expression boundaries. Developmental palaeontology is relevant for the discourse of ecological developmental biology, an area of research where features of growth and variation are fundamental and accessible among fossil mammals. PMID:20071389

The health and cost implications of high body mass index in Australian defence force personnel.

PubMed

Peake, Jonathan; Gargett, Susan; Waller, Michael; McLaughlin, Ruth; Cosgrove, Tegan; Wittert, Gary; Nasveld, Peter; Warfe, Peter

2012-06-19

Frequent illness and injury among workers with high body mass index (BMI) can raise the costs of employee healthcare and reduce workforce maintenance and productivity. These issues are particularly important in vocational settings such as the military, which require good physical health, regular attendance and teamwork to operate efficiently. The purpose of this study was to compare the incidence of injury and illness, absenteeism, productivity, healthcare usage and administrative outcomes among Australian Defence Force personnel with varying BMI. Personnel were grouped into cohorts according to the following ranges for (BMI): normal (18.5 - 24.9 kg/m2; n = 197), overweight (25-29.9 kg/m2; n = 154) and obese (≥30 kg/m2) with restricted body fat (≤28% for females, ≤24% for males) (n = 148) and with no restriction on body fat (n = 180). Medical records for each individual were audited retrospectively to record the incidence of injury and illness, absenteeism, productivity, healthcare usage (i.e., consultation with medical specialists, hospital stays, medical investigations, prescriptions) and administrative outcomes (e.g., discharge from service) over one year. These data were then grouped and compared between the cohorts. The prevalence of injury and illness, cost of medical specialist consultations and cost of medical scans were all higher (p < 0.05) in both obese cohorts compared with the normal cohort. The estimated productivity losses from restricted work days were also higher (p < 0.05) in the obese cohort with no restriction on body fat compared with the normal cohort. Within the obese cohort, the prevalence of injury and illness, healthcare usage and productivity were not significantly greater in the obese cohort with no restriction on body fat compared with the cohort with restricted body fat. The number of restricted work days, the rate of re-classification of Medical Employment Classification and the rate of discharge from service were similar between all four cohorts. High BMI in the military increases healthcare usage, but does not disrupt workforce maintenance. The greater prevalence of injury and illness, greater healthcare usage and lower productivity in obese Australian Defence Force personnel is not related to higher levels of body fat.

Excess androgen during puberty disrupts circadian organization in female rats.

PubMed

Sellix, Michael T; Murphy, Zachary C; Menaker, Michael

2013-04-01

Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5α-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.

Excess Androgen During Puberty Disrupts Circadian Organization in Female Rats

PubMed Central

Murphy, Zachary C.; Menaker, Michael

2013-01-01

Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5α-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes. PMID:23417420

Spectral features of tidal disruption candidates and alternative origins for such transient flares

NASA Astrophysics Data System (ADS)

Saxton, Curtis J.; Perets, Hagai B.; Baskin, Alexei

2018-03-01

UV and optically selected candidates for stellar tidal disruption events (TDEs) often exhibit broad spectral features (He II emission, H α emission, or absorption lines) on a blackbody-like continuum (104 K≲ T≲ 105 K). The lines presumably emit from TDE debris or circumnuclear clouds photoionized by the flare. Line velocities however are much lower than expected from a stellar disruption by supermassive black hole (SMBH), and are somewhat faster than expected for the broad line region (BLR) clouds of a persistently active galactic nucleus (AGN). The distinctive spectral states are not strongly related to observed luminosity and velocity, nor to SMBH mass estimates. We use exhaustive photoionization modelling to map the domain of fluxes and cloud properties that yield (e.g.) an He-overbright state where a large He II(4686 Å)/H α line ratio creates an illusion of helium enrichment. Although observed line ratios occur in a plausible minority of cases, AGN-like illumination cannot reproduce the observed equivalent widths. We therefore propose to explain these properties by a light-echo photoionization model: the initial flash of a hot blackbody (detonation) excites BLR clouds, which are then seen superimposed on continuum from a later, expanded, cooled stage of the luminous source. The implied cloud mass is substellar, which may be inconsistent with a TDE. Given these and other inconsistencies with TDE models (e.g. host-galaxies distribution) we suggest to also consider alternative origins for these nuclear flares, which we briefly discuss (e.g. nuclear supernovae and starved/subluminous AGNs).

Quasi-Love phases between Tonga and Hawaii: Observations, simulations, and explanations

NASA Astrophysics Data System (ADS)

Levin, Vadim; Park, Jeffrey

1998-10-01

Seismograms of some shallow Tonga earthquakes observed at Hawaii contain SV-polarized phases in the Love wave time window, most prominently on the vertical component. Given the geometry of the observations (Δ ≈ 40-45°), such phases may be explained either as body waves or as mode-converted surface waves. Detailed synthetic seismogram modeling of representative events reveals several instances where the body wave explanation is inadequate, even when plausible uncertainties in the source mechanism are taken into account. The observed, SV-polarized phase can instead be generated through Love-Rayleigh scattering, which requires laterally varying seismic anisotropy along the Tonga-Hawaii path. Trial-and-error forward modeling with simple structures based on the transversely isotropic mid-Pacific velocity model PA5 of Gaherty et al [1996] obtains velocity structure that yields synthetic seismograms matching the observations. This model, while non unique, suggests first-order constraints on the lateral variation in anisotropic properties, and associated mantle flow, along the Tonga-Hawaii path. By examining trade-offs in model parameters, we conclude that robust features of the model are: (1) a transition from radial to mixed radial and azimuthal anisotropy 3°-5° from Hawaii; (2) the NW-SE alignment of the axis of azimuthal anisotropy; (3) higher degree of P anisotropy relative to S anisotropy; and (4) the presence of azimuthal anisotropy within upper 200-250 km of the mantle. Taken together, these features imply a disruption of mantle fabric by the processes forming Hawaii-Emperor volcanic system. A model with anisotropic gradients in both the lithospheric lid and shallow asthenosphere is the simplest extension of our starting model. However, an equivalent data fit can be obtained if the azimuthal-anisotropy gradients are restricted to line beneath the high-velocity "lid" of model PA5, so that mantle hot spot flow need not penetrate the lithospheric lid.

Ash Shutbah: A possible impact structure in Saudi Arabia

NASA Astrophysics Data System (ADS)

Gnos, Edwin; Hofmann, Beda A.; Schmieder, Martin; Al-Wagdani, Khalid; Mahjoub, Ayman; Al-Solami, Abdulaziz A.; Habibullah, Siddiq N.; Matter, Albert; Alwmark, Carl

2014-10-01

We have investigated the Ash Shutbah circular structure in central Saudi Arabia (21°37'N 45°39'E) using satellite imagery, field mapping, thin-section petrography, and X-ray diffraction of collected samples. The approximately 2.1 km sized structure located in flat-lying Jurassic Tuwaiq Mountain Limestone has been nearly peneplained by erosional processes. Satellite and structural data show a central area consisting of Dhruma Formation sandstones with steep bedding and tight folds plunging radially outward. Open folding occurs in displaced, younger Tuwaiq Mountain Limestone Formation blocks surrounding the central area, but is absent outside the circular structure. An approximately 60 cm thick, unique folded and disrupted orthoquartzitic sandstone marker bed occurring in the central area of the structure is found 140 m deeper in undisturbed escarpment outcrops located a few hundred meters west of the structure. With exception of a possible concave shatter cone found in the orthoquartzite of the central area, other diagnostic shock features are lacking. Some quartz-rich sandstones from the central area show pervasive fracturing of quartz grains with common concussion fractures. This deformation was followed by an event of quartz dissolution and calcite precipitation consistent with local sea- or groundwater heating. The combination of central stratigraphic uplift of 140 m, concussion features in discolored sandstone, outward-dipping concentric folds in the central area, deformation restricted to the rocks of the ring structure, a complex circular structure of 2.1 km diameter that appears broadly consistent with what one would expect from an impact structure in sedimentary targets, and a possible shatter cone all point to an impact origin of the Ash Shutbah structure. In fact, the Ash Shutbah structure appears to be a textbook example of an eroded, complex impact crater located in flat-lying sedimentary rocks, where the undisturbed stratigraphic section can be studied in escarpment outcrops in the vicinity of the structure.

Cognitive remediation and social cognitive training for violence in schizophrenia: a systematic review.

PubMed

Darmedru, C; Demily, C; Franck, N

2017-05-01

A significant correlation exists between violence and schizophrenia (SCZ). Recent studies matched some cognitive deficits like strong risk factors for violence with interesting applications in terms of treatment. Our objective was to conduct a systematic review of the effectiveness of cognitive remediation (CR) and social cognitive training (SCT) in the management of violent and aggressive behaviors in SCZ. The electronic databases Pubmed, Web of Science, Cochrane Library and ScienceDirect were searched in, using combinations of terms relating to SCZ, CR and violence. Studies were selected and data were extracted using a PRISMA statement. Inclusion criteria were adults with SCZ and a documented collection of disruptive and violent behaviors, for whom researchers had used a CR or SCT program. Eleven studies were identified, two related to non-specific CR intervention and nine to codified CR or SCT programs. Results showed that these programs had a positive impact on the control and reduction of global aggressive attitudes and physical assaults. Therapeutic targets were social cognition and executive functions through the improvement of interpersonal relationships and impulsivity feature respectively. Effectiveness was proved at various stages of the illness, in different types of patients and units, with effects persisting for up to 12 months after interruption of CR. Conclusions are limited by some methodological restrictions. Although current evidences need to be completed with further randomized studies, CR and SCT appear to be promising approaches in the management of violence in SCZ. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex.

PubMed

Romanov, Roman A; Lasher, Robert S; High, Brigit; Savidge, Logan E; Lawson, Adam; Rogachevskaja, Olga A; Zhao, Haitian; Rogachevsky, Vadim V; Bystrova, Marina F; Churbanov, Gleb D; Adameyko, Igor; Harkany, Tibor; Yang, Ruibiao; Kidd, Grahame J; Marambaud, Philippe; Kinnamon, John C; Kolesnikov, Stanislav S; Finger, Thomas E

2018-05-08

Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which fuse with the plasma membrane to release neurotransmitters that activate postsynaptic receptors. In taste buds, type II receptor cells do not have conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP, through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry revealed that CALHM1 was localized to points of contact between the receptor cells and sensory nerve fibers. Ultrastructural and super-resolution light microscopy showed that the CALHM1 channels were consistently associated with distinctive, large (1- to 2-μm) mitochondria spaced 20 to 40 nm from the presynaptic membrane. Pharmacological disruption of the mitochondrial respiratory chain limited the ability of taste cells to release ATP, suggesting that the immediate source of released ATP was the mitochondrion rather than a cytoplasmic pool of ATP. These large mitochondria may serve as both a reservoir of releasable ATP and the site of synthesis. The juxtaposition of the large mitochondria to areas of membrane displaying CALHM1 also defines a restricted compartment that limits the influx of Ca 2+ upon opening of the nonselective CALHM1 channels. These findings reveal a distinctive organelle signature and functional organization for regulated, focal release of purinergic signals in the absence of synaptic vesicles. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene.

PubMed

Chester, N; Kuo, F; Kozak, C; O'Hara, C D; Leder, P

1998-11-01

Bloom's syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease include proportional dwarfism and a predisposition to develop a wide variety of malignancies. The human BLM gene has been cloned recently and encodes a DNA helicase. Mouse embryos homozygous for a targeted mutation in the murine Bloom's syndrome gene (Blm) are developmentally delayed and die by embryonic day 13.5. The fact that the interrupted gene is the homolog of the human BLM gene was confirmed by its homologous sequence, its chromosomal location, and by demonstrating high numbers of SCEs in cultured murine Blm-/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12-24 hr) seen during mid-gestation in murine Blm-/- embryos. Interestingly, the growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early post-implantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm-/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes.

Disease Severity and Thin Filament Regulation in M9R TPM3 Nemaline Myopathy

PubMed Central

Ilkovski, Biljana; Mokbel, Nancy; Lewis, Raymond A.; Walker, Kendall; Nowak, Kristen J.; Domazetovska, Ana; Laing, Nigel G.; Fowler, Velia M.; North, Kathryn N.; Cooper, Sandra T.

2009-01-01

The mechanism of muscle weakness was investigated in an Australian family with a M9R mutation in TPM3 (α-tropomyosinslow). Detailed protein analyses of five muscle samples from two patients showed that nemaline bodies are restricted to atrophied type 1 (slow) fibers in which the TPM3 gene is expressed. Developmental expression studies showed that α-tropomyosinslow is not expressed at significant levels until after birth, thereby likely explaining the childhood (rather than congenital) disease onset in TPM3 nemaline myopathy. Isoelectric focusing demonstrated that α-tropomyosinslow dimers, comprised of equal ratios of wild-type and M9R-α-tropomyosinslow, are the dominant tropomyosin species in three separate muscle groups from an affected patient. These findings suggest that myopathy-related slow fiber predominance likely contributes to the severity of weakness in TPM3 nemaline myopathy because of increased proportions of fibers that express the mutant protein. Using recombinant proteins and far Western blot we demonstrated a higher affinity of tropomodulin for α-tropomyosinslow compared to β-tropomyosin; the M9R substitution within α-tropomyosinslow greatly reduced this interaction. Finally, transfection of the M9R mutated and wild-type α-tropomyosinslow into myoblasts revealed reduced incorporation into stress fibers and disruption of the filamentous actin network by the mutant protein. Collectively, these results provide insights into the clinical features and pathogenesis of M9R-TPM3 nemaline myopathy. PMID:18716557

Residual neural processing of musical sound features in adult cochlear implant users.

PubMed

Timm, Lydia; Vuust, Peter; Brattico, Elvira; Agrawal, Deepashri; Debener, Stefan; Büchner, Andreas; Dengler, Reinhard; Wittfoth, Matthias

2014-01-01

Auditory processing in general and music perception in particular are hampered in adult cochlear implant (CI) users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioral study comparing adult CI users with normal-hearing age-matched controls (NH controls). We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20 min. The presentation of stimuli did not require the participants' attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timber. No other group differences in MMN parameters were found to changes in intensity and saxophone timber. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients' age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioral and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood. -Automatic brain responses to musical feature changes reflect the limitations of central auditory processing in adult Cochlear Implant users.-The brains of adult CI users automatically process sound features changes even when inserted in a musical context.-CI users show disrupted automatic discriminatory abilities for rhythm in the brain.-Our fast paradigm demonstrate residual musical abilities in the brains of adult CI users giving hope for their future rehabilitation.

Residual Neural Processing of Musical Sound Features in Adult Cochlear Implant Users

PubMed Central

Timm, Lydia; Vuust, Peter; Brattico, Elvira; Agrawal, Deepashri; Debener, Stefan; Büchner, Andreas; Dengler, Reinhard; Wittfoth, Matthias

2014-01-01

Auditory processing in general and music perception in particular are hampered in adult cochlear implant (CI) users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioral study comparing adult CI users with normal-hearing age-matched controls (NH controls). We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20 min. The presentation of stimuli did not require the participants’ attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timber. No other group differences in MMN parameters were found to changes in intensity and saxophone timber. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients’ age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioral and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood. Highlights: -Automatic brain responses to musical feature changes reflect the limitations of central auditory processing in adult Cochlear Implant users.-The brains of adult CI users automatically process sound features changes even when inserted in a musical context.-CI users show disrupted automatic discriminatory abilities for rhythm in the brain.-Our fast paradigm demonstrate residual musical abilities in the brains of adult CI users giving hope for their future rehabilitation. PMID:24772074

Visual feature-tolerance in the reading network.

PubMed

Rauschecker, Andreas M; Bowen, Reno F; Perry, Lee M; Kevan, Alison M; Dougherty, Robert F; Wandell, Brian A

2011-09-08

A century of neurology and neuroscience shows that seeing words depends on ventral occipital-temporal (VOT) circuitry. Typically, reading is learned using high-contrast line-contour words. We explored whether a specific VOT region, the visual word form area (VWFA), learns to see only these words or recognizes words independent of the specific shape-defining visual features. Word forms were created using atypical features (motion-dots, luminance-dots) whose statistical properties control word-visibility. We measured fMRI responses as word form visibility varied, and we used TMS to interfere with neural processing in specific cortical circuits, while subjects performed a lexical decision task. For all features, VWFA responses increased with word-visibility and correlated with performance. TMS applied to motion-specialized area hMT+ disrupted reading performance for motion-dots, but not line-contours or luminance-dots. A quantitative model describes feature-convergence in the VWFA and relates VWFA responses to behavioral performance. These findings suggest how visual feature-tolerance in the reading network arises through signal convergence from feature-specialized cortical areas. Copyright © 2011 Elsevier Inc. All rights reserved.

Quantifying camouflage: how to predict detectability from appearance.

PubMed

Troscianko, Jolyon; Skelhorn, John; Stevens, Martin

2017-01-06

Quantifying the conspicuousness of objects against particular backgrounds is key to understanding the evolution and adaptive value of animal coloration, and in designing effective camouflage. Quantifying detectability can reveal how colour patterns affect survival, how animals' appearances influence habitat preferences, and how receiver visual systems work. Advances in calibrated digital imaging are enabling the capture of objective visual information, but it remains unclear which methods are best for measuring detectability. Numerous descriptions and models of appearance have been used to infer the detectability of animals, but these models are rarely empirically validated or directly compared to one another. We compared the performance of human 'predators' to a bank of contemporary methods for quantifying the appearance of camouflaged prey. Background matching was assessed using several established methods, including sophisticated feature-based pattern analysis, granularity approaches and a range of luminance and contrast difference measures. Disruptive coloration is a further camouflage strategy where high contrast patterns disrupt they prey's tell-tale outline, making it more difficult to detect. Disruptive camouflage has been studied intensely over the past decade, yet defining and measuring it have proven far more problematic. We assessed how well existing disruptive coloration measures predicted capture times. Additionally, we developed a new method for measuring edge disruption based on an understanding of sensory processing and the way in which false edges are thought to interfere with animal outlines. Our novel measure of disruptive coloration was the best predictor of capture times overall, highlighting the importance of false edges in concealment over and above pattern or luminance matching. The efficacy of our new method for measuring disruptive camouflage together with its biological plausibility and computational efficiency represents a substantial advance in our understanding of the measurement, mechanism and definition of disruptive camouflage. Our study also provides the first test of the efficacy of many established methods for quantifying how conspicuous animals are against particular backgrounds. The validation of these methods opens up new lines of investigation surrounding the form and function of different types of camouflage, and may apply more broadly to the evolution of any visual signal.

Encouraging top-down attention in visual search:A developmental perspective.

PubMed

Lookadoo, Regan; Yang, Yingying; Merrill, Edward C

2017-10-01

Four experiments are reported in which 60 younger children (7-8 years old), 60 older children (10-11 years old), and 60 young adults (18-25 years old) performed a conjunctive visual search task (15 per group in each experiment). The number of distractors of each feature type was unbalanced across displays to evaluate participants' ability to restrict search to the smaller subset of features. The use of top-down attention processes to restrict search was encouraged by providing external aids for identifying and maintaining attention on the smaller set. In Experiment 1, no external assistance was provided. In Experiment 2, precues and instructions were provided to focus attention on that subset. In Experiment 3, trials in which the smaller subset was represented by the same feature were presented in alternating blocks to eliminate the need to switch attention between features from trial to trial. In Experiment 4, consecutive blocks of the same subset features were presented in the first or second half of the experiment, providing additional consistency. All groups benefited from external support of top-down attention, although the pattern of improvement varied across experiments. The younger children benefited most from precues and instruction, using the subset search strategy when instructed. Furthermore, younger children benefited from blocking trials only when blocks of the same features did not alternate. Older participants benefited from the blocking of trials in both Experiments 3 and 4, but not from precues and instructions. Hence, our results revealed both malleability and limits of children's top-down control of attention.

Risk perceptions and trust following the 2010 and 2011 Icelandic volcanic ash crises.

PubMed

Eiser, J Richard; Donovan, Amy; Sparks, R Stephen J

2015-02-01

Eruptions at the Icelandic volcanoes of Eyjafjallajökull (2010) and Grimsvötn (2011) produced plumes of ash posing hazards to air traffic over northern Europe. In imposing restrictions on air traffic, regulators needed to balance the dangers of accidents or aircraft damage against the cost and inconvenience to travelers and industry. Two surveys examined how members of the public viewed the necessity of the imposed restrictions and their trust in different agencies as estimators of the level of risk. Study 1 was conducted with 213 British citizens (112 males, 101 females), who completed questionnaires while waiting for flights at London City Airport during May 2012. Study 2 involved an online survey of 301 Icelandic citizens (172 males, 127 females, 2 undeclared gender) during April 2012. In both samples, there was general support for the air traffic restrictions, especially among those who gave higher estimates of the likelihood of an air accident or mishap having otherwise happened. However, in both countries, the (minority of) respondents who had personally experienced travel disruption were less convinced that these restrictions were all necessary. Scientists, the International Civil Aviation Organization, and (in Iceland) the Icelandic Department of Civil Protection were all highly trusted, and seen as erring on the side of caution in their risk estimates. Airlines were seen as more likely to underestimate any risk. We conclude that perceptions of the balance between risk and caution in judgments under uncertainty are influenced by one's own motives and those attributed to others. © 2014 Society for Risk Analysis.

MedlinePlus FAQ: Copyrighted and Non-Copyrighted Material

MedlinePlus

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"Calories in, calories out" and macronutrient intake: the hope, hype, and science of calories.

PubMed

Howell, Scott; Kones, Richard

2017-11-01

One of the central tenets in obesity prevention and management is caloric restriction. This perspective presents salient features of how calories and energy balance matter, also called the "calories in, calories out" paradigm. Determinants of energy balance and relationships to dietary macronutrient content are reviewed. The rationale and features of the carbohydrate-insulin hypothesis postulate that carbohydrate restriction confers a metabolic advantage. According to this model, a large amount of fat intake is enabled without weight gain. Evidence concerning this possibility is detailed. The relationship and application of the laws of thermodynamics are then clarified with current primary research. Strong data indicate that energy balance is not materially changed during isocaloric substitution of dietary fats for carbohydrates. Results from a number of sources refute both the theory and effectiveness of the carbohydrate-insulin hypothesis. Instead, risk for obesity is primarily determined by total calorie intake. Copyright © 2017 the American Physiological Society.

Can High Quality Overcome Consumer Resistance to Restricted Provider Access? Evidence from a Health Plan Choice Experiment

PubMed Central

Harris, Katherine M

2002-01-01

Objective To investigate the impact of quality information on the willingness of consumers to enroll in health plans that restrict provider access. Data Sources and Setting A survey administered to respondents between the ages of 25 and 64 in the West Los Angeles area with private health insurance. Study Design An experimental approach is used to measure the effect of variation in provider network features and information about the quality of network physicians on hypothetical plan choices. Conditional logit models are used to analyze the experimental choice data. Next, choice model parameter estimates are used to simulate the impact of changes in plan features on the market shares of competing health plans and to calculate the quality level required to make consumers indifferent to changes in provider access. Principal Findings The presence of quality information reduced the importance of provider network features in plan choices as hypothesized. However, there were not statistically meaningful differences by type of quality measure (i.e., consumer assessed versus expert assessed). The results imply that large quality differences are required to make consumers indifferent to changes in provider access. The impact of quality on plan choices depended more on the particular measure and less on the type of measure. Quality ratings based on the proportion of survey respondents “extremely satisfied with results of care” had the greatest impact on plan choice while the proportion of network doctors “affiliated with university medical centers” had the least. Other consumer and expert assessed measures had more comparable effects. Conclusions Overall the results provide empirical evidence that consumers are willing to trade high quality for restrictions on provider access. This willingness to trade implies that relatively small plans that place restrictions on provider access can successfully compete against less restrictive plans when they can demonstrate high quality. However, the results of this study suggest that in many cases, the level of quality required for consumers to accept access restrictions may be so high as to be unattainable. The results provide empirical support for the current focus of decision support efforts on consumer assessed quality measures. At the same time, however, the results suggest that consumers would also value quality measures based on expert assessments. This finding is relevant given the lack of comparative quality information based on expert judgment and research suggesting that consumers have apprehensions about their ability to meaningfully interpret performance-based quality measures. PMID:12132595

Minireview: CNS Mechanisms of Leptin Action

PubMed Central

Flak, Jonathan N.

2016-01-01

Leptin is an adipocytokine that circulates in proportion to body fat to signal the repletion of long-term energy stores. Leptin acts via its receptor, LepRb, on specialized neuronal populations in the brain (mainly in the hypothalamus and brainstem) to alter motivation and satiety, as well as to permit energy expenditure and appropriate glucose homeostasis. Decreased leptin, as with prolonged caloric restriction, promotes a powerful orexigenic signal, decreases energy use via a number of neuroendocrine and autonomic axes, and disrupts glucose homeostasis. Here, we review what is known about cellular leptin action and focus on the roles for specific populations of LepRb-expressing neurons for leptin action. PMID:26484582

Unaltered ethical standards for individual physicians in the face of drastically reduced resources resulting from an improvised nuclear device event.

PubMed

Caro, J Jaime; Coleman, C Norman; Knebel, Ann; DeRenzo, Evan G

2011-01-01

When disaster disrupts healthcare and other systems, the ethical allocation of resources should follow principles of justice, defined as fairness, established for normal clinical practice. Standards of clinical practice may be altered during disaster, but ethical standards must remain centered on prioritizing the treatment of patients according to need and the effectiveness of treatment. Should resources become extremely limited, it is fair to restrict their use to patients who have the highest needs, provided that the intervention is effective. When resources become more available, patients with lower priority can be increasingly accommodated.

Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy.

PubMed

Holleran, Laurena; Kim, Joong Hee; Gangolli, Mihika; Stein, Thor; Alvarez, Victor; McKee, Ann; Brody, David L

2017-03-01

Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm 3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.

Los1p, involved in yeast pre-tRNA splicing, positively regulates members of the SOL gene family.

PubMed

Shen, W C; Stanford, D R; Hopper, A K

1996-06-01

To understand the role of Los1p in pre-tRNA splicing, we sought los1 multicopy suppressors. We found SOL1 that suppresses both point and null LOS1 mutations. Since, when fused to the Ga14p DNA-binding domain, Los1p activates transcription, we tested whether Los1p regulates SOL1. We found that las1 mutants have depleted levels of SOL1 mRNA and Sol1p. Thus, LOS1 appears to positively regulate SOL1. SOL1 belongs to a multigene family with at least two additional members, SOL2 and SOL3. Sol proteins have extensive similarity to an unusual group of glucose-6-phosphate dehydrogenases. As the similarities are restricted to areas separate from the catalytic domain, these G6PDs may have more than one function. The SOL family appears to be unessential since cells with a triple disruption of all three SOL genes are viable. SOL gene disruptions negatively affect tRNA-mediated nonsense suppression and the severity increases with the number of mutant SOL genes. However, tRNA levels do not vary with either multicopy SOL genes or with SOL disruptions. Therefore, the Sol proteins affect tRNA expression/ function at steps other than transcription or splicing. We propose that LOS1 regulates gene products involved in tRNA expression/function as well as pre-tRNA splicing.

Sleep-related problems in common medical conditions.

PubMed

Parish, James M

2009-02-01

Common medical problems are often associated with abnormalities of sleep. Patients with chronic medical disorders often have fewer hours of sleep and less restorative sleep compared to healthy individuals, and this poor sleep may worsen the subjective symptoms of the disorder. Individuals with lung disease often have disturbed sleep related to oxygen desaturations, coughing, or dyspnea. Both obstructive lung disease and restrictive lung diseases are associated with poor quality sleep. Awakenings from sleep are common in untreated or undertreated asthma, and cause sleep disruption. Gastroesophageal reflux is a major cause of disrupted sleep due to awakenings from heartburn, dyspepsia, acid brash, coughing, or choking. Patients with chronic renal disease commonly have sleep complaints often due to insomnia, insufficient sleep, sleep apnea, or restless legs syndrome. Complaints related to sleep are very common in patients with fibromyalgia and other causes of chronic pain. Sleep disruption increases the sensation of pain and decreases quality of life. Patients with infectious diseases, including acute viral illnesses, HIV-related disease, and Lyme disease, may have significant problems with insomnia and hypersomnolence. Women with menopause have from insomnia, sleep-disordered breathing, restless legs syndrome, or fibromyalgia. Patients with cancer or receiving cancer therapy are often bothered by insomnia or other sleep disturbances that affect quality of life and daytime energy. The objective of this article is to review frequently encountered medical conditions and examine their impact on sleep, and to review frequent sleep-related problems associated with these common medical conditions.

A splice junction-targeted CRISPR approach (spJCRISPR) reveals human FOXO3B to be a protein-coding gene.

PubMed

Santo, Evan E; Paik, Jihye

2018-06-17

The rapid development of CRISPR technology is revolutionizing molecular approaches to the dissection of complex biological phenomena. Here we describe an alternative generally applicable implementation of the CRISPR-Cas9 system that allows for selective knockdown of extremely homologous genes. This strategy employs the lentiviral delivery of paired sgRNAs and nickase Cas9 (Cas9D10A) to achieve targeted deletion of splice junctions. This general strategy offers several advantages over standard single-guide exon-targeting CRISPR-Cas9 such as greatly reduced off-target effects, more restricted genomic editing, routine disruption of target gene mRNA expression and the ability to differentiate between closely related genes. Here we demonstrate the utility of this strategy by achieving selective knockdown of the highly homologous human genes FOXO3A and suspected pseudogene FOXO3B. We find the spJCRISPR strategy to efficiently and selectively disrupt FOXO3A and FOXO3B mRNA and protein expression; thus revealing that the human FOXO3B locus encodes a bona fide human gene. Unlike FOXO3A, we find the FOXO3B protein to be cytosolically localized in both the presence and absence of active Akt. The ability to selectively target and efficiently disrupt the expression of the closely-related FOXO3A and FOXO3B genes demonstrates the efficacy of the spJCRISPR approach. Copyright © 2018. Published by Elsevier B.V.

Protein kinase C activation modulates reversible increase in cortical blood-brain barrier permeability and tight junction protein expression during hypoxia and posthypoxic reoxygenation.

PubMed

Willis, Colin L; Meske, Diana S; Davis, Thomas P

2010-11-01

Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood-brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced loss of BBB integrity are not fully understood. We examined the role of protein kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of global Hx. The Hx (6% O(2)) induced increased hippocampal and cortical vascular permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC-θ distribution, increased nPKC-θ and aPKC-ζ protein expression, and activation by phosphorylation of nPKC-θ (Thr538) and aPKC-ζ (Thr410) residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted organization at endothelial cell margins, whereas Western blot analysis showed increased TJ protein expression after Hx. The PKC inhibition with chelerythrine chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular permeability and claudin-5, PKC (θ and ζ) expression, and phosphorylation. This study supports the hypothesis that nPKC-θ and aPKC-ζ signaling mediates TJ protein disruption resulting in increased BBB permeability.

Mitigating Disruptive Effects of Interruptions through Training: What Needs to Be Practiced?

ERIC Educational Resources Information Center

Cades, David M.; Boehm-Davis, Deborah A.; Trafton, J. Gregory; Monk, Christopher A.

2011-01-01

It is generally accepted that, with practice, people improve on most tasks. However, when tasks have multiple parts, it is not always clear what aspects of the tasks practice or training should focus on. This research explores the features that allow training to improve the ability to resume a task after an interruption, specifically focusing on…

A Helitron-like Transposon Superfamily from Lepidoptera Disrupts (GAAA)n Microsatellites and is Responsible for Flanking Sequence Similarity within a Microsatellite Family

USDA-ARS?s Scientific Manuscript database

Transposable elements (TEs) are mobile DNA regions that alter host genome structure and gene expression. A novel 588 bp non-autonomous high copy number TE in the Ostrinia nubilalis genome has features in common with miniature inverted-repeat transposable elements (MITEs): high A+T content (62.3%),...

Genetic disruption of Pten in a novel mouse model of tomaculous neuropathy

PubMed Central

Goebbels, Sandra; Oltrogge, Jan H; Wolfer, Susanne; Wieser, Georg L; Nientiedt, Tobias; Pieper, Alexander; Ruhwedel, Torben; Groszer, Matthias; Sereda, Michael W; Nave, Klaus-Armin

2012-01-01

‘Tomacula’ and myelin outfoldings are striking neuropathological features of a diverse group of inherited demyelinating neuropathies. Whereas the underlying genetic defects are well known, the molecular mechanisms of tomacula formation have remained obscure. We hypothesized that they are caused by uncontrolled, excessive myelin membrane growth, a process, which is regulated in normal development by neuregulin-1/ErbB2, PI3 Kinase signalling and ERK/MAPK signalling. Here, we demonstrate by targeted disruption of Pten in Schwann cells that hyperactivation of the endogenous PI3 Kinase pathway causes focal hypermyelination, myelin outfoldings and tomacula, even when induced in adult animals by tamoxifen, and is associated with progressive peripheral neuropathy. Activated AKT kinase is associated with PtdIns(3,4,5)P3 at paranodal loops and Schmidt–Lanterman incisures. This striking myelin pathology, with features of human CMT type 4B1 and HNPP, is dependent on AKT/mTOR signalling, as evidenced by a significant amelioration of the pathology in mice treated with rapamycin. We suggest that regions of non-compact myelin are under lifelong protection by PTEN against abnormal membrane outgrowth, and that dysregulated phosphoinositide levels play a critical role in the pathology of tomaculous neuropathies. PMID:22488882

Multimodal imaging findings in 'hyper-early' stage MEWDS.

PubMed

Cahuzac, Armelle; Wolff, Benjamin; Mathis, Thibaud; Errera, Marie-Hélène; Sahel, José-Alain; Mauget-Faÿsse, Martine

2017-10-01

To describe a new stage of multiple evanescent white dot syndrome (MEWDS), occurring at a very early phase of the disease. Retrospective analysis of clinical, angiographic and tomographic findings in four patients with 'hyper-early' stage MEWDS. In four patients seen within 1 week of the onset of symptoms, fundus analysis revealed macular granity and the classic yellow-white dots, some having no corresponding hyperautofluorescent pattern. Spectral-domain optical coherence tomography (SD-OCT) showed central foveal disruption of the ellipsoid zone (EZ) and interdigitation layer with a hyper-reflective dome-shaped lesion. In two patients, fluorescein angiography (FA) revealed an intermediate hypofluorescent perimacular halo, whereas late indocyanine green angiography (ICGA) showed a hyperfluorescent halo as well as the classic MEWDS features. After a few days, the EZ disruption appeared complete on OCT and fundus autofluorescence (FAF) in all patients. Visual acuity, OCT and FAF findings had fully recovered within 3 months. We have shown a new feature of MEWDS on FAF, OCT, FA and ICGA, corresponding to a very early stage of the disease. 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/.

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma.

PubMed

Danilovic, Debora Lucia Seguro; de Mello, Evandro Sobroza; Frazzato, Eliana Salgado Turri; Wakamatsu, Alda; de Lima Jorge, Alexander Augusto; Hoff, Ana Oliveira; Marui, Suemi

2018-06-01

Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. Coding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. Although no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. We identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences. © 2018 Wiley Periodicals, Inc.

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

Klise, Katherine A.; Murray, Regan; Bynum, Michael

Water utilities are vulnerable to a wide variety of human-caused and natural disasters. These disruptive events can result in loss of water service, contaminated water, pipe breaks, and failed equipment. Furthermore, long term changes in water supply and customer demand can have a large impact on the operating conditions of the network. The ability to maintain drinking water service during and following these types of events is critical. Simulation and analysis tools can help water utilities explore how their network will respond to disruptive events and plan effective mitigation strategies. The U.S. Environmental Protection Agency and Sandia National Laboratories aremore » developing new software tools to meet this need. The Water Network Tool for Resilience (WNTR, pronounced winter) is a Python package designed to help water utilities investigate resilience of water distribution systems over a wide range of hazardous scenarios and to evaluate resilience-enhancing actions. The following documentation includes installation instructions and examples, description of software features, and software license. It is assumed that the reader is familiar with the Python Programming Language. References are included for additional background on software components. Online documentation, hosted at http://wntr.readthedocsio/, will be updated as new features are added. The online version includes API documentation and information for developers.« less

The Operator Shell: A means of privilege distribution under Unix

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

Neuman, M.; Christoph, G.

1994-03-01

The Operator Shell (Osh) is a setuid root, security enhanced, restricted shell for providing fine-grain distribution of system privileges for a wide range of usages and requirements. Osh offers a marked improvement over other Unix privilege distribution systems in its ability to specify access to both commands and files, auditing features, and familiar interface. This paper describes the design, features, security considerations, internals, and applications of the Operator Shell.

Infrared Spectroscopic Imaging for Prostate Pathology Practice

DTIC Science & Technology

2011-04-01

features – geometric properties of epithelial cells/nuclei and lumens – that are quantified based on H&E stained images as well as FT-IR images of...the samples. By restricting the features used to geometric measures, we sought to mimic the pattern recognition process employed by human experts, and...relatively dark and can be modeled as small elliptical areas in the stained images. This geometrical model is often confounded as multiple nuclei can be

Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis.

PubMed

Swann, Alan C; Fava, Maurizio; Tsai, Joyce; Mao, Yongcai; Pikalov, Andrei; Loebel, Antony

2017-04-01

The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability. The data in this analysis were derived from a study of patients meeting DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/d (n=109) or placebo (n=100). We defined "irritability" as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability. Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (-22.6 vs. -9.5, p<0.0001, effect size [ES]=1.4) and without (-19.9 vs. -13.8, p<0.0001, ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (-1.4 vs. -0.3, p=0.0012, ES=1.0) and the YMRS disruptive-aggressive item (-1.0 vs. -0.3, p=0.0002, ES=1.2). In our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.

Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.

PubMed

Vermeij, W P; Dollé, M E T; Reiling, E; Jaarsma, D; Payan-Gomez, C; Bombardieri, C R; Wu, H; Roks, A J M; Botter, S M; van der Eerden, B C; Youssef, S A; Kuiper, R V; Nagarajah, B; van Oostrom, C T; Brandt, R M C; Barnhoorn, S; Imholz, S; Pennings, J L A; de Bruin, A; Gyenis, Á; Pothof, J; Vijg, J; van Steeg, H; Hoeijmakers, J H J

2016-09-15

Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1 ∆/- ) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg -/- (also known as Ercc5 -/- ) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1 ∆/- mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1 ∆/- mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of γH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1 ∆/- mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.

Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas

PubMed Central

Brooks, Joseph L.; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

2012-01-01

Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG. PMID:22947116

Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic Oscillation in Cancer.

PubMed

Altman, Brian J

2016-01-01

Circadian rhythms are 24-h oscillations present in most eukaryotes and many prokaryotes that synchronize activity to the day-night cycle. They are an essential feature of organismal and cell physiology that coordinate many of the metabolic, biosynthetic, and signal transduction pathways studied in biology. The molecular mechanism of circadian rhythm is controlled both by signal transduction and gene transcription as well as by metabolic feedback. The role of circadian rhythm in cancer cell development and survival is still not well understood, but as will be discussed in this Review, accumulated research suggests that circadian rhythm may be altered or disrupted in many human cancers downstream of common oncogenic alterations. Thus, a complete understanding of the genetic and metabolic alterations in cancer must take potential circadian rhythm perturbations into account, as this disruption itself will influence how gene expression and metabolism are altered in the cancer cell compared to its non-transformed neighbor. It will be important to better understand these circadian changes in both normal and cancer cell physiology to potentially design treatment modalities to exploit this insight.

Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic Oscillation in Cancer

PubMed Central

Altman, Brian J.

2016-01-01

Circadian rhythms are 24-h oscillations present in most eukaryotes and many prokaryotes that synchronize activity to the day-night cycle. They are an essential feature of organismal and cell physiology that coordinate many of the metabolic, biosynthetic, and signal transduction pathways studied in biology. The molecular mechanism of circadian rhythm is controlled both by signal transduction and gene transcription as well as by metabolic feedback. The role of circadian rhythm in cancer cell development and survival is still not well understood, but as will be discussed in this Review, accumulated research suggests that circadian rhythm may be altered or disrupted in many human cancers downstream of common oncogenic alterations. Thus, a complete understanding of the genetic and metabolic alterations in cancer must take potential circadian rhythm perturbations into account, as this disruption itself will influence how gene expression and metabolism are altered in the cancer cell compared to its non-transformed neighbor. It will be important to better understand these circadian changes in both normal and cancer cell physiology to potentially design treatment modalities to exploit this insight. PMID:27500134

Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease.

PubMed

Argaw, Azeb Tadesse; Asp, Linnea; Zhang, Jingya; Navrazhina, Kristina; Pham, Trinh; Mariani, John N; Mahase, Sean; Dutta, Dipankar J; Seto, Jeremy; Kramer, Elisabeth G; Ferrara, Napoleone; Sofroniew, Michael V; John, Gareth R

2012-07-01

In inflammatory CNS conditions such as multiple sclerosis (MS), current options to treat clinical relapse are limited, and more selective agents are needed. Disruption of the blood-brain barrier (BBB) is an early feature of lesion formation that correlates with clinical exacerbation, leading to edema, excitotoxicity, and entry of serum proteins and inflammatory cells. Here, we identify astrocytic expression of VEGF-A as a key driver of BBB permeability in mice. Inactivation of astrocytic Vegfa expression reduced BBB breakdown, decreased lymphocyte infiltration and neuropathology in inflammatory and demyelinating lesions, and reduced paralysis in a mouse model of MS. Knockdown studies in CNS endothelium indicated activation of the downstream effector eNOS as the principal mechanism underlying the effects of VEGF-A on the BBB. Systemic administration of the selective eNOS inhibitor cavtratin in mice abrogated VEGF-A-induced BBB disruption and pathology and protected against neurologic deficit in the MS model system. Collectively, these data identify blockade of VEGF-A signaling as a protective strategy to treat inflammatory CNS disease.

Why mental disorders are just mental dysfunctions (and nothing more): some Darwinian arguments.

PubMed

De Block, Andreas

2008-09-01

Mental disorders are often thought to be harmful dysfunctions. Jerome Wakefield has argued that such dysfunctions should be understood as failures of naturally selected functions. This suggests, implicitly, that evolutionary biology and other Darwinian disciplines hold important information for anyone working on answering the philosophical question, 'what is a mental disorder?'. In this article, the author argues that Darwinian theory is not only relevant to the understanding of the disrupted functions, but it also sheds light on the disruption itself, as well as on the harm that attends the disruption. The arguments advanced here are partially based on the view that a core feature of Darwinism is that it stresses the environmental relativity of functions and dysfunctions. These arguments show a very close empirical connection between social judgments (values) and dysfunctions (psychopathology), which is of interest for psychiatric theory. Philosophically, they lead to the conclusion that the concept of mental disorder is identical to the concept of mental dysfunction. Consequently, it is both misleading and redundant to conceptualize mental disorders as 'harmful dysfunctions', and not simply as 'mental dysfunctions'.

Cool Core Disruption in Abell 1763

NASA Astrophysics Data System (ADS)

Douglass, Edmund; Blanton, Elizabeth L.; Clarke, Tracy E.; Randall, Scott W.; Edwards, Louise O. V.; Sabry, Ziad

2017-01-01

We present the analysis of a 20 ksec Chandra archival observation of the massive galaxy cluster Abell 1763. A model-subtracted image highlighting excess cluster emission reveals a large spiral structure winding outward from the core to a radius of ~950 kpc. We measure the gas of the inner spiral to have significantly lower entropy than non-spiral regions at the same radius. This is consistent with the structure resulting from merger-induced motion of the cluster’s cool core, a phenomenon seen in many systems. Atypical of spiral-hosting clusters, an intact cool core is not detected. Its absence suggests the system has experienced significant disruption since the initial dynamical encounter that set the sloshing core in motion. Along the major axis of the elongated ICM distribution we detect thermal features consistent with the merger event most likely responsible for cool core disruption. The merger-induced transition towards non-cool core status will be discussed. The interaction between the powerful (P1.4 ~ 1026 W Hz-1) cluster-center WAT radio source and its ICM environment will also be discussed.

The contribution of animal models to the study of obesity.

PubMed

Speakman, John; Hambly, Catherine; Mitchell, Sharon; Król, Elzbieta

2008-10-01

Obesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. The second approach is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The third type of models are mice and rats where a specific gene has been disrupted or over-expressed as a deliberate act. Such genetically-engineered disruptions may be generated through the entire body for the entire life (global transgenic manipulations) or restricted in both time and to certain tissue or cell types. In all these genetically-engineered scenarios, there are two types of situation that lead to insights: where a specific gene hypothesized to play a role in the regulation of energy balance is targeted, and where a gene is disrupted for a different purpose, but the consequence is an unexpected obese or lean phenotype. A fourth group of animal models concern experiments where selective breeding has been utilized to derive strains of rodents that differ in their degree of fatness. Finally, studies have been made of other species including non-human primates and dogs. In addition to studies of the physiological and genetic basis of obesity, studies of animal models have also informed us about the environmental aspects of the condition. Studies in this context include exploring the responses of animals to high fat or high fat/high sugar (Cafeteria) diets, investigations of the effects of dietary restriction on body mass and fat loss, and studies of the impact of candidate pharmaceuticals on components of energy balance. Despite all this work, there are many gaps in our understanding of how body composition and energy storage are regulated, and a continuing need for the development of pharmaceuticals to treat obesity. Accordingly, reductions in the use of animal models, while ethically desirable, will not be feasible in the short to medium term, and indeed an expansion in activity using animal models is anticipated as the epidemic continues and spreads geographically.

New Probe of Early Phases of Jet Formation and Evolution using Stellar Tidal Disruption Flares

NASA Astrophysics Data System (ADS)

Ranga Reddy Pasham, Dheeraj; van Velzen, Sjoert

2018-01-01

The tidal disruption of a star by a supermassive black hole can result in transient radio emission. The electrons producing these synchrotron radio flares could either be accelerated inside a relativistic jet or externally by shocks resulting from an outflow interacting with the circumnuclear medium. Until now, evidence for the internal emission mechanism has been lacking; nearly all tidal disruption flare studies have adopted the external shock model to explain the observed properties of radio flares. I will talk about a result that presents a challenge to external emission models: we discovered a cross-correlation between the soft X-ray (0.3-1 keV) and 16 GHz radio flux of Rosetta Stone tidal disruption flare ASASSN-14li. Variability features in the X-ray light curve appear again in the radio light curve, but after a time lag of about 13 days. This demonstrates that soft X-ray emitting accretion disk regulates the radio emission. This coupling appears to be inconsistent with all previous external emission models for this source but is naturally explained if the radio emission originates from a freely expanding jet. I will show that emission internal to an adiabatically expanding jet can also reproduce the observed evolution of the radio spectral energy distribution. Furthermore, both the correlation between X-ray and radio luminosity as well as our radio spectral modeling imply an approximately linear coupling between the accretion rate and jet power. I will also discuss how future tidal disruption events can help us understand how jets form and evolve in general.

Disruptive innovations for designing and diffusing evidence-based interventions.

PubMed

Rotheram-Borus, Mary Jane; Swendeman, Dallas; Chorpita, Bruce F

2012-09-01

Evidence-based therapeutic and preventive intervention programs (EBIs) have been growing exponentially. Yet EBIs have not been broadly adopted in the United States. In order for our EBI science to significantly reduce disease burden, we need to critically reexamine our scientific conventions and norms. Innovation may be spurred by reexamining the traditional biomedical model for validating, implementing, and diffusing EBI products and science. The model of disruptive innovations suggests that we reengineer EBIs on the basis of their most robust features in order to serve more people in less time and at lower cost. A disruptive innovation provides a simpler and less expensive alternative that meets the essential needs for the majority of consumers and is more accessible, scalable, replicable, and sustainable. Examples of disruptive innovations from other fields include minute clinics embedded in retail chain drug stores, $2 generic eyeglasses, automated teller machines, and telemedicine. Four new research approaches will be required to support disruptive innovations in EBI science: synthesize common elements across EBIs; experiment with new delivery formats (e.g., consumer controlled, self-directed, brief, paraprofessional, coaching, and technology and media strategies); adopt market strategies to promote and diffuse EBI science, knowledge, and products; and adopt continuous quality improvement as a research paradigm for systematically improving EBIs, based on ongoing monitoring data and feedback. EBI science can have more impact if it can better leverage what we know from existing EBIs in order to inspire, engage, inform, and support families and children to adopt and sustain healthy daily routines and lifestyles. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Secondhand Smoke/“Light” Tobacco/ Smokeless Tobacco | NIH MedlinePlus the Magazine

MedlinePlus

... turn Javascript on. Feature: Quit Smoking Secondhand Smoke/"Light" Tobacco/ Smokeless Tobacco Past Issues / Winter 2011 Table ... pneumonia Source: Centers for Disease Control and Prevention "Light" Tobacco = Heavy Health Risks Federal law restricts the ...

0-6711 : short radius MASH TL-3 guardrail treatment.

DOT National Transportation Integrated Search

2014-11-01

When a roadway intersects a highway with : restrictive features, such as a bridge rail, it becomes : difficult to fit a guardrail with the proper length, : transitions, and end treatment along the highway. : Possible solutions include relocating the ...

Dark matter phenomenology of high-speed galaxy cluster collisions

DOE PAGES

Mishchenko, Yuriy; Ji, Chueng-Ryong

2017-07-29

Here, we perform a general computational analysis of possible post-collision mass distributions in high-speed galaxy cluster collisions in the presence of self-interacting dark matter. Using this analysis, we show that astrophysically weakly self-interacting dark matter can impart subtle yet measurable features in the mass distributions of colliding galaxy clusters even without significant disruptions to the dark matter halos of the colliding galaxy clusters themselves. Most profound such evidence is found to reside in the tails of dark matter halos’ distributions, in the space between the colliding galaxy clusters. Such features appear in our simulations as shells of scattered dark mattermore » expanding in alignment with the outgoing original galaxy clusters, contributing significant densities to projected mass distributions at large distances from collision centers and large scattering angles of up to 90°. Our simulations indicate that as much as 20% of the total collision’s mass may be deposited into such structures without noticeable disruptions to the main galaxy clusters. Such structures at large scattering angles are forbidden in purely gravitational high-speed galaxy cluster collisions.Convincing identification of such structures in real colliding galaxy clusters would be a clear indication of the self-interacting nature of dark matter. Our findings may offer an explanation for the ring-like dark matter feature recently identified in the long-range reconstructions of the mass distribution of the colliding galaxy cluster CL0024+017.« less

Dark matter phenomenology of high-speed galaxy cluster collisions

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

Mishchenko, Yuriy; Ji, Chueng-Ryong

Here, we perform a general computational analysis of possible post-collision mass distributions in high-speed galaxy cluster collisions in the presence of self-interacting dark matter. Using this analysis, we show that astrophysically weakly self-interacting dark matter can impart subtle yet measurable features in the mass distributions of colliding galaxy clusters even without significant disruptions to the dark matter halos of the colliding galaxy clusters themselves. Most profound such evidence is found to reside in the tails of dark matter halos’ distributions, in the space between the colliding galaxy clusters. Such features appear in our simulations as shells of scattered dark mattermore » expanding in alignment with the outgoing original galaxy clusters, contributing significant densities to projected mass distributions at large distances from collision centers and large scattering angles of up to 90°. Our simulations indicate that as much as 20% of the total collision’s mass may be deposited into such structures without noticeable disruptions to the main galaxy clusters. Such structures at large scattering angles are forbidden in purely gravitational high-speed galaxy cluster collisions.Convincing identification of such structures in real colliding galaxy clusters would be a clear indication of the self-interacting nature of dark matter. Our findings may offer an explanation for the ring-like dark matter feature recently identified in the long-range reconstructions of the mass distribution of the colliding galaxy cluster CL0024+017.« less

SPAK and OSR1 play essential roles in potassium homeostasis through actions on the distal convoluted tubule

PubMed Central

Ferdaus, Mohammed Z.; Barber, Karl W.; López‐Cayuqueo, Karen I.; Terker, Andrew S.; Argaiz, Eduardo R.; Gassaway, Brandon M.; Chambrey, Régine; Gamba, Gerardo; Rinehart, Jesse

2016-01-01

Key points STE20 (Sterile 20)/SPS‐1 related proline/alanine‐rich kinase (SPAK) and oxidative stress‐response kinase‐1 (OSR1) phosphorylate and activate the renal Na+–K+–2Cl− cotransporter 2 (NKCC2) and Na+Cl− cotransporter (NCC).Mouse models suggest that OSR1 mainly activates NKCC2‐mediated sodium transport along the thick ascending limb, while SPAK mainly activates NCC along the distal convoluted tubule, but the kinases may compensate for each other. We hypothesized that disruption of both kinases would lead to polyuria and severe salt‐wasting, and generated SPAK/OSR1 double knockout mice to test this.Despite a lack of SPAK and OSR1, phosphorylated NKCC2 abundance was still high, suggesting the existence of an alternative activating kinase.Compensatory changes in SPAK/OSR1‐independent phosphorylation sites on both NKCC2 and NCC and changes in sodium transport along the collecting duct were also observed.Potassium restriction revealed that SPAK and OSR1 play essential roles in the emerging model that NCC activation is central to sensing changes in plasma [K+]. Abstract STE20 (Sterile 20)/SPS‐1 related proline/alanine‐rich kinase (SPAK) and oxidative stress‐response kinase‐1 (OSR1) activate the renal cation cotransporters Na+–K+–2Cl− cotransporter (NKCC2) and Na+–Cl− cotransporter (NCC) via phosphorylation. Knockout mouse models suggest that OSR1 mainly activates NKCC2, while SPAK mainly activates NCC, with possible cross‐compensation. We tested the hypothesis that disrupting both kinases causes severe polyuria and salt‐wasting by generating SPAK/OSR1 double knockout (DKO) mice. DKO mice displayed lower systolic blood pressure compared with SPAK knockout (SPAK‐KO) mice, but displayed no severe phenotype even after dietary salt restriction. Phosphorylation of NKCC2 at SPAK/OSR1‐dependent sites was lower than in SPAK‐KO mice, but still significantly greater than in wild type mice. In the renal medulla, there was significant phosphorylation of NKCC2 at SPAK/OSR1‐dependent sites despite a complete absence of SPAK and OSR1, suggesting the existence of an alternative activating kinase. The distal convoluted tubule has been proposed to sense plasma [K+], with NCC activation serving as the primary effector pathway that modulates K+ secretion, by metering sodium delivery to the collecting duct. Abundance of phosphorylated NCC (pNCC) is dramatically lower in SPAK‐KO mice than in wild type mice, and the additional disruption of OSR1 further reduced pNCC. SPAK‐KO and kidney‐specific OSR1 single knockout mice maintained plasma [K+] following dietary potassium restriction, but DKO mice developed severe hypokalaemia. Unlike mice lacking SPAK or OSR1 alone, DKO mice displayed an inability to phosphorylate NCC under these conditions. These data suggest that SPAK and OSR1 are essential components of the effector pathway that maintains plasma [K+]. PMID:27068441

Remembering Complex Objects in Visual Working Memory: Do Capacity Limits Restrict Objects or Features?

PubMed Central

Hardman, Kyle; Cowan, Nelson

2014-01-01

Visual working memory stores stimuli from our environment as representations that can be accessed by high-level control processes. This study addresses a longstanding debate in the literature about whether storage limits in visual working memory include a limit to the complexity of discrete items. We examined the issue with a number of change-detection experiments that used complex stimuli which possessed multiple features per stimulus item. We manipulated the number of relevant features of the stimulus objects in order to vary feature load. In all of our experiments, we found that increased feature load led to a reduction in change-detection accuracy. However, we found that feature load alone could not account for the results, but that a consideration of the number of relevant objects was also required. This study supports capacity limits for both feature and object storage in visual working memory. PMID:25089739

A novel murmur-based heart sound feature extraction technique using envelope-morphological analysis

NASA Astrophysics Data System (ADS)

Yao, Hao-Dong; Ma, Jia-Li; Fu, Bin-Bin; Wang, Hai-Yang; Dong, Ming-Chui

2015-07-01

Auscultation of heart sound (HS) signals serves as an important primary approach to diagnose cardiovascular diseases (CVDs) for centuries. Confronting the intrinsic drawbacks of traditional HS auscultation, computer-aided automatic HS auscultation based on feature extraction technique has witnessed explosive development. Yet, most existing HS feature extraction methods adopt acoustic or time-frequency features which exhibit poor relationship with diagnostic information, thus restricting the performance of further interpretation and analysis. Tackling such a bottleneck problem, this paper innovatively proposes a novel murmur-based HS feature extraction method since murmurs contain massive pathological information and are regarded as the first indications of pathological occurrences of heart valves. Adapting discrete wavelet transform (DWT) and Shannon envelope, the envelope-morphological characteristics of murmurs are obtained and three features are extracted accordingly. Validated by discriminating normal HS and 5 various abnormal HS signals with extracted features, the proposed method provides an attractive candidate in automatic HS auscultation.

Loss of Mitochondrial Function Impairs Lysosomes.

PubMed

Demers-Lamarche, Julie; Guillebaud, Gérald; Tlili, Mouna; Todkar, Kiran; Bélanger, Noémie; Grondin, Martine; Nguyen, Angela P; Michel, Jennifer; Germain, Marc

2016-05-06

Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A functional magnetic resonance imaging investigation of short-term source and item memory for negative pictures.

PubMed

Mitchell, Karen J; Mather, Mara; Johnson, Marcia K; Raye, Carol L; Greene, Erich J

2006-10-02

We investigated the hypothesis that arousal recruits attention to item information, thereby disrupting working memory processes that help bind items to context. Using functional magnetic resonance imaging, we compared brain activity when participants remembered negative or neutral picture-location conjunctions (source memory) versus pictures only. Behaviorally, negative trials showed disruption of short-term source, but not picture, memory; long-term picture recognition memory was better for negative than for neutral pictures. Activity in areas involved in working memory and feature integration (precentral gyrus and its intersect with superior temporal gyrus) was attenuated on negative compared with neutral source trials relative to picture-only trials. Visual processing areas (middle occipital and lingual gyri) showed greater activity for negative than for neutral trials, especially on picture-only trials.

DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis

PubMed Central

Starokadomskyy, Petro; Gemelli, Terry; Rios, Jonathan J.; Xing, Chao; Wang, Richard C.; Li, Haiying; Pokatayev, Vladislav; Dozmorov, Igor; Khan, Shaheen; Miyata, Naoteru; Fraile, Guadalupe; Raj, Prithvi; Xu, Zhe; Xu, Zigang; Ma, Lin; Lin, Zhimiao; Wang, Huijun; Yang, Yong; Ben-Amitai, Dan; Orenstein, Naama; Mussaffi, Huda; Baselga, Eulalia; Tadini, Gianluca; Grunebaum, Eyal; Sarajlija, Adrijan; Krzewski, Konrad; Wakeland, Edward K.; Yan, Nan; de la Morena, Maria Teresa; Zinn, Andrew R.; Burstein, Ezra

2016-01-01

Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations disrupting nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts expression of POLA1, the gene encoding the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency results in increased type I interferon production. This enzyme is necessary for RNA:DNA primer synthesis during DNA replication and strikingly, POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Altogether, this work identified POLA1 as a critical regulator of the type I interferon response. PMID:27019227

Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.

PubMed

Chen, L; Yue, J; Han, X; Li, J; Hu, Y

2016-02-01

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

PubMed

Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

2015-01-01

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

Effects of Chronic REM Sleep Restriction on D1 Receptor and Related Signal Pathways in Rat Prefrontal Cortex

PubMed Central

Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

2015-01-01

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function. PMID:25793215

Rabex-5 ubiquitin ligase activity restricts Ras signaling to establish pathway homeostasis in Drosophila.

PubMed

Yan, Hua; Jahanshahi, Maryam; Horvath, Elizabeth A; Liu, Hsiu-Yu; Pfleger, Cathie M

2010-08-10

The Ras signaling pathway allows cells to translate external cues into diverse biological responses. Depending on context and the threshold reached, Ras signaling can promote growth, proliferation, differentiation, or cell survival. Failure to maintain precise control of Ras can have adverse physiological consequences. Indeed, excess Ras signaling disrupts developmental patterning and causes developmental disorders [1, 2], and in mature tissues, it can lead to cancer [3-5]. We identify Rabex-5 as a new component of Ras signaling crucial for achieving proper pathway outputs in multiple contexts in vivo. We show that Drosophila Rabex-5 restricts Ras signaling to establish organism size, wing vein pattern, and eye versus antennal fate. Rabex-5 has both Rab5 guanine nucleotide exchange factor (GEF) activity that regulates endocytic trafficking [6] and ubiquitin ligase activity [7, 8]. Surprisingly, overexpression studies demonstrate that Rabex-5 ubiquitin ligase activity, not its Rab5 GEF activity, is required to restrict wing vein specification and to suppress the eye phenotypes of oncogenic Ras expression. Furthermore, genetic interaction experiments indicate that Rabex-5 acts at the step of Ras, and tissue culture studies show that Rabex-5 promotes Ras ubiquitination. Together, these findings reveal a new mechanism for attenuating Ras signaling in vivo and suggest an important role for Rabex-5-mediated Ras ubiquitination in pathway homeostasis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Impaired visual search in rats reveals cholinergic contributions to feature binding in visuospatial attention.

PubMed

Botly, Leigh C P; De Rosa, Eve

2012-10-01

The visual search task established the feature integration theory of attention in humans and measures visuospatial attentional contributions to feature binding. We recently demonstrated that the neuromodulator acetylcholine (ACh), from the nucleus basalis magnocellularis (NBM), supports the attentional processes required for feature binding using a rat digging-based task. Additional research has demonstrated cholinergic contributions from the NBM to visuospatial attention in rats. Here, we combined these lines of evidence and employed visual search in rats to examine whether cortical cholinergic input supports visuospatial attention specifically for feature binding. We trained 18 male Long-Evans rats to perform visual search using touch screen-equipped operant chambers. Sessions comprised Feature Search (no feature binding required) and Conjunctive Search (feature binding required) trials using multiple stimulus set sizes. Following acquisition of visual search, 8 rats received bilateral NBM lesions using 192 IgG-saporin to selectively reduce cholinergic afferentation of the neocortex, which we hypothesized would selectively disrupt the visuospatial attentional processes needed for efficient conjunctive visual search. As expected, relative to sham-lesioned rats, ACh-NBM-lesioned rats took significantly longer to locate the target stimulus on Conjunctive Search, but not Feature Search trials, thus demonstrating that cholinergic contributions to visuospatial attention are important for feature binding in rats.

Rotation and scale invariant shape context registration for remote sensing images with background variations

NASA Astrophysics Data System (ADS)

Jiang, Jie; Zhang, Shumei; Cao, Shixiang

2015-01-01

Multitemporal remote sensing images generally suffer from background variations, which significantly disrupt traditional region feature and descriptor abstracts, especially between pre and postdisasters, making registration by local features unreliable. Because shapes hold relatively stable information, a rotation and scale invariant shape context based on multiscale edge features is proposed. A multiscale morphological operator is adapted to detect edges of shapes, and an equivalent difference of Gaussian scale space is built to detect local scale invariant feature points along the detected edges. Then, a rotation invariant shape context with improved distance discrimination serves as a feature descriptor. For a distance shape context, a self-adaptive threshold (SAT) distance division coordinate system is proposed, which improves the discriminative property of the feature descriptor in mid-long pixel distances from the central point while maintaining it in shorter ones. To achieve rotation invariance, the magnitude of Fourier transform in one-dimension is applied to calculate angle shape context. Finally, the residual error is evaluated after obtaining thin-plate spline transformation between reference and sensed images. Experimental results demonstrate the robustness, efficiency, and accuracy of this automatic algorithm.

Binding in visual working memory: the role of the episodic buffer.

PubMed

Baddeley, Alan D; Allen, Richard J; Hitch, Graham J

2011-05-01

The episodic buffer component of working memory is assumed to play a central role in the binding of features into objects, a process that was initially assumed to depend upon executive resources. Here, we review a program of work in which we specifically tested this assumption by studying the effects of a range of attentionally demanding concurrent tasks on the capacity to encode and retain both individual features and bound objects. We found no differential effect of concurrent load, even when the process of binding was made more demanding by separating the shape and color features spatially, temporally or across visual and auditory modalities. Bound features were however more readily disrupted by subsequent stimuli, a process we studied using a suffix paradigm. This suggested a need to assume a feature-based attentional filter followed by an object based storage process. Our results are interpreted within a modified version of the multicomponent working memory model. We also discuss work examining the role of the hippocampus in visual feature binding. Copyright © 2011 Elsevier Ltd. All rights reserved.

12q14 microdeletion associated with HMGA2 gene disruption and growth restriction.

PubMed

Alyaqoub, Fadel; Pyatt, Robert E; Bailes, Andrea; Brock, Amanda; Deeg, Carol; McKinney, Aimee; Astbury, Caroline; Reshmi, Shalini; Shane, Kate P; Thrush, Devon Lamb; Sommer, Annemarie; Gastier-Foster, Julie M

2012-11-01

The 12q14 microdeletion syndrome is a rare condition that has previously been characterized by pre- and postnatal growth restriction, proportionate short stature, failure to thrive, developmental delay, and osteopoikilosis. Previously reported microdeletions within this region have ranged in size from 1.83 to 10.12 Mb with a proposed 2.61 Mb smallest region of overlap containing the LEMD3, HMGA2, and GRIP1 genes. Here, we report on the identification of a 12q14 microdeletion in a female child presenting with proportionate short stature, failure to thrive, and speech delay. The genomic loss (minimum size 4.17 Mb, maximum size 4.21 Mb) contained 25 RefSeq genes including IRAK3, GRIP1, and the 3' portion of the HMGA2 gene. This is the first partial deletion of HMGA2 associated with the 12q14 microdeletion syndrome. This case further clarifies the association of LEMD3 deletions with the 12q14 microdeletion syndrome and provides additional support for the role of the HMGA2 gene in human growth. Copyright © 2012 Wiley Periodicals, Inc.

Reorienting Hypnosis Education.

PubMed

Alter, David S; Sugarman, Laurence Irwin

2017-01-01

The legacy model of professional clinical hypnosis training presents a restrictive frame increasingly incompatible with our evolving understanding of psychobiology, health, and care. Emerging science recognizes human experience not as disease and diagnosis, but as manifestations of individual, uniquely-endowed, adaptively self-regulating systems. Hypnosis is a particularly well-suited discipline for effecting beneficial change in this paradigm. Training in clinical hypnosis must progress from the current linearly-structured, diagnosis-based, reductionist model toward a more responsive, naturalistic, and client-centered curriculum in order to remain relevant and accessible to clinicians beginning to integrate it into their practices. To that end, this article extends Hope and Sugarman's (2015) thesis of hypnosis as a skill set for systemic perturbation and reorientation to consider what those skills may be, the principles on which they are based, and how they may be taught. Parsing a clinical vignette reveals how incorporation of novelty and uncertainty results in less restrictive and more naturalistic hypnotic encounters that, in response to client-generated cues, elicit psychophysiological plasticity. This disruptive hypnosis education and training framework extends the utility and benefit of applied clinical hypnosis.

The Impact of Sleep Deprivation on the Brain

PubMed

Trošt Bobić, Tatjana; Šečić, Ana; Zavoreo, Iris; Matijević, Valentina; Filipović, Branimir; Kolak, Željka; Bašić Kes, Vanja; Ciliga, Dubravka; Sajković, Dubravka

2016-09-01

Each sleep phase is characterized by specific chemical, cellular and anatomic events of vital importance for normal neural functioning. Different forms of sleep deprivation may lead to a decline of cognitive functions in individuals. Studies in this field make a distinction between total sleep deprivation, chronic sleep restriction, and the situation of sleep disruption. Investigations covering the acute effects of sleep deprivation on the brain show that the discovered behavioral deficits in most cases regenerate after two nights of complete sleep. However, some studies done on mice emphasize the possible chronic effects of long-term sleep deprivation or chronic restriction on the occurrence of neurodegenerative diseases such as Alzheimer’s disease and dementia. In order to better understand the acute and chronic effects of sleep loss, the mechanisms of neural adaptation in the situations of insufficient sleep need to be further investigated. Future integrative research on the impact of sleep deprivation on neural functioning measured through the macro level of cognitive functions and the micro molecular and cell level could contribute to more accurate conclusions about the basic cellular mechanisms responsible for the detected behavioral deficits occurring due to sleep deprivation.

Combretastatin A-4 derived 5-(1-methyl-4-phenyl-imidazol-5-yl)indoles with superior cytotoxic and anti-vascular effects on chemoresistant cancer cells and tumors.

PubMed

Mahal, Katharina; Biersack, Bernhard; Schruefer, Sebastian; Resch, Marcus; Ficner, Ralf; Schobert, Rainer; Mueller, Thomas

2016-08-08

5-(1-Methyl-4-phenyl-imidazol-5-yl)indoles 5 were prepared and tested as analogs of the natural vascular-disrupting agent combretastatin A-4 (CA-4). The 3-bromo-4,5-dimethoxyphenyl derivative 5c was far more active than CA-4 with low nanomolar IC50 concentrations against multidrug-resistant KB-V1/Vbl cervix and MCF-7/Topo mamma carcinoma cells, and also against CA-4-resistant HT-29 colon carcinoma cells. While not interfering markedly with the polymerization of tubulin in vitro, indole 5c completely disrupted the microtubule cytoskeleton of cancer cells at low concentrations. It also destroyed real blood vessels, both in the chorioallantoic membrane (CAM) of fertilized chicken eggs and within tumor xenografts in mice, without harming embryo or mouse, respectively. Indole 5c was less toxic than CA-4 to endothelial cells, fibroblasts, and cardiomyocytes. In highly vascularized xenograft tumors 5c induced distinct discolorations and histological features typical of vascular-disrupting agents, such as disrupted vessel structures, hemorrhages, and extensive necrosis. In a first preliminary therapy trial, indole 5c retarded the growth of resistant xenograft tumors in mice. © 2016 Elsevier Science Ltd. All rights reserved. Copyright © 2016 Elsevier Masson SAS. All rights reserved.