Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

PubMed Central

Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

2013-01-01

Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

Relating Worry and Executive Functioning During Childhood: The Moderating Role of Age.

PubMed

Geronimi, Elena M C; Patterson, Heather L; Woodruff-Borden, Janet

2016-06-01

The associations between worry and executive functioning across development have not been previously explored. Examining the interrelationships between these variables in childhood may further elucidate the cognitive nature of worry as well as its developmental course. Hypotheses predicted that difficulties with executive functioning would correlate with child worry; based on extant literature, age-related hypotheses were proposed for particular aspects of executive functioning. Children (N = 130) participated in the present study. Difficulties with executive functioning and child worry were assessed. Results demonstrated that each executive functioning subscale correlated with worry. The relations between worry and several facets of executive functioning were no longer significant at older ages, while the relations between worry and the facets of inhibition, shifting, and emotional control did not demonstrate age-related interaction effects. Overall, the findings suggest that worry is associated with executive functioning at young ages and that this association takes distinct forms during different childhood stages.

Finding a common path: predicting gene function using inferred evolutionary trees.

PubMed

Reynolds, Kimberly A

2014-07-14

Reporting in Cell, Li and colleagues (2014) describe an innovative method to functionally classify genes using evolutionary information. This approach demonstrates broad utility for eukaryotic gene annotation and suggests an intriguing new decomposition of pathways and complexes into evolutionarily conserved modules. Copyright © 2014 Elsevier Inc. All rights reserved.

N-Functionalized MXenes: ultrahigh carrier mobility and multifunctional properties.

PubMed

Shao, Yangfan; Zhang, Fang; Shi, Xingqiang; Pan, Hui

2017-11-01

Two dimensional (2D) nanomaterials have demonstrated huge potential in wide applications from nanodevices to energy harvesting/storage. In this work, we propose a new class of 2D monolayers, nitrogen-functionalized MXenes (Nb 2 CN 2 and Ta 2 CN 2 ), based on density-functional theory (DFT). We find that these monolayers are direct semiconductors with near linear energy dispersions at the Γ point. M 2 CN 2 monolayers have significant small effective mass and show an ultra-high mobility of up to 10 6 cm 2 V -1 s -1 . We show that the electronic structures of the M 2 CN 2 monolayers can be easily controlled by biaxial and uniaxial strains. Importantly, the carrier mobility and direct band gap can be dramatically increased within a certain range of strain. A direct-indirect band gap transition can be triggered and the band gap can be tuned under strain. The tunable electronic properties are attributed to the structural changes and charge redistribution under stain. Our findings demonstrate that N-functionalized MXenes are promising materials for nanodevices with high speed and low power.

B cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen

PubMed Central

Weinstein, Jason S.; Bertino, Sarah A.; Hernandez, Sairy G.; Poholek, Amanda C.; Teplitzky, Taylor B.; Nowyhed, Heba N.; Craft, Joe

2014-01-01

B cells are required for follicular helper T (Tfh) cell development, as is the ligand for ICOS (ICOS-L); however, the separable contributions of Ag and ICOS-L delivery by cognate B cells to Tfh-cell development and function are unknown. We find that Tfh-cell and germinal center differentiation are dependent upon cognate B-cell display of ICOS-L, but only when Ag presentation by the latter is limiting, with the requirement for B-cell expression of ICOS-L overcome by robust Ag delivery. These findings demonstrate that Ag-specific B cells provide different, yet compensatory signals for Tfh-cell differentiation, while reconciling conflicting data indicating a requirement for ICOS-L expression on cognate B cells for Tfh-cell development with those demonstrating this requirement could be bypassed in lieu of that tendered by non-cognate B cells. Our findings clarify the separable roles of delivery of Ag and ICOS-L by cognate B cells for Tfh-cell maturation and function, and have implications for using therapeutic ICOS blockade in settings of abundantly available Ag, such as in systemic autoimmunity. PMID:24610013

Measurement of complete and continuous Wigner functions for discrete atomic systems

NASA Astrophysics Data System (ADS)

Tian, Yali; Wang, Zhihui; Zhang, Pengfei; Li, Gang; Li, Jie; Zhang, Tiancai

2018-01-01

We measure complete and continuous Wigner functions of a two-level cesium atom in both a nearly pure state and highly mixed states. We apply the method [T. Tilma et al., Phys. Rev. Lett. 117, 180401 (2016), 10.1103/PhysRevLett.117.180401] of strictly constructing continuous Wigner functions for qubit or spin systems. We find that the Wigner function of all pure states of a qubit has negative regions and the negativity completely vanishes when the purity of an arbitrary mixed state is less than 2/3 . We experimentally demonstrate these findings using a single cesium atom confined in an optical dipole trap, which undergoes a nearly pure dephasing process. Our method can be applied straightforwardly to multi-atom systems for measuring the Wigner function of their collective spin state.

Is Work-Related Rumination Associated with Deficits in Executive Functioning?

PubMed Central

Cropley, Mark; Zijlstra, Fred R. H.; Querstret, Dawn; Beck, Sarah

2016-01-01

Work-related rumination, that is, perseverative thinking about work during leisure time, has been associated with a range of negative health and wellbeing issues. The present paper examined the association between work-related rumination and cognitive processes centerd around the theoretical construct of executive functioning. Executive functioning is an umbrella term for high level cognitive processes such as planning, working memory, inhibition, mental flexibility; and it underlies how people manage and regulate their goal directed behavior. Three studies are reported. Study I, reports the results of a cross-sectional study of 240 employees, and demonstrates significant correlations between work-related rumination and three proxy measures of executive functioning: cognitive failures (0.33), cognitive flexibility (-0.24), and situational awareness at work (-0.28). Study II (n = 939), expands on the findings from study 1 and demonstrates that workers reporting medium and high work-related rumination were 2.8 and 5 times, respectively, more likely to report cognitive failures relative to low ruminators. High ruminators also demonstrated greater difficulties with ‘lapses of attention’ (OR = 4.8), ‘lack of focus of attention’ (OR = 3.4), and ‘absent mindedness’ (OR = 4.3). The final study, examined the association between work-related rumination and executive functioning using interview data from 2460 full time workers. Workers were divided into tertiles low, medium, and high. The findings showed that high work-related rumination was associated with deficits in starting (OR = 2.3) and finishing projects (OR = 2.4), fidgeting (OR = 1.9), memory (OR = 2.2), pursuing tasks in order (OR = 1.8), and feeling compelled to do things (OR = 2.0). It was argued that work-related rumination may not be related to work demands per se, but appears to be an executive functioning/control issue. Such findings are important for the design and delivery of intervention programes aimed at helping people to switch off and unwind from work. PMID:27746759

Is Work-Related Rumination Associated with Deficits in Executive Functioning?

PubMed

Cropley, Mark; Zijlstra, Fred R H; Querstret, Dawn; Beck, Sarah

2016-01-01

Work-related rumination, that is, perseverative thinking about work during leisure time, has been associated with a range of negative health and wellbeing issues. The present paper examined the association between work-related rumination and cognitive processes centerd around the theoretical construct of executive functioning. Executive functioning is an umbrella term for high level cognitive processes such as planning, working memory, inhibition, mental flexibility; and it underlies how people manage and regulate their goal directed behavior. Three studies are reported. Study I, reports the results of a cross-sectional study of 240 employees, and demonstrates significant correlations between work-related rumination and three proxy measures of executive functioning: cognitive failures (0.33), cognitive flexibility (-0.24), and situational awareness at work (-0.28). Study II ( n = 939), expands on the findings from study 1 and demonstrates that workers reporting medium and high work-related rumination were 2.8 and 5 times, respectively, more likely to report cognitive failures relative to low ruminators. High ruminators also demonstrated greater difficulties with 'lapses of attention' (OR = 4.8), 'lack of focus of attention' (OR = 3.4), and 'absent mindedness' (OR = 4.3). The final study, examined the association between work-related rumination and executive functioning using interview data from 2460 full time workers. Workers were divided into tertiles low, medium, and high. The findings showed that high work-related rumination was associated with deficits in starting (OR = 2.3) and finishing projects (OR = 2.4), fidgeting (OR = 1.9), memory (OR = 2.2), pursuing tasks in order (OR = 1.8), and feeling compelled to do things (OR = 2.0). It was argued that work-related rumination may not be related to work demands per se , but appears to be an executive functioning/control issue. Such findings are important for the design and delivery of intervention programes aimed at helping people to switch off and unwind from work.

An essential cell-autonomous role for hepcidin in cardiac iron homeostasis

PubMed Central

Lakhal-Littleton, Samira; Wolna, Magda; Chung, Yu Jin; Christian, Helen C; Heather, Lisa C; Brescia, Marcella; Ball, Vicky; Diaz, Rebeca; Santos, Ana; Biggs, Daniel; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A

2016-01-01

Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin. We find that while both models maintain normal systemic iron homeostasis, they nonetheless develop fatal contractile and metabolic dysfunction as a consequence of cardiomyocyte iron deficiency. These findings are the first demonstration of a cell-autonomous role for hepcidin in iron homeostasis. They raise the possibility that such function may also be important in other tissues that express both hepcidin and ferroportin, such as the kidney and the brain. DOI: http://dx.doi.org/10.7554/eLife.19804.001 PMID:27897970

Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery.

PubMed

Mei, Feng; Lehmann-Horn, Klaus; Shen, Yun-An A; Rankin, Kelsey A; Stebbins, Karin J; Lorrain, Daniel S; Pekarek, Kara; A Sagan, Sharon; Xiao, Lan; Teuscher, Cory; von Büdingen, H-Christian; Wess, Jürgen; Lawrence, J Josh; Green, Ari J; Fancy, Stephen Pj; Zamvil, Scott S; Chan, Jonah R

2016-09-27

Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination.

Does neuropsychological performance in OCD relate to different symptoms? A meta-analysis comparing the symmetry and obsessing dimensions.

PubMed

Bragdon, Laura B; Gibb, Brandon E; Coles, Meredith E

2018-06-19

Investigations of neuropsychological functioning in obsessive-compulsive disorder (OCD) have produced mixed results for deficits in executive functioning (EF), attention, and memory. One potential explanation for varied findings may relate to the heterogeneity of symptom presentations, and different clinical or neurobiological characteristics may underlie these different symptoms. We investigated differences in neuropsychological functioning between two symptoms groups, obsessing/checking (O/C) and symmetry/ordering (S/O), based on data suggesting an association with different motivations: harm avoidance and incompleteness, respectively. Ten studies (with 628 patients) were included and each investigation assessed at least one of 14 neuropsychological domains. The S/O domain demonstrated small, negative correlations with overall neuropsychological functioning, performance in EF, memory, visuospatial ability, cognitive flexibility, and verbal working memory. O/C symptoms demonstrated small, negative correlations with memory and verbal memory performance. A comparison of functioning between symptom groups identified large effect sizes showing that the S/O dimension was more strongly related to poorer neuropsychological performance overall, and in the domains of attention, visuospatial ability, and the subdomain of verbal working memory. Findings support existing evidence suggesting that different OCD symptoms, and their associated core motivations, relate to unique patterns of neuropsychological functioning, and, potentially dysfunction in different neural circuits. © 2018 Wiley Periodicals, Inc.

Effects of a Sedentary Intervention on Cognitive Function.

PubMed

Edwards, Meghan K; Loprinzi, Paul D

2018-03-01

To examine the effects of a free-living, sedentary-inducing intervention on cognitive function. Randomized controlled, parallel group intervention. University campus. Thirty-three young adults (n = 23 intervention; n = 10 control). The intervention group was asked to eliminate all exercise and minimize steps to ≤5000 steps/day for 1 week, whereas the control group was asked to continue normal physical activity (PA) levels for 1 week. Both groups completed a series of 8 cognitive function assessments (assessing multiple parameters of cognition) preintervention and immediately postintervention. The intervention group was asked to resume normal PA levels for 1 week postintervention and completed the cognitive assessments for a third time at 2 weeks postintervention. Split-plot repeated-measures analysis of variance. The results of our statistical analyses showed that the group × time interaction effect was not significant ( P > .05) for any of the evaluated cognitive parameters. These findings demonstrate the need for future experimental investigations of sedentary behavior to better understand its effects on cognitive function. However, although previous work has demonstrated favorable effects of acute and chronic PA on cognitive function, our findings suggest that a 1-week period of reduced PA does not detrimentally affect cognitive function, which may have encouraging implications for individuals going through a temporary relapse in PA.

Is the self a higher-order or fundamental function of the brain? The "basis model of self-specificity" and its encoding by the brain's spontaneous activity.

PubMed

Northoff, Georg

2016-01-01

What is the self? This is a question that has long been discussed in (Western) philosophy where the self is traditionally conceived a higher-order function at the apex or pinnacle of all functions. This tradition has been transferred to recent neuroscience where the self is often considered to be a higher-order cognitive function reflected in memory and other high-level judgements. However, other lines of research demonstrate a close and intimate relationship between self-specificity and more basic functions like perceptions, emotions and reward. This paper focuses on the relationship between self-specificity and other basic functions relating to emotions, reward and perception. I propose the basis model that conceives self-specificity as a fundamental feature of the brain's spontaneous activity. This is supported by recent findings showing rest-self overlap in midline regions as well as findings demonstrating that the resting state can predict subsequent degrees of self-specificity. I conclude that such self-specificity in the brain's spontaneous activity may be central in linking the self to either internal or external stimuli. This may also provide the basis for coding the self as subject in relation to internal (i.e., self-consciousness) or external (i.e., phenomenal consciousness) mental events.

An Example of the Estimation and Display of a Smoothly Varying Function of Time and Space--The Incidence of the Disease Mumps.

ERIC Educational Resources Information Center

Eddy, William F.; Mockus, Audris

1994-01-01

Describes animation algorithms for creating smooth functions of time- and space-varying phenomenon. The incidence of the disease mumps from 1968-88 in the United States is used to demonstrate the algorithms. Figures that illustrate the findings are included. (14 references) (KRN)

Unidirectional transmission using array of zero-refractive-index metamaterials

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

Fu, Yangyang; Xu, Lin; Hong Hang, Zhi

2014-05-12

In this Letter, we find that high efficient unidirectional transmission occurs for an array of prisms made of zero-refractive-index metamaterials. As a specific demonstration, we further design the device using Dirac-cone-like photonic crystals. The device can function for a broadband of spectrum. Numerical simulations are performed to verify the one-way wave functionality.

Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex.

PubMed

Stehberg, Jimmy; Dang, Phat T; Frostig, Ron D

2014-01-01

Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed.

Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

PubMed Central

Stehberg, Jimmy; Dang, Phat T.; Frostig, Ron D.

2014-01-01

Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed. PMID:25309339

Age and amyloid-related alterations in default network habituation to stimulus repetition

PubMed Central

Vannini, Patrizia; Hedden, Trey; Becker, John A.; Sullivan, Caroline; Putcha, Deepti; Rentz, Dorene; Johnson, Keith A.; Sperling, Reisa. A.

2011-01-01

The neural networks supporting encoding of new information are thought to decline with age, although mnemonic techniques such as repetition may enhance performance in older individuals. Accumulation of amyloid-β, one hallmark pathology of Alzheimer’s disease (AD), may contribute to functional alterations in memory networks measured with functional magnetic resonance imaging (fMRI) prior to onset of cognitive impairment. We investigated the effects of age and amyloid burden on fMRI activity in the default network and hippocampus during repetitive encoding. Older individuals, particularly those with high amyloid burden, demonstrated decreased task-induced deactivation in the posteromedial cortices during initial stimulus presentation and failed to modulate fMRI activity in response to repeated trials, whereas young subjects demonstrated a stepwise decrease in deactivation with repetition. The hippocampus demonstrated similar patterns across the groups, showing task-induced activity that decreased in response to repetition. These findings demonstrate that age and amyloid have dissociable functional effects on specific nodes within a distributed memory network, and suggest that functional brain changes may begin far in advance of symptomatic AD. PMID:21334099

A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites.

PubMed

Ghaedi, Hamid; Bastami, Milad; Jahani, Mohammad Mehdi; Alipoor, Behnam; Tabasinezhad, Maryam; Ghaderi, Omar; Nariman-Saleh-Fam, Ziba; Mirfakhraie, Reza; Movafagh, Abolfazl; Omrani, Mir Davood; Masotti, Andrea

2016-06-01

The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.

Omics Data Complementarity Underlines Functional Cross-Communication in Yeast.

PubMed

Malod-Dognin, Noël; Pržulj, Nataša

2017-06-10

Mapping the complete functional layout of a cell and understanding the cross-talk between different processes are fundamental challenges. They elude us because of the incompleteness and noisiness of molecular data and because of the computational intractability of finding the exact answer. We perform a simple integration of three types of baker's yeast omics data to elucidate the functional organization and lines of cross-functional communication. We examine protein-protein interaction (PPI), co-expression (COEX) and genetic interaction (GI) data, and explore their relationship with the gold standard of functional organization, the Gene Ontology (GO). We utilize a simple framework that identifies functional cross-communication lines in each of the three data types, in GO, and collectively in the integrated model of the three omics data types; we present each of them in our new Functional Organization Map (FOM) model. We compare the FOMs of the three omics datasets with the FOM of GO and find that GI is in best agreement with GO, followed COEX and PPI. We integrate the three FOMs into a unified FOM and find that it is in better agreement with the FOM of GO than those of any omics dataset alone, demonstrating functional complementarity of different omics data.

An evaluation of health information technology outsourcing success.

PubMed

Malovec, Shannon N; Borycki, Elizabeth M; Kushniruk, Andre W

2015-01-01

Outsourcing involves contracting out functions performed by an organization to another organization. Many healthcare organizations are exploring outsourcing as a way to address demands for health information technology (HIT). This study researches the success of outsourcing in the health informatics industry in Canada. The study is designed to help understand whether outsourcing four functions of HIT (i.e. development, implementation, operations, and maintenance) can prove successful for an organization. Findings demonstrate that outsourcing these four functions occurs in Canada; however, the research from the semi-structured interviews finds that operations and maintenance may be more commonly outsourced in Canada, over development and implementation functions. Despite this, findings from this research suggest that outsourcing development and implementation may offer more benefits and fewer challenges than outsourcing operations and maintenance. The research also finds that there can be benefits of outsourcing, such as gaining access to expertise and improving service levels. A weakness of outsourcing may be that internal knowledge is lost and having to manage the change required from outsourcing. The study proposes that there are many factors that need to be considered when outsourcing to ensure it is successful.

The Mediating Role of Posttraumatic Stress Disorder with Tendency to Forgive, Social Support, and Psychosocial Functioning of Terror Survivors.

PubMed

Weinberg, Michael

2018-06-12

The study reported in this article examined the relationship between psychosocial functioning and tendency to forgive, social support, and posttraumatic stress disorder (PTSD) symptoms of terror survivors (N = 108). Structural equation modeling was used to examine whether PTSD symptoms mediated the association between tendency to forgive, social support, and psychosocial functioning. The findings demonstrated that the association between tendency to forgive and psychosocial functioning was mediated exclusively by PTSD symptoms, whereas the association between social support and psychosocial functioning was partially mediated by PTSD symptoms. The study reinforces the importance of addressing trauma survivors' psychosocial functioning as an emotional state associated with tendency to forgive, social support, and PTSD symptoms. In addition, the findings suggest that when treating trauma survivors, therapists should be aware of PTSD not only as an emotional consequence of trauma, but also as a mediator of numerous emotional and cognitive coping mechanisms.

Further studies of crania from ancient northern Africa: an analysis of crania from first dynasty Egyptian tombs, using discriminant functions.

PubMed

Keita, S O

1992-03-01

An analysis of First Dynasty crania from Abydos was undertaken using multiple discriminant functions. The results demonstrate greater affinity with Upper Nile Valley patterns, but also suggest change from earlier craniometric trends. Gene flow and movement of northern officials to the important southern city may explain the findings.

Excited-State Effective Masses in Lattice QCD

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

George Fleming, Saul Cohen, Huey-Wen Lin

2009-10-01

We apply black-box methods, i.e. where the performance of the method does not depend upon initial guesses, to extract excited-state energies from Euclidean-time hadron correlation functions. In particular, we extend the widely used effective-mass method to incorporate multiple correlation functions and produce effective mass estimates for multiple excited states. In general, these excited-state effective masses will be determined by finding the roots of some polynomial. We demonstrate the method using sample lattice data to determine excited-state energies of the nucleon and compare the results to other energy-level finding techniques.

Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice

PubMed Central

Johnson, Matthew L; Lalia, Antigoni Z; Dasari, Surendra; Pallauf, Maximilian; Fitch, Mark; Hellerstein, Marc K; Lanza, Ian R

2015-01-01

Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age-related declines in physical function. Early evidence suggests that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age-related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large-scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post-translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age-related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti-inflammatory properties of n-3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti-inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n-3 PUFAs. PMID:26010060

Reduced hippocampal functional connectivity in Alzheimer disease.

PubMed

Allen, Greg; Barnard, Holly; McColl, Roderick; Hester, Andrea L; Fields, Julie A; Weiner, Myron F; Ringe, Wendy K; Lipton, Anne M; Brooker, Matthew; McDonald, Elizabeth; Rubin, Craig D; Cullum, C Munro

2007-10-01

To determine if functional connectivity of the hippocampus is reduced in patients with Alzheimer disease. Functional connectivity magnetic resonance imaging was used to investigate coherence in the magnetic resonance signal between the hippocampus and all other regions of the brain. Eight patients with probable Alzheimer disease and 8 healthy volunteers. Control subjects showed hippocampal functional connectivity with diffuse cortical, subcortical, and cerebellar sites, while patients demonstrated markedly reduced functional connectivity, including an absence of connectivity with the frontal lobes. These findings suggest a functional disconnection between the hippocampus and other brain regions in patients with Alzheimer disease.

Short-Term Memory for Space and Time Flexibly Recruit Complementary Sensory-Biased Frontal Lobe Attention Networks.

PubMed

Michalka, Samantha W; Kong, Lingqiang; Rosen, Maya L; Shinn-Cunningham, Barbara G; Somers, David C

2015-08-19

The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and auditory attention networks in the frontal lobe, independent of sensory modality. These findings not only demonstrate that both sensory modality and information domain influence frontal lobe functional organization, they also demonstrate that spatial processing co-localizes with visual processing and that temporal processing co-localizes with auditory processing in lateral frontal cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

Improving late life depression and cognitive control through the use of therapeutic video game technology: A proof-of-concept randomized trial.

PubMed

Anguera, Joaquin A; Gunning, Faith M; Areán, Patricia A

2017-06-01

Existing treatments for depression are known to have only modest effects, are insufficiently targeted, and are inconsistently utilized, particularly in older adults. Indeed, older adults with impaired cognitive control networks tend to demonstrate poor response to a majority of existing depression interventions. Cognitive control interventions delivered using entertainment software have the potential to not only target the underlying cerebral dysfunction associated with depression, but to do so in a manner that is engaging and engenders adherence to treatment protocol. In this proof-of-concept trial (Clinicaltrials.gov #: NCT02229188), individuals with late life depression (LLD) (22; 60+ years old) were randomized to either problem solving therapy (PST, n = 10) or a neurobiologically inspired digital platform designed to enhance cognitive control faculties (Project: EVO™, n = 12). Given the overlapping functional neuroanatomy of mood disturbances and executive dysfunction, we explored the impact of an intervention targeting cognitive control abilities, functional disability, and mood in older adults suffering from LLD, and how those outcomes compare to a therapeutic gold standard. EVO participants demonstrated similar improvements in mood and self-reported function after 4 weeks of treatment to PST participants. The EVO participants also showed generalization to untrained measures of working memory and attention, as well as negativity bias, a finding not evident in the PST condition. Individuals assigned to EVO demonstrated 100% adherence. This study provides preliminary findings that this therapeutic video game targeting cognitive control deficits may be an efficacious LLD intervention. Future research is needed to confirm these findings. © 2016 Wiley Periodicals, Inc.

Bioinformatic analysis of Msx1 and Msx2 involved in craniofacial development.

PubMed

Dai, Jiewen; Mou, Zhifang; Shen, Shunyao; Dong, Yuefu; Yang, Tong; Shen, Steve Guofang

2014-01-01

Msx1 and Msx2 were revealed to be candidate genes for some craniofacial deformities, such as cleft lip with/without cleft palate (CL/P) and craniosynostosis. Many other genes were demonstrated to have a cross-talk with MSX genes in causing these defects. However, there is no systematic evaluation for these MSX gene-related factors. In this study, we performed systematic bioinformatic analysis for MSX genes by combining using GeneDecks, DAVID, and STRING database, and the results showed that there were numerous genes related to MSX genes, such as Irf6, TP63, Dlx2, Dlx5, Pax3, Pax9, Bmp4, Tgf-beta2, and Tgf-beta3 that have been demonstrated to be involved in CL/P, and Fgfr2, Fgfr1, Fgfr3, and Twist1 that were involved in craniosynostosis. Many of these genes could be enriched into different gene groups involved in different signaling ways, different craniofacial deformities, and different biological process. These findings could make us analyze the function of MSX gens in a gene network. In addition, our findings showed that Sumo, a novel gene whose polymorphisms were demonstrated to be associated with nonsyndromic CL/P by genome-wide association study, has protein-protein interaction with MSX1, which may offer us an alternative method to perform bioinformatic analysis for genes found by genome-wide association study and can make us predict the disrupted protein function due to the mutation in a gene DNA sequence. These findings may guide us to perform further functional studies in the future.

Finding Multiple Internal Rates of Return for a Project with Non-Conventional Cash Flows: Utilizing Popular Financial/Graphing Calculators and Spreadsheet Software

ERIC Educational Resources Information Center

Chen, Jeng-Hong

2008-01-01

This study demonstrates that a popular graphing calculator among students, TI-83 Plus, has a powerful function to draw the NPV profile and find the accurate multiple IRRs for a project with non-conventional cash flows. However, finance textbooks or related supplementary materials do not provide students instructions for this part. The detailed…

Dynamic Modulation of Human Motor Activity When Observing Actions

PubMed Central

Press, Clare; Cook, Jennifer; Blakemore, Sarah-Jayne; Kilner, James

2012-01-01

Previous studies have demonstrated that when we observe somebody else executing an action many areas of our own motor systems are active. It has been argued that these motor activations are evidence that we motorically simulate observed actions; this motoric simulation may support various functions such as imitation and action understanding. However, whether motoric simulation is indeed the function of motor activations during action observation is controversial, due to inconsistency in findings. Previous studies have demonstrated dynamic modulations in motor activity when we execute actions. Therefore, if we do motorically simulate observed actions, our motor systems should also be modulated dynamically, and in a corresponding fashion, during action observation. Using magnetoencephalography, we recorded the cortical activity of human participants while they observed actions performed by another person. Here, we show that activity in the human motor system is indeed modulated dynamically during action observation. The finding that activity in the motor system is modulated dynamically when observing actions can explain why studies of action observation using functional magnetic resonance imaging have reported conflicting results, and is consistent with the hypothesis that we motorically simulate observed actions. PMID:21414901

Further evidence that similar principles govern recall from episodic and semantic memory: the Canadian prime ministerial serial position function.

PubMed

Neath, Ian; Saint-Aubin, Jean

2011-06-01

The serial position function, with its characteristic primacy and recency effects, is one of the most ubiquitous findings in episodic memory tasks. In contrast, there are only two demonstrations of such functions in tasks thought to tap semantic memory. Here, we provide a third demonstration, showing that free recall of the prime ministers of Canada also results in a serial position function. Scale Independent Memory, Perception, and Learning (SIMPLE), a local distinctiveness model of memory that was designed to account for serial position effects in episodic memory, fit the data. According to SIMPLE, serial position functions observed in episodic and semantic memory all reflect the relative distinctiveness principle: items will be well remembered to the extent that they are more distinct than competing items at the time of retrieval. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Calibrated work function mapping by Kelvin probe force microscopy

NASA Astrophysics Data System (ADS)

Fernández Garrillo, Pablo A.; Grévin, Benjamin; Chevalier, Nicolas; Borowik, Łukasz

2018-04-01

We propose and demonstrate the implementation of an alternative work function tip calibration procedure for Kelvin probe force microscopy under ultrahigh vacuum, using monocrystalline metallic materials with known crystallographic orientation as reference samples, instead of the often used highly oriented pyrolytic graphite calibration sample. The implementation of this protocol allows the acquisition of absolute and reproducible work function values, with an improved uncertainty with respect to unprepared highly oriented pyrolytic graphite-based protocols. The developed protocol allows the local investigation of absolute work function values over nanostructured samples and can be implemented in electronic structures and devices characterization as demonstrated over a nanostructured semiconductor sample presenting Al0.7Ga0.3As and GaAs layers with variable thickness. Additionally, using our protocol we find that the work function of annealed highly oriented pyrolytic graphite is equal to 4.6 ± 0.03 eV.

Novel transform for image description and compression with implementation by neural architectures

NASA Astrophysics Data System (ADS)

Ben-Arie, Jezekiel; Rao, Raghunath K.

1991-10-01

A general method for signal representation using nonorthogonal basis functions that are composed of Gaussians are described. The Gaussians can be combined into groups with predetermined configuration that can approximate any desired basis function. The same configuration at different scales forms a set of self-similar wavelets. The general scheme is demonstrated by representing a natural signal employing an arbitrary basis function. The basic methodology is demonstrated by two novel schemes for efficient representation of 1-D and 2- D signals using Gaussian basis functions (BFs). Special methods are required here since the Gaussian functions are nonorthogonal. The first method employs a paradigm of maximum energy reduction interlaced with the A* heuristic search. The second method uses an adaptive lattice system to find the minimum-squared error of the BFs onto the signal, and a lateral-vertical suppression network to select the most efficient representation in terms of data compression.

Short-term music training enhances verbal intelligence and executive function.

PubMed

Moreno, Sylvain; Bialystok, Ellen; Barac, Raluca; Schellenberg, E Glenn; Cepeda, Nicholas J; Chau, Tom

2011-11-01

Researchers have designed training methods that can be used to improve mental health and to test the efficacy of education programs. However, few studies have demonstrated broad transfer from such training to performance on untrained cognitive activities. Here we report the effects of two interactive computerized training programs developed for preschool children: one for music and one for visual art. After only 20 days of training, only children in the music group exhibited enhanced performance on a measure of verbal intelligence, with 90% of the sample showing this improvement. These improvements in verbal intelligence were positively correlated with changes in functional brain plasticity during an executive-function task. Our findings demonstrate that transfer of a high-level cognitive skill is possible in early childhood.

Intraindividual variability in physical and emotional functioning: comparison of adults with traumatic brain injuries and healthy adults.

PubMed

Burton, Catherine L; Hultsch, David F; Strauss, Esther; Hunter, Michael A

2002-08-01

Recent research has shown that individuals with certain neurological conditions demonstrate greater intraindividual variability on cognitive tasks compared to healthy controls. The present study investigated intraindividual variability in the domains of physical functioning and affect/stress in three groups: adults with mild head injuries, adults with moderate/severe head injuries, and healthy adults. Participants were assessed on 10 occasions and results indicated that (a) individuals with head injuries demonstrated greater variability in dominant finger dexterity and right grip strength than the healthy controls; (b) increased variability tended to be associated with poorer performance/report both within and across tasks; and (c) increased variability on one task was associated with increased variability on other tasks. The findings suggest that increased variability in physical function, as well as cognitive function, represents an indicator of neurological compromise.

Stability of the DSM-5 Section III pathological personality traits and their longitudinal associations with psychosocial functioning in personality disordered individuals.

PubMed

Wright, Aidan G C; Calabrese, William R; Rudick, Monica M; Yam, Wern How; Zelazny, Kerry; Williams, Trevor F; Rotterman, Jane H; Simms, Leonard J

2015-02-01

This study was conducted to establish (a) the stability of the DSM-5 Section III personality disorder (PD) traits, (b) whether these traits predict future psychosocial functioning, and (c) whether changes in traits track with changes in psychosocial functioning across time. Ninety-three outpatients (61% female) diagnosed with at least 1 PD completed patient-report measures at 2 time-points (M time between assessments = 1.44 years), including the Personality Inventory for the DSM-5 and several measures of psychosocial functioning. Effect sizes of rank-order and mean-level change were calculated. In addition, Time 1 traits were used to predict functioning measures at Time 2. Finally, latent change score models were estimated for DSM-5 Section III traits and functioning measures, and correlations among latent change scores were calculated to establish the relationship between change in traits and functional outcomes. Findings demonstrated that the DSM-5 Section III traits were highly stable in terms of normative (i.e., mean-level) change and rank-order stability over the course of the study. Furthermore, traits prospectively predicted psychosocial functioning. However, at the individual level traits and functioning were not entirely static over the study, and change in individuals' functioning tracked with changes in trait levels. These findings demonstrate that the DSM-5 Section III traits are highly stable consistent with the definition of PD, prospectively predictive of psychosocial functioning, and are dynamically associated with functioning over time. This study provides important evidence in support of the DSM-5 Section III PD model. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Evidence-Based Annotation of Gene Function in Shewanella oneidensis MR-1 Using Genome-Wide Fitness Profiling across 121 Conditions

PubMed Central

Deutschbauer, Adam; Price, Morgan N.; Wetmore, Kelly M.; Shao, Wenjun; Baumohl, Jason K.; Xu, Zhuchen; Nguyen, Michelle; Tamse, Raquel; Davis, Ronald W.; Arkin, Adam P.

2011-01-01

Most genes in bacteria are experimentally uncharacterized and cannot be annotated with a specific function. Given the great diversity of bacteria and the ease of genome sequencing, high-throughput approaches to identify gene function experimentally are needed. Here, we use pools of tagged transposon mutants in the metal-reducing bacterium Shewanella oneidensis MR-1 to probe the mutant fitness of 3,355 genes in 121 diverse conditions including different growth substrates, alternative electron acceptors, stresses, and motility. We find that 2,350 genes have a pattern of fitness that is significantly different from random and 1,230 of these genes (37% of our total assayed genes) have enough signal to show strong biological correlations. We find that genes in all functional categories have phenotypes, including hundreds of hypotheticals, and that potentially redundant genes (over 50% amino acid identity to another gene in the genome) are also likely to have distinct phenotypes. Using fitness patterns, we were able to propose specific molecular functions for 40 genes or operons that lacked specific annotations or had incomplete annotations. In one example, we demonstrate that the previously hypothetical gene SO_3749 encodes a functional acetylornithine deacetylase, thus filling a missing step in S. oneidensis metabolism. Additionally, we demonstrate that the orphan histidine kinase SO_2742 and orphan response regulator SO_2648 form a signal transduction pathway that activates expression of acetyl-CoA synthase and is required for S. oneidensis to grow on acetate as a carbon source. Lastly, we demonstrate that gene expression and mutant fitness are poorly correlated and that mutant fitness generates more confident predictions of gene function than does gene expression. The approach described here can be applied generally to create large-scale gene-phenotype maps for evidence-based annotation of gene function in prokaryotes. PMID:22125499

Dexamethasone-Loaded, PEGylated, Vertically Aligned, Multiwalled Carbon Nanotubes for Potential Ischemic Stroke Intervention.

PubMed

Komane, Patrick P; Kumar, Pradeep; Marimuthu, Thashree; Toit, Lisa C du; Kondiah, Pierre P D; Choonara, Yahya E; Pillay, Viness

2018-06-10

The complete synthesis, optimization, purification, functionalization and evaluation of vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) was reported for potential application in dexamethasone delivery to the ischemic brain tissue. The conditions for high yield were optimized and carbon nanotubes functionalized and PEGylated prior to dexamethasone loading. Morphological changes were confirmed by SEM and TEM. Addition of functional groups to MWCNTs was demonstrated by FTIR. Thermal stability reduced following MWCNTs functionalization as demonstrated in TGA. The presence of carbon at 2θ of 25° and iron at 2θ of 45° in MWCNTs was illustrated by XRD. Polydispersive index and zeta potential were found to be 0.261 and −15.0 mV, respectively. Dexamethasone release increased by 55%, 65% and 95% in pH of 7.4, 6.5 and 5.5 respectively as evaluated by UV-VIS. The functionalized VA-MWCNTs were demonstrated to be less toxic in PC-12 cells in the concentration range from 20 to 20,000 µg/mL. These findings have demonstrated the potential of VA-MWCNTs in the enhancement of fast and prolonged release of dexamethasone which could lead to the effective treatment of ischemic stroke. More work is under way for targeting ischemic sites using atrial natriuretic peptide antibody in stroke rats.

Warm Dense Matter Demonstrating Non-Drude Conductivity from Observations of Nonlinear Plasmon Damping

NASA Astrophysics Data System (ADS)

Witte, B. B. L.; Fletcher, L. B.; Galtier, E.; Gamboa, E.; Lee, H. J.; Zastrau, U.; Redmer, R.; Glenzer, S. H.; Sperling, P.

2017-06-01

We present simulations using finite-temperature density-functional-theory molecular dynamics to calculate the dynamic electrical conductivity in warm dense aluminum. The comparison between exchange-correlation functionals in the Perdew-Burke-Enzerhof and Heyd-Scuseria-Enzerhof (HSE) approximation indicates evident differences in the density of states and the dc conductivity. The HSE calculations show excellent agreement with experimental Linac Coherent Light Source x-ray plasmon scattering spectra revealing plasmon damping below the widely used random phase approximation. These findings demonstrate non-Drude-like behavior of the dynamic conductivity that needs to be taken into account to determine the optical properties of warm dense matter.

Genetic analysis of an overlapping functional requirement for L1- and NCAM-type proteins during sensory axon guidance in Drosophila.

PubMed

Kristiansen, Lars V; Velasquez, Emma; Romani, Susana; Baars, Sigrid; Berezin, Vladimir; Bock, Elisabeth; Hortsch, Michael; Garcia-Alonso, Luis

2005-01-01

L1- and NCAM-type cell adhesion molecules represent distinct protein families that function as specific receptors for different axon guidance cues. However, both L1 and NCAM proteins promote axonal growth by inducing neuronal tyrosine kinase activity and are coexpressed in subsets of axon tracts in arthropods and vertebrates. We have studied the functional requirements for the Drosophila L1- and NCAM-type proteins, Neuroglian (Nrg) and Fasciclin II (FasII), during postembryonic sensory axon guidance. The rescue of the Neuroglian loss-of-function (LOF) phenotype by transgenically expressed L1- and NCAM-type proteins demonstrates a functional interchangeability between these proteins in Drosophila photoreceptor pioneer axons, where both proteins are normally coexpressed. In contrast, the ectopic expression of Fasciclin II in mechanosensory neurons causes a strong enhancement of the axonal misguidance phenotype. Moreover, our findings demonstrate that this functionally redundant specificity to mediate axon guidance has been conserved in their vertebrate homologs, L1-CAM and NCAM.

Improvements on the minimax algorithm for the Laplace transformation of orbital energy denominators

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

Helmich-Paris, Benjamin, E-mail: b.helmichparis@vu.nl; Visscher, Lucas, E-mail: l.visscher@vu.nl

2016-09-15

We present a robust and non-heuristic algorithm that finds all extremum points of the error distribution function of numerically Laplace-transformed orbital energy denominators. The extremum point search is one of the two key steps for finding the minimax approximation. If pre-tabulation of initial guesses is supposed to be avoided, strategies for a sufficiently robust algorithm have not been discussed so far. We compare our non-heuristic approach with a bracketing and bisection algorithm and demonstrate that 3 times less function evaluations are required altogether when applying it to typical non-relativistic and relativistic quantum chemical systems.

The mere exposure effect in patients with schizophrenia.

PubMed

Marie, A; Gabrieli, J D; Vaidya, C; Brown, B; Pratto, F; Zajonc, R B; Shaw, R J

2001-01-01

The mere exposure effect refers to the development of an emotional preference for previously unfamiliar material because of frequent exposure to that material. This study compared schizophrenia subjects (n = 20) to normal controls (n = 21) to determine whether implicit memory, as demonstrated by the mere exposure effect, was intact. Patients with schizophrenia demonstrated a normal preference for both verbal and visual materials seen earlier relative to novel materials, despite impaired performance on a recognition task for explicit memory using similar materials. Previous studies of schizophrenia subjects have shown a dissociation between implicit and explicit memory on verbal tasks. We found a similar dissociation demonstrated by normal functioning on an implicit memory task and impaired functioning on an explicit memory task. Potential implications of these findings are discussed with regard to treatment and rehabilitation.

Spousal associations between functional limitation and depressive symptom trajectories: Longitudinal findings from the study of Asset and Health Dynamics Among the Oldest Old (AHEAD).

PubMed

Hoppmann, Christiane A; Gerstorf, Denis; Hibbert, Anita

2011-03-01

To examine spousal associations between functional limitation and depressive symptom trajectories in a national sample of older long-term married couples. We used 14.5-year longitudinal data on functional limitations and depressive symptoms from 1,704 couples participating in the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD). Activities of daily living and a short version of the Center for Epidemiologic Studies Depression scale were used. Between-person difference findings corroborate previous research by showing that levels and changes in functional limitations and depressive symptoms are closely interrelated among wives and husbands. Our results further demonstrate sizable associations in levels and changes in functional limitations and depressive symptoms between spouses. For example, functional limitation levels in one spouse were associated with depressive symptom levels in the other spouse. Spousal associations remained after controlling for individual (age, education, cognition) and spousal covariates (marriage duration, number of children) and did not differ between women and men. Our findings highlight the important role of marital relationships in shaping health trajectories in old age because they show that some of the well-documented between-person differences in functional limitations and depressive symptoms are in fact related to spouses. (c) 2011 APA, all rights reserved

Dissociated language functions: a matter of atypical language lateralization or cerebral plasticity?

PubMed

Acioly, Marcus Andre; Gharabaghi, Alireza; Zimmermann, Christoph; Erb, Michael; Heckl, Stefan; Tatagiba, Marcos

2014-01-01

The left hemisphere is generally considered to harbor language functions. Atypical cortical language lateralization is mainly demonstrated in left-handed and ambidextrous individuals, whereas dissociated language functions have been reported in association with brain injuries as a part of the reorganization process. We present a thoughtful discussion on the underlying mechanisms of dissociated language functions through an illustrative case of dissociated expressive language. A 31-year-old left-handed woman presented with a recurrent left frontal glioma. Preoperative language functional magnetic resonance imaging (fMRI) panel revealed right-sided dominance for two different language tasks (verbal fluency and visual naming), and the word chain task demonstrated maximal activation in the left hemisphere at the posterior margin of the tumor. The patient was operated on awake to assess language functions intraoperatively. Preoperative fMRI findings were confirmed revealing a task-specific dissociation of expressive language functions. Surgical resection was taken to the functional boundaries. Postoperatively, no language dysfunction occurred. Dissociated language functions are prone to occur in long-standing lesions. Different patterns of dissociation may be encountered due to interindividual particularities and cerebral plasticity. The presented patient is unique by demonstrating new insight into expressive language dissociation, emphasizing the role of a preoperative language fMRI panel and the capability of intraoperative language mapping for identifying special language networks. Georg Thieme Verlag KG Stuttgart · New York.

Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice.

PubMed

Johnson, Matthew L; Lalia, Antigoni Z; Dasari, Surendra; Pallauf, Maximilian; Fitch, Mark; Hellerstein, Marc K; Lanza, Ian R

2015-10-01

Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age-related declines in physical function. Early evidence suggests that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age-related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large-scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post-translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age-related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti-inflammatory properties of n-3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti-inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n-3 PUFAs. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Coordination of meristem and boundary functions by transcription factors in the SHOOT MERISTEMLESS regulatory network.

PubMed

Scofield, Simon; Murison, Alexander; Jones, Angharad; Fozard, John; Aida, Mitsuhiro; Band, Leah R; Bennett, Malcolm; Murray, James A H

2018-04-30

The Arabidopsis homeodomain transcription factor SHOOT MERISTEMLESS (STM) is crucial for shoot apical meristem (SAM) function, yet the components and structure of the STM gene regulatory network (GRN) are largely unknown. Here, we show that transcriptional regulators are overrepresented among STM-regulated genes and, using these as GRN components in Bayesian network analysis, we infer STM GRN associations and reveal regulatory relationships between STM and factors involved in multiple aspects of SAM function. These include hormone regulation, TCP-mediated control of cell differentiation, AIL/PLT-mediated regulation of pluripotency and phyllotaxis, and specification of meristem-organ boundary zones via CUC1. We demonstrate a direct positive transcriptional feedback loop between STM and CUC1, despite their distinct expression patterns in the meristem and organ boundary, respectively. Our further finding that STM activates expression of the CUC1-targeting microRNA miR164c combined with mathematical modelling provides a potential solution for this apparent contradiction, demonstrating that these proposed regulatory interactions coupled with STM mobility could be sufficient to provide a mechanism for CUC1 localisation at the meristem-organ boundary. Our findings highlight the central role for the STM GRN in coordinating SAM functions. © 2018. Published by The Company of Biologists Ltd.

Altered resting brain function and structure in professional badminton players.

PubMed

Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

2012-01-01

Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

Academic and social achievement goals: Their additive, interactive, and specialized effects on school functioning.

PubMed

Liem, Gregory Arief D

2016-03-01

Students' pursuit of academic and social goals has implications for school functioning. However, studies on academic and social achievement goals have been relatively independent and mainly conducted with students in culturally Western settings. Guided by multiple-goal perspectives, this study examined the role of academic and social achievement goals in outcome variables relevant to academic (achievement, effort/persistence), social (peer relationship satisfaction, loneliness), and socio-academic (cooperative learning, competitive learning, socially regulated, and self-regulated learning) functioning. A total of 356 Indonesian high-school students (mean age = 16 years; 36% girls) participated in the study. A self-report survey comprising items drawn from pre-existing instruments was administered to measure distinct dimensions of achievement goals and outcomes under focus. Regression analysis was performed to examine additive, interactive, and specialized effects of achievement goals on outcomes. Aligned with the hierarchical model of goal relationships (Wentzel, 2000, Contemp. Educ. Psychol., 25, 105), academic and social achievement goals bore additive effects on most outcomes. Findings also revealed a specialized effect on academic achievement and notable interactive effects on cooperative learning. In general, mastery-approach and performance-approach goals were more adaptive than their avoidance counterparts. The effects of social development goals were positive, whereas those of social demonstration-approach goals were mixed. Contrary to prior findings, social demonstration-avoidance goals did not appear to be inimical for school functioning. Findings underscore the importance of both academic and social achievement goals in day-to-day school functioning and the need to consider the meaning of goals and the coordination of multiple goals from cultural lenses. © 2015 The British Psychological Society.

Exact models for isotropic matter

NASA Astrophysics Data System (ADS)

Thirukkanesh, S.; Maharaj, S. D.

2006-04-01

We study the Einstein-Maxwell system of equations in spherically symmetric gravitational fields for static interior spacetimes. The condition for pressure isotropy is reduced to a recurrence equation with variable, rational coefficients. We demonstrate that this difference equation can be solved in general using mathematical induction. Consequently, we can find an explicit exact solution to the Einstein-Maxwell field equations. The metric functions, energy density, pressure and the electric field intensity can be found explicitly. Our result contains models found previously, including the neutron star model of Durgapal and Bannerji. By placing restrictions on parameters arising in the general series, we show that the series terminate and there exist two linearly independent solutions. Consequently, it is possible to find exact solutions in terms of elementary functions, namely polynomials and algebraic functions.

Executive Functioning, Cortisol Reactivity, and Symptoms of Psychopathology in Girls with Premature Adrenarche

PubMed Central

Sontag-Padilla, Lisa M.; Dorn, Lorah D.; Tissot, Abbigail; Susman, Elizabeth J.; Beers, Sue R.; Rose, Susan R.

2012-01-01

The study examined the interaction between early maturational timing [as measured by premature adrenarche (PA)] and executive functioning and cortisol reactivity on symptoms of psychopathology. The study included 76 girls aged 6 through 8 years (mean = 7.50; SD = .85) with PA (n = 40) and on-time adrenarche (n = 36). Girls completed a battery of psychological and neuropsychological tests and blood sampling for cortisol. Parents completed the Child Behavior Checklist. Results demonstrated that girls with PA with lower levels of executive functioning had higher externalizing and anxious symptoms compared to other girls. Additionally, girls with PA who demonstrated increases in serum cortisol had higher externalizing symptoms than those with stable patterns. Finally, girls with PA who demonstrated decreases in cortisol reported higher depressive symptoms. Findings from this study provide important information concerning the impact of cognitive functioning and stress reactivity on adjustment to early maturation in girls with PA. Results of this research may inform screening and intervention efforts for girls who may be at greatest risk for emotional and behavioral problems as a result of early maturation. PMID:22293005

Increased premotor cortex activation in high functioning autism during action observation.

PubMed

Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

2015-04-01

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neural correlates of cognitive processing in monolinguals and bilinguals

PubMed Central

Grundy, John G.; Anderson, John A.E.; Bialystok, Ellen

2017-01-01

Here we review the neural correlates of cognitive control associated with bilingualism. We demonstrate that lifelong practice managing two languages orchestrates global changes to both the structure and function of the brain. Compared with monolinguals, bilinguals generally show greater gray matter volume, especially in perceptual/motor regions, greater white matter integrity, and greater functional connectivity between gray matter regions. These changes complement electroencephalography findings showing that bilinguals devote neural resources earlier than monolinguals. Parallel functional findings emerge from the functional magnetic resonance imaging literature: bilinguals show reduced frontal activity, suggesting that they do not need to rely on top-down mechanisms to the same extent as monolinguals. This shift for bilinguals to rely more on subcortical/posterior regions, which we term the bilingual anterior-to-posterior and subcortical shift (BAPSS), fits with results from cognitive aging studies and helps to explain why bilinguals experience cognitive decline at later stages of development than monolinguals. PMID:28415142

Hospitalwide Education and Training.

ERIC Educational Resources Information Center

Munk, Robert J.; Lovett, Marc

Findings and recommendations of a five-year demonstration project designed to clarify the role and organized structure of employee education and training in health care institutions are presented. In the first section of the book, hospitalwide education functions that were implemented at sixteen individual hospitals are examined. Identified are…

Construct validity of the PROMIS® sexual function and satisfaction measures in patients with cancer

PubMed Central

2013-01-01

Background With data from a diverse sample of patients either in treatment for cancer or post-treatment for cancer, we examine inter-domain and cross-domain correlations among the core domains of the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measures (PROMIS® SexFS) and the corresponding domains from conceptually-similar measures of sexual function, the International Index of Erectile Function and the Female Sexual Function Index. Findings Men (N=389) and women (N=430) were recruited from a tumor registry, oncology clinics, and an internet panel. The PROMIS SexFS, International Index of Erectile Function, and Female Sexual Function Index were used to collect participants’ self-reported sexual function. The domains shared among the measures include desire/interest in sexual activity, lubrication and vaginal discomfort/pain (women), erectile function (men), orgasm, and satisfaction. We examined correlations among different domains within the same instrument (discriminant validity) and correlations among similar domains measured by different instruments (convergent validity). Correlations demonstrating discriminant validity ranged from 0.38 to 0.73 for men and 0.48 to 0.74 for women, while correlations demonstrating convergent validity ranged from 0.62 to 0.83 for men and 0.71 to 0.92 for women. As expected, correlations demonstrating convergent validity were higher than correlations demonstrating discriminant validity, with one exception (orgasm for men). Conclusions Construct validity was supported by convergent and discriminant validity in a diverse sample of patients with cancer. For patients with cancer who may or may not have sexual dysfunction, the PROMIS SexFS measures provide a comprehensive assessment of key domains of sexual function and satisfaction. PMID:23497200

Critical Analysis of Cluster Models and Exchange-Correlation Functionals for Calculating Magnetic Shielding in Molecular Solids.

PubMed

Holmes, Sean T; Iuliucci, Robbie J; Mueller, Karl T; Dybowski, Cecil

2015-11-10

Calculations of the principal components of magnetic-shielding tensors in crystalline solids require the inclusion of the effects of lattice structure on the local electronic environment to obtain significant agreement with experimental NMR measurements. We assess periodic (GIPAW) and GIAO/symmetry-adapted cluster (SAC) models for computing magnetic-shielding tensors by calculations on a test set containing 72 insulating molecular solids, with a total of 393 principal components of chemical-shift tensors from 13C, 15N, 19F, and 31P sites. When clusters are carefully designed to represent the local solid-state environment and when periodic calculations include sufficient variability, both methods predict magnetic-shielding tensors that agree well with experimental chemical-shift values, demonstrating the correspondence of the two computational techniques. At the basis-set limit, we find that the small differences in the computed values have no statistical significance for three of the four nuclides considered. Subsequently, we explore the effects of additional DFT methods available only with the GIAO/cluster approach, particularly the use of hybrid-GGA functionals, meta-GGA functionals, and hybrid meta-GGA functionals that demonstrate improved agreement in calculations on symmetry-adapted clusters. We demonstrate that meta-GGA functionals improve computed NMR parameters over those obtained by GGA functionals in all cases, and that hybrid functionals improve computed results over the respective pure DFT functional for all nuclides except 15N.

Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN

PubMed Central

Elf, Shannon; Abdelfattah, Nouran S.; Baral, April J.; Beeson, Danielle; Rivera, Jeanne F.; Ko, Amy; Florescu, Natalie; Birrane, Gabriel; Chen, Edwin

2018-01-01

Mutations in calreticulin (CALR) are phenotypic drivers in the pathogenesis of myeloproliferative neoplasms. Mechanistic studies have demonstrated that mutant CALR binds to the thrombopoietin receptor MPL, and that the positive electrostatic charge of the mutant CALR C terminus is required for mutant CALR-mediated activation of JAK-STAT signaling. Here we demonstrate that although binding between mutant CALR and MPL is required for mutant CALR to transform hematopoietic cells; binding alone is insufficient for cytokine independent growth. We further show that the threshold of positive charge in the mutant CALR C terminus influences both binding of mutant CALR to MPL and activation of MPL signaling. We find that mutant CALR binds to the extracellular domain of MPL and that 3 tyrosine residues within the intracellular domain of MPL are required to activate signaling. With respect to mutant CALR function, we show that its lectin-dependent function is required for binding to MPL and for cytokine independent growth, whereas its chaperone and polypeptide-binding functionalities are dispensable. Together, our findings provide additional insights into the mechanism of the pathogenic mutant CALR-MPL interaction in myeloproliferative neoplasms. PMID:29288169

Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN.

PubMed

Elf, Shannon; Abdelfattah, Nouran S; Baral, April J; Beeson, Danielle; Rivera, Jeanne F; Ko, Amy; Florescu, Natalie; Birrane, Gabriel; Chen, Edwin; Mullally, Ann

2018-02-15

Mutations in calreticulin ( CALR ) are phenotypic drivers in the pathogenesis of myeloproliferative neoplasms. Mechanistic studies have demonstrated that mutant CALR binds to the thrombopoietin receptor MPL, and that the positive electrostatic charge of the mutant CALR C terminus is required for mutant CALR-mediated activation of JAK-STAT signaling. Here we demonstrate that although binding between mutant CALR and MPL is required for mutant CALR to transform hematopoietic cells; binding alone is insufficient for cytokine independent growth. We further show that the threshold of positive charge in the mutant CALR C terminus influences both binding of mutant CALR to MPL and activation of MPL signaling. We find that mutant CALR binds to the extracellular domain of MPL and that 3 tyrosine residues within the intracellular domain of MPL are required to activate signaling. With respect to mutant CALR function, we show that its lectin-dependent function is required for binding to MPL and for cytokine independent growth, whereas its chaperone and polypeptide-binding functionalities are dispensable. Together, our findings provide additional insights into the mechanism of the pathogenic mutant CALR-MPL interaction in myeloproliferative neoplasms. © 2018 by The American Society of Hematology.

Respiratory bronchiolitis-associated interstitial lung disease secondary to electronic nicotine delivery system use confirmed with open lung biopsy.

PubMed

Flower, Mark; Nandakumar, Lakshmy; Singh, Mahendra; Wyld, David; Windsor, Morgan; Fielding, David

2017-05-01

As a modern phenomenon, there is currently limited understanding of the possible toxic effects and broader implications of electronic nicotine delivery systems (ENDS). Large volumes of aerosolized particles are inhaled during "vaping" and there are now an increasing number of case reports demonstrating toxic effects of ENDS, as well as human studies demonstrating impaired lung function in users. This article presents a case of respiratory bronchiolitis interstitial lung disease (RB-ILD) precipitated by vaping in a 33-year-old male with 10 pack years of traditional cigarette and prior treatment for mixed germ cell tumour. The patient had started vaping 10-15 times per day while continuing to smoke 10 traditional cigarettes per day. After 3 months of exposure to e-cigarette vapour, chest computed tomography demonstrated multiple new poorly defined pulmonary nodules with fluffy parenchyma opacification centred along the terminal bronchovascular units. Video-assisted thoracoscopy with lung biopsy of the right upper and right middle lobes was undertaken. The microscopic findings were overall consistent with RB-ILD. This case demonstrates toxicity with use of ENDS on open lung biopsy with resolution of radiographic findings on cessation. We believe that this is the first case where open lung biopsy has demonstrated this and our findings are consistent with RB-ILD.

[The role of computed tomography after functional surgery on the paranasal sinuses. Normal findings and an assessment of the surgical failures].

PubMed

Scribano, E; Ascenti, G; Cascio, F; Bellinvia, A; Mazziotti, S; Lamberto, S

1999-09-01

Functional endoscopic sinus surgery has become the technique of choice to treat benign or inflammatory diseases of paranasal sinuses resistant to medical therapy. The goal of this type of surgery is to open the obstructed sinus ostia and restore normal aeration and mucociliary clearance. Messerklinger's is the most widely used technique. We investigated the role of CT after functional endoscopic sinus surgery and describe CT findings of postoperative anatomical changes together with frequent complications and surgical failures. Twenty-seven patients with relapsing symptoms were examined with CT of paranasal sinuses 8-32 weeks after functional endoscopic sinus surgery. In all cases both preoperative CT and surgical reports were available: CT and surgical results were compared. In 21/27 patients nasosinusal changes were demonstrated with CT. Recurrent disease secondary to inflammation and/or fibrosis was observed in 14 cases. Residual disease was seen in 5 patients. A major orbital complication was found in 1 patient with diplopia. One patient exhibited a large interruption of cribriform plate with CSF fistula. CT permitted an accurate assessment of extension and results of functional endoscopic sinus surgery. CT is indicated in the postoperative study of the patients who a) present symptoms of cerebral and ocular complications (early after functional endoscopic sinus surgery); and b) do not respond to medical treatments 8-32 weeks after unsuccessful functional endoscopic sinus surgery. In these patients CT can demonstrate recurrent and/or residual nasosinusal disease and bony defects unintentionally caused by the surgeon during the procedure.

Stigma and functioning in patients with bipolar disorder.

PubMed

Vázquez, G H; Kapczinski, F; Magalhaes, P V; Córdoba, R; Lopez Jaramillo, C; Rosa, A R; Sanchez de Carmona, M; Tohen, M

2011-04-01

The aim of this study was to investigate the impact of self-rated stigma and functioning in patients with bipolar disorder in Latin-America. Two-hundred and forty-one participants with bipolar disorder were recruited from three Latin American countries (Argentina, Brazil, and Colombia). Functional impairment was assessed with the Functioning Assessment Short Test (FAST) and experiences with and impact of perceived stigma was evaluated using the Inventory of Stigmatizing Experiences (ISE). Higher scores of self-perceived stigma were correlated with lower scores of functioning. After multiple regression analysis, being on disability benefit, current mood symptoms and functioning were associated with self-perceived stigma. This is the first study to demonstrate an association between stigma and poor functioning in bipolar disorder. Possible implications of such findings for practitioners are discussed. The main limitation of this study is that the Inventory of Stigmatizing Experiences has not yet been validated in a population of bipolar patients in our countries. The sample size and heterogeneous clinical subjects from different countries and cultures limit the generalization of the present findings. Copyright © 2010 Elsevier B.V. All rights reserved.

Intellectual Functioning in Offspring of Parents with Bipolar Disorder: A Review of the Literature

PubMed Central

Klimes-Dougan, Bonnie; Jeong, Jake; Kennedy, Kevin P.; Allen, Timothy A.

2017-01-01

Impaired intellectual functioning is an important risk factor for the emergence of severe mental illness. Unlike many other forms of mental disorder however, the association between bipolar disorder and intellectual deficits is unclear. In this narrative review, we examine the current evidence on intellectual functioning in children and adolescents at risk for developing bipolar disorder. The results are based on 18 independent, peer-reviewed publications from 1980 to 2017 that met criteria for this study. The findings yielded no consistent evidence of lower or higher intellectual quotient (IQ) in offspring of parents diagnosed with bipolar disorder. Some tentative evidence was found for lower performance IQ in offspring of bipolar parents as compared to controls. It is recommended that future research examine variability in intellectual functioning and potential moderators. These findings demonstrate the need to examine how intellectual functioning unfolds across development given the potential role of IQ as a marker of vulnerability or resilience in youth at high risk for affective disorders. PMID:29143763

Bioengineering and Stem Cell Technology in the Treatment of Congenital Heart Disease

PubMed Central

Bosman, Alexis; Edel, Michael J.; Blue, Gillian; Dilley, Rodney J.; Harvey, Richard P.; Winlaw, David S.

2015-01-01

Congenital heart disease places a significant burden on the individual, family and community despite significant advances in our understanding of aetiology and treatment. Early research in ischaemic heart disease has paved the way for stem cell technology and bioengineering, which promises to improve both structural and functional aspects of disease. Stem cell therapy has demonstrated significant improvements in cardiac function in adults with ischaemic heart disease. This finding, together with promising case studies in the paediatric setting, demonstrates the potential for this treatment in congenital heart disease. Furthermore, induced pluripotent stems cell technology, provides a unique opportunity to address aetiological, as well as therapeutic, aspects of disease. PMID:26239354

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

Huey-Wen Lin; Robert G. Edwards; Balint Joo

In this work, we perform parameter tuning with dynamical anisotropic clover lattices using the Schr\\"odinger functional and stout-smearing in the fermion field. We find thatmore » $$\\xi_R/\\xi_0$$ is relatively close to 1 in our parameter search, which allows us to fix $$\\xi_0$$ in our runs. We proposed to determine the gauge and fermion anisotropy in a Schr\\"odinger-background small box using Wilson loop ratios and PCAC masses. We demonstrate that these ideas are equivalent to but more efficient than the conventional meson dispersion approach. The spatial and temporal clover coefficients are fixed to the tree-level tadpole-improved clover values, and we demonstrate that they satisfy the nonperturbative condition determined by Schr\\"odinger functional method.« less

[Changes in respiratory function tests of healthy miners in accordance with length of service].

PubMed

Shishkin, G S; Ustiuzhaninova, N V; Krasulina, G P

2010-01-01

The study covered respiratory function tests in healthy miners with variable length of service. Findings are that the first year of mining is characterized by slower interchange of gases in respiratory parts of lungs, by induced protective reaction that increases dilution of inspired air. The years from second to fifth demonstrate stabilized changes and external respiratory system fixed in new functional state kept over next 15-18 years. After 20 years of service in mine, the external respiration system becomes overstrained with intensified compensatory pulmonary ventilation and protective reaction.

On the feasibility of p-type Ga2O3

NASA Astrophysics Data System (ADS)

Kyrtsos, Alexandros; Matsubara, Masahiko; Bellotti, Enrico

2018-01-01

We investigate the various cation substitutional dopants in Ga2O3 for the possibility of p-type conductivity using density functional theory. Our calculations include both standard density functional theory and hybrid functional calculations. We demonstrate that all the investigated dopants result in deep acceptor levels, not able to contribute to the p-type conductivity of Ga2O3. In light of these results, we compare our findings with other wide bandgap oxides and reexamine previous experiments on zinc doping in Ga2O3.

Findings in resting-state fMRI by differences from K-means clustering.

PubMed

Chyzhyk, Darya; Graña, Manuel

2014-01-01

Resting state fMRI has growing number of studies with diverse aims, always centered on some kind of functional connectivity biomarker obtained from correlation regarding seed regions, or by analytical decomposition of the signal towards the localization of the spatial distribution of functional connectivity patterns. In general, studies are computationally costly and very sensitive to noise and preprocessing of data. In this paper we consider clustering by K-means as a exploratory procedure which can provide some results with little computational effort, due to efficient implementations that are readily available. We demonstrate the approach on a dataset of schizophrenia patients, finding differences between patients with and without auditory hallucinations.

Humor theories and the physiological benefits of laughter.

PubMed

Wilkins, Julia; Eisenbraun, Amy Janel

2009-01-01

There are 3 main theories used to explain the functions of humor: (1) the relief theory, (2) the incongruity theory, and (3) the superiority theory. While these theories focus on the specific role that humor plays for people in situations such as dealing with misfortune, making sense of rule violations, and bonding with others, we propose that underlying each of these theories are the physiological benefits of laughter. We draw on findings from empirical studies on laughter to demonstrate that these physiological benefits occur regardless of the theory that is used to explain the humor function. Findings from these studies have important implications for nurse practitioners working in hospice settings, long-term care facilities, nursing homes, and hospitals.

Analysis of scattering statistics and governing distribution functions in optical coherence tomography.

PubMed

Sugita, Mitsuro; Weatherbee, Andrew; Bizheva, Kostadinka; Popov, Ivan; Vitkin, Alex

2016-07-01

The probability density function (PDF) of light scattering intensity can be used to characterize the scattering medium. We have recently shown that in optical coherence tomography (OCT), a PDF formalism can be sensitive to the number of scatterers in the probed scattering volume and can be represented by the K-distribution, a functional descriptor for non-Gaussian scattering statistics. Expanding on this initial finding, here we examine polystyrene microsphere phantoms with different sphere sizes and concentrations, and also human skin and fingernail in vivo. It is demonstrated that the K-distribution offers an accurate representation for the measured OCT PDFs. The behavior of the shape parameter of K-distribution that best fits the OCT scattering results is investigated in detail, and the applicability of this methodology for biological tissue characterization is demonstrated and discussed.

On the effectiveness of and preference for punishment and extinction components of function-based interventions.

PubMed

Hanley, Gregory P; Piazza, Cathleen C; Fisher, Wayne W; Maglieri, Kristen A

2005-01-01

The current study describes an assessment sequence that may be used to identify individualized, effective, and preferred interventions for severe problem behavior in lieu of relying on a restricted set of treatment options that are assumed to be in the best interest of consumers. The relative effectiveness of functional communication training (FCT) with and without a punishment component was evaluated with 2 children for whom functional analyses demonstrated behavioral maintenance via social positive reinforcement. The results showed that FCT plus punishment was more effective than FCT in reducing problem behavior. Subsequently, participants' relative preference for each treatment was evaluated in a concurrent-chains arrangement, and both participants demonstrated a dear preference for FCT with punishment. These findings suggest that the treatment-selection process may be guided by person-centered and evidence-based values.

Genetic predictor of working memory and prefrontal function in women with HIV.

PubMed

Sundermann, Erin E; Bishop, Jeffrey R; Rubin, Leah H; Little, Deborah M; Meyer, Vanessa J; Martin, Eileen; Weber, Kathleen; Cohen, Mardge; Maki, Pauline M

2015-02-01

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.

Fast state transfer in a Λ-system: a shortcut-to-adiabaticity approach to robust and resource optimized control

NASA Astrophysics Data System (ADS)

Mortensen, Henrik Lund; Sørensen, Jens Jakob W. H.; Mølmer, Klaus; Sherson, Jacob Friis

2018-02-01

We propose an efficient strategy to find optimal control functions for state-to-state quantum control problems. Our procedure first chooses an input state trajectory, that can realize the desired transformation by adiabatic variation of the system Hamiltonian. The shortcut-to-adiabaticity formalism then provides a control Hamiltonian that realizes the reference trajectory exactly but on a finite time scale. As the final state is achieved with certainty, we define a cost functional that incorporates the resource requirements and a perturbative expression for robustness. We optimize this functional by systematically varying the reference trajectory. We demonstrate the method by application to population transfer in a laser driven three-level Λ-system, where we find solutions that are fast and robust against perturbations while maintaining a low peak laser power.

The Role of Sleep in Emotional Brain Function

PubMed Central

Goldstein, Andrea N.; Walker, Matthew P.

2014-01-01

Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by longstanding clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression. PMID:24499013

Spousal Associations Between Functional Limitation and Depressive Symptom Trajectories: Longitudinal Findings from the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD)

PubMed Central

Hoppmann, Christiane A.; Gerstorf, Denis; Hibbert, Anita

2010-01-01

Objective To examine spousal associations between functional limitation and depressive symptom trajectories in a national sample of older long-term married couples. Design We use 14.5-year longitudinal data on functional limitations and depressive symptoms from 1,704 couples participating in the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD). Main Outcome Measures Activities of Daily Living and a short version of the Center for Epidemiologic Studies Depression Scale were used. Results Between-person difference findings corroborate previous research by showing that levels and changes in functional limitations and depressive symptoms are closely interrelated among wives and husbands. Importantly, our results further demonstrate sizeable associations in levels and changes in functional limitations and depressive symptoms between spouses. For example, functional limitation levels in one spouse were associated with depressive symptom levels in the respective other spouse. Spousal associations remained after controlling for individual (age, education, cognition) and spousal covariates (marriage duration, number of children) and did not differ between women and men. Conclusion Our findings highlight the important role of marital relationships in shaping health trajectories in old age because they show that some of the well-documented between-person differences in functional limitations and depressive symptoms are in fact related to spouses. PMID:21401249

Learning about Functions through Learner-Generated Examples

ERIC Educational Resources Information Center

Dinkelman, Martha O.; Cavey, Laurie O.

2015-01-01

In many mathematics classrooms, the teacher provides "worked examples" to demonstrate how students should perform certain algorithms or processes. Some students find it difficult to generalize from the examples that teachers provide and cannot apply what they have learned in new situations (Watson and Mason 2002). Instead, teachers might…

Academic Attainment Findings in Children with Sickle Cell Disease

ERIC Educational Resources Information Center

Epping, Amanda S.; Myrvik, Matthew P.; Newby, Robert F.; Panepinto, Julie A.; Brandow, Amanda M.; Scott, J. Paul

2013-01-01

Background: Children with sickle cell disease (SCD) demonstrate deficits in cognitive and academic functioning. This study compared the academic attainment of children with SCD relative to national, state, and local school district rates for African American students. Methods: A retrospective chart review of children with SCD was completed and…

Long-Term Effects of Neurofeedback Treatment in Autism

ERIC Educational Resources Information Center

Kouijzer, Mirjam E. J.; de Moor, Jan M. H.; Gerrits, Berrie J. L.; Buitelaar, Jan K.; van Schie, Hein T.

2009-01-01

Previously we demonstrated significant improvement of executive functions and social behavior in children with autism spectrum disorders (ASD) treated with 40 sessions of EEG neurofeedback in a nonrandomized waiting list control group design. In this paper we extend these findings by reporting the long-term results of neurofeedback treatment in…

Error Processing and Gender-Shared and -Specific Neural Predictors of Relapse in Cocaine Dependence

ERIC Educational Resources Information Center

Luo, Xi; Zhang, Sheng; Hu, Sien; Bednarski, Sarah R.; Erdman, Emily; Farr, Olivia M.; Hong, Kwang-Ik; Sinha, Rajita; Mazure, Carolyn M.; Li, Chiang-shan R.

2013-01-01

Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were…

Hyperconnectivity is a fundamental response to neurological disruption.

PubMed

Hillary, Frank G; Roman, Cristina A; Venkatesan, Umesh; Rajtmajer, Sarah M; Bajo, Ricardo; Castellanos, Nazareth D

2015-01-01

In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Reduced ventilation-perfusion (V/Q) mismatch following endobronchial valve insertion demonstrated by Gallium-68 V/Q photon emission tomography/computed tomography.

PubMed

Leong, Paul; Le Roux, Pierre-Yves; Callahan, Jason; Siva, Shankar; Hofman, Michael S; Steinfort, Daniel P

2017-09-01

Endobronchial valves (EBVs) are increasingly deployed in the management of severe emphysema. Initial studies focussed on volume reduction as the mechanism, with subsequent improvement in forced expiratory volume in 1 s (FEV 1 ). More recent studies have emphasized importance of perfusion on predicting outcomes, though findings have been inconsistent. Gallium-68 ventilation-perfusion (V/Q) photon emission tomography (PET)/computed tomography (CT) is a novel imaging modality with advantages in spatial resolution, quantitation, and speed over conventional V/Q scintigraphy. We report a pilot case in which V/Q-PET/CT demonstrated discordant findings compared with quantitative CT analysis, and directed left lower lobe EBV placement. The patient experienced a significant improvement in 6-min walk distance (6MWD) without change in spirometry. Post-EBV V/Q-PET/CT demonstrated a marked decrease in unmatched (detrimental) V/Q areas and improvement in overall V/Q matching on post-EBV V/Q-PET/CT. These preliminary novel findings suggest that EBVs improve V/Q matching and may explain the observed functional improvements.

Evaluation of Heterogeneous Metal-Organic Framework Organocatalysts Prepared by Postsynthetic Modification

PubMed Central

Garibay, Sergio J.; Wang, Zhenqiang; Cohen, Seth M.

2010-01-01

A metal-organic framework (MOF) containing 2-amino-1,4-benzenedicarboxylate (NH2-BDC) as a building block is shown to undergo chemical modification with a set of cyclic anhydrides. The modification of the aluminum-based MOF known as MIL-53(Al)-NH2 (MIL = Matérial Institut Lavoisier) by these reagents is demonstrated by using a variety of methods, including NMR and ESI-MS, and the structural integrity of the modified MOFs has been confirmed by TGA, PXRD, and gas sorption analysis. Reaction with these cyclic anhydrides produces MOFs that display carboxylic acid functional groups within their pores. Furthermore, it is shown that maleic acid functionalized MIL-53(Al)-AMMal can act as a Brønsted acid catalyst and facilitate the methanolysis of several small epoxides. Experiments show that MIL-53(Al)-AMMal acts in a heterogeneous manner and is recyclable with consistent activity over at least three catalytic cycles. The findings presented here demonstrate several important features of covalent postsynthetic modification (PSM) on MOFs, including: 1) facile introduction of catalytic functionality using simple organic reagents (e.g. anhydrides); 2) the ability to utilize and recycle organocatalytic MOFs; 3) control of catalytic activity through choice of functional group. The findings clearly illustrate that covalent postsynthetic modification represents a powerful means to access new MOF compounds that serve as organocatalytic materials. PMID:20698561

Cognitive, psychophysical, and neural correlates of vulvar pain in primary and secondary provoked vestibulodynia: a pilot study.

PubMed

Sutton, Katherine; Pukall, Caroline; Wild, Conor; Johnsrude, Ingrid; Chamberlain, Susan

2015-05-01

Provoked vestibulodynia (PVD) is a common condition characterized by localized, provoked pain that can be present since first vaginal penetration attempt (primary) or can develop after a period of pain-free penetration (secondary). Research has demonstrated psychosocial and psychophysical differences between women with these subtypes of PVD, but the question of whether neural responses to pain also differ remains to be investigated. This study aims to examine whether cognitive, psychophysical, and neural responses to vulvar pressure pain differ between women with PVD1 and PVD2. Women with PVD1 and PVD2 were compared for group differences using multiple modalities, including questionnaires, psychophysical testing, and neuroimaging. Pain ratings were held constant across groups, rather than amount of pressure applied. Demographics, sexual functioning, four questionnaires examining anxiety and catastrophizing, quantitative sensory testing at the vulvar vestibule using a vulvalgesiometer, and functional and structural magnetic resonance imaging (MRI). Findings suggest that women with PVD1 are more anxious and that they catastrophize more about their vulvar and nonvulvar pain than women with PVD2. Overall, MRI results demonstrated structural and functional similarities to other chronic pain findings for both groups of women. Gray matter (GM) density also differed between groups: women with PVD1 showed significant decreases in GM throughout areas associated with pain processing. Functionally, between-groups differences were found during painful vulvar stimulation despite lower pressures applied to the vulva for women with PVD1 because of their heightened sensitivity; the determination of the level of vulvar pressure to elicit pain was based on subjective ratings. Findings are limited by sample size and liberal alpha values; however, future research is certainly warranted based on the preliminary findings of this study suggesting both similarities and differences between PVD1 and PVD2. Overall, women with PVD1 seem to fare worse on several pain-related and psychosocial variables compared with women with PVD2. © 2015 International Society for Sexual Medicine.

Non-caloric artificial sweeteners and the microbiome: findings and challenges

PubMed Central

Suez, Jotham; Korem, Tal; Zilberman-Schapira, Gili; Segal, Eran; Elinav, Eran

2015-01-01

Non-caloric artificial sweeteners (NAS) are common food supplements consumed by millions worldwide as means of combating weight gain and diabetes, by retaining sweet taste without increasing caloric intake. While they are considered safe, there is increasing controversy regarding their potential ability to promote metabolic derangements in some humans. We recently demonstrated that NAS consumption could induce glucose intolerance in mice and distinct human subsets, by functionally altering the gut microbiome. In this commentary, we discuss these findings in the context of previous and recent works demonstrating the effects of NAS on host health and the microbiome, and the challenges and open questions that need to be addressed in understanding the effects of NAS consumption on human health. PMID:25831243

Non-caloric artificial sweeteners and the microbiome: findings and challenges.

PubMed

Suez, Jotham; Korem, Tal; Zilberman-Schapira, Gili; Segal, Eran; Elinav, Eran

2015-01-01

Non-caloric artificial sweeteners (NAS) are common food supplements consumed by millions worldwide as means of combating weight gain and diabetes, by retaining sweet taste without increasing caloric intake. While they are considered safe, there is increasing controversy regarding their potential ability to promote metabolic derangements in some humans. We recently demonstrated that NAS consumption could induce glucose intolerance in mice and distinct human subsets, by functionally altering the gut microbiome. In this commentary, we discuss these findings in the context of previous and recent works demonstrating the effects of NAS on host health and the microbiome, and the challenges and open questions that need to be addressed in understanding the effects of NAS consumption on human health.

Altered Resting Brain Function and Structure in Professional Badminton Players

PubMed Central

Di, Xin; Zhu, Senhua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan

2012-01-01

Abstract Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills. PMID:22840241

Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function.

PubMed

Conti, Valerio; Aracri, Patrizia; Chiti, Laura; Brusco, Simone; Mari, Francesco; Marini, Carla; Albanese, Maria; Marchi, Angela; Liguori, Claudio; Placidi, Fabio; Romigi, Andrea; Becchetti, Andrea; Guerrini, Renzo

2015-04-14

We assessed the mutation frequency in nicotinic acetylcholine receptor (nAChR) subunits CHRNA4, CHRNB2, and CHRNA2 in a cohort including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and sporadic nocturnal frontal lobe epilepsy (NFLE). Upon finding a novel mutation in CHRNA2 in a large family, we tested in vitro its functional effects. We sequenced all the coding exons and their flanking intronic regions in 150 probands (73 NFLE, 77 ADNFLE), in most of whom diagnosis had been validated by EEG recording of seizures. Upon finding a missense mutation in CHRNA2, we measured whole-cell currents in human embryonic kidney cells in both wild-type and mutant α2β4 and α2β2 nAChR subtypes stimulated with nicotine. We found a c.889A>T (p.Ile297Phe) mutation in the proband (≈0.6% of the whole cohort) of a large ADNFLE family (1.2% of familial cases) and confirmed its segregation in all 6 living affected individuals. Video-EEG studies demonstrated sleep-related paroxysmal epileptic arousals in all mutation carriers. Oxcarbazepine treatment was effective in all. Whole-cell current density was reduced to about 40% in heterozygosity and to 0% in homozygosity, with minor effects on channel permeability and sensitivity to nicotine. ADNFLE had previously been associated with CHRNA2 dysfunction in one family, in which a gain of function mutation was demonstrated. We confirm the causative role of CHRNA2 mutations in ADNFLE and demonstrate that also loss of function of α2 nAChRs may have pathogenic effects. CHRNA2 mutations are a rare cause of ADNFLE but this gene should be included in mutation screening. © 2015 American Academy of Neurology.

Clinical Findings Documenting Cellular and Molecular Abnormalities of Glia in Depressive Disorders

PubMed Central

Czéh, Boldizsár; Nagy, Szilvia A.

2018-01-01

Depressive disorders are complex, multifactorial mental disorders with unknown neurobiology. Numerous theories aim to explain the pathophysiology. According to the “gliocentric theory”, glial abnormalities are responsible for the development of the disease. The aim of this review article is to summarize the rapidly growing number of cellular and molecular evidences indicating disturbed glial functioning in depressive disorders. We focus here exclusively on the clinical studies and present the in vivo neuroimaging findings together with the postmortem molecular and histopathological data. Postmortem studies demonstrate glial cell loss while the in vivo imaging data reveal disturbed glial functioning and altered white matter microstructure. Molecular studies report on altered gene expression of glial specific genes. In sum, the clinical findings provide ample evidences on glial pathology and demonstrate that all major glial cell types are affected. However, we still lack convincing theories explaining how the glial abnormalities develop and how exactly contribute to the emotional and cognitive disturbances. Abnormal astrocytic functioning may lead to disturbed metabolism affecting ion homeostasis and glutamate clearance, which in turn, affect synaptic communication. Abnormal oligodendrocyte functioning may disrupt the connectivity of neuronal networks, while microglial activation indicates neuroinflammatory processes. These cellular changes may relate to each other or they may indicate different endophenotypes. A theory has been put forward that the stress-induced inflammation—mediated by microglial activation—triggers a cascade of events leading to damaged astrocytes and oligodendroglia and consequently to their dysfunctions. The clinical data support the “gliocentric” theory, but future research should clarify whether these glial changes are truly the cause or simply the consequences of this devastating disorder. PMID:29535607

Functional dissociations between four basic arithmetic operations in the human posterior parietal cortex: A cytoarchitectonic mapping study

PubMed Central

Rosenberg-Lee, Miriam; Chang, Ting Ting; Young, Christina B; Wu, Sarah; Menon, Vinod

2011-01-01

Although lesion studies over the past several decades have focused on functional dissociations in posterior parietal cortex (PPC) during arithmetic, no consistent view has emerged of its differential involvement in addition, subtraction, multiplication, and division. To circumvent problems with poor anatomical localization, we examined functional overlap and dissociations in cytoarchitectonically-defined subdivisions of the intraparietal sulcus (IPS), superior parietal lobule (SPL) and angular gyrus (AG), across these four operations. Compared to a number identification control task, all operations except addition, showed a consistent profile of left posterior IPS activation and deactivation in the right posterior AG. Multiplication and subtraction differed significantly in right, but not left, IPS and AG activity, challenging the view that the left AG differentially subserves retrieval during multiplication. Although addition and multiplication both rely on retrieval, multiplication evoked significantly greater activation in right posterior IPS, as well as the prefrontal cortex, lingual and fusiform gyri, demonstrating that addition and multiplication engage different brain processes. Comparison of PPC responses to the two pairs of inverse operations: division vs. multiplication and subtraction vs. addition revealed greater activation of left lateral SPL during division, suggesting that processing inverse relations is operation specific. Our findings demonstrate that individual IPS, SPL and AG subdivisions are differentially modulated by the four arithmetic operations and they point to significant functional heterogeneity and individual differences in activation and deactivation within the PPC. Critically, these effects are related to retrieval, calculation and inversion, the three key cognitive processes that are differentially engaged by arithmetic operations. Our findings point to distributed representation of these processes in the human PPC and also help explain why lesion and previous imaging studies have yielded inconsistent findings. PMID:21616086

Functional dissociations between four basic arithmetic operations in the human posterior parietal cortex: a cytoarchitectonic mapping study.

PubMed

Rosenberg-Lee, Miriam; Chang, Ting Ting; Young, Christina B; Wu, Sarah; Menon, Vinod

2011-07-01

Although lesion studies over the past several decades have focused on functional dissociations in posterior parietal cortex (PPC) during arithmetic, no consistent view has emerged of its differential involvement in addition, subtraction, multiplication, and division. To circumvent problems with poor anatomical localization, we examined functional overlap and dissociations in cytoarchitectonically defined subdivisions of the intraparietal sulcus (IPS), superior parietal lobule (SPL) and angular gyrus (AG), across these four operations. Compared to a number identification control task, all operations except addition, showed a consistent profile of left posterior IPS activation and deactivation in the right posterior AG. Multiplication and subtraction differed significantly in right, but not left, IPS and AG activity, challenging the view that the left AG differentially subserves retrieval during multiplication. Although addition and multiplication both rely on retrieval, multiplication evoked significantly greater activation in right posterior IPS, as well as the prefrontal cortex, lingual and fusiform gyri, demonstrating that addition and multiplication engage different brain processes. Comparison of PPC responses to the two pairs of inverse operations: division versus multiplication and subtraction versus addition revealed greater activation of left lateral SPL during division, suggesting that processing inverse relations is operation specific. Our findings demonstrate that individual IPS, SPL and AG subdivisions are differentially modulated by the four arithmetic operations and they point to significant functional heterogeneity and individual differences in activation and deactivation within the PPC. Critically, these effects are related to retrieval, calculation and inversion, the three key cognitive processes that are differentially engaged by arithmetic operations. Our findings point to distribute representation of these processes in the human PPC and also help explain why lesion and previous imaging studies have yielded inconsistent findings. Copyright © 2011 Elsevier Ltd. All rights reserved.

Understanding Early Elementary Children's Conceptual Knowledge of Plant Structure and Function through Drawings

PubMed Central

Ellis, Jane P.; Jones, Alan M.

2014-01-01

This study examined children's drawings to explain children's conceptual understanding of plant structure and function. The study explored whether the children's drawings accurately reflect their conceptual understanding about plants in a manner that can be interpreted by others. Drawing, survey, interview, and observational data were collected from 182 students in grades K and 1 in rural southeastern United States. Results demonstrated the children held a wide range of conceptions concerning plant structure and function. These young children held very simple ideas about plants with respect to both their structure and function. Consistent with the drawings, the interviews presented similar findings. PMID:25185222

The Double-edged Sword of Pedagogy: Instruction limits spontaneous exploration and discovery

PubMed Central

Shafto, Patrick; Gweon, Hyowon; Goodman, Noah D.; Spelke, Elizabeth; Schulz, Laura

2012-01-01

Motivated by computational analyses, we look at how teaching affects exploration and discovery. In Experiment 1, we investigated children’s exploratory play after an adult pedagogically demonstrated a function of a toy, after an interrupted pedagogical demonstration, after a naïve adult demonstrated the function, and at baseline. Preschoolers in the pedagogical condition focused almost exclusively on the target function; by contrast, children in the other conditions explored broadly. In Experiment 2, we show that children restrict their exploration both after direct instruction to themselves and after overhearing direct instruction given to another child; they do not show this constraint after observing direct instruction given to an adult or after observing a non-pedagogical intentional action. We discuss these findings as the result of rational inductive biases. In pedagogical contexts, a teacher’s failure to provide evidence for additional functions provides evidence for their absence; such contexts generalize from child to child (because children are likely to have comparable states of knowledge) but not from adult to child. Thus, pedagogy promotes efficient learning but at a cost: children are less likely to perform potentially irrelevant actions but also less likely to discover novel information. PMID:21216395

The double-edged sword of pedagogy: Instruction limits spontaneous exploration and discovery.

PubMed

Bonawitz, Elizabeth; Shafto, Patrick; Gweon, Hyowon; Goodman, Noah D; Spelke, Elizabeth; Schulz, Laura

2011-09-01

Motivated by computational analyses, we look at how teaching affects exploration and discovery. In Experiment 1, we investigated children's exploratory play after an adult pedagogically demonstrated a function of a toy, after an interrupted pedagogical demonstration, after a naïve adult demonstrated the function, and at baseline. Preschoolers in the pedagogical condition focused almost exclusively on the target function; by contrast, children in the other conditions explored broadly. In Experiment 2, we show that children restrict their exploration both after direct instruction to themselves and after overhearing direct instruction given to another child; they do not show this constraint after observing direct instruction given to an adult or after observing a non-pedagogical intentional action. We discuss these findings as the result of rational inductive biases. In pedagogical contexts, a teacher's failure to provide evidence for additional functions provides evidence for their absence; such contexts generalize from child to child (because children are likely to have comparable states of knowledge) but not from adult to child. Thus, pedagogy promotes efficient learning but at a cost: children are less likely to perform potentially irrelevant actions but also less likely to discover novel information. Copyright © 2010. Published by Elsevier B.V.

Atomic Layer Deposition of the Solid Electrolyte LiPON

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

Kozen, Alexander C.; Pearse, Alexander J.; Lin, Chuan -Fu

We demonstrate an atomic layer deposition (ALD) process for the solid electrolyte lithium phosphorousoxynitride (LiPON) using lithium tert-butoxide (LiO tBu), H 2O, trimethylphosphate (TMP), and plasma N 2 ( PN 2) as precursors. We use in-situ spectroscopic ellipsometry to determine growth rates for process optimization to design a rational, quaternary precursor ALD process where only certain substrate–precursor chemical reactions are favorable. We demonstrate via in-situ XPS tunable nitrogen incorporation into the films by variation of the PN 2 dose and find that ALD films over approximately 4.5% nitrogen are amorphous, whereas LiPON ALD films with less than 4.5% nitrogen aremore » polycrystalline. Lastly, we characterize the ionic conductivity of the ALD films as a function of nitrogen content and demonstrate their functionality on a model battery electrode—a Si anode on a Cu current collector.« less

Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome1

PubMed Central

Johansson, Linda; Dahesh, Samira; Van Sorge, Nina M.; Darenberg, Jessica; Norgren, Mari; Sjölin, Jan; Nizet, Victor; Norrby-Teglund, Anna

2009-01-01

We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes. PMID:19193266

Atomic Layer Deposition of the Solid Electrolyte LiPON

DOE PAGES

Kozen, Alexander C.; Pearse, Alexander J.; Lin, Chuan -Fu; ...

2015-07-09

We demonstrate an atomic layer deposition (ALD) process for the solid electrolyte lithium phosphorousoxynitride (LiPON) using lithium tert-butoxide (LiO tBu), H 2O, trimethylphosphate (TMP), and plasma N 2 ( PN 2) as precursors. We use in-situ spectroscopic ellipsometry to determine growth rates for process optimization to design a rational, quaternary precursor ALD process where only certain substrate–precursor chemical reactions are favorable. We demonstrate via in-situ XPS tunable nitrogen incorporation into the films by variation of the PN 2 dose and find that ALD films over approximately 4.5% nitrogen are amorphous, whereas LiPON ALD films with less than 4.5% nitrogen aremore » polycrystalline. Lastly, we characterize the ionic conductivity of the ALD films as a function of nitrogen content and demonstrate their functionality on a model battery electrode—a Si anode on a Cu current collector.« less

Bacterial phenotype variants in group B streptococcal toxic shock syndrome.

PubMed

Sendi, Parham; Johansson, Linda; Dahesh, Samira; Van-Sorge, Nina M; Darenberg, Jessica; Norgren, Mari; Sjölin, Jan; Nizet, Victor; Norrby-Teglund, Anna

2009-02-01

We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes.

Unconventional secretion of FABP4 by endosomes and secretory lysosomes.

PubMed

Villeneuve, Julien; Bassaganyas, Laia; Lepreux, Sebastien; Chiritoiu, Marioara; Costet, Pierre; Ripoche, Jean; Malhotra, Vivek; Schekman, Randy

2018-02-05

An appreciation of the functional properties of the cytoplasmic fatty acid binding protein 4 (FABP4) has advanced with the recent demonstration that an extracellular form secreted by adipocytes regulates a wide range of physiological functions. Little, however, is known about the mechanisms that mediate the unconventional secretion of FABP4. Here, we demonstrate that FABP4 secretion is mediated by a membrane-bounded compartment, independent of the conventional endoplasmic reticulum-Golgi secretory pathway. We show that FABP4 secretion is also independent of GRASP proteins, autophagy, and multivesicular bodies but involves enclosure within endosomes and secretory lysosomes. We highlight the physiological significance of this pathway with the demonstration that an increase in plasma levels of FABP4 is inhibited by chloroquine treatment of mice. These findings chart the pathway of FABP4 secretion and provide a potential therapeutic means to control metabolic disorders associated with its dysregulated secretion. © 2018 Villeneuve et al.

Anti-correlated Networks, Global Signal Regression, and the Effects of Caffeine in Resting-State Functional MRI

PubMed Central

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T.

2012-01-01

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. PMID:22743194

Global-local visual biases correspond with visual-spatial orientation.

PubMed

Basso, Michael R; Lowery, Natasha

2004-02-01

Within the past decade, numerous investigations have demonstrated reliable associations of global-local visual processing biases with right and left hemisphere function, respectively (cf. Van Kleeck, 1989). Yet the relevance of these biases to other cognitive functions is not well understood. Towards this end, the present research examined the relationship between global-local visual biases and perception of visual-spatial orientation. Twenty-six women and 23 men completed a global-local judgment task (Kimchi and Palmer, 1982) and the Judgment of Line Orientation Test (JLO; Benton, Sivan, Hamsher, Varney, and Spreen, 1994), a measure of visual-spatial orientation. As expected, men had better performance on JLO. Extending previous findings, global biases were related to better visual-spatial acuity on JLO. The findings suggest that global-local biases and visual-spatial orientation may share underlying cerebral mechanisms. Implications of these findings for other visually mediated cognitive outcomes are discussed.

Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior

PubMed Central

Burke, Mary V; Small, Dana M

2017-01-01

Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning. PMID:29619405

Solving the quantum many-body problem with artificial neural networks

NASA Astrophysics Data System (ADS)

Carleo, Giuseppe; Troyer, Matthias

2017-02-01

The challenge posed by the many-body problem in quantum physics originates from the difficulty of describing the nontrivial correlations encoded in the exponential complexity of the many-body wave function. Here we demonstrate that systematic machine learning of the wave function can reduce this complexity to a tractable computational form for some notable cases of physical interest. We introduce a variational representation of quantum states based on artificial neural networks with a variable number of hidden neurons. A reinforcement-learning scheme we demonstrate is capable of both finding the ground state and describing the unitary time evolution of complex interacting quantum systems. Our approach achieves high accuracy in describing prototypical interacting spins models in one and two dimensions.

Transfer and scaffolding of perceptual grouping occurs across organizing principles in 3- to 7-month-old infants.

PubMed

Quinn, Paul C; Bhatt, Ramesh S

2009-08-01

Previous research has demonstrated that organizational principles become functional over different time courses of development: Lightness similarity is available at 3 months of age, but form similarity is not readily in evidence until 6 months of age. We investigated whether organization would transfer across principles and whether perceptual scaffolding can occur from an already functional principle to a not-yet-operational principle. Six- to 7-month-old infants (Experiment 1) and 3- to 4-month-old infants (Experiment 2) who were familiarized with arrays of elements organized by lightness similarity displayed a subsequent visual preference for a novel organization defined by form similarity. Results with the older infants demonstrate transfer in perceptual grouping: The organization defined by one grouping principle can direct a visual preference for a novel organization defined by a different grouping principle. Findings with the younger infants suggest that learning based on an already functional organizational process enables an organizational process that is not yet functional through perceptual scaffolding.

An intelligent value-driven scheduling system for Space Station Freedom with special emphasis on the electric power system

NASA Technical Reports Server (NTRS)

Krupp, Joseph C.

1991-01-01

The Electric Power Control System (EPCS) created by Decision-Science Applications, Inc. (DSA) for the Lewis Research Center is discussed. This system makes decisions on what to schedule and when to schedule it, including making choices among various options or ways of performing a task. The system is goal-directed and seeks to shape resource usage in an optimal manner using a value-driven approach. Discussed here are considerations governing what makes a good schedule, how to design a value function to find the best schedule, and how to design the algorithm that finds the schedule that maximizes this value function. Results are shown which demonstrate the usefulness of the techniques employed.

p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells

PubMed Central

Deng, Wen; Zhou, Yuan; Tiwari, Agnes FY; Su, Hang; Yang, Jie; Zhu, Dandan; Lau, Victoria Ming Yi; Hau, Pok Man; Yip, Yim Ling; Cheung, Annie LM; Guan, Xin-Yuan; Tsao, Sai Wah

2015-01-01

Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21. PMID:25131797

Investigating Years 7 to 12 students' knowledge of linear relationships through different contexts and representations

NASA Astrophysics Data System (ADS)

Wilkie, Karina J.; Ayalon, Michal

2018-02-01

A foundational component of developing algebraic thinking for meaningful calculus learning is the idea of "function" that focuses on the relationship between varying quantities. Students have demonstrated widespread difficulties in learning calculus, particularly interpreting and modeling dynamic events, when they have a poor understanding of relationships between variables. Yet, there are differing views on how to develop students' functional thinking over time. In the Australian curriculum context, linear relationships are introduced to lower secondary students with content that reflects a hybrid of traditional and reform algebra pedagogy. This article discusses an investigation into Australian secondary students' understanding of linear functional relationships from Years 7 to 12 (approximately 12 to 18 years old; n = 215) in their approaches to three tasks (finding rate of change, pattern generalisation and interpretation of gradient) involving four different representations (table, geometric growing pattern, equation and graph). From the findings, it appears that these students' knowledge of linear functions remains context-specific rather than becoming connected over time.

Locus of control and utilization of social support among mothers of young children with physical disabilities.

PubMed

Rimmerman, A; Stanger, V

1992-01-01

Sixty mothers of young children with physical disabilities were studied with respect to the effect of the mothers' locus of control on the utilization of social support. The initial findings failed to support the thesis that mothers with an 'internally' focused locus of control would demonstrate greater utilization of their support system, both in terms of descriptive and functional measures. A secondary analysis showed that the mothers' age, the children's level of functioning, and the existence of additional members of the family with a disability served as intervening variables. Only among older mothers, who perceived their children's functioning as severe, was there significant association between the locus of control ('internal') and greater use of their social support system. 'Internal' mothers who had no additional extended family members with a disability reported higher levels of functional social support, as compared to 'external' mothers. Findings are interpreted with respect to social support theory and its implications to applied research.

Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation.

PubMed

Takeoka, Aya; Jindrich, Devin L; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L; Ziegler, Matthias D; Ramón-Cueto, Almudena; Roy, Roland R; Edgerton, V Reggie; Phelps, Patricia E

2011-03-16

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function.

Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

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

Ivanov, Sergey V., E-mail: Sergey.Ivanov@med.nyu.edu; Ivanova, Alla V.; Goparaju, Chandra M.V.

2009-05-08

Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-Cmore » demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.« less

Axon Regeneration Can Facilitate or Suppress Hindlimb Function after Olfactory Ensheathing Glia Transplantation

PubMed Central

Takeoka, Aya; Jindrich, Devin L.; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L.; Ziegler, Matthias D.; Ramón-Cueto, Almudena; Roy, Roland R.; Edgerton, V. Reggie

2011-01-01

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function. PMID:21411671

Comparison of multifocal visual evoked potential, static automated perimetry, and optical coherence tomography findings for assessing visual pathways in patients with pituitary adenomas.

PubMed

Qiao, Nidan; Zhang, Yichao; Ye, Zhao; Shen, Ming; Shou, Xuefei; Wang, Yongfei; Li, Shiqi; Wang, Min; Zhao, Yao

2015-10-01

There have been no studies investigating the correlation between structural [thickness of the retinal nerve fiber layer (RNFL) as determined by optical coherence tomography (OCT)] and functional [Humphrey visual field (HVF) or visual evoked potential (VEP) amplitude] measures of optic nerve integrity in patients with pituitary adenomas (PA). Patients with PAs were recruited between September 2010 and September 2013. OCT, standard automated perimetry (SAP), and multifical VEP (mfVEP) were performed. Agreement between OCT, SAP, and mfVEP values in classifying eyes/quadrants was determined using AC1 statistics. Pearson's correlation was used to examine relationships between structural and functional data. In total, 88.7% of the eyes tested showed abnormal SAP findings and 93.7% showed abnormal mfVEP findings. Only 14.8% of the eyes showed abnormal OCT findings. The agreement between SAP and mfVEP findings was 88.9% (AC1 = 0.87). The agreement between OCT and mfVEP findings was 24.2% (AC1 = -0.52), and that between OCT and SAP findings was 21.5% (AC1 = -0.56). The correlation values between RNFL thickness and the functional measurements were -0.601 for the mfVEP score (P = 0.000) and -0.441 for the SAP score (P = 0.000). The correlation between the mfVEP and SAP scores was -0.617 (P = 0.000). mfVEP, SAP, and OCT provided complementary information for detecting visual pathway abnormalities in patients with PAs. Good agreement was demonstrated between SAP and mfVEP and quantitative analysis of structure-function measurements revealed a moderate correlation.

Evidence for hubs in human functional brain networks

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

2013-01-01

Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

Analyzing the financial crisis using the entropy density function

NASA Astrophysics Data System (ADS)

Oh, Gabjin; Kim, Ho-yong; Ahn, Seok-Won; Kwak, Wooseop

2015-02-01

The risk that is created by nonlinear interactions among subjects in economic systems is assumed to increase during an abnormal state of a financial market. Nevertheless, investigating the systemic risk in financial markets following the global financial crisis is not sufficient. In this paper, we analyze the entropy density function in the return time series for several financial markets, such as the S&P500, KOSPI, and DAX indices, from October 2002 to December 2011 and analyze the variability in the entropy value over time. We find that the entropy density function of the S&P500 index during the subprime crisis exhibits a significant decrease compared to that in other periods, whereas the other markets, such as those in Germany and Korea, exhibit no significant decrease during the market crisis. These findings demonstrate that the S&P500 index generated a regular pattern in the return time series during the financial crisis.

Momentum distribution functions in ensembles: the inequivalence of microcannonical and canonical ensembles in a finite ultracold system.

PubMed

Wang, Pei; Xianlong, Gao; Li, Haibin

2013-08-01

It is demonstrated in many thermodynamic textbooks that the equivalence of the different ensembles is achieved in the thermodynamic limit. In this present work we discuss the inequivalence of microcanonical and canonical ensembles in a finite ultracold system at low energies. We calculate the microcanonical momentum distribution function (MDF) in a system of identical fermions (bosons). We find that the microcanonical MDF deviates from the canonical one, which is the Fermi-Dirac (Bose-Einstein) function, in a finite system at low energies where the single-particle density of states and its inverse are finite.

Manipulating Motivating Operations to Facilitate the Emergence of Mands for a Child with Autism

ERIC Educational Resources Information Center

Davis, Barbara Janine; Kahng, SungWoo; Coryat, Kaitlin

2012-01-01

Research on the functional independence of verbal operants (Skinner, 1957) has demonstrated inconsistent findings. One explanation may be that these studies have not manipulated the motivating operation (MO) to facilitate the emergence of mands (Hall & Sundberg, 1987; Lamarre & Holland, 1985). In the current study, 1 participant, diagnosed with…

Intermittent and Flexible Work Schedules and Welfare Mothers' Employment. Phase 2.

ERIC Educational Resources Information Center

Franklin, David S.

The project worked closely and supportively with California welfare mothers, helping them find suitable employment which meshed with their parenting functions, to demonstrate and test the impact of flexible work schedules and to determine whether business and industry could provide flexibly scheduled work (part-time, temporary, or intermittent).…

Density functional theory fragment descriptors to quantify the reactivity of a molecular family: application to amino acids.

PubMed

Senet, P; Aparicio, F

2007-04-14

By using the exact density functional theory, one demonstrates that the value of the local electronic softness of a molecular fragment is directly related to the polarization charge (Coulomb hole) induced by a test electron removed (or added) from (at) the fragment. Our finding generalizes to a chemical group a formal relation between these molecular descriptors recently obtained for an atom in a molecule using an approximate atomistic model [P. Senet and M. Yang, J. Chem. Sci. 117, 411 (2005)]. In addition, a practical ab initio computational scheme of the Coulomb hole and related local descriptors of reactivity of a molecular family having in common a similar fragment is presented. As a blind test, the method is applied to the lateral chains of the 20 isolated amino acids. One demonstrates that the local softness of the lateral chain is a quantitative measure of the similarity of the amino acids. It predicts the separation of amino acids in different biochemical groups (aliphatic, basic, acidic, sulfur contained, and aromatic). The present approach may find applications in quantitative structure activity relationship methodology.

Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Drosophila Males

PubMed Central

Andrews, Jonathan C.; Fernández, María Paz; Yu, Qin; Leary, Greg P.; Leung, Adelaine K. W.; Kavanaugh, Michael P.; Kravitz, Edward A.; Certel, Sarah J.

2014-01-01

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-FruM neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway. PMID:24852170

Occipital cortex of blind individuals is functionally coupled with executive control areas of frontal cortex.

PubMed

Deen, Ben; Saxe, Rebecca; Bedny, Marina

2015-08-01

In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity.

Demographic and obstetric factors affecting women's sexual functioning during pregnancy.

PubMed

Abouzari-Gazafroodi, Kobra; Najafi, Fatemeh; Kazemnejad, Ehsan; Rahnama, Parvin; Montazeri, Ali

2015-08-19

Sexual desire and frequency of sexual relationships during pregnancy remains challenging. This study aimed to assess factors that affect women's sexual functioning during pregnancy. This was a cross sectional study carried out at prenatal care clinics of public health services in Iran. An author-designed structured questionnaire including items on socio-demographic characteristics, obstetric history, the current pregnancy, and women's sexual functioning during pregnancy was used to collect data. The generalized linear model was performed in order to find out factors that affect women's sexual functioning during pregnancy. In all, 518 pregnant women participated in the study. The mean age of participants was 26.4 years (SD = 4.7). Overall 309 women (59.7%) scored less than mean on sexual functioning. The results obtained from generalized linear model demonstrated that that lower education, unwanted pregnancy, earlier stage of pregnancy, older age, and longer duration of marriage were the most important factors contributing to disturbed sexual functioning among couples. The findings suggest that sexual function during pregnancy might be disturbed due to several factors. Indeed issues on sexual relationship should be included as part of prenatal care and reproductive health programs for every woman.

PML–RARA-RXR Oligomers Mediate Retinoid and Rexinoid/cAMP Cross-Talk in Acute Promyelocytic Leukemia Cell Differentiation

PubMed Central

Kamashev, Dmitrii; Vitoux, Dominique; de Thé, Hugues

2004-01-01

PML–RARA was proposed to initiate acute promyelocytic leukemia (APL) through PML–RARA homodimer–triggered repression. Here, we examined the nature of the PML–RARA protein complex and of its DNA targets in APL cells. Using a selection/amplification approach, we demonstrate that PML–RARA targets consist of two AGGTCA elements in an astonishing variety of orientations and spacings, pointing to highly relaxed structural constrains for DNA binding and identifying a major gain of function of this oncogene. PML–RARA-specific response elements were identified, which all conveyed a major transcriptional response to RA only in APL cells. In these cells, we demonstrate that PML–RARA oligomers are complexed to RXR. Directly probing PML–RARA function in APL cells, we found that the differentiation enhancer cyclic AMP (cAMP) boosted transcriptional activation by RA. cAMP also reversed the normal silencing (subordination) of the transactivating function of RXR when bound to RARA or PML–RARA, demonstrating that the alternate rexinoid/cAMP-triggered APL differentiation pathway also activates PML–RARA targets. Finally, cAMP restored both RA-triggered differentiation and PML–RARA transcriptional activation in mutant RA-resistant APL cells. Collectively, our findings directly demonstrate that APL cell differentiation parallels transcriptional activation through PML–RARA-RXR oligomers and that those are functionally targeted by cAMP, identifying this agent as another oncogene-targeted therapy. PMID:15096541

Pattern of executive functioning in adolescents with epilepsy: A multimethod measurement approach.

PubMed

Modi, Avani C; Vannest, Jennifer; Combs, Angela; Turnier, Luke; Wade, Shari L

2018-03-01

Youth with epilepsy demonstrate deficits in executive functioning (EF), the skills necessary for goal-directed behavior (e.g., problem-solving, initiating, monitoring, organization, planning, and working memory). Despite 30-50% of youth with epilepsy demonstrating EF deficits, no extant studies have utilized both performance and questionnaire-based measures to examine the pattern of EF deficits in adolescents with epilepsy. Study aims were to 1) identify the pattern of EF deficits in adolescents with epilepsy and 2) identify which assessment tools are most sensitive to EF deficits in this population (adolescents, ages 13-17, with epilepsy). An exploratory aim was to examine group differences on measures of EF by epilepsy type. Standard performance-based neuropsychological measures (Wechsler Intelligence Scale for Children - Version V or Wechsler Adult Intelligence Scale Working Memory Index-Version IV, Delis Kaplan Executive Functioning System, NIH Toolbox, Test of Everyday Attention for Children) and the Behavior Rating Inventory of Executive Functioning (BRIEF) comprised the multimethod assessment battery. Depending on the measure, 30% of adolescents with epilepsy had deficits in working memory, 17% in cognitive flexibility/problem solving, 6% in inhibition, and 18% in planning/organization. Attention was a significant problem for 15% of adolescents with epilepsy. Correlations among the various EF measures were quite poor. Across various EF domains, results indicated that adolescents with localization-related epilepsy demonstrated better EF skills compared to adolescents with unclassified epilepsy. Overall, our findings suggest that executive functioning deficits are selective and different from those observed in other neurological populations (e.g., attention deficit hyperactivity disorder (ADHD), traumatic brain injury) where problems with self-regulation (i.e., inhibition, planning/organization) are more pronounced. These findings support utilizing multiple measures, including both performance-based neuropsychological tests and parent- and self-reports, to assess executive functioning difficulties in adolescents with epilepsy as they are uniquely sensitive to executive functioning domains. Adolescents with unclassified epilepsy also appear to be at higher risk for EF deficits and thus represent an important group to target for intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Unravelling the Intrinsic Functional Organization of the Human Striatum: A Parcellation and Connectivity Study Based on Resting-State fMRI

PubMed Central

Jung, Wi Hoon; Jang, Joon Hwan; Park, Jin Woo; Kim, Euitae; Goo, Eun-Hoe; Im, Oh-Soo; Kwon, Jun Soo

2014-01-01

As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders. PMID:25203441

Political violence, collective functioning and health: a review of the literature.

PubMed

Sousa, Cindy A

2013-01-01

Political violence is implicated in a range of mental health outcomes, including PTSD, depression, and anxiety. The social and political contexts of people's lives, however, offer considerable protection from the mental health effects of political violence. In spite of the importance of people's social and political environments for health, there is limited scholarship on how political violence compromises necessary social and political systems and inhibits individuals from participating in social and political life. Drawing on literature from multiple disciplines, including public health, anthropology, and psychology, this narrative review uses a multi-level, social ecological framework to enhance current knowledge about the ways that political violence affects health. Findings from over 50 studies were analysed and used to build a conceptual model demonstrating how political violence threatens three inter-related domains of functioning: individual functioning in relationship to their environment; community functioning and social fabric; and governmental functioning and delivery of services to populations. Results illustrate the need for multilevel frameworks that move beyond individual pathology towards more nuanced conceptualizations about how political violence affects health; findings contribute to the development of prevention programmes addressing political violence.

High-order time-marching reinitialization for regional level-set functions

NASA Astrophysics Data System (ADS)

Pan, Shucheng; Lyu, Xiuxiu; Hu, Xiangyu Y.; Adams, Nikolaus A.

2018-02-01

In this work, the time-marching reinitialization method is extended to compute the unsigned distance function in multi-region systems involving arbitrary number of regions. High order and interface preservation are achieved by applying a simple mapping that transforms the regional level-set function to the level-set function and a high-order two-step reinitialization method which is a combination of the closest point finding procedure and the HJ-WENO scheme. The convergence failure of the closest point finding procedure in three dimensions is addressed by employing a proposed multiple junction treatment and a directional optimization algorithm. Simple test cases show that our method exhibits 4th-order accuracy for reinitializing the regional level-set functions and strictly satisfies the interface-preserving property. The reinitialization results for more complex cases with randomly generated diagrams show the capability our method for arbitrary number of regions N, with a computational effort independent of N. The proposed method has been applied to dynamic interfaces with different types of flows, and the results demonstrate high accuracy and robustness.

Atypical within- and between-hemisphere motor network functional connections in children with developmental coordination disorder and attention-deficit/hyperactivity disorder.

PubMed

McLeod, Kevin R; Langevin, Lisa Marie; Dewey, Deborah; Goodyear, Bradley G

2016-01-01

Developmental coordination disorder (DCD) and attention-deficit hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders; however, the neural mechanisms of this comorbidity are poorly understood. Previous research has demonstrated that children with DCD and ADHD have altered brain region communication, particularly within the motor network. The structure and function of the motor network in a typically developing brain exhibits hemispheric dominance. It is plausible that functional deficits observed in children with DCD and ADHD are associated with neurodevelopmental alterations in within- and between-hemisphere motor network functional connection strength that disrupt this hemispheric dominance. We used resting-state functional magnetic resonance imaging to examine functional connections of the left and right primary and sensory motor (SM1) cortices in children with DCD, ADHD and DCD + ADHD, relative to typically developing children. Our findings revealed that children with DCD, ADHD and DCD + ADHD exhibit atypical within- and between-hemisphere functional connection strength between SM1 and regions of the basal ganglia, as well as the cerebellum. Our findings further support the assertion that development of atypical motor network connections represents common and distinct neural mechanisms underlying DCD and ADHD. In children with DCD and DCD + ADHD (but not ADHD), a significant correlation was observed between clinical assessment of motor function and the strength of functional connections between right SM1 and anterior cingulate cortex, supplementary motor area, and regions involved in visuospatial processing. This latter finding suggests that behavioral phenotypes associated with atypical motor network development differ between individuals with DCD and those with ADHD.

Housing First for People With Severe Mental Illness Who Are Homeless: A Review of the Research and Findings From the At Home–Chez soi Demonstration Project

PubMed Central

Aubry, Tim; Nelson, Geoffrey; Tsemberis, Sam

2015-01-01

Objective: To provide a review of the extant research literature on Housing First (HF) for people with severe mental illness (SMI) who are homeless and to describe the findings of the recently completed At Home (AH)–Chez soi (CS) demonstration project. HF represents a paradigm shift in the delivery of community mental health services, whereby people with SMI who are homeless are supported through assertive community treatment or intensive case management to move into regular housing. Method: The AH–CS demonstration project entailed a randomized controlled trial conducted in 5 Canadian cities between 2009 and 2013. Mixed methods were used to examine the implementation of HF programs and participant outcomes, comparing 1158 people receiving HF to 990 people receiving standard care. Results: Initial research conducted in the United States shows HF to be a promising approach, yielding superior outcomes in helping people to rapidly exit homelessness and establish stable housing. Findings from the AH–CS demonstration project reveal that HF can be successfully adapted to different contexts and for different populations without losing its fidelity. People receiving HF achieved superior housing outcomes and showed more rapid improvements in community functioning and quality of life than those receiving treatment as usual. Conclusions: Knowledge translation efforts have been undertaken to disseminate the positive findings and lessons learned from the AH–CS project and to scale up the HF approach across Canada. PMID:26720504

Housing First for People With Severe Mental Illness Who Are Homeless: A Review of the Research and Findings From the At Home-Chez soi Demonstration Project.

PubMed

Aubry, Tim; Nelson, Geoffrey; Tsemberis, Sam

2015-11-01

To provide a review of the extant research literature on Housing First (HF) for people with severe mental illness (SMI) who are homeless and to describe the findings of the recently completed At Home (AH)-Chez soi (CS) demonstration project. HF represents a paradigm shift in the delivery of community mental health services, whereby people with SMI who are homeless are supported through assertive community treatment or intensive case management to move into regular housing. The AH-CS demonstration project entailed a randomized controlled trial conducted in 5 Canadian cities between 2009 and 2013. Mixed methods were used to examine the implementation of HF programs and participant outcomes, comparing 1158 people receiving HF to 990 people receiving standard care. Initial research conducted in the United States shows HF to be a promising approach, yielding superior outcomes in helping people to rapidly exit homelessness and establish stable housing. Findings from the AH-CS demonstration project reveal that HF can be successfully adapted to different contexts and for different populations without losing its fidelity. People receiving HF achieved superior housing outcomes and showed more rapid improvements in community functioning and quality of life than those receiving treatment as usual. Knowledge translation efforts have been undertaken to disseminate the positive findings and lessons learned from the AH-CS project and to scale up the HF approach across Canada.

Finding the authentic self in a communal culture: developmental goals in emerging adulthood.

PubMed

Scharf, Miri; Mayseless, Ofra

2010-01-01

Finding and cultivating a sense of authentic self is an important life goal for emerging adults. In collectivist cultures, youngsters might need to distance themselves to find and discover their authentic selves separate of the expectations of society and significant others. Creating an autonomous time bubble that focuses on the present allows youngsters to forge a sense of personal meaning and authenticity that subsequently paves the way to reintegration into long-term life goals. The results focusing on Israeli emerging adults demonstrate that a sense of authentic self plays a central role in their well-being and socioemotional functioning. © Wiley Periodicals, Inc.

fMRI functional connectivity of the periaqueductal gray in PTSD and its dissociative subtype.

PubMed

Harricharan, Sherain; Rabellino, Daniela; Frewen, Paul A; Densmore, Maria; Théberge, Jean; McKinnon, Margaret C; Schore, Allan N; Lanius, Ruth A

2016-12-01

Posttraumatic stress disorder (PTSD) is associated with hyperarousal and active fight or flight defensive responses. By contrast, the dissociative subtype of PTSD, characterized by depersonalization and derealization symptoms, is frequently accompanied by additional passive or submissive defensive responses associated with autonomic blunting. Here, the periaqueductal gray (PAG) plays a central role in defensive responses, where the dorsolateral (DL-PAG) and ventrolateral PAG (VL-PAG) are thought to mediate active and passive defensive responses, respectively. We examined PAG subregion (dorsolateral and ventrolateral) resting-state functional connectivity in three groups: PTSD patients without the dissociative subtype ( n  = 60); PTSD patients with the dissociative subtype ( n  = 37); and healthy controls ( n  = 40) using a seed-based approach via PickAtlas and SPM12. All PTSD patients showed extensive DL- and VL-PAG functional connectivity at rest with areas associated with emotional reactivity and defensive action as compared to controls ( n  = 40). Although all PTSD patients demonstrated DL-PAG functional connectivity with areas associated with initiation of active coping strategies and hyperarousal (e.g., dorsal anterior cingulate; anterior insula), only dissociative PTSD patients exhibited greater VL-PAG functional connectivity with brain regions linked to passive coping strategies and increased levels of depersonalization (e.g., temporoparietal junction; rolandic operculum). These findings suggest greater defensive posturing in PTSD patients even at rest and demonstrate that those with the dissociative subtype show unique patterns of PAG functional connectivity when compared to those without the subtype. Taken together, these findings represent an important first step toward identifying neural and behavioral targets for therapeutic interventions that address defensive strategies in trauma-related disorders.

Mitochondrial Pyruvate Carrier Function and Cancer Metabolism

PubMed Central

Rauckhorst, Adam J.

2016-01-01

Metabolic reprograming in cancer supports the increased biosynthesis required for unchecked proliferation. Increased glucose utilization is a defining feature of many cancers that is accompanied by altered pyruvate partitioning and mitochondrial metabolism. Cancer cells also require mitochondrial tricarboxylic acid cycle activity and electron transport chain function for biosynthetic competency and proliferation. Recent evidence demonstrates that mitochondrial pyruvate carrier (MPC) function is abnormal in some cancers and that increasing MPC activity may decrease cancer proliferation. Here we examine recent findings on MPC function and cancer metabolism. Special emphasis is placed on the compartmentalization of pyruvate metabolism and the alternative routes of metabolism that maintain the cellular biosynthetic pools required for unrestrained proliferation in cancer. PMID:27269731

Neurocognitive mechanisms of mathematical giftedness: A literature review.

PubMed

Zhang, Li; Gan, John Q; Wang, Haixian

2017-01-01

Mathematically gifted children/adolescents have demonstrated exceptional abilities and traits in logical reasoning, mental imagery, and creative thinking. In the field of cognitive neuroscience, the past studies on mathematically gifted brains have concentrated on investigating event-related brain activation regions, cerebral laterality of cognitive functions, functional specialization that is uniquely dedicated for specific cognitive purposes, and functional interactions among discrete brain regions. From structural and functional perspectives, these studies have witnessed both "general" and "unique" neural characteristics of mathematically gifted brains. In this article, the theoretical background, empirical studies, and neurocognitive mechanisms of mathematically gifted children/adolescents are reviewed. Based on the integration of the findings, some potential directions for the future research are identified and discussed.

Quantum Chemistry Study of Cycloaddition Pathways for the Reaction of o-Benzyne with Fullerenes and Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Jaffe, Richard; Han, Jie; Langhoff, Stephen R. (Technical Monitor)

1997-01-01

Functionalization of fullerenes via the [2+2] cycloaddition reaction with o-benzyne has been demonstrated in the laboratory. In contrast, [2+4) cycloaddition products are formed when benzyne reacts with planar polycyclic aromatic hydrocarbons. Using density functional theory (DFT) calculations with Becke's hybrid functional and small contracted gaussian basis sets, we are able to reproduce these product preferences. The objective of this work is to explore the functionalization of carbon nanotubes. We have studied o-benzyne cycloaddition products with a [14,0] single-walled nanotube. We find both the [2+2] and [2+4] adducts to be stable, with the latter product being somewhat favored.

Intact imitation of emotional facial actions in autism spectrum conditions.

PubMed

Press, Clare; Richardson, Daniel; Bird, Geoffrey

2010-09-01

It has been proposed that there is a core impairment in autism spectrum conditions (ASC) to the mirror neuron system (MNS): If observed actions cannot be mapped onto the motor commands required for performance, higher order sociocognitive functions that involve understanding another person's perspective, such as theory of mind, may be impaired. However, evidence of MNS impairment in ASC is mixed. The present study used an 'automatic imitation' paradigm to assess MNS functioning in adults with ASC and matched controls, when observing emotional facial actions. Participants performed a pre-specified angry or surprised facial action in response to observed angry or surprised facial actions, and the speed of their action was measured with motion tracking equipment. Both the ASC and control groups demonstrated automatic imitation of the facial actions, such that responding was faster when they acted with the same emotional expression that they had observed. There was no difference between the two groups in the magnitude of the effect. These findings suggest that previous apparent demonstrations of impairments to the MNS in ASC may be driven by a lack of visual attention to the stimuli or motor sequencing impairments, and therefore that there is, in fact, no MNS impairment in ASC. We discuss these findings with reference to the literature on MNS functioning and imitation in ASC, as well as theories of the role of the MNS in sociocognitive functioning in typical development. Copyright 2010 Elsevier Ltd. All rights reserved.

Functional Magnetic Resonance Imaging of Working Memory and Executive Dysfunction in Systemic Lupus Erythematosus and Antiphospholipid Antibody-Positive Patients.

PubMed

Kozora, E; Uluğ, A M; Erkan, D; Vo, A; Filley, C M; Ramon, G; Burleson, A; Zimmerman, R; Lockshin, M D

2016-11-01

Standardized cognitive tests and functional magnetic resonance imaging (fMRI) studies of systemic lupus erythematosus (SLE) patients demonstrate deficits in working memory and executive function. These neurobehavioral abnormalities are not well studied in antiphospholipid syndrome, which may occur independently of or together with SLE. This study compares an fMRI paradigm involving motor skills, working memory, and executive function in SLE patients without antiphospholipid antibody (aPL) (the SLE group), aPL-positive non-SLE patients (the aPL-positive group), and controls. Brain MRI, fMRI, and standardized cognitive assessment results were obtained from 20 SLE, 20 aPL-positive, and 10 healthy female subjects with no history of neuropsychiatric abnormality. Analysis of fMRI data showed no differences in performance across groups on bilateral motor tasks. When analysis of variance was used, significant group differences were found in 2 executive function tasks (word generation and word rhyming) and in a working memory task (N-Back). Patients positive for aPL demonstrated higher activation in bilateral frontal, temporal, and parietal cortices compared to controls during working memory and executive function tasks. SLE patients also demonstrated bilateral frontal and temporal activation during working memory and executive function tasks. Compared to controls, both aPL-positive and SLE patients had elevated cortical activation, primarily in the frontal lobes, during tasks involving working memory and executive function. These findings are consistent with cortical overactivation as a compensatory mechanism for early white matter neuropathology in these disorders. © 2016, American College of Rheumatology.

Language and social functioning in children and adolescents with epilepsy.

PubMed

Byars, Anna W; deGrauw, Ton J; Johnson, Cynthia S; Perkins, Susan M; Fastenau, Philip S; Dunn, David W; Austin, Joan K

2014-02-01

Individuals with epilepsy have difficulties with social function that are not adequately accounted for by seizure severity or frequency. This study examined the relationship between language ability and social functioning in 193 children with epilepsy over a period of 36months following their first recognized seizure. The findings show that children with persistent seizures have poorer language function, even at the onset of their seizures, than do their healthy siblings, children with no recurrent seizures, and children with recurrent but not persistent seizures. They continue to demonstrate poorer language function 36months later. This poor language function is associated with declining social competence. Intervention aimed at improving social competence should include consideration of potential language deficits that accompany epilepsy and social difficulty. Copyright © 2013 Elsevier Inc. All rights reserved.

Production of interleukin-10 by human bronchogenic carcinoma.

PubMed Central

Smith, D. R.; Kunkel, S. L.; Burdick, M. D.; Wilke, C. A.; Orringer, M. B.; Whyte, R. I.; Strieter, R. M.

1994-01-01

Interleukin-10 (IL-10) is a recently characterized cytokine with suppressive activity against various aspects of the cellular immune response. Our laboratory has previously demonstrated that another anti-inflammatory cytokine, IL-1 receptor antagonist (IRAP) is produced and secreted by human bronchogenic carcinomas. We speculated that tumor production of IRAP may mitigate host responses and confer increased tumor viability. In this study, we investigated the capacity of human bronchogenic tumors to produce IL-10 as another possible mechanism to attenuate host defenses. We found increased levels of antigenic IL-10 in tissue homogenates of human bronchogenic carcinomas compared with normal lung tissue (13.69 +/- 2.87 versus 5.84 +/- 0.84 ng/mg total protein). Immunohistochemical staining of tumors illustrate primary localization of antigenic IL-10 to individual tumor cells. Analysis of supernatants of several unstimulated human bronchogenic cell lines in vitro demonstrated the ability of tumor cells to constitutively produce IL-10. Functional studies of mononuclear cells, cultured in the presence of conditioned medium from a bronchogenic cell line, demonstrated their increased tumor necrosis factor and IL-6 production with the addition of neutralizing antibodies to IL-10. These findings demonstrate that human bronchogenic carcinomas elaborate functional IL-10, which may significantly impair immune effector cell function and enable the tumor to evade host defenses. Images Figure 1 Figure 2 PMID:8030748

Neural Correlates of Consumer Buying Motivations: A 7T functional Magnetic Resonance Imaging (fMRI) Study

PubMed Central

Goodman, Adam M.; Wang, Yun; Kwon, Wi-Suk; Byun, Sang-Eun; Katz, Jeffrey S.; Deshpande, Gopikrishna

2017-01-01

Consumer buying motivations can be distinguished into three categories: functional, experiential, or symbolic motivations (Keller, 1993). Although prior neuroimaging studies have examined the neural substrates which enable these motivations, direct comparisons between these three types of consumer motivations have yet to be made. In the current study, we used 7 Tesla (7T) functional magnetic resonance imaging (fMRI) to assess the neural correlates of each motivation by instructing participants to view common consumer goods while emphasizing either functional, experiential, or symbolic values of these products. The results demonstrated mostly consistent activations between symbolic and experiential motivations. Although, these motivations differed in that symbolic motivation was associated with medial frontal gyrus (MFG) activation, whereas experiential motivation was associated with posterior cingulate cortex (PCC) activation. Functional motivation was associated with dorsolateral prefrontal cortex (DLPFC) activation, as compared to other motivations. These findings provide a neural basis for how symbolic and experiential motivations may be similar, yet different in subtle ways. Furthermore, the dissociation of functional motivation within the DLPFC supports the notion that this motivation relies on executive function processes relatively more than hedonic motivation. These findings provide a better understanding of the underlying neural functioning which may contribute to poor self-control choices. PMID:28959182

Rising to the Bilingual Challenge: Self-Reported Experiences of Managing Life with Two Languages

ERIC Educational Resources Information Center

Tytus, Agnieszka Ewa

2018-01-01

A recent surge of findings on bilingual cognitive advantage has attracted attention from both researchers and the media. An advantage has been demonstrated with regard to, inter alia, inhibiting, switching, monitoring and updating. However, Paap et al. argue that the advantage does not exist or is only limited to executive functioning. Both sides…

Anterior Cingulate Cortex and Cognitive Control: Neuropsychological and Electrophysiological Findings in Two Patients with Lesions to Dorsomedial Prefrontal Cortex

ERIC Educational Resources Information Center

Lovstad, M.; Funderud, I.; Meling, T.; Kramer, U. M.; Voytek, B.; Due-Tonnessen, P.; Endestad, T.; Lindgren, M.; Knight, R. T.; Solbakk, A. K.

2012-01-01

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial…

The Influence of Rural/Urban Residence on Health in the Oldest-Old.

ERIC Educational Resources Information Center

Clayton, Gloria M.; And Others

1994-01-01

Used data from Georgia Centenarian Study to examine differences between rural (n=18) and urban (n=66) centenarians across physical health, activities of daily living, mental health, and life satisfaction. Found higher levels of morale in rural residents and higher levels of functional health in urban elders. Findings demonstrated absence of robust…

Differential Amygdala Response to Lower Face in Patients with Autistic Spectrum Disorders: An fMRI Study

ERIC Educational Resources Information Center

Ishitobi, Makoto; Kosaka, Hirotaka; Omori, Masao; Matsumura, Yukiko; Munesue, Toshio; Mizukami, Kimiko; Shimoyama, Tomohiro; Murata, Tetsuhito; Sadato, Norihiro; Okazawa, Hidehiko; Wada, Yuji

2011-01-01

Much functional neuroimaging evidence indicates that autistic spectrum disorders (ASD) demonstrate marked brain abnormalities in face processing. Most of these findings were obtained from studies using tasks related to whole faces. However, individuals with ASD tend to rely more on individual parts of the face for identification than on the…

Rapid and Programmable Protein Mutagenesis Using Plasmid Recombineering.

PubMed

Higgins, Sean A; Ouonkap, Sorel V Y; Savage, David F

2017-10-20

Comprehensive and programmable protein mutagenesis is critical for understanding structure-function relationships and improving protein function. There is thus a need for robust and unbiased molecular biological approaches for the construction of the requisite comprehensive protein libraries. Here we demonstrate that plasmid recombineering is a simple and robust in vivo method for the generation of protein mutants for both comprehensive library generation as well as programmable targeting of sequence space. Using the fluorescent protein iLOV as a model target, we build a complete mutagenesis library and find it to be specific and comprehensive, detecting 99.8% of our intended mutations. We then develop a thermostability screen and utilize our comprehensive mutation data to rapidly construct a targeted and multiplexed library that identifies significantly improved variants, thus demonstrating rapid protein engineering in a simple protocol.

[The Prevalence and Risk Factors of Dementia in Centenarians].

PubMed

Arai, Yasumichi

2017-07-01

Centenarians are less susceptible to the diseases, functional losses and dependencies related to old age than the general public, and are therefore regarded as model cases of successful aging. For this reason, an important focus of the study of centenarians is their relative resilience to age-related cognitive decline or dementia. In the Tokyo Centenarian Study, we found approximately 60% of centenarians to have dementia; however, supercentenarians (those people living at least 110 years) maintained normal cognitive function at 100 years of age. Our preliminary data also demonstrated extremely low frequencies of the apolipoprotein E4 allele in supercentenarians. Moreover, postmortem brain samples from supercentenarians demonstrated relatively mild age-related neuropathological findings. Therefore, a more extensive investigation of supercentenarian populations might provide insight into successful brain aging.

Political attitudes bias the mental representation of a presidential candidate's face.

PubMed

Young, Alison I; Ratner, Kyle G; Fazio, Russell H

2014-02-01

Using a technique known as reverse-correlation image classification, we demonstrated that the face of Mitt Romney as represented in people's minds varies as a function of their attitudes toward Mitt Romney. Our findings provide evidence that attitudes bias how people see something as concrete and well learned as the face of a political candidate during an election. Practically, our findings imply that citizens may not merely interpret political information about a candidate to fit their opinion, but also may construct a political world in which they literally see candidates differently.

Thermodynamic theory of intrinsic finite size effects in PbTiO3 nanocrystals. II. Dielectric and piezoelectric properties

NASA Astrophysics Data System (ADS)

Akdogan, E. K.; Safari, A.

2007-03-01

We compute the intrinsic dielectric and piezoelectric properties of single domain, mechanically free, and surface charge compensated PbTiO3 nanocrystals (n-Pt) with no depolarization fields, undergoing a finite size induced first order tetragonal→cubic ferrodistortive phase transition. By using a Landau-Devonshire type free energy functional, in which Landau coefficients are a function of nanoparticle size, we demonstrate substantial deviations from bulk properties in the range <150 nm. We find a decrease in dielectric susceptibility at the transition temperature with decreasing particle size, which we verify to be in conformity with predictions of lattice dynamics considerations. We also find an anomalous increase in piezocharge coefficients near ˜15 nm , the critical size for n-Pt.

Masking functions and fixed-signal functions for low-level 1000-Hz tones.

PubMed

Shepherd, Daniel; Hautus, Michael J; Jesteadt, Walt

2013-06-01

Masking functions and fixed-signal functions were constructed using a narrow range of pedestal intensities for 10-ms, 1000-Hz gated tones. Data from three experiments agreed with previously reported data, clearly demonstrating negative masking and the pedestal effect. The data extend earlier findings by showing (1) the resilience of the pedestal effect when a background noise masker is introduced; (2) a possible indifference of the fixed-signal function to stimulus duration; (3) the ability of a set of psychometric functions to produce both masking and fixed-signal functions; (4) depending on method, the impact of unit choice on the interpretation of both the pedestal effect and negative masking data. Results are discussed in relation to current psychophysical models, and suggest that accounting for the auditory system's sensitivity to differences in low-level sounds remains a challenge.

Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI.

PubMed

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T

2012-10-15

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. Copyright © 2012 Elsevier Inc. All rights reserved.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies

PubMed Central

Pietsch, E C; Dong, J; Cardoso, R; Zhang, X; Chin, D; Hawkins, R; Dinh, T; Zhou, M; Strake, B; Feng, P-H; Rocca, M; Santos, C Dos; Shan, X; Danet-Desnoyers, G; Shi, F; Kaiser, E; Millar, H J; Fenton, S; Swanson, R; Nemeth, J A; Attar, R M

2017-01-01

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices. PMID:28234345

Brown Adipose Tissue Function Is Enhanced in Long-Lived, Male Ames Dwarf Mice

PubMed Central

McFadden, Samuel; Fang, Yimin; Huber, Joshua A.; Zhang, Chi; Sun, Liou Y.; Bartke, Andrzej

2016-01-01

Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity. PMID:27740871

Motor functioning in autistic spectrum disorders: a preliminary analysis.

PubMed

Behere, Aniruddh; Shahani, Lokesh; Noggle, Chad A; Dean, Raymond

2012-01-01

The study sought to identify differences in motor functioning between autism and Asperger syndrome while also assessing the diagnostic contribution of such assessment. A sample of 16 individuals with autism and 10 with Asperger syndrome completed the Dean-Woodcock Sensory-Motor Battery, and outcomes were compared. Significant differences were found in measures of cerebellar functioning, favoring Asperger subjects. Deficits in coordination, ambulation, and the Romberg test were associated with both disorders. On the basis of motor outcomes alone, 100% were accurately differentiated. Findings support the idea that motor dysfunction is a core feature of these presentations and demonstrated the utility of motor assessment in diagnostic practice.

Novel function of Trim44 promotes an antiviral response by stabilizing VISA.

PubMed

Yang, Bo; Wang, Jie; Wang, Yanming; Zhou, Haiyan; Wu, Xiaodong; Tian, Zhigang; Sun, Bing

2013-04-01

Virus-induced signaling adaptor (VISA) functions as a critical adaptor in the regulation of both the production of type I IFNs and the subsequent control of the innate antiviral response. In this study, we demonstrate that tripartite motif (Trim)44 interacts with VISA and promotes VISA-mediated antiviral responses. The overexpression of Trim44 enhances the cellular response to viral infection, whereas Trim44 knockdown yields the opposite effect. Trim44 stabilizes VISA by preventing VISA ubiquitination and degradation. These findings suggest that Trim44 functions as a positive regulator of the virus-triggered immune response by enhancing the stability of VISA.

The Herschel ATLAS: Evolution of the 250 Micrometer Luminosity Function Out to z = 0.5

NASA Technical Reports Server (NTRS)

Dye, S.; Dunne, L.; Eales, S.; Smith, D. J. B.; Amblard, A.; Auld, R.; Baes, M.; Baldry, I. K.; Bamford, S.; Blain, A. W.;

[Rupture of lateral ligaments of the ankle joint: MR imaging before and after functional therapy].

PubMed

Grebe, P; Kreitner, K F; Roeder, W; Kersjes, W; Hennes, R; Runkel, M

1995-09-01

Documentation via MRI of the healing of ruptured lateral collateral ankle ligaments after functional therapy. 35 patients with ankle sprain were examined by MRI and stress radiographs, 13 were operated afterwards, 22 patients underwent a functional conservative therapy and were examined by MRI and stress radiographs and second time after three months. MRI reports were correct in 12 of 13 operated cases. After conservative therapy we did not find any disrupted ankle ligament. MRI showed intact ligaments thickened by scar. MRI is able to show injuries of the lateral collateral ankle ligaments and demonstrates the healing by scar after conservative therapy.

Visual impairment in children with congenital Zika syndrome.

PubMed

Ventura, Liana O; Ventura, Camila V; Lawrence, Linda; van der Linden, Vanessa; van der Linden, Ana; Gois, Adriana L; Cavalcanti, Milena M; Barros, Eveline A; Dias, Natalia C; Berrocal, Audina M; Miller, Marilyn T

2017-08-01

To describe the visual impairment associated with ocular and neurological abnormalities in a cohort of children with congenital Zika syndrome (CZS). This cross-sectional study included infants with microcephaly born in Pernambuco, Brazil, from May to December 2015. Immunoglobulin M antibody capture enzyme-linked immunosorbent assay for the Zika virus on the cerebrospinal fluid samples was positive for all infants. Clinical evaluation consisted of comprehensive ophthalmologic examination including visual acuity, visual function assessment, visual developmental milestone, neurologic examination, and neuroimaging. A total of 32 infants (18 males [56%]) were included. Mean age at examination was 5.7 ± 0.9 months (range, 4-7 months). Visual function and visual developmental milestone could not be tested in 1 child (3%). Visual impairment was detected in 32 infants (100%). Retinal and/or optic nerve findings were observed in 14 patients (44%). There was no statistical difference between the patients with ocular findings and those without (P = 0.180). All patients (100%) demonstrated neurological and neuroimaging abnormalities; 3 (9%) presented with late-onset of microcephaly. Children with CZS demonstrated visual impairment regardless of retina and/or optic nerve abnormalities. This finding suggests that cortical/cerebral visual impairment may be the most common cause of blindness identified in children with CZS. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Radiofrequency treatment enhances the catalytic function of an immobilized nanobiohybrid catalyst

NASA Astrophysics Data System (ADS)

San, Boi Hoa; Ha, Eun-Ju; Paik, Hyun-Jong; Kim, Kyeong Kyu

2014-05-01

Biocatalysis, the use of enzymes in chemical transformation, has undergone intensive development for a wide range of applications. As such, maximizing the functionality of enzymes for biocatalysis is a major priority to enable industrial use. To date, many innovative technologies have been developed to address the future demand of enzymes for these purposes, but maximizing the catalytic activity of enzymes remains a challenge. In this study, we demonstrated that the functionality of a nanobiocatalyst could be enhanced by combining immobilization and radiofrequency (RF) treatment. Aminopeptidase PepA-encapsulating 2 nm platinum nanoparticles (PepA-PtNPs) with the catalytic activities of hydrolysis and hydrogenation were employed as multifunctional nanobiocatalysts. Immobilizing the nanobiocatalysts in a hydrogel using metal chelation significantly enhanced their functionalities, including catalytic power, thermal-stability, pH tolerance, organic solvent tolerance, and reusability. Most importantly, RF treatment of the hydrogel-immobilized PepA-PtNPs increased their catalytic power by 2.5 fold greater than the immobilized PepA. Our findings indicate that the catalytic activities and functionalities of PepA-PtNPs are greatly enhanced by the combination of hydrogel-immobilization and RF treatment. Based on our findings, we propose that RF treatment of nanobiohybrid catalysts immobilized on the bulk hydrogel represents a new strategy for achieving efficient biocatalysis.Biocatalysis, the use of enzymes in chemical transformation, has undergone intensive development for a wide range of applications. As such, maximizing the functionality of enzymes for biocatalysis is a major priority to enable industrial use. To date, many innovative technologies have been developed to address the future demand of enzymes for these purposes, but maximizing the catalytic activity of enzymes remains a challenge. In this study, we demonstrated that the functionality of a nanobiocatalyst could be enhanced by combining immobilization and radiofrequency (RF) treatment. Aminopeptidase PepA-encapsulating 2 nm platinum nanoparticles (PepA-PtNPs) with the catalytic activities of hydrolysis and hydrogenation were employed as multifunctional nanobiocatalysts. Immobilizing the nanobiocatalysts in a hydrogel using metal chelation significantly enhanced their functionalities, including catalytic power, thermal-stability, pH tolerance, organic solvent tolerance, and reusability. Most importantly, RF treatment of the hydrogel-immobilized PepA-PtNPs increased their catalytic power by 2.5 fold greater than the immobilized PepA. Our findings indicate that the catalytic activities and functionalities of PepA-PtNPs are greatly enhanced by the combination of hydrogel-immobilization and RF treatment. Based on our findings, we propose that RF treatment of nanobiohybrid catalysts immobilized on the bulk hydrogel represents a new strategy for achieving efficient biocatalysis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00407h

The effect of resource history on the functioning of soil microbial communities is maintained across time

NASA Astrophysics Data System (ADS)

Keiser, A. D.; Strickland, M. S.; Fierer, N.; Bradford, M. A.

2011-02-01

Historical resource conditions appear to influence microbial community function. With time, historical influences might diminish as populations respond to the contemporary environment. Alternatively, they may persist given factors such as contrasting genetic potentials for adaptation to a new environment. Using experimental microcosms, we test competing hypotheses that function of distinct soil microbial communities in common environments (H1a) converge or (H1b) remain dissimilar over time. Using a 6 × 2 (soil community inoculum × litter environment) full-factorial design, we compare decomposition rates in experimental microcosms containing grass or hardwood litter environments. After 100 days, communities that develop are inoculated into fresh litters and decomposition followed for another 100 days. We repeat this for a third, 100-day period. In each successive, 100-day period, we find higher decomposition rates (i.e. functioning) suggesting communities function better when they have an experimental history of the contemporary environment. Despite these functional gains, differences in decomposition rates among initially distinct communities persist, supporting the hypothesis that dissimilarity is maintained across time. In contrast to function, community composition is more similar following a common, experimental history. We also find that "specialization" on one experimental environment incurs a cost, with loss of function in the alternate environment. For example, experimental history of a grass-litter environment reduced decomposition when communities were inoculated into a hardwood-litter environment. Our work demonstrates experimentally that despite expectations of fast growth rates, physiological flexibility and rapid evolution, initial functional differences between microbial communities are maintained across time. These findings question whether microbial dynamics can be omitted from models of ecosystem processes if we are to predict reliably global change effects on biogeochemical cycles.

The effect of resource history on the functioning of soil microbial communities is maintained across time

NASA Astrophysics Data System (ADS)

Keiser, A. D.; Strickland, M. S.; Fierer, N.; Bradford, M. A.

2011-06-01

Historical resource conditions appear to influence microbial community function. With time, historical influences might diminish as populations respond to the contemporary environment. Alternatively, they may persist given factors such as contrasting genetic potentials for adaptation to a new environment. Using experimental microcosms, we test competing hypotheses that function of distinct soil microbial communities in common environments (H1a) converge or (H1b) remain dissimilar over time. Using a 6 × 2 (soil community inoculum × litter environment) full-factorial design, we compare decomposition rates in experimental microcosms containing grass or hardwood litter environments. After 100 days, communities that develop are inoculated into fresh litters and decomposition followed for another 100 days. We repeat this for a third, 100-day period. In each successive, 100-day period, we find higher decomposition rates (i.e. functioning) suggesting communities function better when they have an experimental history of the contemporary environment. Despite these functional gains, differences in decomposition rates among initially distinct communities persist, supporting the hypothesis that dissimilarity is maintained across time. In contrast to function, community composition is more similar following a common, experimental history. We also find that "specialization" on one experimental environment incurs a cost, with loss of function in the alternate environment. For example, experimental history of a grass-litter environment reduced decomposition when communities were inoculated into a hardwood-litter environment. Our work demonstrates experimentally that despite expectations of fast growth rates, physiological flexibility and rapid evolution, initial functional differences between microbial communities are maintained across time. These findings question whether microbial dynamics can be omitted from models of ecosystem processes if we are to predict reliably global change effects on biogeochemical cycles.

Nonequilibrium dynamic critical scaling of the quantum Ising chain.

PubMed

Kolodrubetz, Michael; Clark, Bryan K; Huse, David A

2012-07-06

We solve for the time-dependent finite-size scaling functions of the one-dimensional transverse-field Ising chain during a linear-in-time ramp of the field through the quantum critical point. We then simulate Mott-insulating bosons in a tilted potential, an experimentally studied system in the same equilibrium universality class, and demonstrate that universality holds for the dynamics as well. We find qualitatively athermal features of the scaling functions, such as negative spin correlations, and we show that they should be robustly observable within present cold atom experiments.

Co-ordinated structural and functional covariance in the adolescent brain underlies face processing performance

PubMed Central

Joel Shaw, Daniel; Mareček, Radek; Grosbras, Marie-Helene; Leonard, Gabriel; Bruce Pike, G.

2016-01-01

Our ability to process complex social cues presented by faces improves during adolescence. Using multivariate analyses of neuroimaging data collected longitudinally from a sample of 38 adolescents (17 males) when they were 10, 11.5, 13 and 15 years old, we tested the possibility that there exists parallel variations in the structural and functional development of neural systems supporting face processing. By combining measures of task-related functional connectivity and brain morphology, we reveal that both the structural covariance and functional connectivity among ‘distal’ nodes of the face-processing network engaged by ambiguous faces increase during this age range. Furthermore, we show that the trajectory of increasing functional connectivity between the distal nodes occurs in tandem with the development of their structural covariance. This demonstrates a tight coupling between functional and structural maturation within the face-processing network. Finally, we demonstrate that increased functional connectivity is associated with age-related improvements of face-processing performance, particularly in females. We suggest that our findings reflect greater integration among distal elements of the neural systems supporting the processing of facial expressions. This, in turn, might facilitate an enhanced extraction of social information from faces during a time when greater importance is placed on social interactions. PMID:26772669

Vestibulo-ocular and vestibulospinal function before and after cochlear implant surgery

NASA Technical Reports Server (NTRS)

Black, F. O.; Lilly, D. J.; Peterka, R. J.; Fowler, L. P.; Simmons, F. B.

1987-01-01

Vestibular function in cochlear implant candidates varies from normal to total absence of function. In patients with intact vestibular function preoperatively, invasion of the otic capsule places residual vestibular function at risk. Speech-processing strategies that result in large amplitude electrical transients or strategies that employ high amplitude broad frequency carrier signals have the potential for disrupting vestibular function. Five patients were tested with and without electrical stimulation via cochlear electrodes. Two patients experienced subjective vestibular effects that were quickly resolved. No long-term vestibular effects were noted for the two types of second generation cochlear implants evaluated. Histopathological findings from another patient, who had electrically generated vestibular reflex responses to intramodiolar electrodes, indicated that responses elicited were a function of several variables including electrode location, stimulus intensity, stimulus amplitude, and stimulus frequency. Differential auditory, vestibulocolic, and vestibulospinal reflexes were demonstrated from the same electrode as a function of stimulus amplitude, frequency, and duration.

Human Antiviral Protein IFIX Suppresses Viral Gene Expression during Herpes Simplex Virus 1 (HSV-1) Infection and Is Counteracted by Virus-induced Proteasomal Degradation.

PubMed

Crow, Marni S; Cristea, Ileana M

2017-04-01

The interferon-inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes expression of antiviral cytokines. How IFIX exerts its host defense functions and whether it is inhibited by the virus remain unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection. We find that IFIX has a dynamic localization during infection that changes from diffuse nuclear and nucleoli distribution in uninfected cells to discrete nuclear puncta early in infection. This is rapidly followed by a reduction in IFIX protein levels. Indeed, using immunoaffinity purification and mass spectrometry, we define IFIX interactions during HSV-1 infection, finding an association with a proteasome subunit and proteins involved in ubiquitin-proteasome processes. Using synchronized HSV-1 infection, microscopy, and proteasome-inhibition experiments, we demonstrate that IFIX co-localizes with nuclear proteasome puncta shortly after 3 h of infection and that its pyrin domain is rapidly degraded in a proteasome-dependent manner. We further demonstrate that, in contrast to several other host defense factors, IFIX degradation is not dependent on the E3 ubiquitin ligase activity of the viral protein ICP0. However, we show IFIX degradation requires immediate-early viral gene expression, suggesting a viral host suppression mechanism. The IFIX interactome also demonstrated its association with transcriptional regulatory proteins, including the 5FMC complex. We validate this interaction using microscopy and reciprocal isolations and determine it is mediated by the IFIX HIN domain. Finally, we show IFIX suppresses immediate-early and early viral gene expression during infection. Altogether, our study demonstrates that IFIX antiviral functions work in part via viral transcriptional suppression and that HSV-1 has acquired mechanisms to block its functions via proteasome-dependent degradation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Sex differences in face processing are mediated by handedness and sexual orientation.

PubMed

Brewster, Paul W H; Mullin, Caitlin R; Dobrin, Roxana A; Steeves, Jennifer K E

2011-03-01

Previous research has demonstrated sex differences in face processing at both neural and behavioural levels. The present study examined the role of handedness and sexual orientation as mediators of this effect. We compared the performance of LH (left-handed) and RH (right-handed) heterosexual and homosexual male and female participants on a face recognition memory task. Our main findings were that homosexual males have better face recognition memory than both heterosexual males and homosexual women. We also demonstrate better face processing in women than in men. Finally, LH heterosexual participants had better face recognition than LH homosexual participants and also tended to be better than RH heterosexual participants. These findings are consistent with differences in the organisation and laterality of face-processing mechanisms as a function of sex, handedness, and sexual orientation.

Functional linkage between NOXA and Bim in mitochondrial apoptotic events.

PubMed

Han, Jie; Goldstein, Leslie A; Hou, Wen; Rabinowich, Hannah

2007-06-01

NOXA is a BH3-only protein whose expression is induced by certain p53-depenent or independent apoptotic stimuli. Both NOXA and Bim are avid binders of Mcl-1, but a functional linkage between these BH3-only proteins has not yet been reported. In this study, we demonstrate that Mcl-1 binding of endogenously induced NOXA interferes with the ability of Mcl-1 to efficiently sequester endogenous Bim, as Bim is displaced from its complex with Mcl-1. Induced NOXA significantly enhances the UV sensitivity of cells, and the ensuing mitochondrial depolarization is entirely abrogated by Bim knockdown. These results demonstrate a Mcl-1-mediated cross-talk between endogenous NOXA and Bim that occurs upstream of the Bak/Bax-dependent execution of UV-induced mitochondrial depolarization. The current findings demonstrate that the mitochondrial response to an induced expression of NOXA is executed by endogenous Bim and suggest a plausible mechanism for the observed NOXA-Bim linkage.

Embryonic domains of the aorta derived from diverse origins exhibit distinct properties that converge into a common phenotype in the adult

PubMed Central

Pfaltzgraff, Elise R.; Shelton, Elaine L.; Galindo, Cristi L.; Nelms, Brian L.; Hooper, Christopher W.; Poole, Stanley D.; Labosky, Patricia A.; Bader, David M.; Reese, Jeff

2014-01-01

Vascular smooth muscle cells (VSMCs) are derived from distinct embryonic origins. Vessels originating from differing smooth muscle cell populations have distinct vascular and pathological properties involving calcification, atherosclerosis, and structural defects such as aneurysm and coarctation. We hypothesized that domains within a single vessel, such as the aorta, vary in phenotype based on embryonic origin. Gene profiling and myographic analyses demonstrated that embryonic ascending and descending aortic domains exhibited distinct phenotypes. In vitro analyses demonstrated that VSMCs from each region were dissimilar in terms of cytoskeletal and migratory properties, and retention of different gene expression patterns. Using the same analysis, we found that these same two domains are indistinguishable in the adult vessel. Our data demonstrate that VSMCs from different embryonic origins are functionally distinct in the embryonic mouse, but converge to assume a common phenotype in the aorta of healthy adults. These findings have fundamental implications for aortic development, function and disease progression. PMID:24508561

Stable computations with flat radial basis functions using vector-valued rational approximations

NASA Astrophysics Data System (ADS)

Wright, Grady B.; Fornberg, Bengt

2017-02-01

One commonly finds in applications of smooth radial basis functions (RBFs) that scaling the kernels so they are 'flat' leads to smaller discretization errors. However, the direct numerical approach for computing with flat RBFs (RBF-Direct) is severely ill-conditioned. We present an algorithm for bypassing this ill-conditioning that is based on a new method for rational approximation (RA) of vector-valued analytic functions with the property that all components of the vector share the same singularities. This new algorithm (RBF-RA) is more accurate, robust, and easier to implement than the Contour-Padé method, which is similarly based on vector-valued rational approximation. In contrast to the stable RBF-QR and RBF-GA algorithms, which are based on finding a better conditioned base in the same RBF-space, the new algorithm can be used with any type of smooth radial kernel, and it is also applicable to a wider range of tasks (including calculating Hermite type implicit RBF-FD stencils). We present a series of numerical experiments demonstrating the effectiveness of this new method for computing RBF interpolants in the flat regime. We also demonstrate the flexibility of the method by using it to compute implicit RBF-FD formulas in the flat regime and then using these for solving Poisson's equation in a 3-D spherical shell.

Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells.

PubMed

Boo, Kyungjin; Bhin, Jinhyuk; Jeon, Yoon; Kim, Joomyung; Shin, Hi-Jai R; Park, Jong-Eun; Kim, Kyeongkyu; Kim, Chang Rok; Jang, Hyonchol; Kim, In-Hoo; Kim, V Narry; Hwang, Daehee; Lee, Ho; Baek, Sung Hee

2015-04-10

The actions of transcription factors, chromatin modifiers and noncoding RNAs are crucial for the programming of cell states. Although the importance of various epigenetic machineries for controlling pluripotency of embryonic stem (ES) cells has been previously studied, how chromatin modifiers cooperate with specific transcription factors still remains largely elusive. Here, we find that Pontin chromatin remodelling factor plays an essential role as a coactivator for Oct4 for maintenance of pluripotency in mouse ES cells. Genome-wide analyses reveal that Pontin and Oct4 share a substantial set of target genes involved in ES cell maintenance. Intriguingly, we find that the Oct4-dependent coactivator function of Pontin extends to the transcription of large intergenic noncoding RNAs (lincRNAs) and in particular linc1253, a lineage programme repressing lincRNA, is a Pontin-dependent Oct4 target lincRNA. Together, our findings demonstrate that the Oct4-Pontin module plays critical roles in the regulation of genes involved in ES cell fate determination.

Vitamin supplementation by gut symbionts ensures metabolic homeostasis in an insect host

PubMed Central

Salem, Hassan; Bauer, Eugen; Strauss, Anja S.; Vogel, Heiko; Marz, Manja; Kaltenpoth, Martin

2014-01-01

Despite the demonstrated functional importance of gut microbes, our understanding of how animals regulate their metabolism in response to nutritionally beneficial symbionts remains limited. Here, we elucidate the functional importance of the African cotton stainer's (Dysdercus fasciatus) association with two actinobacterial gut symbionts and subsequently examine the insect's transcriptional response following symbiont elimination. In line with bioassays demonstrating the symbionts' contribution towards host fitness through the supplementation of B vitamins, comparative transcriptomic analyses of genes involved in import and processing of B vitamins revealed an upregulation of gene expression in aposymbiotic (symbiont-free) compared with symbiotic individuals; an expression pattern that is indicative of B vitamin deficiency in animals. Normal expression levels of these genes, however, can be restored by either artificial supplementation of B vitamins into the insect's diet or reinfection with the actinobacterial symbionts. Furthermore, the functional characterization of the differentially expressed thiamine transporter 2 through heterologous expression in Xenopus laevis oocytes confirms its role in cellular uptake of vitamin B1. These findings demonstrate that despite an extracellular localization, beneficial gut microbes can be integral to the host's metabolic homeostasis, reminiscent of bacteriome-localized intracellular mutualists. PMID:25339726

FUNCTIONAL LIMITATION AND DEPRESSIVE SYMPTOMATOLOGY: CONSIDERING PERCEIVED STIGMA AND DISCRIMINATION WITHIN A STRESS AND COPING FRAMEWORK

PubMed Central

Brown, Robyn Lewis

2016-01-01

This study examines whether perceived stigma and discrimination moderate the associations between functional limitation, psychosocial coping resources, and depressive symptoms among people with physical disabilities. Using two waves of data from a large community study including a representative sample of persons with physical disabilities (N=417), an SEM-based moderated mediation analysis was performed. Mediation tests demonstrate that mastery significantly mediates the association between functional limitation and depressive symptoms over the study period. Moderated mediation tests reveal that the linkage between functional limitation and mastery varies as a function of perceived stigma and experiences of major discrimination and day-to-day discrimination, however. The implications of these findings are discussed in the context of the stress and coping literature. PMID:28497112

Selective left, right and bilateral stimulation of subthalamic nuclei in Parkinson's disease: differential effects on motor, speech and language function.

PubMed

Schulz, Geralyn M; Hosey, Lara A; Bradberry, Trent J; Stager, Sheila V; Lee, Li-Ching; Pawha, Rajesh; Lyons, Kelly E; Metman, Leo Verhagen; Braun, Allen R

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left- and right-sided stimulation parameters.

Shoulder instability: impact of glenohumeral arthrotomography on treatment.

PubMed

el-Khoury, G Y; Kathol, M H; Chandler, J B; Albright, J P

1986-09-01

We used arthrotomography to study the glenoid labrum in 114 patients. Sixty-nine of the patients had anatomic instability of the shoulder (including recurrent dislocation and subluxation of the shoulder), and 45 patients had functional instability of the shoulder (denoted by chronic pain, clicking of the joint, and the sensation that an unstable condition exists without the objective signs of it). Labral tears were revealed arthrotomographically in 86% of the patients with anatomic instability, while only 40% of the patients with functional instability had labral abnormalities, and these were primarily of minor severity. Fifty-six patients (44 of whom had anatomic instability; 12, functional instability) required surgery. The surgical findings were correlated with the arthrotomographic findings, and no false-positive results were revealed. However, arthrotomography demonstrated only part of the pathologic condition of two patients. These results confirm that there is a strong correlation between labral pathologic conditions and anatomic instability of the shoulder. Arthrotomographic studies have a great impact on the selection of therapy in cases of both anatomic and functional instability of the shoulder.

Brain alterations in paedophilia: a critical review.

PubMed

Mohnke, Sebastian; Müller, Sabine; Amelung, Till; Krüger, Tillmann H C; Ponseti, Jorge; Schiffer, Boris; Walter, Martin; Beier, Klaus M; Walter, Henrik

2014-11-01

Psychosocial and biological factors have been implicated in paedophilia, such as alterations in brain structure and function. The purpose of this paper is to review the expanding body of literature on this topic including brain abnormality case reports, as well as structural and functional neuroimaging studies. Case studies of men who have committed sexual offences against children implicate frontal and temporal abnormalities that may be associated with impaired impulse inhibition. Structural neuroimaging investigations show volume reductions in paedophilic men. Although the findings have been heterogeneous, smaller amygdala volume has been replicated repeatedly. Functional neuroimaging investigations demonstrate an overlap between paedophiles and teleiophiles during sexual arousal processing. While it is controversial among studies regarding group differences, reliable discrimination between paedophilic and teleiophilic men may be achieved using functional activation patterns. Nevertheless, the heterogeneous findings published so far suggest further research is necessary to disentangle the neurobiological mechanisms of paedophilic preference. A number of methodological confounds have been identified, which may account for the inconsistent results that could prove to be beneficial for future investigations. Copyright © 2014 Elsevier Ltd. All rights reserved.

The hippocampal response to psychosocial stress varies with salivary uric acid level

PubMed Central

Goodman, Adam M.; Wheelock, Muriah D.; Harnett, Nathaniel G.; Mrug, Sylvie; Granger, Douglas A.; Knight, David C.

2016-01-01

Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid’s impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health. PMID:27725214

Parent and Youth Priorities during the Transition to Adulthood for Youth with Special Health Care Needs and Developmental Disability

PubMed Central

Rehm, Roberta S.; Fuentes-Afflick, Elena; Fisher, Lucille T.; Chesla, Catherine A.

2014-01-01

Families undertake extensive planning during transition to adulthood so youth with concomitant special health care needs and developmental disabilities will have a long-term high quality of life. Findings from an interpretive field study involving 64 youth and their parents indicated that the meaning of adulthood was functioning as independently as possible with appropriate supports. Parental priorities included protecting health, assuring safety and security in multiple realms, finding meaningful activities after high school, and establishing supportive social relationships. These priorities demonstrated the need to broaden usual health care transition goals that focus on finding adult providers and optimizing self-management. PMID:22869218

Functional Consequences of Sarcopenia and Dynapenia in the Elderly

PubMed Central

Clark, Brian C.; Manini, Todd M.

2010-01-01

Purpose of review The economic burden due to the sequela of sarcopenia (muscle wasting in the elderly) are staggering and rank similarly to the costs associated with osteoporotic fractures. In this article we discuss the societal burden and determinants of the loss of physical function with advancing age, the physiologic mechanisms underlying dynapenia (muscle weakness in the elderly), and provide perspectives on related critical issues to be addressed. Recent findings Recent epidemiological findings from longitudinal aging studies suggest that dynapenia is highly associated with both mortality and physical disability even when adjusting for sarcopenia, indicating that sarcopenia may be secondary to the effects of dynapenia. These findings are consistent with the physiologic underpinnings of muscle strength, as recent evidence demonstrates that alterations in muscle quantity, contractile quality and neural activation all collectively contribute to dynapenia. Summary While muscle mass is essential for regulation of whole body metabolic balance, overall neuromuscular function seems to be a critical factor for maintaining muscle strength and physical independence in the elderly. The relative contribution of physiologic factors contributing to muscle weakness are not fully understood, and further research is needed to better elucidate these mechanisms between muscle groups and across populations. PMID:20154609

Structure-function relationships during segregated and integrated network states of human brain functional connectivity.

PubMed

Fukushima, Makoto; Betzel, Richard F; He, Ye; van den Heuvel, Martijn P; Zuo, Xi-Nian; Sporns, Olaf

2018-04-01

Structural white matter connections are thought to facilitate integration of neural information across functionally segregated systems. Recent studies have demonstrated that changes in the balance between segregation and integration in brain networks can be tracked by time-resolved functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) data and that fluctuations between segregated and integrated network states are related to human behavior. However, how these network states relate to structural connectivity is largely unknown. To obtain a better understanding of structural substrates for these network states, we investigated how the relationship between structural connectivity, derived from diffusion tractography, and functional connectivity, as measured by rs-fMRI, changes with fluctuations between segregated and integrated states in the human brain. We found that the similarity of edge weights between structural and functional connectivity was greater in the integrated state, especially at edges connecting the default mode and the dorsal attention networks. We also demonstrated that the similarity of network partitions, evaluated between structural and functional connectivity, increased and the density of direct structural connections within modules in functional networks was elevated during the integrated state. These results suggest that, when functional connectivity exhibited an integrated network topology, structural connectivity and functional connectivity were more closely linked to each other and direct structural connections mediated a larger proportion of neural communication within functional modules. Our findings point out the possibility of significant contributions of structural connections to integrative neural processes underlying human behavior.

Language Functions and Medical Communication: The Human Body as Text

ERIC Educational Resources Information Center

Kantz, Deirdre; Marenzi, Ivana

2016-01-01

This article presents the findings of a field experiment in medical English with first-year medical students at the University of Pavia, Northern Italy. Working in groups of 8-10, the students were asked to produce a corpus of medical texts in English demonstrating how the human body is itself a meaningful text (Baldry and Thibault 2006: Ch. 1).…

Far from Home: An Experimental Evaluation of the Mother-Child Home Program in Bermuda.

ERIC Educational Resources Information Center

Scarr, Sandra; McCartney, Kathleen

1988-01-01

Effects of the Mother-Child Home Program (MCHP) were evaluated with a broad range of measures on cognition, social behavior, and emotion. Findings indicated that children in Bermuda scored above U.S. norms on cognitive tests and were functioning well in the preschool period. The MCHP had few demonstrable effects on any segment of the sample. (RH)

In vitro evaluation of encapsulated primary rat hepatocytes pre- and post-cryopreservation at -80°C and in liquid nitrogen.

PubMed

Durkut, Serap; Elçin, A Eser; Elçin, Y Murat

2015-02-01

Encapsulation techniques have the potential to protect hepatocytes from cryoinjury. In this study, we comparatively evaluated the viability and metabolic function of primary rat hepatocytes encapsulated in calcium alginate microbeads, in chitosan tripolyphosphate beads, and in three-layered alginate-chitosan-alginate (ACA) microcapsules, before and after cryopreservation at -80°C and in liquid nitrogen (LN2) for 1 and 3 months. Findings demonstrated that LN2 was atop of -80°C in regard to preservation of viability (> 90%) and hepatic functions. LN2-cryopreserved hepatocytes encapsulated in ACA microcapsules retained metabolic function post-thawing, with > 90% of the albumin, total protein and urea syntheses activities, and > 80% of oxidative function.

The modeling of reactive solute transport with sorption to mobile and immobile sorbents 1. Experimental evidence and model development

NASA Astrophysics Data System (ADS)

Knabner, P.; Totsche, K. U.; Kögel-Knabner, I.

Modeling carrier-influenced transport needs to take into account the reactivity of the carrier itself. This paper presents a mathematical model of reactive solute transport with sorption to mobile and immobile sorbents. The mobile sorbent is also considered to be reactive. To justify the assumptions and generality of our modeling approach, experimental findings are reviewed and analyzed. A transformation of the model in terms of total concentrations of solute and mobile sorbents is presented which simplifies the mathematical formulations. Breakthrough data on dissolved organic carbon are presented to exemplify the need to take into account the reactivity of the mobile sorbent. Data on hexachlorobiphenyl and cadmium are presented to demonstrate carrier-introduced increased mobility, whereas data on anthracene and pyrene are presented to demonstrate carrier-introduced reduced mobility. The experimental conditions leading to the different findings are pointed out. The sorption processes considered in the model are both equilibrium and nonequilibrium processes, allowing for different sorption sites and nonlinear isotherms and rate functions. Effective isotherms, which describe the sorption to the immobile sorbent in the presence of a mobile sorbent and rate functions, are introduced and their properties are discussed.

Defect-Engineered Heat Transport in Graphene: A Route to High Efficient Thermal Rectification

PubMed Central

Zhao, Weiwei; Wang, Yanlei; Wu, Zhangting; Wang, Wenhui; Bi, Kedong; Liang, Zheng; Yang, Juekuan; Chen, Yunfei; Xu, Zhiping; Ni, Zhenhua

2015-01-01

Low-dimensional materials such as graphene provide an ideal platform to probe the correlation between thermal transport and lattice defects, which could be engineered at the molecular level. In this work, we perform molecular dynamics simulations and non-contact optothermal Raman measurements to study this correlation. We find that oxygen plasma treatment could reduce the thermal conductivity of graphene significantly even at extremely low defect concentration (∼83% reduction for ∼0.1% defects), which could be attributed mainly to the creation of carbonyl pair defects. Other types of defects such as hydroxyl, epoxy groups and nano-holes demonstrate much weaker effects on the reduction where the sp2 nature of graphene is better preserved. With the capability of selectively functionalizing graphene, we propose an asymmetric junction between graphene and defective graphene with a high thermal rectification ratio of ∼46%, as demonstrated by our molecular dynamics simulation results. Our findings provide fundamental insights into the physics of thermal transport in defective graphene, and two-dimensional materials in general, which could help on the future design of functional applications such as optothermal and electrothermal devices. PMID:26132747

Effects of exercise training on pulmonary hemodynamics, functional capacity and inflammation in pulmonary hypertension

PubMed Central

Richter, Manuel J.; Grimminger, Jan; Krüger, Britta; Ghofrani, Hossein A.; Mooren, Frank C.; Gall, Henning; Pilat, Christian; Krüger, Karsten

2017-01-01

Pulmonary hypertension (PH) is characterized by severe exercise limitation mainly attributed to the impairment of right ventricular function resulting from a concomitant elevation of pulmonary vascular resistance and pressure. The unquestioned cornerstone in the management of patients with pulmonary arterial hypertension (PAH) is specific vasoactive medical therapy to improve pulmonary hemodynamics and strengthen right ventricular function. Nevertheless, evidence for a beneficial effect of exercise training (ET) on pulmonary hemodynamics and functional capacity in patients with PH has been growing during the past decade. Beneficial effects of ET on regulating factors, inflammation, and metabolism have also been described. Small case-control studies and randomized clinical trials in larger populations of patients with PH demonstrated substantial improvements in functional capacity after ET. These findings were accompanied by several studies that suggested an effect of ET on inflammation, although a direct link between this effect and the therapeutic benefit of ET in PH has not yet been demonstrated. On this background, the aim of the present review is to describe current concepts regarding the effects of exercise on the pulmonary circulation and pathophysiological limitations, as well as the clinical and mechanistic effects of exercise in patients with PH. PMID:28680563

Neuropsychological outcome in patients with childhood craniopharyngioma and hypothalamic involvement.

PubMed

Özyurt, Jale; Thiel, Christiane M; Lorenzen, Anna; Gebhardt, Ursel; Calaminus, Gabriele; Warmuth-Metz, Monika; Müller, Hermann L

2014-04-01

To test memory performance and executive functions in patients with childhood craniopharyngioma and hypothalamic involvement. Using standardized neuropsychological tests, we compared cognitive performance in a group of 15 patients with childhood craniopharyngioma and known hypothalamic involvement and a group of 24 age- and intelligence-matched control subjects. In addition, we compared individual patients' results with normative data to detect abnormal performance in the clinically relevant range. Within the patient group, we further tested whether the grade of hypothalamic involvement had an impact on cognitive performance and quality of life. Relative to healthy controls, the patients demonstrated significantly lower performance scores in tests of memory and executive functioning. On the individual performance level, delayed recall performance was severely impaired in one-third of the patients. Compared with patients with low-grade hypothalamic involvement, those with high-grade hypothalamic involvement showed worse performance in executive functions and reduced functional capabilities for daily life actions, indicating lower quality of life. Our findings demonstrate that hypothalamic involvement is related to impairments in memory and executive functioning in patients with childhood craniopharyngioma and indicate that a high grade of hypothalamic involvement is related to worse outcomes. Copyright © 2014 Mosby, Inc. All rights reserved.

Combination of volume and perfusion parameters reveals different types of grey matter changes in schizophrenia.

PubMed

Xu, Lixue; Qin, Wen; Zhuo, Chuanjun; Liu, Huaigui; Zhu, Jiajia; Yu, Chunshui

2017-03-27

Diverse brain structural and functional changes have been reported in schizophrenia. Identifying different types of brain changes may help to understand the neural mechanisms and to develop reliable biomarkers in schizophrenia. We aimed to categorize different grey matter changes in schizophrenia based on grey matter volume (GMV) and cerebral blood flow (CBF). Structural and perfusion magnetic resonance imaging data were acquired in 100 schizophrenia patients and 95 healthy comparison subjects. Voxel-based GMV comparison was used to show structural changes, CBF analysis was used to demonstrate functional changes. We identified three types of grey matter changes in schizophrenia: structural and functional impairments in the anterior cingulate cortex and insular cortex, displaying reduction in both GMV and CBF; structural impairment with preserved function in the frontal and temporal cortices, demonstrating decreased GMV with normal CBF; pure functional abnormality in the anterior cingulate cortex and lateral prefrontal cortex and putamen, showing altered CBF with normal GMV. By combination of GMV and CBF, we identified three types of grey matter changes in schizophrenia. These findings may help to understand the complex manifestations and to develop reliable biomarkers in schizophrenia.

Ecosystem Services Transcend Boundaries: Estuaries Provide Resource Subsidies and Influence Functional Diversity in Coastal Benthic Communities

PubMed Central

Savage, Candida; Thrush, Simon F.; Lohrer, Andrew M.; Hewitt, Judi E.

2012-01-01

Background Estuaries are highly productive ecosystems that can export organic matter to coastal seas (the ‘outwelling hypothesis’). However the role of this food resource subsidy on coastal ecosystem functioning has not been examined. Methodology/Principal Findings We investigated the influence of estuarine primary production as a resource subsidy and the influence of estuaries on biodiversity and ecosystem functioning in coastal mollusk-dominated sediment communities. Stable isotope values (δ13C, δ15N) demonstrated that estuarine primary production was exported to the adjacent coast and contributed to secondary production up to 4 km from the estuary mouth. Further, isotope signatures of suspension feeding bivalves on the adjacent coast (Dosinia subrosea) closely mirrored the isotope values of the dominant bivalves inside the estuaries (Austrovenus stutchburyi), indicating utilization of similar organic matter sources. However, the food subsidies varied between estuaries; with estuarine suspended particulate organic matter (SPOM) dominant at Tairua estuary, while seagrass and fringing vegetation detritus was proportionately more important at Whangapoua estuary, with lesser contributions of estuarine SPOM. Distance from the estuary mouth and the size and density of large bivalves (Dosinia spp.) had a significant influence on the composition of biological traits in the coastal macrobenthic communities, signaling the potential influence of these spatial subsidies on ecosystem functioning. Conclusions/Significance Our study demonstrated that the locations where ecosystem services like productivity are generated are not necessarily where the services are utilized. Further, we identified indirect positive effects of the nutrient subsidies on biodiversity (the estuarine subsidies influenced the bivalves, which in turn affected the diversity and functional trait composition of the coastal sediment macrofaunal communities). These findings highlight the importance of integrative ecosystem-based management that maintains the connectivity of estuarine and coastal ecosystems. PMID:22880089

CD11c identifies a subset of murine liver natural killer cells that responds to adenoviral hepatitis

PubMed Central

Burt, Bryan M.; Plitas, George; Stableford, Jennifer A.; Nguyen, Hoang M.; Bamboat, Zubin M.; Pillarisetty, Venu G.; DeMatteo, Ronald P.

2008-01-01

The liver contains a unique repertoire of immune cells and a particular abundance of NK cells. We have found that CD11c defines a distinct subset of NK cells (NK1.1+CD3−) in the murine liver whose function was currently unknown. In naïve animals, CD11c+ liver NK cells displayed an activated phenotype and possessed enhanced effector functions when compared with CD11c− liver NK cells. During the innate response to adenovirus infection, CD11c+ NK cells were the more common IFN-γ-producing NK cells in the liver, demonstrated enhanced lytic capability, and gained a modest degree of APC function. The mechanism of IFN-γ production in vivo depended on TLR9 ligation as well as IL-12 and -18. Taken together, our findings demonstrate that CD11c+ NK cells are a unique subset of NK cells in the murine liver that contribute to the defense against adenoviral hepatitis. PMID:18664530

Functional expression of IL-12 receptor by human eosinophils: IL-12 promotes eosinophil apoptosis.

PubMed

Nutku, E; Zhuang, Q; Soussi-Gounni, A; Aris, F; Mazer, B D; Hamid, Q

2001-07-15

In murine models of allergic inflammation, IL-12 has been shown to decrease tissue eosinophilia, but the underlying mechanisms are not known. We evaluated the expression of IL-12R and the effect of IL-12 on eosinophil survival. In situ hybridization demonstrated the presence of mRNA and immunoreactivity for IL-12Rbeta1 and -beta2 subunits in human peripheral blood eosinophils. Surface expression of IL-12Rbeta1 and -beta2 subunits on freshly isolated human eosinophils was optimally expressed after incubation with PMA. To determine the functional significance of IL-12R studies, we studied cell viability and apoptosis. Morphological analysis and propidium iodide staining for cell cycle demonstrated that recombinant human IL-12 increased in vitro human eosinophil apoptosis in a dose-dependent manner. Addition of IL-5 together with IL-12 abrogated eosinophil apoptosis, suggesting that IL-12 and IL-5 have antagonistic effects. Our findings provide evidence for a novel role for IL-12 in regulating eosinophil function by increasing eosinophil apoptosis.

Personality, functioning, and recovery from major depression.

PubMed

Casey, P; Meagher, D; Butler, E

1996-04-01

The effect of personality on the effectiveness of electroconvulsive therapy in those with severe depressive illness has been investigated in a few studies, and the results are conflicting, with some demonstrating no effect and others the opposite. These studies, however, used hospital readmission as the only outcome measure, and the methods of personality assessment varied. To study this question in further detail, 40 patients were assessed while receiving inpatient electroconvulsive therapy, at the time of discharge, every 6 weeks for 6 months, and at 1 year after discharge. A number of outcome variables were assessed, including both symptomatic and social functioning measures as well as readmission to hospital. Premorbid personality was also assessed after discharge. The results demonstrate that personality is a predictor of social function at the time of discharge from hospital. In those patients with personality disorders, social recovery is slower than in those with normal personalities. Personality status did not distinguish the speed of symptomatic recovery or of readmission. The significance of these findings is discussed.

Dynamical control on helicity of electromagnetic waves by tunable metasurfaces

PubMed Central

Xu, He-Xiu; Sun, Shulin; Tang, Shiwei; Ma, Shaojie; He, Qiong; Wang, Guang-Ming; Cai, Tong; Li, Hai-Peng; Zhou, Lei

2016-01-01

Manipulating the polarization states of electromagnetic (EM) waves, a fundamental issue in optics, attracted intensive attention recently. However, most of the devices realized so far are either too bulky in size, and/or are passive with only specific functionalities. Here we combine theory and experiment to demonstrate that, a tunable metasurface incorporating diodes as active elements can dynamically control the reflection phase of EM waves, and thus exhibits unprecedented capabilities to manipulate the helicity of incident circular-polarized (CP) EM wave. By controlling the bias voltages imparted on the embedded diodes, we demonstrate that the device can work in two distinct states. Whereas in the “On” state, the metasurface functions as a helicity convertor and a helicity hybridizer within two separate frequency bands, it behaves as a helicity keeper within an ultra-wide frequency band in the “Off” state. Our findings pave the way to realize functionality-switchable devices related to phase control, such as frequency-tunable subwavelength cavities, anomalous reflectors and even holograms. PMID:27272350

Dynamical control on helicity of electromagnetic waves by tunable metasurfaces.

PubMed

Xu, He-Xiu; Sun, Shulin; Tang, Shiwei; Ma, Shaojie; He, Qiong; Wang, Guang-Ming; Cai, Tong; Li, Hai-Peng; Zhou, Lei

2016-06-08

Manipulating the polarization states of electromagnetic (EM) waves, a fundamental issue in optics, attracted intensive attention recently. However, most of the devices realized so far are either too bulky in size, and/or are passive with only specific functionalities. Here we combine theory and experiment to demonstrate that, a tunable metasurface incorporating diodes as active elements can dynamically control the reflection phase of EM waves, and thus exhibits unprecedented capabilities to manipulate the helicity of incident circular-polarized (CP) EM wave. By controlling the bias voltages imparted on the embedded diodes, we demonstrate that the device can work in two distinct states. Whereas in the "On" state, the metasurface functions as a helicity convertor and a helicity hybridizer within two separate frequency bands, it behaves as a helicity keeper within an ultra-wide frequency band in the "Off" state. Our findings pave the way to realize functionality-switchable devices related to phase control, such as frequency-tunable subwavelength cavities, anomalous reflectors and even holograms.

Brain activity and connectivity in response to negative affective stimuli: Impact of dysphoric mood and sex across diagnoses.

PubMed

Mareckova, Klara; Holsen, Laura M; Admon, Roee; Makris, Nikos; Seidman, Larry; Buka, Stephen; Whitfield-Gabrieli, Susan; Goldstein, Jill M

2016-11-01

Negative affective stimuli elicit behavioral and neural responses which vary on a continuum from adaptive to maladaptive, yet are typically investigated in a dichotomous manner (healthy controls vs. psychiatric diagnoses). This practice may limit our ability to fully capture variance from acute responses to negative affective stimuli to psychopathology at the extreme end. To address this, we conducted a functional magnetic resonance imaging study to examine the neural responses to negative valence/high arousal and neutral valence/low arousal images as a function of dysphoric mood and sex across individuals (n = 99) who represented traditional categories of healthy controls, major depressive disorder, bipolar psychosis, and schizophrenia. Observation of negative (vs. neutral) stimuli elicited blood oxygen-level dependent responses in the following circuitry: periaqueductal gray, hypothalamus (HYPO), amygdala (AMYG), hippocampus (HIPP), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and greater connectivity between AMYG and mPFC. Across all subjects, severity of dysphoric mood was associated with hyperactivity of HYPO, and, among females, right (R) AMYG. Females also demonstrated inverse relationships between severity of dysphoric mood and connectivity between HYPO - R OFC, R AMYG - R OFC, and R AMYG - R HIPP. Overall, our findings demonstrated sex-dependent deficits in response to negative affective stimuli increasing as a function of dysphoric mood state. Females demonstrated greater inability to regulate arousal as mood became more dysphoric. These findings contribute to elucidating biosignatures associated with response to negative stimuli across disorders and suggest the importance of a sex-dependent lens in determining these biosignatures. Hum Brain Mapp 37:3733-3744, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

PubMed Central

Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

2012-01-01

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID:23087647

Analytical nuclear gradients for the range-separated many-body dispersion model of noncovalent interactions.

PubMed

Blood-Forsythe, Martin A; Markovich, Thomas; DiStasio, Robert A; Car, Roberto; Aspuru-Guzik, Alán

2016-03-01

An accurate treatment of the long-range electron correlation energy, including van der Waals (vdW) or dispersion interactions, is essential for describing the structure, dynamics, and function of a wide variety of systems. Among the most accurate models for including dispersion into density functional theory (DFT) is the range-separated many-body dispersion (MBD) method [A. Ambrosetti et al. , J. Chem. Phys. , 2014, 140 , 18A508], in which the correlation energy is modeled at short-range by a semi-local density functional and at long-range by a model system of coupled quantum harmonic oscillators. In this work, we develop analytical gradients of the MBD energy with respect to nuclear coordinates, including all implicit coordinate dependencies arising from the partitioning of the charge density into Hirshfeld effective volumes. To demonstrate the efficiency and accuracy of these MBD gradients for geometry optimizations of systems with intermolecular and intramolecular interactions, we optimized conformers of the benzene dimer and isolated small peptides with aromatic side-chains. We find excellent agreement with the wavefunction theory reference geometries of these systems (at a fraction of the computational cost) and find that MBD consistently outperforms the popular TS and D3(BJ) dispersion corrections. To demonstrate the performance of the MBD model on a larger system with supramolecular interactions, we optimized the C 60 @C 60 H 28 buckyball catcher host-guest complex. In our analysis, we also find that neglecting the implicit nuclear coordinate dependence arising from the charge density partitioning, as has been done in prior numerical treatments, leads to an unacceptable error in the MBD forces, with relative errors of ∼20% (on average) that can extend well beyond 100%.

Political violence, collective functioning and health: A review of the literature

PubMed Central

Sousa, Cindy A.

2013-01-01

Political violence is implicated in a range of mental health outcomes, including PTSD, depression, and anxiety. The social and political contexts of people’s lives, however, offer considerable protection from the mental health effects of political violence. In spite of the importance of people’s social and political environments for health, there is limited scholarship on how political violence compromises necessary social and political systems and inhibits individuals from participating in social and political life. Drawing on literature from multiple disciplines, including public health, anthropology, and psychology, this narrative review uses a multi-level, social ecological framework to enhance current knowledge about the ways that political violence affects health. Findings from over 50 studies were analyzed and used to build a conceptual model demonstrating how political violence threatens three inter-related domains of functioning: individual functioning in relationship to their environment; community functioning and social fabric; and governmental functioning and delivery of services to populations. Results illustrate the need for multilevel frameworks that move beyond individual pathology towards more nuanced conceptualizations about how political violence affects health; findings contribute to the development of prevention programs addressing political violence. PMID:24133929

Relating children's attentional capabilities to intelligence, memory, and academic achievement: a test of construct specificity in children with asthma.

PubMed

Annett, Robert D; Bender, Bruce G; Gordon, Michael

2007-01-01

The relationship between attention, intelligence, memory, achievement, and behavior in a large population (N = 939) of children without neuropsychologic problems was investigated in children with mild and moderate asthma. It was hypothesized that different levels of children's attentional capabilities would be associated with different levels of intellectual, memory, and academic abilities. Children ages 6-12 at the eight clinical centers of the Childhood Asthma Management Program (CAMP) were enrolled in this study. Standardized measures of child neuropsychological and behavioral performance were administered to all participants, with analyses examining both the developmental trajectory of child attentional capabilities and the associations between Continuous Performance Test (CPT) scores and intellectual functioning, and measures of memory, academic achievement, and behavioral functioning. Findings demonstrated that correct responses on the CPT increase significantly with age, while commission errors decrease significantly with age. Performance levels on the CPT were associated with differences in child intellectual function, memory, and academic achievement. Overall these findings reveal how impairments in child attention skills were associated with normal levels of performance on measures of children's intelligence, memory, academic achievement, and behavioral functioning, suggesting that CPT performance is a salient marker of brain function.

Partial Functional Diversification of Drosophila melanogaster Septin Genes Sep2 and Sep5.

PubMed

O'Neill, Ryan S; Clark, Denise V

2016-07-07

The septin family of hetero-oligomeric complex-forming proteins can be divided into subgroups, and subgroup members are interchangeable at specific positions in the septin complex. Drosophila melanogaster has five septin genes, including the two SEPT6 subgroup members Sep2 and Sep5 We previously found that Sep2 has a unique function in oogenesis, which is not performed by Sep5 Here, we find that Sep2 is uniquely required for follicle cell encapsulation of female germline cysts, and that Sep2 and Sep5 are redundant for follicle cell proliferation. The five D. melanogaster septins localize similarly in oogenesis, including as rings flanking the germline ring canals. Pnut fails to localize in Sep5; Sep2 double mutant follicle cells, indicating that septin complexes fail to form in the absence of both Sep2 and Sep5. We also find that mutations in septins enhance the mutant phenotype of bazooka, a key component in the establishment of cell polarity, suggesting a link between septin function and cell polarity. Overall, this work suggests that Sep5 has undergone partial loss of ancestral protein function, and demonstrates redundant and unique functions of septins. Copyright © 2016 O'Neill and Clark.

Pulmonary Function, Muscle Strength and Mortality in Old Age

PubMed Central

Buchman, A. S.; Boyle, P. A.; Wilson, R.S.; Gu, Liping; Bienias, Julia L.; Bennett, D. A.

2009-01-01

Numerous reports have linked extremity muscle strength with mortality but the mechanism underlying this association is not known. We used data from 960 older persons without dementia participating in the Rush Memory and Aging Project to test two sequential hypotheses: first, that extremity muscle strength is a surrogate for respiratory muscle strength, and second, that the association of respiratory muscle strength with mortality is mediated by pulmonary function. In a series of proportional hazards models, we first demonstrated that the association of extremity muscle strength with mortality was no longer significant after including a term for respiratory muscle strength, controlling for age, sex, education, and body mass index. Next, the association of respiratory muscle strength with mortality was attenuated by more than 50% and no longer significant after including a term for pulmonary function. The findings were unchanged after controlling for cognitive function, parkinsonian signs, physical frailty, balance, physical activity, possible COPD, use of pulmonary medications, vascular risk factors including smoking, chronic vascular diseases, musculoskeletal joint pain, and history of falls. Overall, these findings suggest that pulmonary function may partially account for the association of muscle strength and mortality. PMID:18755207

Combined copper/zinc attachment to prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Bernholc, Jerry

2013-03-01

Misfolding of prion protein (PrP) is responsible for diseases such as ``mad-cow disease'' in cattle and Creutzfeldt-Jacob in humans. Extensive experimental investigation has established that this protein strongly interacts with copper ions, and this ability has been linked to its still unknown function. Attachment of other metal ions (zinc, iron, manganese) have been demonstrated as well, but none of them could outcompete copper. Recent finding, however, indicates that at intermediate concentrations both copper and zinc ions can attach to the PrP at the octarepeat region, which contains high affinity metal binding sites. Based on this evidence, we have performed density functional theory simulations to investigate the combined Cu/Zn attachment. We consider all previously reported binding modes of copper at the octarepeat region and examine a possibility simultaneous Cu/Zn attachment. We find that this can indeed occur for only one of the known binding sites, when copper changes its coordination mode to allow for attachment of zinc ion. The implications of the simultaneous attachment on neural function remain to be explored.

Brain hyperconnectivity in children with autism and its links to social deficits.

PubMed

Supekar, Kaustubh; Uddin, Lucina Q; Khouzam, Amirah; Phillips, Jennifer; Gaillard, William D; Kenworthy, Lauren E; Yerys, Benjamin E; Vaidya, Chandan J; Menon, Vinod

2013-11-14

Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Evolution of Osteocrin as an activity-regulated factor in the primate brain

PubMed Central

Ataman, Bulent; Boulting, Gabriella L.; Harmin, David A.; Yang, Marty G.; Baker-Salisbury, Mollie; Yap, Ee-Lynn; Malik, Athar N.; Mei, Kevin; Rubin, Alex A.; Spiegel, Ivo; Durresi, Ershela; Sharma, Nikhil; Hu, Linda S.; Pletikos, Mihovil; Griffith, Eric C.; Partlow, Jennifer N.; Stevens, Christine R.; Adli, Mazhar; Chahrour, Maria; Sestan, Nenad; Walsh, Christopher A.; Berezovskii, Vladimir K.; Livingstone, Margaret S.; Greenberg, Michael E.

2017-01-01

Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species- or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons. We find that OSTN has been repurposed in primates through the evolutionary acquisition of DNA regulatory elements that bind the activity-regulated transcription factor MEF2. In addition, we demonstrate that OSTN is expressed in primate neocortex and restricts activity-dependent dendritic growth in human neurons. These findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates. PMID:27830782

GABAergic neurons in ferret visual cortex participate in functionally specific networks

PubMed Central

Wilson, Daniel E.; Smith, Gordon B.; Jacob, Amanda; Walker, Theo; Dimidschstein, Jordane; Fishell, Gord J.; Fitzpatrick, David

2017-01-01

Summary Functional circuits in the visual cortex require the coordinated activity of excitatory and inhibitory neurons. Molecular genetic approaches in the mouse have led to the ‘local nonspecific pooling principle’ of inhibitory connectivity, in which inhibitory neurons are untuned for stimulus features due to the random pooling of local inputs. However, it remains unclear whether this principle generalizes to species with a columnar organization of feature selectivity such as carnivores, primates, and humans. Here we use virally-mediated GABAergic-specific GCaMP6f expression to demonstrate that inhibitory neurons in ferret visual cortex respond robustly and selectively to oriented stimuli. We find that the tuning of inhibitory neurons is inconsistent with the local non-specific pooling of excitatory inputs, and that inhibitory neurons exhibit orientation-specific noise correlations with local and distant excitatory neurons. These findings challenge the generality of the non-specific pooling principle for inhibitory neurons, suggesting different rules for functional excitatory-inhibitory interactions in non-murine species. PMID:28279352

Impact of real-time fMRI working memory feedback training on the interactions between three core brain networks.

PubMed

Zhang, Qiushi; Zhang, Gaoyan; Yao, Li; Zhao, Xiaojie

2015-01-01

Working memory (WM) refers to the temporary holding and manipulation of information during the performance of a range of cognitive tasks, and WM training is a promising method for improving an individual's cognitive functions. Our previous work demonstrated that WM performance can be improved through self-regulation of dorsal lateral prefrontal cortex (PFC) activation using real-time functional magnetic resonance imaging (rtfMRI), which enables individuals to control local brain activities volitionally according to the neurofeedback. Furthermore, research concerning large-scale brain networks has demonstrated that WM training requires the engagement of several networks, including the central executive network (CEN), the default mode network (DMN) and the salience network (SN), and functional connectivity within the CEN and DMN can be changed by WM training. Although a switching role of the SN between the CEN and DMN has been demonstrated, it remains unclear whether WM training can affect the interactions between the three networks and whether a similar mechanism also exists during the training process. In this study, we investigated the dynamic functional connectivity between the three networks during the rtfMRI feedback training using independent component analysis (ICA) and correlation analysis. The results indicated that functional connectivity within and between the three networks were significantly enhanced by feedback training, and most of the changes were associated with the insula and correlated with behavioral improvements. These findings suggest that the insula plays a critical role in the reorganization of functional connectivity among the three networks induced by rtfMRI training and in WM performance, thus providing new insights into the mechanisms of high-level functions and the clinical treatment of related functional impairments.

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study.

PubMed

Cai, Lin; Dong, Qi; Niu, Haijing

2018-04-01

Early childhood (7-8 years old) and early adolescence (11-12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across development. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Source Finding in the Era of the SKA (Precursors): Aegean 2.0

NASA Astrophysics Data System (ADS)

Hancock, Paul J.; Trott, Cathryn M.; Hurley-Walker, Natasha

2018-03-01

In the era of the SKA precursors, telescopes are producing deeper, larger images of the sky on increasingly small time-scales. The greater size and volume of images place an increased demand on the software that we use to create catalogues, and so our source finding algorithms need to evolve accordingly. In this paper, we discuss some of the logistical and technical challenges that result from the increased size and volume of images that are to be analysed, and demonstrate how the Aegean source finding package has evolved to address these challenges. In particular, we address the issues of source finding on spatially correlated data, and on images in which the background, noise, and point spread function vary across the sky. We also introduce the concept of forced or prioritised fitting.

Activity inhibition on municipal activated sludge by single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Parise, Alex; Thakor, Harshrajsinh; Zhang, Xiaoqi

2014-01-01

The objective of this study was to evaluate the respiratory activity inhibition of activated sludge used in a typical wastewater treatment plant by single-walled carbon nanotubes (SWCNTs) with different length and functionality. Four types of SWCNTs were evaluated: short, functionalized short, long, and functionalized long. Based on the effective concentration (EC50) values obtained, we determined that functionalized SWCNTs resulted in a higher microbial respiratory inhibition than non-functionalized nanotubes, and long SWCNTs gave a higher microbial respiratory inhibition than their short counterparts. Among the four types of SWCNTs studied, functionalized long exhibited the highest respiration inhibition. Scanning electron microscopy imaging indicates that the long SWCNTs dispersed more favorably after sonication than the short variety. The findings demonstrated that the toxicity of CNTs (exhibited by respiratory inhibition) is related to their physical properties; the length and functionality of SWCNTs affected the toxicity of SWCNTs in a mixed-cultured biologic system.

Functional myogenic engraftment from mouse iPS cells.

PubMed

Darabi, Radbod; Pan, Weihong; Bosnakovski, Darko; Baik, June; Kyba, Michael; Perlingeiro, Rita C R

2011-11-01

Direct reprogramming of adult fibroblasts to a pluripotent state has opened new possibilities for the generation of patient- and disease-specific stem cells. However the ability of induced pluripotent stem (iPS) cells to generate tissue that mediates functional repair has been demonstrated in very few animal models of disease to date. Here we present the proof of principle that iPS cells may be used effectively for the treatment of muscle disorders. We combine the generation of iPS cells with conditional expression of Pax7, a robust approach to derive myogenic progenitors. Transplantation of Pax7-induced iPS-derived myogenic progenitors into dystrophic mice results in extensive engraftment, which is accompanied by improved contractility of treated muscles. These findings demonstrate the myogenic regenerative potential of iPS cells and provide rationale for their future therapeutic application for muscular dystrophies.

19. Randomized Controlled Trial of a Neurosteroid Intervention in Schizophrenia

PubMed Central

Marx, Chris; Naylor, Jennifer; Kilts, Jason; Allan, Trina; Smith, Karen; Szabo, Steven; Wagner, Ryan; Buchanan, Robert; Keefe, Richard; Shampine, Lawrence

2017-01-01

Abstract Background: Neurosteroids are endogenous molecules synthesized de novo in brain, adrenals, and other tissues. They demonstrate pleiotropic actions that are highly relevant to the neurobiology of schizophrenia. Clozapine markedly elevates neurosteroids in rodent hippocampus, potentially contributing to its superior therapeutic efficacy. Clinical evidence from a randomized controlled trial (RCT) conducted in Singapore suggests that pregnenolone significantly enhances functional capacity (as demonstrated by improvements in the UPSA Total Score and UPSA Communication Subscale Score) and that neurosteroid changes posttreatment predict therapeutic response (Marx et al 2014; Psychopharmacology). We thus conducted an RCT investigating adjunctive pregnenolone in schizophrenia. Methods: After a 2-week placebo lead-in, 88 participants with schizophrenia were randomized to pregnenolone (n = 42) or placebo (n = 46) for 8 weeks. Neurosteroids were quantified at baseline and posttreatment by mass spectrometry. Functional end points included the UPSA Total Score and UPSA Communication Subscale. Cognitive end points included the MCCB Composite Score and MCCB Subscales. Modified intent-to-treat analyses were conducted. Results: Participants randomized to the pregnenolone group did not outperform placebo on the UPSA Total Score or MCCB Composite Score. However, the pregnenolone group demonstrated significantly greater improvement in the UPSA Communication Subscale compared to participants randomized to placebo (P = .034), replicating prior RCT findings from Singapore. Elevations in pregnenolone post-treatment also predicted improvements in UPSA Total Score (r = .373; P = .039), again replicating prior efforts. In addition, the pregnenolone group demonstrated significantly greater improvement in the MCCB Verbal Learning Subscale compared to placebo (P = .023). Pregnenolone did not outperform placebo in the BACS Composite Score, SANS Total Score, or PANSS Total Score. Pregnenolone was well tolerated. Conclusion: Treatment with pregnenolone appears to improve functional capacity in a US population with schizophrenia, as assessed by the UPSA Communication Subscale and also supported by a significant positive correlation between pregnenolone changes and UPSA Total Score improvements—thus replicating findings from a prior RCT conducted in Singapore. Pregnenolone may also improve verbal memory. Given the positive correlation between pregnenolone increases posttreatment and UPSA Total Score improvements, it is possible that higher doses of pregnenolone may be clinically efficacious, and that neurosteroid quantification has biomarker potential for the predication of therapeutic response. Additional dose-finding investigations will be required to test these hypotheses. A pregnenolone decanoate formulation is currently in preclinical development.

Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome

PubMed Central

Saqran, Lubna; Herrick, Scott P.; Frosch, Matthew P.; Hyman, Bradley T.

2017-01-01

Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation. This phenotype is similar to that of transgenic mice that express amyloid precursor protein (APP), which is duplicated in DS and in Ts65DN mice; however, normalizing APP gene copy number in Ts65Dn mice fails to rescue plasticity. Ts1Rhr mice harbor a duplication of the telomeric third of the Ts65Dn-duplicated sequence and demonstrate the same ODP defect, suggesting a gene or genes sufficient to drive the phenotype are located in that smaller duplication. In addition, we find that Ts65Dn mice demonstrate an abnormality in olfactory system connectivity, a defect in the refinement of connections to second-order neurons in the olfactory bulb. Ts1Rhr mice do not demonstrate a defect in glomerular refinement, suggesting that distinct genes or sets of genes underlie visual and olfactory system phenotypes. Importantly, these data suggest that developmental plasticity and connectivity are impaired in sensory systems in DS model mice, that such defects may contribute to functional impairment in DS, and that these phenotypes, present in male and female mice, provide novel means for examining the genetic and molecular bases for neurodevelopmental impairment in model mice in vivo. SIGNIFICANCE STATEMENT Our understanding of the basis for intellectual impairment in Down syndrome is hindered by the large number of genes duplicated in Trisomy 21 and a lack of understanding of the effect of disease pathology on the function of neural circuits in vivo. This work describes early postnatal developmental abnormalities in visual and olfactory sensory systems in Down syndrome model mice, which provide insight into defects in the function of neural circuits in vivo and provide an approach for exploring the genetic and molecular basis for impairment in the disease. In addition, these findings raise the possibility that basic dysfunction in primary sensory circuitry may illustrate mechanisms important for global learning and cognitive impairment in Down syndrome patients. PMID:28899917

The habenula in neurosurgery for depression: A convergence of functional neuroanatomy, psychiatry and imaging.

PubMed

Skandalakis, Georgios P; Koutsarnakis, Christos; Kalyvas, Aristotelis V; Skandalakis, Panagiotis; Johnson, Elizabeth O; Stranjalis, George

2018-05-05

The habenula is a small, mostly underrated structure in the pineal region. Multidisciplinary findings demonstrate an underlying complex connectivity of the habenula with the rest of the brain, subserving its major role in normal behavior and the pathophysiology of depression. These findings suggest the potential application of "habenular psychosurgery" in the treatment of mental disorders. The remission of two patients with treatment-resistant major depression treated with deep brain stimulation of the habenula supported the hypothesis that the habenula is an effective target for deep brain stimulation and initiated a surge of basic science research. This review aims to assess the viability of the deep brain stimulation of the habenula as a treatment option for treatment resistant depression. PubMed and the Cochrane Library databases were searched with no chronological restrictions for the identification of relevant articles. The results of this review are presented in a narrative form describing the functional neuroanatomy of the human habenula, its implications in major depression, findings of electrode implantation of this region and findings of deep brain stimulation of the habenula for the treatment of depression. Data assessing the hypothesis are scarce. Nonetheless, findings highlight the major role of the habenula in normal, as well as in pathological brain function, particularly in depression disorders. Moreover, findings of studies utilizing electrode implantation in the region of the habenula underscore our growing realization that research in neuroscience and deep brain stimulation complement each other in a reciprocal relationship; they are as self-reliant, as much as they depend on each other. Copyright © 2018. Published by Elsevier B.V.

New optimization scheme to obtain interaction potentials for oxide glasses

NASA Astrophysics Data System (ADS)

Sundararaman, Siddharth; Huang, Liping; Ispas, Simona; Kob, Walter

2018-05-01

We propose a new scheme to parameterize effective potentials that can be used to simulate atomic systems such as oxide glasses. As input data for the optimization, we use the radial distribution functions of the liquid and the vibrational density of state of the glass, both obtained from ab initio simulations, as well as experimental data on the pressure dependence of the density of the glass. For the case of silica, we find that this new scheme facilitates finding pair potentials that are significantly more accurate than the previous ones even if the functional form is the same, thus demonstrating that even simple two-body potentials can be superior to more complex three-body potentials. We have tested the new potential by calculating the pressure dependence of the elastic moduli and found a good agreement with the corresponding experimental data.

The hippocampus and visual perception

PubMed Central

Lee, Andy C. H.; Yeung, Lok-Kin; Barense, Morgan D.

2012-01-01

In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe (MTL). Instead, these studies point toward a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates. PMID:22529794

Continuously controlled optical band gap in oxide semiconductor thin films

DOE PAGES

Herklotz, Andreas; Rus, Stefania Florina; Ward, Thomas Zac

2016-02-02

The optical band gap of the prototypical semiconducting oxide SnO 2 is shown to be continuously controlled through single axis lattice expansion of nanometric films induced by low-energy helium implantation. While traditional epitaxy-induced strain results in Poisson driven multidirectional lattice changes shown to only allow discrete increases in bandgap, we find that a downward shift in the band gap can be linearly dictated as a function of out-of-plane lattice expansion. Our experimental observations closely match density functional theory that demonstrates that uniaxial strain provides a fundamentally different effect on the band structure than traditional epitaxy-induced multiaxes strain effects. In conclusion,more » charge density calculations further support these findings and provide evidence that uniaxial strain can be used to drive orbital hybridization inaccessible with traditional strain engineering techniques.« less

Not just a light fingertip touch: A facilitation of functional integration between body sway and visual search in older adults.

PubMed

Chen, Fu-Chen; Chu, Chia-Hua; Pan, Chien-Yu; Tsai, Chia-Liang

2018-05-01

Prior studies demonstrated that, compared to no fingertip touch (NT), a reduction in body sway resulting from the effects of light fingertip touch (LT) facilitates the performance of visual search, buttressing the concept of functional integration. However, previous findings may be confounded by different arm postures required between the NT and LT conditions. Furthermore, in older adults, how LT influences the interactions between body sway and visual search has not been established. (1) Are LT effects valid after excluding the influences of different upper limb configurations? (2) Is functional integration is feasible for older adults? Twenty-two young (age = 21.3 ± 2.0) and 22 older adults (age = 71.8 ± 4.1) were recruited. Participants performed visual inspection and visual searches under NT and LT conditions. The older group significantly reduced AP sway (p < 0.05) in LT compared to NT conditions, of which the LT effects on postural adaptation were more remarkable in older than young adults (p < 0.05). In addition, the older group significantly improved search accuracy (p < 0.05) from the LT to the NT condition, and these effects were equivalent between groups. After controlling for postural configurations, the results demonstrate that light fingertip touch reduces body sway and concurrently enhances visual search performance in older adults. These findings confirmed the effects of LT on postural adaptation as well as supported functional integration in older adults. Copyright © 2018 Elsevier B.V. All rights reserved.

Families' perception of children / adolescents with language impairment through the International Classification of Functioning, Disability, and Health (ICF-CY).

PubMed

Ostroschi, Daniele Theodoro; Zanolli, Maria de Lurdes; Chun, Regina Yu Shon

2017-05-22

To investigate the perception of family members regarding linguistic conditions and social participation of children and adolescents with speech and language impairments using the International Classification of Functioning, Disability and Health - Children and Youth Version (ICF-CY). Quali-quantitative approach research, in which a survey of medical records of 24 children/adolescents undergoing speech-language therapy and interviews with their family members was conducted. A descriptive analysis of the participants' profiles was performed, followed by a categorization of responses using the ICF-CY. All family members mentioned various aspects of speech/language categorized by the ICF-CY. Initially, they approached it as an organic issue, categorized under the component of Body Functions and Structures. Most reported different repercussions of the speech-language impairments on the domains, such as dealing with stress and speaking, qualified from mild to severe. Participants reported Environmental Factors categorized as facilitators in the immediate family's attitudes and as barriers in the social attitudes. These findings, according to the use of the ICF-CY, demonstrate that the children/adolescents' speech-language impairments, from the families' perception, are primarily understood in the body dimension. However, guided by a broader approach to health, the findings in the Activities and Participation and Environmental Factors demonstrate a broader understanding of the participants of the speech-language impairments. The results corroborate the importance of using the ICF-CY as a health care analysis tool, by incorporating functionality and participation aspects and providing subsidies for the construction of unique therapeutic projects in a broader approach to the health of the group studied.

Age-stratified outcomes after robotic-assisted laparoscopic radical prostatectomy.

PubMed

Zorn, Kevin C; Mendiola, Frederick P; Rapp, David E; Mikhail, Albert A; Lin, Shang; Orvieto, Marcelo A; Zagaja, Gregory P; Shalhav, Arieh L

2007-01-01

We sought to evaluate post-operative return of urinary and sexual function in men undergoing robotic-assisted laparoscopic radical prostatectomy (RLRP). Prospective assessment of urinary continence and sexual function was performed in patients undergoing RLRP. Subjective assessment involved the use of the validated RAND-36 Item Health Survey/UCLA Prostate Cancer Index questionnaire. Questionnaires were completed pre-operatively and at 1, 3, 6 and 12 months post-operatively. Subset analyses were performed to assess the effect of age on functional outcomes. A total of 338 consecutive patients underwent RLRP between February 2003 and August 2005. Included patients for evaluation comprised of 21, 129, and 150 patients, aged <50, 50-59, and ≥60 years old, respectively. Kaplan-Meier curve analysis demonstrated that younger men (<60 years) achieved subjective continence significantly earlier than older age group (≥60 years) (P = 0.02). Continence rates, however, equalized among all age groups at 1 year follow-up. Younger men (<50 years) also demonstrated a quicker and greater return of sexual function (P = 0.01), which persisted through assessment at 1 year post-operatively. Our results suggest that younger men may have an earlier return of continence and potency when compared to men > 60 years. Despite this finding, continence outcomes appear to be equal among age groups after 1 year of follow-up. Moreover, men < 60 years continue to report superior potency outcomes compared to men > 60 years at 1 year post-operatively. Such findings are valuable in counseling patients undergoing RLRP.

Linking Inter-Individual Variability in Functional Brain Connectivity to Cognitive Ability in Elderly Individuals

PubMed Central

Li, Rui; Yin, Shufei; Zhu, Xinyi; Ren, Weicong; Yu, Jing; Wang, Pengyun; Zheng, Zhiwei; Niu, Ya-Nan; Huang, Xin; Li, Juan

2017-01-01

Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity–cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases. PMID:29209203

The mediating role of metacognition in the relationship between executive function and self-regulated learning.

PubMed

Follmer, D Jake; Sperling, Rayne A

2016-12-01

Researchers have demonstrated significant relations among executive function, metacognition, and self-regulated learning. However, prior research emphasized the use of indirect measures of executive function and did not evaluate how specific executive functions are related to participants' self-regulated learning. The primary goals of the current study were to examine and test the relations among executive function, metacognition, and self-regulated learning as well as to examine how self-regulated learning is informed by executive function. The sample comprised 117 undergraduate students attending a large, Mid-Atlantic research university in the United States. Participants were individually administered direct and indirect measures of executive function, metacognition, and self-regulated learning. A mediation model specifying the relations among the regulatory constructs was proposed. In multiple linear regression analyses, executive function predicted metacognition and self-regulated learning. Direct measures of inhibition and shifting accounted for a significant amount of the variance in metacognition and self-regulated learning beyond an indirect measure of executive functioning. Separate mediation analyses indicated that metacognition mediated the relationship between executive functioning and self-regulated learning as well as between specific executive functions and self-regulated learning. The findings of this study are supported by previous research documenting the relations between executive function and self-regulated learning, and extend prior research by examining the manner in which executive function and self-regulated learning are linked. The findings provide initial support for executive functions as key processes, mediated by metacognition, that predict self-regulated learning. Implications for the contribution of executive functions to self-regulated learning are discussed. © 2016 The British Psychological Society.

Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

2016-04-01

The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

miRNAs in brain development

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

Petri, Rebecca; Malmevik, Josephine; Fasching, Liana

2014-02-01

MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs havemore » been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function.« less

Thermodynamic Modeling of Donor Splice Site Recognition in pre-mRNA

NASA Astrophysics Data System (ADS)

Aalberts, Daniel P.; Garland, Jeffrey A.

2004-03-01

When eukaryotic genes are edited by the spliceosome, the first step in intron recognition is the binding of a U1 snRNA with the donor (5') splice site. We model this interaction thermodynamically to identify splice sites. Applied to a set of 65 annotated genes, our Finding with Binding method achieves a significant separation between real and false sites. Analyzing binding patterns allows us to discard a large number of decoy sites. Our results improve statistics-based methods for donor site recognition, demonstrating the promise of physical modeling to find functional elements in the genome.

Thermodynamic modeling of donor splice site recognition in pre-mRNA

NASA Astrophysics Data System (ADS)

Garland, Jeffrey A.; Aalberts, Daniel P.

2004-04-01

When eukaryotic genes are edited by the spliceosome, the first step in intron recognition is the binding of a U1 small nuclear RNA with the donor ( 5' ) splice site. We model this interaction thermodynamically to identify splice sites. Applied to a set of 65 annotated genes, our “finding with binding” method achieves a significant separation between real and false sites. Analyzing binding patterns allows us to discard a large number of decoy sites. Our results improve statistics-based methods for donor site recognition, demonstrating the promise of physical modeling to find functional elements in the genome.

Global field synchronization in gamma range of the sleep EEG tracks sleep depth: Artifact introduced by a rectangular analysis window.

PubMed

Rusterholz, Thomas; Achermann, Peter; Dürr, Roland; Koenig, Thomas; Tarokh, Leila

2017-06-01

Investigating functional connectivity between brain networks has become an area of interest in neuroscience. Several methods for investigating connectivity have recently been developed, however, these techniques need to be applied with care. We demonstrate that global field synchronization (GFS), a global measure of phase alignment in the EEG as a function of frequency, must be applied considering signal processing principles in order to yield valid results. Multichannel EEG (27 derivations) was analyzed for GFS based on the complex spectrum derived by the fast Fourier transform (FFT). We examined the effect of window functions on GFS, in particular of non-rectangular windows. Applying a rectangular window when calculating the FFT revealed high GFS values for high frequencies (>15Hz) that were highly correlated (r=0.9) with spectral power in the lower frequency range (0.75-4.5Hz) and tracked the depth of sleep. This turned out to be spurious synchronization. With a non-rectangular window (Tukey or Hanning window) these high frequency synchronization vanished. Both, GFS and power density spectra significantly differed for rectangular and non-rectangular windows. Previous papers using GFS typically did not specify the applied window and may have used a rectangular window function. However, the demonstrated impact of the window function raises the question of the validity of some previous findings at higher frequencies. We demonstrated that it is crucial to apply an appropriate window function for determining synchronization measures based on a spectral approach to avoid spurious synchronization in the beta/gamma range. Copyright © 2017 Elsevier B.V. All rights reserved.

Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks

PubMed Central

Vaudano, Anna Elisabetta; Ruggieri, Andrea; Avanzini, Pietro; Gessaroli, Giuliana; Cantalupo, Gaetano; Coppola, Antonietta; Sisodiya, Sanjay M.

2017-01-01

Abstract See Hamandi (doi:10.1093/awx049) for a scientific commentary on this article. Photosensitivity is a condition in which lights induce epileptiform activities. This abnormal electroencephalographic response has been associated with hyperexcitability of the visuo-motor system. Here, we evaluate if intrinsic dysfunction of this network is present in brain activity at rest, independently of any stimulus and of any paroxysmal electroencephalographic activity. To address this issue, we investigated the haemodynamic correlates of the spontaneous alpha rhythm, which is considered the hallmark of the brain resting state, in photosensitive patients and in people without photosensitivity. Second, we evaluated the whole-brain functional connectivity of the visual thalamic nuclei in the various populations of subjects under investigation. Forty-four patients with epilepsy and 16 healthy control subjects underwent an electroencephalography-correlated functional magnetic resonance imaging study, during an eyes-closed condition. The following patient groups were included: (i) genetic generalized epilepsy with photosensitivity, 16 subjects (mean age 25 ± 10 years); (ii) genetic generalized epilepsy without photosensitivity, 13 patients (mean age 25 ± 11 years); (iii) focal epilepsy, 15 patients (mean age 25 ± 9 years). For each subject, the posterior alpha power variations were convolved with the standard haemodynamic response function and used as a regressor. Within- and between-groups second level analyses were performed. Whole brain functional connectivity was evaluated for two thalamic regions of interest, based on the haemodynamic findings, which included the posterior thalamus (pulvinar) and the medio-dorsal thalamic nuclei. Genetic generalized epilepsy with photosensitivity demonstrated significantly greater mean alpha-power with respect to controls and other epilepsy groups. In photosensitive epilepsy, alpha-related blood oxygen level-dependent signal changes demonstrated lower decreases relative to all other groups in the occipital, sensory-motor, anterior cingulate and supplementary motor cortices. Coherently, the same brain regions demonstrated abnormal connectivity with the visual thalamus only in epilepsy patients with photosensitivity. As predicted, our findings indicate that the cortical-subcortical network generating the alpha oscillation at rest is different in people with epilepsy and visual sensitivity. This difference consists of a decreased alpha-related inhibition of the visual cortex and sensory-motor networks at rest. These findings represent the substrate of the clinical manifestations (i.e. myoclonus) of the photoparoxysmal response. Moreover, our results provide the first evidence of the existence of a functional link between the circuits that trigger the visual sensitivity phenomenon and those that generate the posterior alpha rhythm. PMID:28334965

Trajectory of change in pain, depression, and physical functioning after physical activity adoption in fibromyalgia.

PubMed

Steiner, Jennifer L; Bigatti, Silvia M; Ang, Dennis C

2015-07-01

Fibromyalgia is associated with widespread pain, depression, and declines in physical functioning. The purpose of this study was to examine the trajectory of these symptoms over time related to physical activity adoption and maintenance via motivational interviewing versus education, to increase physical activity. There were no treatment group differences; we divided the sample (n = 184) based on changes in physical activity. Repeated measures analyses demonstrated differential patterns in depression, pain, and physical functioning at 24 and 36 weeks. Findings suggest increased physical activity may serve as a multiple-target intervention that provides moderate to large, long-lasting benefits for individuals with fibromyalgia. © The Author(s) 2013.

Fractional Wigner Crystal in the Helical Luttinger Liquid.

PubMed

Traverso Ziani, N; Crépin, F; Trauzettel, B

2015-11-13

The properties of the strongly interacting edge states of two dimensional topological insulators in the presence of two-particle backscattering are investigated. We find an anomalous behavior of the density-density correlation functions, which show oscillations that are neither of Friedel nor of Wigner type: they, instead, represent a Wigner crystal of fermions of fractional charge e/2, with e the electron charge. By studying the Fermi operator, we demonstrate that the state characterized by such fractional oscillations still bears the signatures of spin-momentum locking. Finally, we compare the spin-spin correlation functions and the density-density correlation functions to argue that the fractional Wigner crystal is characterized by a nontrivial spin texture.

Home health care cost-function analysis

PubMed Central

Hay, Joel W.; Mandes, George

1984-01-01

An exploratory home health care (HHC) cost-function model is estimated using State rate-setting data for the 74 traditional (nonprofit) Connecticut agencies. The analysis demonstrates U-shaped average costs curves for agencies' provision of skilled nursing visits, with substantial diseconomies of scale in the observable range. It is determined from the estimated cost function that the sample representative agency is providing fewer visits than optimal, and its marginal cost is significantly below average cost. The finding that an agency's costs are predominantly related to output levels, with little systematic variation due to other agency or patient characteristics, suggests that the economic inefficiency in a cost-based HHC reimbursement policy may be substantial. PMID:10310596

Observations of non-linear plasmon damping in dense plasmas

NASA Astrophysics Data System (ADS)

Witte, B. B. L.; Sperling, P.; French, M.; Recoules, V.; Glenzer, S. H.; Redmer, R.

2018-05-01

We present simulations using finite-temperature density-functional-theory molecular-dynamics to calculate dynamic dielectric properties in warm dense aluminum. The comparison between exchange-correlation functionals in the Perdew, Burke, Ernzerhof approximation, Strongly Constrained and Appropriately Normed Semilocal Density Functional, and Heyd, Scuseria, Ernzerhof (HSE) approximation indicates evident differences in the electron transition energies, dc conductivity, and Lorenz number. The HSE calculations show excellent agreement with x-ray scattering data [Witte et al., Phys. Rev. Lett. 118, 225001 (2017)] as well as dc conductivity and absorption measurements. These findings demonstrate non-Drude behavior of the dynamic conductivity above the Cooper minimum that needs to be taken into account to determine optical properties in the warm dense matter regime.

Shot noise at high temperatures

NASA Astrophysics Data System (ADS)

Gutman, D. B.; Gefen, Yuval

2003-07-01

We consider the possibility of measuring nonequilibrium properties of the current correlation functions at high temperatures (and small bias). Through the example of the third cumulant of the current (S3) we demonstrate that odd-order correlation functions represent nonequilibrium physics even at small external bias and high temperatures. We calculate S3=y(eV/T)e2I for a quasi-one-dimensional diffusive constriction. We calculate the scaling function y in two regimes: when the scattering processes are purely elastic and when the inelastic electron-electron scattering is strong. In both cases we find that y interpolates between two constants. In the low- (high-) temperature limit y is strongly (weakly) enhanced (suppressed) by the electron-electron scattering.

Metacognition as a Mediating Variable Between Neurocognition and Functional Outcome in First Episode Psychosis.

PubMed

Davies, Geoff; Fowler, David; Greenwood, Kathryn

2017-07-01

Neurocognitive and functional outcome deficits have long been acknowledged in schizophrenia and neurocognition has been found to account for functional disability to a greater extent than psychopathology. Much of the variance in functional outcome however still remains unexplained and metacognition may mediate the relationship between neurocognition, functional capacity, and self-reported social and occupational function. Eighty first episode psychosis participants were recruited and completed measures of neurocognition (memory, executive function, and intelligence quotient), metacognition (Beck Cognitive Insight Scale, Metacognitive Awareness Interview), psychopathology (PANSS), and both functional capacity (UPSA) and real-life social and occupational function (The Time Use Survey). Path analyses investigated the relationships between variables through structural equation modeling. A series of path models demonstrated that metacognition partially mediates the relationship between neurocognition and functional capacity, and fully mediates the relationship between functional capacity and social and occupational function. The present study findings identify that metacognition may be critical to translating cognitive and functional skills into real-world contexts, and this relationship is found at early stages of illness. Understanding how individuals translate cognitive and functional skills into the real-world (the competence-performance gap) may offer valuable guidance to intervention programs. This finding is important to models of recovery as it suggests that intervention programs that focus on enhancing metacognition abilities may have a greater impact than traditional rehabilitation programs focusing on cognitive abilities, on social and occupational outcomes. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Myoferlin is a novel exosomal protein and functional regulator of cancer-derived exosomes.

PubMed

Blomme, Arnaud; Fahmy, Karim; Peulen, Olivier; Costanza, Brunella; Fontaine, Marie; Struman, Ingrid; Baiwir, Dominique; de Pauw, Edwin; Thiry, Marc; Bellahcène, Akeila; Castronovo, Vincent; Turtoi, Andrei

2016-12-13

Exosomes are communication mediators participating in the intercellular exchange of proteins, metabolites and nucleic acids. Recent studies have demonstrated that exosomes are characterized by a unique proteomic composition that is distinct from the cellular one. The mechanisms responsible for determining the proteome content of the exosomes remain however obscure. In the current study we employ ultrastructural approach to validate a novel exosomal protein myoferlin. This is a multiple C2-domain containing protein, known for its conserved physiological function in endocytosis and vesicle fusion biology. Emerging studies demonstrate that myoferlin is frequently overexpressed in cancer, where it promotes cancer cell migration and invasion. Our data expand these findings by showing that myoferlin is a general component of cancer cell derived exosomes from different breast and pancreatic cancer cell lines. Using proteomic analysis, we demonstrate for the first time that myoferlin depletion in cancer cells leads to a significantly modulated exosomal protein load. Such myoferlin-depleted exosomes were also functionally deficient as shown by their reduced capacity to transfer nucleic acids to human endothelial cells (HUVEC). Beyond this, myoferlin-depleted cancer exosomes also had a significantly reduced ability to induce migration and proliferation of HUVEC. The present study highlights myoferlin as a new functional player in exosome biology, calling for novel strategies to target this emerging oncogene in human cancer.

Effects of Animal-Assisted Activities with Guinea Pigs in the Primary School Classroom

PubMed Central

O’Haire, Marguerite E.; McKenzie, Samantha J.; McCune, Sandra; Slaughter, Virginia

2013-01-01

This study investigated the effects of a classroom-based animal-assisted activities (AAA) program with guinea pigs on the social functioning of primary school children. We hypothesized that participants in the experimental condition (n = 64), compared with a waitlist control group (n = 64), would demonstrate improvements in social functioning following the program. Parents and teachers used the Social Skills Rating System (SSRS) to evaluate the social skills and problem behaviors of 128 participating children (age range = 4.8 to 12.7 years) before and after an 8-week period. Teachers also rated academic competence at both time points. Children who participated in the AAA program demonstrated significantly greater improvements in social functioning than their control group peers, as defined by greater increases in social skills (teacher SSRS) and decreases in problem behaviors (parent and teacher SSRS). There were no significant differences between the groups in academic competence. AAA participants demonstrated significant increases in social skills and decreases in problem behaviors from pre- to post-program on the teacher version of the SSRS. Control group participants did not show significant changes on these measures. These findings suggest that an AAA program with guinea pigs may be a feasible addition to the primary school classroom in order to improve social functioning. Further component analysis will be necessary to determine whether the animal is the active ingredient in AAA programs of this nature. PMID:24265514

Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders.

PubMed

Zhang, Jie; Cheng, Wei; Liu, Zhaowen; Zhang, Kai; Lei, Xu; Yao, Ye; Becker, Benjamin; Liu, Yicen; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

2016-08-01

SEE MATTAR ET AL DOI101093/AWW151 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Functional brain networks demonstrate significant temporal variability and dynamic reconfiguration even in the resting state. Currently, most studies investigate temporal variability of brain networks at the scale of single (micro) or whole-brain (macro) connectivity. However, the mechanism underlying time-varying properties remains unclear, as the coupling between brain network variability and neural activity is not readily apparent when analysed at either micro or macroscales. We propose an intermediate (meso) scale analysis and characterize temporal variability of the functional architecture associated with a particular region. This yields a topography of variability that reflects the whole-brain and, most importantly, creates an analytical framework to establish the fundamental relationship between variability of regional functional architecture and its neural activity or structural connectivity. We find that temporal variability reflects the dynamical reconfiguration of a brain region into distinct functional modules at different times and may be indicative of brain flexibility and adaptability. Primary and unimodal sensory-motor cortices demonstrate low temporal variability, while transmodal areas, including heteromodal association areas and limbic system, demonstrate the high variability. In particular, regions with highest variability such as hippocampus/parahippocampus, inferior and middle temporal gyrus, olfactory gyrus and caudate are all related to learning, suggesting that the temporal variability may indicate the level of brain adaptability. With simultaneously recorded electroencephalography/functional magnetic resonance imaging and functional magnetic resonance imaging/diffusion tensor imaging data, we also find that variability of regional functional architecture is modulated by local blood oxygen level-dependent activity and α-band oscillation, and is governed by the ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Predictors of Adolescent Outcomes among 4–6 Year Old Children with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Lahey, Benjamin B.; Lee, Steve S.; Sibley, Margaret H.; Applegate, Brooks; Molina, Brooke S. G.; Pelham, William E.

2015-01-01

Children who met DSM-IV criteria for attention-deficit/hyperactivity disorder (ADHD) with functional impairment in at least one setting at 4–6 years of age were followed prospectively through age 18 years. On average, the 125 children (107 boys) with ADHD at baseline improved over time, but still continued to exhibit more symptoms, functional impairment, and risky behavior through adolescence than demographically matched healthy comparison children. These findings support the predictive validity of the diagnosis of ADHD at younger ages by demonstrating that the symptoms and impairment are enduring. Nonetheless, there were marked variations in developmental outcomes. Among children with ADHD, higher numbers of inattention and hyperactivity-impulsivity symptoms and higher number of concurrent symptoms (oppositional, conduct disorder, anxiety, and depression) measured at baseline each predicted higher future levels of the same dimension of symptoms. In addition, higher baseline levels of inattention, oppositional, conduct disorder, and anxiety symptoms predicted greater future functional impairment. Among children with ADHD, girls and children from families with lower family incomes had relatively poorer outcomes. Although outcomes varied along a continuum, approximately 10% of the children with ADHD at 4–6 years could be classified as functioning in the normative range on multiple measures during 15–18 years. Although this finding awaits replication, lower levels of hyperactivity-impulsivity symptoms at 4–6 years predicted more normative functioning during adolescence. These findings suggest that ADHD identified in early childhood predicts an increased likelihood of functional impairment through adolescence for most, but not all, children. PMID:26854503

Systemic lupus erythematosus with organic brain syndrome: serial electroencephalograms accurately evaluate therapeutic efficacy.

PubMed

Kato, Takashi; Shiratori, Kyoji; Kobashigawa, Tsuyoshi; Hidaka, Yuji

2006-01-01

A 48-year-old man with systemic lupus erythematosus developed organic brain syndrome. High-dose prednisolone was ineffective, and somnolence without focal signs rapidly developed. Electroencephalogram (EEG) demonstrated a slow basic rhythm (3 Hz), but brain magnetic resonance imaging was normal. Somnolence resolved soon after performing plasma exchange (two sessions). However, memory dysfunction persisted, with EEG demonstrating mild abnormalities (7-8 Hz basic rhythm). Double-filtration plasmapheresis (three sessions) was done, followed by intravenous cyclophosphamide. Immediately after the first plasmapheresis session, memory dysfunction began to improve. After the second dose of cyclophosphamide, intellectual function resolved completely and EEG findings also normalized (basic rhythm of 10 Hz waves). Serial EEG findings precisely reflected the neurological condition and therapeutic efficacy in this patient. In contrast, protein levels in cerebrospinal fluid remained high and did not seem to appropriately reflect the neurological condition in this patient.

Gratitude and prosocial behavior: helping when it costs you.

PubMed

Bartlett, Monica Y; DeSteno, David

2006-04-01

The ability of the emotion gratitude to shape costly prosocial behavior was examined in three studies employing interpersonal emotion inductions and requests for assistance. Study 1 demonstrated that gratitude increases efforts to assist a benefactor even when such efforts are costly (i.e., hedonically negative), and that this increase differs from the effects of a general positive affective state. Additionally, mediational analyses revealed that gratitude, as opposed to simple awareness of reciprocity norms, drove helping behavior. Furthering the theory that gratitude mediates prosocial behavior, Study 2 replicated the findings of Study 1 and demonstrated gratitude's ability to function as an incidental emotion by showing it can increase assistance provided to strangers. Study 3 revealed that this incidental effect dissipates if one is made aware of the true cause of the emotional state. Implications of these findings for the role of gratitude in building relationships are discussed.

Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium.

PubMed

Smith, I M; Baker, A; Arneborg, N; Jespersen, L

2015-11-01

The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast-mediated epithelial cell barrier protection from Salmonella invasion, thus encouraging future efforts aimed at confirming the observed effects in vivo and driving further strain development towards novel yeast probiotics. © 2015 The Society for Applied Microbiology.

Family Literacy Works: Key Findings from the NFER Evaluation of the Basic Skills Agency's Demonstration Programmes

ERIC Educational Resources Information Center

Basic Skills Agency, 2006

2006-01-01

The Basic Skills Agency (formerly the Adult Literacy and Basic Skills Unit--ALBSU) is the national development agency for literacy, numeracy and related basic skills in England and Wales. This agency defines basic skills as " the ability to read, write, and speak in English and use mathematics at a level necessary to function and progress at…

Natural history of echocardiographic abnormalities in mucopolysaccharidosis III.

PubMed

Wilhelm, Carolyn M; Truxal, Kristen V; McBride, Kim L; Kovalchin, John P; Flanigan, Kevin M

2018-06-01

Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials. A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3). Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range. Copyright © 2018 Elsevier Inc. All rights reserved.

Conflict between object structural and functional affordances in peripersonal space.

PubMed

Kalénine, Solène; Wamain, Yannick; Decroix, Jérémy; Coello, Yann

2016-10-01

Recent studies indicate that competition between conflicting action representations slows down planning of object-directed actions. The present study aims to assess whether similar conflict effects exist during manipulable object perception. Twenty-six young adults performed reach-to-grasp and semantic judgements on conflictual objects (with competing structural and functional gestures) and non-conflictual objects (with similar structural and functional gestures) presented at difference distances in a 3D virtual environment. Results highlight a space-dependent conflict between structural and functional affordances. Perceptual judgments on conflictual objects were slower that perceptual judgments on non-conflictual objects, but only when objects were presented within reach. Findings demonstrate that competition between structural and functional affordances during object perception induces a processing cost, and further show that object position in space can bias affordance competition. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

PubMed

Egawa, Junji; Schilling, Jan M; Cui, Weihua; Posadas, Edmund; Sawada, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E; Fannon-Pavlich, McKenzie J; Mandyam, Chitra D; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P

2017-08-01

Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. © FASEB.

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

Seal, Brian; Huque, Aminul; Rogers, Lindsey

In 2011, EPRI began a four-year effort under the Department of Energy (DOE) SunShot Initiative Solar Energy Grid Integration Systems - Advanced Concepts (SEGIS-AC) to demonstrate smart grid ready inverters with utility communication. The objective of the project was to successfully implement and demonstrate effective utilization of inverters with grid support functionality to capture the full value of distributed photovoltaic (PV). The project leveraged ongoing investments and expanded PV inverter capabilities, to enable grid operators to better utilize these grid assets. Developing and implementing key elements of PV inverter grid support capabilities will increase the distribution system’s capacity for highermore » penetration levels of PV, while reducing the cost. The project team included EPRI, Yaskawa-Solectria Solar, Spirae, BPL Global, DTE Energy, National Grid, Pepco, EDD, NPPT and NREL. The project was divided into three phases: development, deployment, and demonstration. Within each phase, the key areas included: head-end communications for Distributed Energy Resources (DER) at the utility operations center; methods for coordinating DER with existing distribution equipment; back-end PV plant master controller; and inverters with smart-grid functionality. Four demonstration sites were chosen in three regions of the United States with different types of utility operating systems and implementations of utility-scale PV inverters. This report summarizes the project and findings from field demonstration at three utility sites.« less

Working memory and executive function: the influence of content and load on the control of attention.

PubMed

Hester, Robert; Garavan, Hugh

2005-03-01

In a series of three experiments, increasing working memory (WM) load was demonstrated to reduce the executive control of attention, measured via task-switching and inhibitory control paradigms. Uniquely, our paradigms allowed comparison of the ability to exert executive control when the stimulus was either part of the currently rehearsed memory set or an unrelated distractor item. The results demonstrated a content-specific effect-insofar as switching attention away from, or exerting inhibitory control over, items currently held in WM was especially difficult-compounded by increasing WM load. This finding supports the attentional control theory that active maintenance of competing task goals is critical to executive function and WM capacity; however, it also suggests that the increased salience provided to the contents of WM through active rehearsal exerts a content-specific influence on attentional control. These findings are discussed in relation to cue-induced ruminations, where active rehearsal of evocative information (e.g., negative thoughts in depression or drug-related thoughts in addiction) in WM typically results from environmental cuing. The present study has demonstrated that when information currently maintained in WM is reencountered, it is harder to exert executive control over it. The difficulty with suppressing the processing of these stimuli presumably reinforces the maintenance of these items in WM, due to the greater level of attention they are afforded, and may help to explain how the cue-induced craving/rumination cycle is perpetuated.

Talking Science: The research evidence on the use of small group discussions in science teaching

NASA Astrophysics Data System (ADS)

Bennett, Judith; Hogarth, Sylvia; Lubben, Fred; Campbell, Bob; Robinson, Alison

2010-01-01

This paper reports the findings of two systematic reviews of the use and effects of small group discussions in high school science teaching. Ninety-four studies were included in an overview (systematic map) of work in the area, and 24 studies formed the basis of the in-depth reviews. The reviews indicate that there is considerable diversity in the topics used to promote small group discussions. They also demonstrate that students often struggle to formulate and express coherent arguments, and demonstrate a low level of engagement with tasks. The reviews suggest that groups function more purposefully, and understanding improves most, when specifically constituted such that differing views are represented, when some form of training is provided for students on effective group work, and when help in structuring discussions is provided in the form of "cues". Single-sex groups function more purposefully than mixed-sex groups, though improvements in understanding are independent of gender composition of groups. Finally, the reviews demonstrate very clearly that, for small group discussions to be effective, teachers and students need to be given explicit teaching in the skills associated with the development of arguments and the characteristics associated with effective group discussions. In addition to the substantive findings, the paper also reports on key features of the methods employed to gather and analyse data. Of particular note are the two contrasting approaches to data analysis, one adopting a grounded theory approach and the other drawing on established methods of discourse analysis.

Romantic Partner Selection and Socialization during Early Adolescence

PubMed Central

Simon, Valerie A.; Aikins, Julie Wargo; Prinstein, Mitchell J.

2012-01-01

This prospective study examined romantic partner selection and socialization among a sample of 78 young adolescents (6th–8th graders). Independent assessments of adolescent and romantic partner adjustment were collected before and after relationships initiated via peer nomination and self-report. Prior to their relationship, adolescents and partners were significantly alike on popularity, physical attraction, and depressive symptoms. Controlling for initial similarity, partners' popularity, depressive symptoms, relational aggression and relational victimization significantly predicted changes in adolescents' functioning in these areas over time. However, the magnitude and direction of change varied according to adolescents' and partners' pre-relationship functioning. In general, adolescents who dated high-functioning partners changed more than those who dated low-functioning partners, and partner characteristics predicted greater change among low versus high-functioning adolescents. Results were consistent even when controlling for best friend characteristics. The current findings are among the first to demonstrate unique contributions of romantic partner characteristics to adolescents' psychosocial functioning. PMID:19037942

ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function

PubMed Central

Sharma, Aarti; Lyashchenko, Alexander K.; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z.; Shneider, Neil A.

2016-01-01

Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations. PMID:26842965

School function in students with Down syndrome.

PubMed

Daunhauer, Lisa A; Fidler, Deborah J; Will, Elizabeth

2014-01-01

People with Down syndrome (DS) are predisposed to specific areas of relative developmental strength and challenge, but it is unclear whether and how this profile affects participation in school and community settings. In this study we characterized the nature of school participation and performance of functional tasks in the school context for 26 elementary students with DS (mean age = 7.86 yr; standard deviation = 1.75). Students participated in assessments of cognitive status and language development. Their teachers completed the School Function Assessment (Coster, Deeney, Haltiwanger, & Haley, 1998) questionnaire and a standardized questionnaire on executive functioning (EF). Students demonstrated a pronounced pattern of assistance- and adaptation-related needs across various domains of school function. The strongest predictor of school function was EF skills, as reported by teachers (adjusted R² = .47, p = .003). Findings from this study should inform future intervention and school-related planning for elementary school students with DS. Copyright © 2014 by the American Occupational Therapy Association, Inc.

Abnormal functional motor lateralization in healthy siblings of patients with schizophrenia.

PubMed

Altamura, Mario; Fazio, Leonardo; De Salvia, Michela; Petito, Annamaria; Blasi, Giuseppe; Taurisano, Paolo; Romano, Raffaella; Gelao, Barbara; Bellomo, Antonello; Bertolino, Alessandro

2012-07-30

Earlier neuroimaging studies of motor function in schizophrenia have demonstrated reduced functional lateralization in the motor network during motor tasks. Here, we used event-related functional magnetic resonance imaging during a visually guided motor task in 18 clinically unaffected siblings of patients with schizophrenia and 24 matched controls to investigate if abnormal functional lateralization is related to genetic risk for this brain disorder. Whereas activity associated with motor task performance was mainly contralateral with only a marginal ipsilateral component in healthy participants, unaffected siblings had strong bilateral activity with significantly greater response in ipsilateral and contralateral premotor areas as well as in contralateral subcortical motor regions relative to controls. Reduced lateralization in siblings was also identified with a measure of laterality quotient. These findings suggest that abnormal functional lateralization of motor circuitry is related to genetic risk of schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function.

PubMed

Sharma, Aarti; Lyashchenko, Alexander K; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z; Shneider, Neil A

2016-02-04

Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations.

Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

PubMed

Varadi, Mihaly; Zsolyomi, Fruzsina; Guharoy, Mainak; Tompa, Peter

2015-01-01

Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation. We conclude that the functional role of intrinsically disordered protein segments in RNA-binding is two-fold: first, these regions establish extended, conserved electrostatic interfaces with RNAs via induced fit. Second, conformational flexibility enables them to target different RNA partners, providing multi-functionality, while also ensuring specificity. These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

Functional Abdominal Pain: "Get" the Function, Loose the Pain.

PubMed

Draeger-Muenke, Reinhild

2015-07-01

Functional abdominal pain is a mind-body, psychosocial, and self-reinforcing experience with significant consequences for the sufferer and the surrounding support network. The occurrence of unpredictable symptoms and their severity add an element of dread and feeling out-of-control to daily life and often reduce overall functioning in a downward spiral. Two clinical presentations of functional abdominal pain are offered in this article (composites to protect confidentiality) dealing with abdominal pain syndrome and abdominal migraines. The treatment demonstrates the use of hypnotic principles for self-regulation, exploration, and meaning-making. Hypnosis treatment is conducted in combination with mindfulness-based interventions and Traditional Chinese Medicine's (TCM) teachings regarding abdominal health and illness. The clinical examples illustrate medical findings that suggest children with early life stress and an early onset of gastrointestinal somatization may not simply outgrow their functional abdominal pain but may suffer into adulthood.

Robotic assessment of sensorimotor deficits after traumatic brain injury.

PubMed

Debert, Chantel T; Herter, Troy M; Scott, Stephen H; Dukelow, Sean

2012-06-01

Robotic technology is commonly used to quantify aspects of typical sensorimotor function. We evaluated the feasibility of using robotic technology to assess visuomotor and position sense impairments following traumatic brain injury (TBI). We present results of robotic sensorimotor function testing in 12 subjects with TBI, who had a range of initial severities (9 severe, 2 moderate, 1 mild), and contrast these results with those of clinical tests. We also compared these with robotic test outcomes in persons without disability. For each subject with TBI, a review of the initial injury and neuroradiologic findings was conducted. Following this, each subject completed a number of standardized clinical measures (Fugl-Meyer Assessment, Purdue Peg Board, Montreal Cognitive Assessment, Rancho Los Amigos Scale), followed by two robotic tasks. A visually guided reaching task was performed to assess visuomotor control of the upper limb. An arm position-matching task was used to assess position sense. Robotic task performance in the subjects with TBI was compared with findings in a cohort of 170 person without disabilities. Subjects with TBI demonstrated a broad range of sensory and motor deficits on robotic testing. Notably, several subjects with TBI displayed significant deficits in one or both of the robotic tasks, despite normal scores on traditional clinical motor and cognitive assessment measures. The findings demonstrate the potential of robotic assessments for identifying deficits in visuomotor control and position sense following TBI. Improved identification of neurologic impairments following TBI may ultimately enhance rehabilitation.

Isolation of canine mesenchymal stem cells from amniotic fluid and differentiation into hepatocyte-like cells.

PubMed

Choi, Seon-A; Choi, Hoon-Sung; Kim, Keun Jung; Lee, Dong-Soo; Lee, Ji Hey; Park, Jie Yeun; Kim, Eun Young; Li, Xiaoxia; Oh, Hyun-Yang; Lee, Dong-Seok; Kim, Min Kyu

2013-01-01

Recent findings have demonstrated that amniotic fluid cells are an interesting and potential source of mesenchymal stem cells (MSCs). In this study, we isolated MSCs from canine amniotic fluid and then characterized their multilineage differentiation ability. Canine amniotic fluid stem (cAFS) cells at passage 5 had a fibroblast-like morphology instead of forming colonies and were positive for pluripotent stem cell markers such as OCT4, NANOG, and SOX2. Flow cytometry analysis showed the expression of MSC surface markers CD44, CD29, and CD90 on the cAFS cells. In addition, these cells were cultured under conditions favorable for adipogenic, chondrogenic, and osteogenic induction. The results of this experiment confirmed the mesenchymal nature of cAFS cells and their multipotent potential. Interestingly, although the cells exhibited a fibroblast-like morphology after hepatogenic induction, reverse transcription-polymerase chain reaction revealed that the expression of several hepatic genes, such as albumin, tyrosine aminotransferase, and alpha-1 antiproteinase, increased following maturation and differentiation. These findings indicated that cAFS cells have functional properties similar to those of hepatocytes. Taken together, the results of our study demonstrated that cAFS cells with mesenchymal characteristics can be successfully isolated from canine amniotic fluid and possess functional properties characteristic of hepatocytes. The findings of our work suggest that cAFS cells have the potential to be a resource for cell-based therapies in a canine model of hepatic disease.

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

PubMed Central

Havens, AM; Jung, Y; Sun, YX; Wang, J; Shah, RB; Bühring, HJ; Pienta, KJ; Taichman, RS

2006-01-01

Background The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. Results Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. Conclusion Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes. PMID:16859559

Rolled-up Functionalized Nanomembranes as Three-Dimensional Cavities for Single Cell Studies

PubMed Central

2014-01-01

We use micropatterning and strain engineering to encapsulate single living mammalian cells into transparent tubular architectures consisting of three-dimensional (3D) rolled-up nanomembranes. By using optical microscopy, we demonstrate that these structures are suitable for the scrutiny of cellular dynamics within confined 3D-microenvironments. We show that spatial confinement of mitotic mammalian cells inside tubular architectures can perturb metaphase plate formation, delay mitotic progression, and cause chromosomal instability in both a transformed and nontransformed human cell line. These findings could provide important clues into how spatial constraints dictate cellular behavior and function. PMID:24598026

Mind, brain, body, and soul: a review of the electrophysiological undercurrents for Dr. Frankenstein.

PubMed

Kaplan, Peter W

2004-01-01

Mary Shelley's Frankenstein is perhaps the most famous work of medical science fiction. She and her husband, the poet Percy Shelley, were aware of nascent neuroscience experimentation and the effects of electricity on neuromuscular function. Such experiments generated theories of voluntary, involuntary, and unconscious neuromuscular function; animal electricity; and the anima--the human vital principle. In Germany and Italy, investigators were performing bizarre electrical experiments on animals and humans to "reanimate" lifeless limbs and bodies. These demonstrations and theories find expression in Frankenstein and provide models for Dr. Frankenstein and his creation.

Exact traveling-wave and spatiotemporal soliton solutions to the generalized (3+1)-dimensional Schrödinger equation with polynomial nonlinearity of arbitrary order.

PubMed

Petrović, Nikola Z; Belić, Milivoj; Zhong, Wei-Ping

2011-02-01

We obtain exact traveling wave and spatiotemporal soliton solutions to the generalized (3+1)-dimensional nonlinear Schrödinger equation with variable coefficients and polynomial Kerr nonlinearity of an arbitrarily high order. Exact solutions, given in terms of Jacobi elliptic functions, are presented for the special cases of cubic-quintic and septic models. We demonstrate that the widely used method for finding exact solutions in terms of Jacobi elliptic functions is not applicable to the nonlinear Schrödinger equation with saturable nonlinearity. ©2011 American Physical Society

[Correlates between Munich Functional Development Diagnostics and postural reactivity findings based on seven provovoked postural reactions modus Vojta during the first period of child's life].

PubMed

Gajewska, Ewa; Sobieska, Magdalena; Samborski, Włodzimierz

2006-01-01

This work presents two diagnostic methods which were used to examine 57 children during their first three months of life. By classifying abnormalities of central nervous coordination we compared seven postural reactions according to Vojta with spontaneous behaviour of the child according to Munich Functional Development Diagnostics. It was demonstrated that both methods for the detection of early lesions in the central nervous system are sensitive. Good coherence of the results suggests that both methods may be used interchangeably.

Curative effect and safety of vascularized fibula grafting in renal transplant recipients with osteonecrosis of the femoral head: three case reports.

PubMed

Guo, Y J; Jin, D X; Zhang, C Q; Chen, S B; Sheng, J G; Lee, H S; Zhang, K G; Zeng, B F

2009-11-01

Osteonecrosis of the femoral head is a common and severe complication after renal transplantation. It is characterized by deterioration of hip joint function, which impairs quality of life. We present 3 renal transplant case reports of patients with osteonecrosis of the femoral head who underwent free vascularized fibular grafting at our hospital. Follow-up was from 1(1/2) to 2 years. All 3 patients exhibited good recovery with substantial improvement in joint function. Intraoperative and postoperative findings demonstrated the safety of this surgical procedure.

The tortuous road to an ideal CGRP function blocker for the treatment of migraine.

PubMed

Davis, Carl D; Xu, Cen

2008-01-01

The critical role of Calcitonin Gene-Related Peptide (CGRP) in migraine has been validated, with two small molecule CGRP antagonists BIBN4096BS and MK-0974 demonstrating efficacy in the reversal of acute migraine attack. Multiple approaches have been taken to find the ideal agent that most effectively inhibits CGRP's function. Here, we have summarized the progress made in recent years, including the identification and optimization of an orally bioavailable small molecule CGRP receptor antagonist. We also describe other interventions such as scavenging of CGRP itself. The advantages and disadvantages of these distinct approaches are discussed.

Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

PubMed Central

2015-01-01

Finding transition paths for chemical reactions can be computationally costly owing to the level of quantum-chemical theory needed for accuracy. Here, we show that a multilevel preconditioning scheme that was recently introduced (Tempkin et al. J. Chem. Phys.2014, 140, 184114) can be used to accelerate quantum-chemical string calculations. We demonstrate the method by finding minimum-energy paths for two well-characterized reactions: tautomerization of malonaldehyde and Claissen rearrangement of chorismate to prephanate. For these reactions, we show that preconditioning density functional theory (DFT) with a semiempirical method reduces the computational cost for reaching a converged path that is an optimum under DFT by several fold. The approach also shows promise for free energy calculations when thermal noise can be controlled. PMID:25516726

Co-ordinated structural and functional covariance in the adolescent brain underlies face processing performance.

PubMed

Shaw, Daniel Joel; Mareček, Radek; Grosbras, Marie-Helene; Leonard, Gabriel; Pike, G Bruce; Paus, Tomáš

2016-04-01

Our ability to process complex social cues presented by faces improves during adolescence. Using multivariate analyses of neuroimaging data collected longitudinally from a sample of 38 adolescents (17 males) when they were 10, 11.5, 13 and 15 years old, we tested the possibility that there exists parallel variations in the structural and functional development of neural systems supporting face processing. By combining measures of task-related functional connectivity and brain morphology, we reveal that both the structural covariance and functional connectivity among 'distal' nodes of the face-processing network engaged by ambiguous faces increase during this age range. Furthermore, we show that the trajectory of increasing functional connectivity between the distal nodes occurs in tandem with the development of their structural covariance. This demonstrates a tight coupling between functional and structural maturation within the face-processing network. Finally, we demonstrate that increased functional connectivity is associated with age-related improvements of face-processing performance, particularly in females. We suggest that our findings reflect greater integration among distal elements of the neural systems supporting the processing of facial expressions. This, in turn, might facilitate an enhanced extraction of social information from faces during a time when greater importance is placed on social interactions. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Platform for combined analysis of functional and biomolecular phenotypes of the same cell.

PubMed

Kelbauskas, L; Ashili, S; Zeng, J; Rezaie, A; Lee, K; Derkach, D; Ueberroth, B; Gao, W; Paulson, T; Wang, H; Tian, Y; Smith, D; Reid, B; Meldrum, Deirdre R

2017-03-16

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression.

Role of a new Rho family member in cell migration and axon guidance in C. elegans.

PubMed

Zipkin, I D; Kindt, R M; Kenyon, C J

1997-09-05

Rho family GTPases are thought to regulate actin-dependent processes, but their functions in vivo are still poorly understood. We have investigated the function of a new, widely expressed Rho family member in C. elegans by analyzing mutations in the endogenous gene. Activated and null alleles all inhibit cell migration, demonstrating that this protein is required for cell migration in vivo. Only a small subset of the migrations inhibited by activating mutations are inhibited by null mutations, suggesting that considerable functional redundancy exists within this system. Our findings support this conclusion and show that mig-2 functions redundantly with another pathway to regulate nuclear migration. Surprisingly, activated alleles also cause misguided axon growth, suggesting that Rho family GTPases may couple guidance cues to process outgrowth.

A Focus on Reward Prediction and the Lateral Habenula: Functional Alterations and the Behavioral Outcomes Induced by Drugs of Abuse.

PubMed

Graziane, Nicholas M; Neumann, Peter A; Dong, Yan

2018-01-01

The lateral habenula (LHb) regulates reward learning and controls the updating of reward-related information. Drugs of abuse have the capacity to hijack the cellular and neurocircuit mechanisms mediating reward learning, forming non-adaptable, compulsive behaviors geared toward obtaining illicit substances. Here, we discuss current findings demonstrating how drugs of abuse alter intrinsic and synaptic LHb neuronal function. Additionally, we discuss evidence for how drug-induced LHb alterations may affect the ability to predict reward, potentially facilitating an addiction-like state. Altogether, we combine ex vivo and in vivo results for an overview of how drugs of abuse alter LHb function and how these functional alterations affect the ability to learn and update behavioral responses to hedonic external stimuli.

Functional Inference of Complex Anatomical Tendinous Networks at a Macroscopic Scale via Sparse Experimentation

PubMed Central

Saxena, Anupam; Lipson, Hod; Valero-Cuevas, Francisco J.

2012-01-01

In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16th century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver's middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [<4%] and resembling the known network have the smallest cross-validation errors [∼5%]. The low training set [<4%] and cross validation [<7.2%] errors for models for the cadaveric specimen demonstrate what, to our knowledge, is the first experimental inference of the functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines. PMID:23144601

Functional inference of complex anatomical tendinous networks at a macroscopic scale via sparse experimentation.

PubMed

Saxena, Anupam; Lipson, Hod; Valero-Cuevas, Francisco J

2012-01-01

In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16(th) century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver's middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [<4%] and resembling the known network have the smallest cross-validation errors [∼5%]. The low training set [<4%] and cross validation [<7.2%] errors for models for the cadaveric specimen demonstrate what, to our knowledge, is the first experimental inference of the functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines.

Functional connectivity with the retrosplenial cortex predicts cognitive aging in rats.

PubMed

Ash, Jessica A; Lu, Hanbing; Taxier, Lisa R; Long, Jeffrey M; Yang, Yihong; Stein, Elliot A; Rapp, Peter R

2016-10-25

Changes in the functional connectivity (FC) of large-scale brain networks are a prominent feature of brain aging, but defining their relationship to variability along the continuum of normal and pathological cognitive outcomes has proved challenging. Here we took advantage of a well-characterized rat model that displays substantial individual differences in hippocampal memory during aging, uncontaminated by slowly progressive, spontaneous neurodegenerative disease. By this approach, we aimed to interrogate the underlying neural network substrates that mediate aging as a uniquely permissive condition and the primary risk for neurodegeneration. Using resting state (rs) blood oxygenation level-dependent fMRI and a restrosplenial/posterior cingulate cortex seed, aged rats demonstrated a large-scale network that had a spatial distribution similar to the default mode network (DMN) in humans, consistent with earlier findings in younger animals. Between-group whole brain contrasts revealed that aged subjects with documented deficits in memory (aged impaired) displayed widespread reductions in cortical FC, prominently including many areas outside the DMN, relative to both young adults (Y) and aged rats with preserved memory (aged unimpaired, AU). Whereas functional connectivity was relatively preserved in AU rats, they exhibited a qualitatively distinct network signature, comprising the loss of an anticorrelated network observed in Y adults. Together the findings demonstrate that changes in rs-FC are specifically coupled to variability in the cognitive outcome of aging, and that successful neurocognitive aging is associated with adaptive remodeling, not simply the persistence of youthful network dynamics.

Brain damage and behavioural disorders in fish induced by plastic nanoparticles delivered through the food chain.

PubMed

Mattsson, Karin; Johnson, Elyse V; Malmendal, Anders; Linse, Sara; Hansson, Lars-Anders; Cedervall, Tommy

2017-09-13

The tremendous increases in production of plastic materials has led to an accumulation of plastic pollution worldwide. Many studies have addressed the physical effects of large-sized plastics on organisms, whereas few have focused on plastic nanoparticles, despite their distinct chemical, physical and mechanical properties. Hence our understanding of their effects on ecosystem function, behaviour and metabolism of organisms remains elusive. Here we demonstrate that plastic nanoparticles reduce survival of aquatic zooplankton and penetrate the blood-to-brain barrier in fish and cause behavioural disorders. Hence, for the first time, we uncover direct interactions between plastic nanoparticles and brain tissue, which is the likely mechanism behind the observed behavioural disorders in the top consumer. In a broader perspective, our findings demonstrate that plastic nanoparticles are transferred up through a food chain, enter the brain of the top consumer and affect its behaviour, thereby severely disrupting the function of natural ecosystems.

Investigating paranormal phenomena: Functional brain imaging of telepathy.

PubMed

Venkatasubramanian, Ganesan; Jayakumar, Peruvumba N; Nagendra, Hongasandra R; Nagaraja, Dindagur; Deeptha, R; Gangadhar, Bangalore N

2008-07-01

"Telepathy" is defined as "the communication of impressions of any kind from one mind to another, independently of the recognized channels of sense". Meta-analyses of "ganzfield" studies as well as "card-guessing task" studies provide compelling evidence for the existence of telepathic phenomena. The aim of this study was to elucidate the neural basis of telepathy by examining an individual with this special ability. Using functional MRI, we examined a famous "mentalist" while he was performing a telepathic task in a 1.5 T scanner. A matched control subject without this special ability was also examined under similar conditions. The mentalist demonstrated significant activation of the right parahippocampal gyrus after successful performance of a telepathic task. The comparison subject, who did not show any telepathic ability, demonstrated significant activation of the left inferior frontal gyrus. The findings of this study are suggestive of a limbic basis for telepathy and warrant further systematic research.

Mutual 3:1 subharmonic synchronization in a micromachined silicon disk resonator

NASA Astrophysics Data System (ADS)

Taheri-Tehrani, Parsa; Guerrieri, Andrea; Defoort, Martial; Frangi, Attilio; Horsley, David A.

2017-10-01

We demonstrate synchronization between two intrinsically coupled oscillators that are created from two distinct vibration modes of a single micromachined disk resonator. The modes have a 3:1 subharmonic frequency relationship and cubic, non-dissipative electromechanical coupling between the modes enables their two frequencies to synchronize. Our experimental implementation allows the frequency of the lower frequency oscillator to be independently controlled from that of the higher frequency oscillator, enabling study of the synchronization dynamics. We find close quantitative agreement between the experimental behavior and an analytical coupled-oscillator model as a function of the energy in the two oscillators. We demonstrate that the synchronization range increases when the lower frequency oscillator is strongly driven and when the higher frequency oscillator is weakly driven. This result suggests that synchronization can be applied to the frequency-selective detection of weak signals and other mechanical signal processing functions.

Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated radical addition.

PubMed

Devery Iii, James J; Douglas, James J; Nguyen, John D; Cole, Kevin P; Flowers Ii, Robert A; Stephenson, Corey R J

2015-01-01

Knowledge of the kinetic behavior of catalysts under synthetically relevant conditions is vital for the efficient use of compounds that mediate important transformations regardless of their composition or driving force. In particular, these data are of great importance to add perspective to the growing number of applications of photoactive transition metal complexes. Here we present kinetic, synthetic, and spectroscopic evidence of the mechanistic behavior of fac -Ir(ppy) 3 in a visible light-mediated radical addition to 3-methylindole, demonstrating the instability of fac -Ir(ppy) 3 under these conditions. During the reaction, rapid in situ functionalization of the photocatalyst occurs, eventually leading to deactivation. These findings demonstrate a conceivable deactivation process for catalytic single electron reactions in the presence of radicophilic ligands. Attempts to inhibit photocatalyst deactivation through structural modification provide further insight into catalyst selection for a given system of interest.

TURNING IT UPSIDE DOWN: AREAS OF PRESERVED COGNITIVE FUNCTION IN SCHIZOPHRENIA

PubMed Central

Gold, James M.; Hahn, Britta; Strauss, Gregory P.; Waltz, James A.

2013-01-01

Patients with schizophrenia demonstrate marked impairments on most clinical neuropsychological tests. These findings suggest that patients suffer from a generalized form of cognitive impairment, with little evidence of spared performance documented in several large meta-analytic reviews of the clinical literature. In contrast, we review evidence for relative sparing of aspects of attention, procedural memory, and emotional processing observed in studies that have employed experimental approaches adapted from the cognitive and affective neuroscience literature. These islands of preserved performance suggest that the cognitive deficits in schizophrenia are not as general as they appear to be when assayed with clinical neuropsychological methods. The apparent contradiction in findings across methods may offer important clues about the nature of cognitive impairment in schizophrenia. The documentation of preserved cognitive function in schizophrenia may serve to sharpen hypotheses about the biological mechanisms that are implicated in the illness. PMID:19452280

In vivo determination of total knee arthroplasty kinematics

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

Komistek, Richard D; Mahfouz, Mohamed R; Bertin, Kim

2008-01-01

The objective of this study was to determine if consistent posterior femoral rollback of an asymmetrical posterior cruciate retaining (PCR) total knee arthroplasty was mostly influenced by the implant design, surgical technique, or presence of a well-functioning posterior cruciate ligament (PCL). Three-dimensional femorotibial kinematics was determined for 80 subjects implanted by 3 surgeons, and each subject was evaluated under fluoroscopic surveillance during a deep knee bend. All subjects in this present study having an intact PCL had a well-functioning PCR knee and experienced normal kinematic patterns, although less in magnitude than the normal knee. In addition, a surprising finding wasmore » that, on average, subjects without a PCL still achieved posterior femoral rollback from full extension to maximum knee flexion. The findings in this study revealed that implant design did contribute to the normal kinematics demonstrated by subjects having this asymmetrical PCR total knee arthroplasty.« less

Sheep genome functional annotation reveals proximal regulatory elements contributed to the evolution of modern breeds.

PubMed

Naval-Sanchez, Marina; Nguyen, Quan; McWilliam, Sean; Porto-Neto, Laercio R; Tellam, Ross; Vuocolo, Tony; Reverter, Antonio; Perez-Enciso, Miguel; Brauning, Rudiger; Clarke, Shannon; McCulloch, Alan; Zamani, Wahid; Naderi, Saeid; Rezaei, Hamid Reza; Pompanon, Francois; Taberlet, Pierre; Worley, Kim C; Gibbs, Richard A; Muzny, Donna M; Jhangiani, Shalini N; Cockett, Noelle; Daetwyler, Hans; Kijas, James

2018-02-28

Domestication fundamentally reshaped animal morphology, physiology and behaviour, offering the opportunity to investigate the molecular processes driving evolutionary change. Here we assess sheep domestication and artificial selection by comparing genome sequence from 43 modern breeds (Ovis aries) and their Asian mouflon ancestor (O. orientalis) to identify selection sweeps. Next, we provide a comparative functional annotation of the sheep genome, validated using experimental ChIP-Seq of sheep tissue. Using these annotations, we evaluate the impact of selection and domestication on regulatory sequences and find that sweeps are significantly enriched for protein coding genes, proximal regulatory elements of genes and genome features associated with active transcription. Finally, we find individual sites displaying strong allele frequency divergence are enriched for the same regulatory features. Our data demonstrate that remodelling of gene expression is likely to have been one of the evolutionary forces that drove phenotypic diversification of this common livestock species.

Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

PubMed

Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

2017-09-01

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN. Copyright © 2017 the American Physiological Society.

Visual imagery and functional connectivity in blindness: a single-case study

PubMed Central

Boucard, Christine C.; Rauschecker, Josef P.; Neufang, Susanne; Berthele, Achim; Doll, Anselm; Manoliu, Andrej; Riedl, Valentin; Sorg, Christian; Wohlschläger, Afra; Mühlau, Mark

2016-01-01

We present a case report on visual brain plasticity after total blindness acquired in adulthood. SH lost her sight when she was 27. Despite having been totally blind for 43 years, she reported to strongly rely on her vivid visual imagery. Three-Tesla magnetic resonance imaging (MRI) of SH and age-matched controls was performed. The MRI sequence included anatomical MRI, resting-state functional MRI, and task-related functional MRI where SH was instructed to imagine colours, faces, and motion. Compared to controls, voxel-based analysis revealed white matter loss along SH's visual pathway as well as grey matter atrophy in the calcarine sulci. Yet we demonstrated activation in visual areas, including V1, using functional MRI. Of the four identified visual resting-state networks, none showed alterations in spatial extent; hence, SH's preserved visual imagery seems to be mediated by intrinsic brain networks of normal extent. Time courses of two of these networks showed increased correlation with that of the inferior posterior default mode network, which may reflect adaptive changes supporting SH's strong internal visual representations. Overall, our findings demonstrate that conscious visual experience is possible even after years of absence of extrinsic input. PMID:25690326

Visual imagery and functional connectivity in blindness: a single-case study.

PubMed

Boucard, Christine C; Rauschecker, Josef P; Neufang, Susanne; Berthele, Achim; Doll, Anselm; Manoliu, Andrej; Riedl, Valentin; Sorg, Christian; Wohlschläger, Afra; Mühlau, Mark

2016-05-01

We present a case report on visual brain plasticity after total blindness acquired in adulthood. SH lost her sight when she was 27. Despite having been totally blind for 43 years, she reported to strongly rely on her vivid visual imagery. Three-Tesla magnetic resonance imaging (MRI) of SH and age-matched controls was performed. The MRI sequence included anatomical MRI, resting-state functional MRI, and task-related functional MRI where SH was instructed to imagine colours, faces, and motion. Compared to controls, voxel-based analysis revealed white matter loss along SH's visual pathway as well as grey matter atrophy in the calcarine sulci. Yet we demonstrated activation in visual areas, including V1, using functional MRI. Of the four identified visual resting-state networks, none showed alterations in spatial extent; hence, SH's preserved visual imagery seems to be mediated by intrinsic brain networks of normal extent. Time courses of two of these networks showed increased correlation with that of the inferior posterior default mode network, which may reflect adaptive changes supporting SH's strong internal visual representations. Overall, our findings demonstrate that conscious visual experience is possible even after years of absence of extrinsic input.

Item response theory analyses of the Delis-Kaplan Executive Function System card sorting subtest.

PubMed

Spencer, Mercedes; Cho, Sun-Joo; Cutting, Laurie E

2018-02-02

In the current study, we examined the dimensionality of the 16-item Card Sorting subtest of the Delis-Kaplan Executive Functioning System assessment in a sample of 264 native English-speaking children between the ages of 9 and 15 years. We also tested for measurement invariance for these items across age and gender groups using item response theory (IRT). Results of the exploratory factor analysis indicated that a two-factor model that distinguished between verbal and perceptual items provided the best fit to the data. Although the items demonstrated measurement invariance across age groups, measurement invariance was violated for gender groups, with two items demonstrating differential item functioning for males and females. Multigroup analysis using all 16 items indicated that the items were more effective for individuals whose IRT scale scores were relatively high. A single-group explanatory IRT model using 14 non-differential item functioning items showed that for perceptual ability, females scored higher than males and that scores increased with age for both males and females; for verbal ability, the observed increase in scores across age differed for males and females. The implications of these findings are discussed.

Perifoveal function in patients with North Carolina macular dystrophy: the importance of accounting for fixation locus.

PubMed

Seiple, William; Szlyk, Janet P; Paliga, Jennifer; Rabb, Maurice F

2006-04-01

To quantify the extent of visual function losses in patients with North Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting for eccentric fixation when making comparisons with normal data. Five patients with NCMD who were from a single family were examined. Multifocal electroretinograms (mfERGs) and psychophysical assessments of acuity and luminance visual field sensitivities were measured throughout the central retina. Comparisons of responses from equivalent retinal areas were accomplished by shifting normal templates to be centered at the locus of fixation for each patient. Losses of psychophysically measured visual function in patients with NCMD extend to areas adjacent to the locations of visible lesions. The multifocal ERG amplitude was reduced only within the area of visible lesion. Multifocal ERG implicit times were delayed throughout the entire central retinal area assessed. ERG timing is a sensitive assay of retinal function, and our results indicate that NCMD has a widespread effect at the level of the mid and outer retina. The findings also demonstrated that it is necessary to account for fixation locus and to ensure that equivalent retinal areas are compared when testing patients with macular disease who have eccentric fixation.

Predictability and Quantification of Complex Groundwater Table Dynamics Driven by Irregular Surface Water Fluctuations

NASA Astrophysics Data System (ADS)

Xin, Pei; Wang, Shen S. J.; Shen, Chengji; Zhang, Zeyu; Lu, Chunhui; Li, Ling

2018-03-01

Shallow groundwater interacts strongly with surface water across a quarter of global land area, affecting significantly the terrestrial eco-hydrology and biogeochemistry. We examined groundwater behavior subjected to unimodal impulse and irregular surface water fluctuations, combining physical experiments, numerical simulations, and functional data analysis. Both the experiments and numerical simulations demonstrated a damped and delayed response of groundwater table to surface water fluctuations. To quantify this hysteretic shallow groundwater behavior, we developed a regression model with the Gamma distribution functions adopted to account for the dependence of groundwater behavior on antecedent surface water conditions. The regression model fits and predicts well the groundwater table oscillations resulting from propagation of irregular surface water fluctuations in both laboratory and large-scale aquifers. The coefficients of the Gamma distribution function vary spatially, reflecting the hysteresis effect associated with increased amplitude damping and delay as the fluctuation propagates. The regression model, in a relatively simple functional form, has demonstrated its capacity of reproducing high-order nonlinear effects that underpin the surface water and groundwater interactions. The finding has important implications for understanding and predicting shallow groundwater behavior and associated biogeochemical processes, and will contribute broadly to studies of groundwater-dependent ecology and biogeochemistry.

Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment.

PubMed

Kesler, Shelli R; Adams, Marjorie; Packer, Melissa; Rao, Vikram; Henneghan, Ashley M; Blayney, Douglas W; Palesh, Oxana

2017-03-01

Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers. Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing. Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics ( p  = .046) and cognitive functioning ( p  < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering ( p  < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls ( p  = .03). This hyper-correlation between structural and functional topologies was significantly associated with cognitive dysfunction ( p  = .005). Our findings could not be accounted for by psychological distress and suggest that non-CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

Sleep, Affect, and Social Competence from Preschool to Preadolescence: Distinct Pathways to Emotional and Social Adjustment for Boys and for Girls

PubMed Central

Foley, Joan E.; Weinraub, Marsha

2017-01-01

Using a normative sample of 1,057 children studied across 4 waves over 6 years with multiple informants, we investigated transactional relations for sleep problems, anxious-depressed symptoms, and social functioning from preschool to preadolescence, assessing cumulative effects on children's emotional and social adjustment. To examine sex differences in the developmental processes, we conducted separate analyses for boys and girls. For both boys and girls, longitudinal cross-lagged panel analyses showed that preschool sleep problems directly predicted anxious-depressed symptoms 2 years later; indirect effects continued into preadolescence. For girls, early and later sleep problems directly or indirectly predicted a wide variety of preadolescent emotional and social adjustment domains (e.g., depressive symptoms, school competence, emotion regulation, risk-taking behaviors). For boys, social competence played a more important role than sleep problems in predicting preadolescent adjustment. Among the first set of findings that demonstrate longitudinal relations between sleep problems and social functioning in middle childhood and preadolescence, these results support Dahl's and Walker's neurological models of sleep and emotional functioning. We discuss these findings in light of relations between sleep and affect during pre-pubertal development and discuss differential findings for boys and girls. PMID:28588517

Modifying Surface Energy of Graphene via Plasma-Based Chemical Functionalization to Tune Thermal and Electrical Transport at Metal Interfaces.

PubMed

Foley, Brian M; Hernández, Sandra C; Duda, John C; Robinson, Jeremy T; Walton, Scott G; Hopkins, Patrick E

2015-08-12

The high mobility exhibited by both supported and suspended graphene, as well as its large in-plane thermal conductivity, has generated much excitement across a variety of applications. As exciting as these properties are, one of the principal issues inhibiting the development of graphene technologies pertains to difficulties in engineering high-quality metal contacts on graphene. As device dimensions decrease, the thermal and electrical resistance at the metal/graphene interface plays a dominant role in degrading overall performance. Here we demonstrate the use of a low energy, electron-beam plasma to functionalize graphene with oxygen, fluorine, and nitrogen groups, as a method to tune the thermal and electrical transport properties across gold-single layer graphene (Au/SLG) interfaces. We find that while oxygen and nitrogen groups improve the thermal boundary conductance (hK) at the interface, their presence impairs electrical transport leading to increased contact resistance (ρC). Conversely, functionalization with fluorine has no impact on hK, yet ρC decreases with increasing coverage densities. These findings indicate exciting possibilities using plasma-based chemical functionalization to tailor the thermal and electrical transport properties of metal/2D material contacts.

White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults.

PubMed

Fernández-Cabello, Sara; Valls-Pedret, Cinta; Schurz, Matthias; Vidal-Piñeiro, Dídac; Sala-Llonch, Roser; Bargallo, Nuria; Ros, Emilio; Bartrés-Faz, David

2016-12-01

Cognitive reserve (CR) models posit that lifestyle factors such as education modulate the relationship between brain damage and cognition. However, the functional correlates of CR in healthy aging are still under investigation. White matter hyperintensities (WMHs) are a common age-associated finding that impacts cognition. In this study, we used functional magnetic resonance imaging to characterize the patterns of brain activation during a working memory task in older participants with high and low levels of education (as a proxy of CR) and high and low WMH volumes. Ninety older volunteers (aged 63-76 years) and 16 young adults (aged 21-27) completed the study. We found that older adults with higher education had better working memory performance than their less educated peers. Among the highly educated participants, those with WMH over-recruited areas engaged by young volunteers and showed activation in additional cortical and subcortical structures. However, those with low WMH differed little with respect to their younger counterparts. Our findings demonstrate that the functional mechanisms subtending the effects of education, as a proxy of CR, are modulated according to the WMH burden. Copyright © 2016 Elsevier Inc. All rights reserved.

Can sleep deprivation studies explain why human adults sleep?

PubMed

Brown, Lee K

2012-11-01

This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.

Nitinol-based Nanotubular and Nanowell Coatings for the Modulation of Human Vascular Cell Functions

NASA Astrophysics Data System (ADS)

Lee, Phin Peng

Current approaches to reducing restenosis do not balance the reduction of vascular smooth muscle cell proliferation with the increase in the healing of the endothelium. Here, I present my study on the synthesis and characterization of a nanotubular coating on Nitinol substrates. I found that the coating demonstrated 'pro-healing' properties by increasing primary human aortic endothelial cell spreading, migration and collagen and elastin production. Certain cellular functions such as collagen and elastin production were also found to be affected by changes in nanotube diameter. The coating also reduced the proliferation and mRNA expression of collagen I and MMP2 for primary human aortic smooth muscle cells. I will also demonstrate the synthesis of a nanowell coating on Nitinol stents as well as an additional poly(lactic-co-glycolic acid) coating on top of the nanowells that has the potential for controlling drug release. These findings demonstrate the potential for the coatings to aid in the prevention of restenosis and sets up future explorations of ex vivo and in vivo studies.

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

PubMed

Gan, Yuanyuan; Han, Nana; He, Xiaoqin; Yu, Jiajun; Zhang, Meixia; Zhou, Yujie; Liang, Huiling; Deng, Junjian; Zheng, Yongfa; Ge, Wei; Long, Zhixiong; Xu, Ximing

2017-06-01

Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.

The Impact of Working in a Green Certified Building on Cognitive Function and Health.

PubMed

MacNaughton, Piers; Satish, Usha; Laurent, Jose Guillermo Cedeno; Flanigan, Skye; Vallarino, Jose; Coull, Brent; Spengler, John D; Allen, Joseph G

2017-03-01

Thirty years of public health research have demonstrated that improved indoor environmental quality is associated with better health outcomes. Recent research has demonstrated an impact of the indoor environment on cognitive function. We recruited 109 participants from 10 high-performing buildings (i.e. buildings surpassing the ASHRAE Standard 62.1-2010 ventilation requirement and with low total volatile organic compound concentrations) in five U.S. cities. In each city, buildings were matched by week of assessment, tenant, type of worker and work functions. A key distinction between the matched buildings was whether they had achieved green certification. Workers were administered a cognitive function test of higher order decision-making performance twice during the same week while indoor environmental quality parameters were monitored. Workers in green certified buildings scored 26.4% (95% CI: [12.8%, 39.7%]) higher on cognitive function tests, controlling for annual earnings, job category and level of schooling, and had 30% fewer sick building symptoms than those in non-certified buildings. These outcomes may be partially explained by IEQ factors, including thermal conditions and lighting, but the findings suggest that the benefits of green certification standards go beyond measureable IEQ factors. We describe a holistic "buildingomics" approach for examining the complexity of factors in a building that influence human health.

The Impact of Working in a Green Certified Building on Cognitive Function and Health

PubMed Central

MacNaughton, Piers; Satish, Usha; Laurent, Jose Guillermo Cedeno; Flanigan, Skye; Vallarino, Jose; Coull, Brent; Spengler, John D.; Allen, Joseph G.

2017-01-01

Thirty years of public health research have demonstrated that improved indoor environmental quality is associated with better health outcomes. Recent research has demonstrated an impact of the indoor environment on cognitive function. We recruited 109 participants from 10 high-performing buildings (i.e. buildings surpassing the ASHRAE Standard 62.1-2010 ventilation requirement and with low total volatile organic compound concentrations) in five U.S. cities. In each city, buildings were matched by week of assessment, tenant, type of worker and work functions. A key distinction between the matched buildings was whether they had achieved green certification. Workers were administered a cognitive function test of higher order decision-making performance twice during the same week while indoor environmental quality parameters were monitored. Workers in green certified buildings scored 26.4% (95% CI: [12.8%, 39.7%]) higher on cognitive function tests, controlling for annual earnings, job category and level of schooling, and had 30% fewer sick building symptoms than those in non-certified buildings. These outcomes may be partially explained by IEQ factors, including thermal conditions and lighting, but the findings suggest that the benefits of green certification standards go beyond measureable IEQ factors. We describe a holistic “buildingomics” approach for examining the complexity of factors in a building that influence human health. PMID:28785124

Insufficient DNA methylation affects healthy aging and promotes age-related health problems.

PubMed

Liu, Liang; van Groen, Thomas; Kadish, Inga; Li, Yuanyuan; Wang, Deli; James, Smitha R; Karpf, Adam R; Tollefsbol, Trygve O

2011-08-01

DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains genomic methylation stability. To further elucidate the function of Dnmt1 in aging and age-related diseases, we exploited the Dnmt1+/- mouse model to investigate how Dnmt1 haploinsufficiency impacts the aging process by assessing the changes of several major aging phenotypes. We confirmed that Dnmt1 haploinsufficiency indeed decreases DNA methylation as a result of reduced Dnmt1 expression. To assess the effect of Dnmt1 haploinsufficiency on general body composition, we performed dual-energy X-ray absorptiometry analysis and showed that reduced Dnmt1 activity decreased bone mineral density and body weight, but with no significant impact on mortality or body fat content. Using behavioral tests, we demonstrated that Dnmt1 haploinsufficiency impairs learning and memory functions in an age-dependent manner. Taken together, our findings point to the interesting likelihood that reduced genomic methylation activity adversely affects the healthy aging process without altering survival and mortality. Our studies demonstrated that cognitive functions of the central nervous system are modulated by Dnmt1 activity and genomic methylation, highlighting the significance of the original epigenetic hypothesis underlying memory coding and function.

Functional brain networks for learning predictive statistics.

PubMed

Giorgio, Joseph; Karlaftis, Vasilis M; Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew; Kourtzi, Zoe

2017-08-18

Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. This skill relies on extracting regular patterns in space and time by mere exposure to the environment (i.e., without explicit feedback). Yet, we know little about the functional brain networks that mediate this type of statistical learning. Here, we test whether changes in the processing and connectivity of functional brain networks due to training relate to our ability to learn temporal regularities. By combining behavioral training and functional brain connectivity analysis, we demonstrate that individuals adapt to the environment's statistics as they change over time from simple repetition to probabilistic combinations. Further, we show that individual learning of temporal structures relates to decision strategy. Our fMRI results demonstrate that learning-dependent changes in fMRI activation within and functional connectivity between brain networks relate to individual variability in strategy. In particular, extracting the exact sequence statistics (i.e., matching) relates to changes in brain networks known to be involved in memory and stimulus-response associations, while selecting the most probable outcomes in a given context (i.e., maximizing) relates to changes in frontal and striatal networks. Thus, our findings provide evidence that dissociable brain networks mediate individual ability in learning behaviorally-relevant statistics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modeling the Radio Foreground for Detection of CMB Spectral Distortions from the Cosmic Dawn and the Epoch of Reionization

NASA Astrophysics Data System (ADS)

Sathyanarayana Rao, Mayuri; Subrahmanyan, Ravi; Udaya Shankar, N.; Chluba, Jens

2017-05-01

Cosmic baryon evolution during the Cosmic Dawn and Reionization results in redshifted 21-cm spectral distortions in the cosmic microwave background (CMB). These encode information about the nature and timing of first sources over redshifts 30-6 and appear at meter wavelengths as a tiny CMB distortion along with the Galactic and extragalactic radio sky, which is orders of magnitude brighter. Therefore, detection requires precise methods to model foregrounds. We present a method of foreground fitting using maximally smooth (MS) functions. We demonstrate the usefulness of MS functions over traditionally used polynomials to separate foregrounds from the Epoch of Reionization (EoR) signal. We also examine the level of spectral complexity in plausible foregrounds using GMOSS, a physically motivated model of the radio sky, and find that they are indeed smooth and can be modeled by MS functions to levels sufficient to discern the vanilla model of the EoR signal. We show that MS functions are loss resistant and robustly preserve EoR signal strength and turning points in the residuals. Finally, we demonstrate that in using a well-calibrated spectral radiometer and modeling foregrounds with MS functions, the global EoR signal can be detected with a Bayesian approach with 90% confidence in 10 minutes’ integration.

Neural Integration in Body Perception.

PubMed

Ramsey, Richard

2018-06-19

The perception of other people is instrumental in guiding social interactions. For example, the appearance of the human body cues a wide range of inferences regarding sex, age, health, and personality, as well as emotional state and intentions, which influence social behavior. To date, most neuroscience research on body perception has aimed to characterize the functional contribution of segregated patches of cortex in the ventral visual stream. In light of the growing prominence of network architectures in neuroscience, the current article reviews neuroimaging studies that measure functional integration between different brain regions during body perception. The review demonstrates that body perception is not restricted to processing in the ventral visual stream but instead reflects a functional alliance between the ventral visual stream and extended neural systems associated with action perception, executive functions, and theory of mind. Overall, these findings demonstrate how body percepts are constructed through interactions in distributed brain networks and underscore that functional segregation and integration should be considered together when formulating neurocognitive theories of body perception. Insight from such an updated model of body perception generalizes to inform the organizational structure of social perception and cognition more generally and also informs disorders of body image, such as anorexia nervosa, which may rely on atypical integration of body-related information.

Cooling Models for Old White Dwarfs

NASA Astrophysics Data System (ADS)

Hansen, Brad M. S.

1999-08-01

We present new white dwarf cooling models that incorporate an accurate outer boundary condition based on new opacity and detailed radiative transfer calculations. We find that helium-atmosphere dwarfs cool considerably faster than has previously been claimed, while old hydrogen-atmosphere dwarfs will deviate significantly from blackbody appearance. We use our new models to derive age limits for the Galactic disk. We find that the Liebert, Dahn, & Monet luminosity function yields an age of only 6 Gyr if it is complete to stated limits. However, age estimates of individual dwarfs and the luminosity function of Oswalt et al. are both consistent with disk ages as large as ~11 Gyr. We have also used our models to place constraints on white dwarf dark matter in the Galactic halo. We find that previous attempts using inadequate cooling models were too severe and that direct detection limits allow a halo that is 11 Gyr old. If the halo is composed solely of helium-atmosphere dwarfs, the lower age limit is only 7.5 Gyr. We also demonstrate the importance of studying the cooling sequences of white dwarfs in globular clusters.

The magnetic particle in a box: Analytic and micromagnetic analysis of probe-localized spin wave modes

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

Adur, Rohan, E-mail: adur@physics.osu.edu; Du, Chunhui; Manuilov, Sergei A.

2015-05-07

The dipole field from a probe magnet can be used to localize a discrete spectrum of standing spin wave modes in a continuous ferromagnetic thin film without lithographic modification to the film. Obtaining the resonance field for a localized mode is not trivial due to the effect of the confined and inhomogeneous magnetization precession. We compare the results of micromagnetic and analytic methods to find the resonance field of localized modes in a ferromagnetic thin film, and investigate the accuracy of these methods by comparing with a numerical minimization technique that assumes Bessel function modes with pinned boundary conditions. Wemore » find that the micromagnetic technique, while computationally more intensive, reveals that the true magnetization profiles of localized modes are similar to Bessel functions with gradually decaying dynamic magnetization at the mode edges. We also find that an analytic solution, which is simple to implement and computationally much faster than other methods, accurately describes the resonance field of localized modes when exchange fields are negligible, and demonstrating the accessibility of localized mode analysis.« less

First description of NOD2 variant associated with defective neutrophil responses in a woman with granulomatous mastitis related to corynebacteria.

PubMed

Bercot, Béatrice; Kannengiesser, Caroline; Oudin, Claire; Grandchamp, Bernard; Sanson-le Pors, Marie-José; Mouly, Stéphane; Elbim, Carole

2009-09-01

We report the first case of granulomatous mastitis due to Corynebacterium kroppenstedtii linked to strongly impaired neutrophil responses to Nod2 agonist and a single nucleotide polymorphism within the NOD2 gene (SNP13 [Leu1007fsinsC]) in a heterozygous state. These findings provided the first demonstration of impaired Nod2 function associated with corynebacterial infection.

Symmetry Breaking in Few Layer Graphene Films

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

Bostwick, A.; Ohta, T.; McChesney, J.L.

2007-05-25

Recently, it was demonstrated that the quasiparticledynamics, the layer-dependent charge and potential, and the c-axisscreening coefficient could be extracted from measurements of thespectral function of few layer graphene films grown epitaxially on SiCusing angle-resolved photoemission spectroscopy (ARPES). In this articlewe review these findings, and present detailed methodology for extractingsuch parameters from ARPES. We also present detailed arguments againstthe possibility of an energy gap at the Dirac crossing ED.

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

PubMed

Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

2017-03-01

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Rule-Based Category Learning in Children: The Role of Age and Executive Functioning

PubMed Central

Rabi, Rahel; Minda, John Paul

2014-01-01

Rule-based category learning was examined in 4–11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working memory and inhibitory control were related to rule-based categorization and improved with age, working memory specifically was found to marginally mediate the age-related improvements in categorization. When analyses focused only on the sample of children, results showed that working memory ability and inhibitory control were associated with categorization performance and strategy use. The current findings track changes in categorization performance across childhood, demonstrating at which points performance begins to mature and resemble that of adults. Additionally, findings highlight the potential role that working memory and inhibitory control may play in rule-based category learning. PMID:24489658

Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression

PubMed Central

Blessing, Alicia M.; Rajapakshe, Kimal; Reddy Bollu, Lakshmi; Shi, Yan; White, Mark A.; Pham, Alexander H.; Lin, Chenchu; Jonsson, Philip; Cortes, Constanza J.; Cheung, Edwin; La Spada, Albert R.; Bast, Robert C.; Merchant, Fatima A.; Coarfa, Cristian; Frigo, Daniel E.

2017-01-01

ABSTRACT AR (androgen receptor) signaling is crucial for the development and maintenance of the prostate as well as the initiation and progression of prostate cancer. Despite the AR's central role in prostate cancer progression, it is still unclear which AR-mediated processes drive the disease. Here, we identified 4 core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of AR in prostate cancer. These findings were significant in light of our recent observation that androgens promoted prostate cancer cell growth in part through the induction of autophagy. Expression of these 5 genes was essential for maximal androgen-mediated autophagy and cell proliferation. In addition, expression of each of these 5 genes alone or in combination was sufficient to increase prostate cancer cell growth independent of AR activity. Further, bioinformatic analysis demonstrated that the expression of these genes correlated with disease progression in 3 separate clinical cohorts. Collectively, these findings demonstrate a functional role for increased autophagy in prostate cancer progression, provide a mechanism for how autophagy is augmented, and highlight the potential of targeting this process for the treatment of advanced prostate cancer. PMID:27977328

Melanophore migration and survival during zebrafish adult pigment stripe development require the immunoglobulin superfamily adhesion molecule Igsf11.

PubMed

Eom, Dae Seok; Inoue, Shinya; Patterson, Larissa B; Gordon, Tiffany N; Slingwine, Rebecca; Kondo, Shigeru; Watanabe, Masakatsu; Parichy, David M

2012-01-01

The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11). We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation.

Melanophore Migration and Survival during Zebrafish Adult Pigment Stripe Development Require the Immunoglobulin Superfamily Adhesion Molecule Igsf11

PubMed Central

Patterson, Larissa B.; Gordon, Tiffany N.; Slingwine, Rebecca; Kondo, Shigeru; Watanabe, Masakatsu; Parichy, David M.

2012-01-01

The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11). We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation. PMID:22916035

Communication: Recovering the flat-plane condition in electronic structure theory at semi-local DFT cost

NASA Astrophysics Data System (ADS)

Bajaj, Akash; Janet, Jon Paul; Kulik, Heather J.

2017-11-01

The flat-plane condition is the union of two exact constraints in electronic structure theory: (i) energetic piecewise linearity with fractional electron removal or addition and (ii) invariant energetics with change in electron spin in a half filled orbital. Semi-local density functional theory (DFT) fails to recover the flat plane, exhibiting convex fractional charge errors (FCE) and concave fractional spin errors (FSE) that are related to delocalization and static correlation errors. We previously showed that DFT+U eliminates FCE but now demonstrate that, like other widely employed corrections (i.e., Hartree-Fock exchange), it worsens FSE. To find an alternative strategy, we examine the shape of semi-local DFT deviations from the exact flat plane and we find this shape to be remarkably consistent across ions and molecules. We introduce the judiciously modified DFT (jmDFT) approach, wherein corrections are constructed from few-parameter, low-order functional forms that fit the shape of semi-local DFT errors. We select one such physically intuitive form and incorporate it self-consistently to correct semi-local DFT. We demonstrate on model systems that jmDFT represents the first easy-to-implement, no-overhead approach to recovering the flat plane from semi-local DFT.

Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression.

PubMed

Blessing, Alicia M; Rajapakshe, Kimal; Reddy Bollu, Lakshmi; Shi, Yan; White, Mark A; Pham, Alexander H; Lin, Chenchu; Jonsson, Philip; Cortes, Constanza J; Cheung, Edwin; La Spada, Albert R; Bast, Robert C; Merchant, Fatima A; Coarfa, Cristian; Frigo, Daniel E

2017-03-04

AR (androgen receptor) signaling is crucial for the development and maintenance of the prostate as well as the initiation and progression of prostate cancer. Despite the AR's central role in prostate cancer progression, it is still unclear which AR-mediated processes drive the disease. Here, we identified 4 core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of AR in prostate cancer. These findings were significant in light of our recent observation that androgens promoted prostate cancer cell growth in part through the induction of autophagy. Expression of these 5 genes was essential for maximal androgen-mediated autophagy and cell proliferation. In addition, expression of each of these 5 genes alone or in combination was sufficient to increase prostate cancer cell growth independent of AR activity. Further, bioinformatic analysis demonstrated that the expression of these genes correlated with disease progression in 3 separate clinical cohorts. Collectively, these findings demonstrate a functional role for increased autophagy in prostate cancer progression, provide a mechanism for how autophagy is augmented, and highlight the potential of targeting this process for the treatment of advanced prostate cancer.

Parcellation of left parietal tool representations by functional connectivity

PubMed Central

Garcea, Frank E.; Z. Mahon, Bradford

2014-01-01

Manipulating a tool according to its function requires the integration of visual, conceptual, and motor information, a process subserved in part by left parietal cortex. How these different types of information are integrated and how their integration is reflected in neural responses in the parietal lobule remains an open question. Here, participants viewed images of tools and animals during functional magnetic resonance imaging (fMRI). K-means clustering over time series data was used to parcellate left parietal cortex into subregions based on functional connectivity to a whole brain network of regions involved in tool processing. One cluster, in the inferior parietal cortex, expressed privileged functional connectivity to the left ventral premotor cortex. A second cluster, in the vicinity of the anterior intraparietal sulcus, expressed privileged functional connectivity with the left medial fusiform gyrus. A third cluster in the superior parietal lobe expressed privileged functional connectivity with dorsal occipital cortex. Control analyses using Monte Carlo style permutation tests demonstrated that the clustering solutions were outside the range of what would be observed based on chance ‘lumpiness’ in random data, or mere anatomical proximity. Finally, hierarchical clustering analyses were used to formally relate the resulting parcellation scheme of left parietal tool representations to previous work that has parcellated the left parietal lobule on purely anatomical grounds. These findings demonstrate significant heterogeneity in the functional organization of manipulable object representations in left parietal cortex, and outline a framework that generates novel predictions about the causes of some forms of upper limb apraxia. PMID:24892224

[Supercomputer investigation of the protein-ligand system low-energy minima].

PubMed

Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

2015-01-01

The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

HSPA5 is an essential host factor for Ebola virus infection.

PubMed

Reid, St Patrick; Shurtleff, Amy C; Costantino, Julie A; Tritsch, Sarah R; Retterer, Cary; Spurgers, Kevin B; Bavari, Sina

2014-09-01

Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures. Published by Elsevier B.V.

Single-photon decision maker

NASA Astrophysics Data System (ADS)

Naruse, Makoto; Berthel, Martin; Drezet, Aurélien; Huant, Serge; Aono, Masashi; Hori, Hirokazu; Kim, Song-Ju

2015-08-01

Decision making is critical in our daily lives and for society in general and is finding evermore practical applications in information and communication technologies. Herein, we demonstrate experimentally that single photons can be used to make decisions in uncertain, dynamically changing environments. Using a nitrogen-vacancy in a nanodiamond as a single-photon source, we demonstrate the decision-making capability by solving the multi-armed bandit problem. This capability is directly and immediately associated with single-photon detection in the proposed architecture, leading to adequate and adaptive autonomous decision making. This study makes it possible to create systems that benefit from the quantum nature of light to perform practical and vital intelligent functions.

Quantum interference in DNA bases probed by graphene nanoribbons

NASA Astrophysics Data System (ADS)

Jeong, Heejeong; Seul Kim, Han; Lee, Sung-Hoon; Lee, Dongho; Hoon Kim, Yong; Huh, Nam

2013-07-01

Based on first-principles nonequilibrium Green's function calculations, we demonstrate quantum interference (QI) effects on the tunneling conductance of deoxyribonucleic acid bases placed between zigzag graphene nanoribbon electrodes. With the analogy of QI in hydrocarbon ring structures, we hypothesize that QI can be well preserved in the π-π coupling between the carbon-based electrode and a single DNA base. We demonstrate indications of QI, such as destructively interfered anti-resonance or Fano-resonance, that affect the variation of tunneling conductance depending on the orientation of a base. We find that guanine, with a 10-fold higher transverse conductance, can be singled out from the other bases.

Aqueous Exfoliation of Graphite into Graphene Assisted by Sulfonyl Graphene Quantum Dots for Photonic Crystal Applications.

PubMed

Zeng, Minxiang; Shah, Smit A; Huang, Dali; Parviz, Dorsa; Yu, Yi-Hsien; Wang, Xuezhen; Green, Micah J; Cheng, Zhengdong

2017-09-13

We investigate the π-π stacking of polyaromatic hydrocarbons (PAHs) with graphene surfaces, showing that such interactions are general across a wide range of PAH sizes and species, including graphene quantum dots. We synthesized a series of graphene quantum dots with sulfonyl, amino, and carboxylic functional groups and employed them to exfoliate and disperse pristine graphene in water. We observed that sulfonyl-functionalized graphene quantum dots were able to stabilize the highest concentration of graphene in comparison to other functional groups; this is consistent with prior findings by pyrene. The graphene nanosheets prepared showed excellent colloidal stability, indicating great potential for applications in electronics, solar cells, and photonic displays which was demonstrated in this work.

Transmission function properties for multi-layered structures: application to super-resolution.

PubMed

Mattiucci, N; D'Aguanno, G; Scalora, M; Bloemer, M J; Sibilia, C

2009-09-28

We discuss the properties of the transmission function in the k-space for a generic multi-layered structure. In particular we analytically demonstrate that a transmission greater than one in the evanescent spectrum (amplification of the evanescent modes) can be directly linked to the guided modes supported by the structure. Moreover we show that the slope of the phase of the transmission function in the propagating spectrum is inversely proportional to the ability of the structure to compensate the diffraction of the propagating modes. We apply these findings to discuss several examples where super-resolution is achieved thanks to the simultaneous availability of the amplification of the evanescent modes and the diffraction compensation of the propagating modes.

Cellular Engineering with Membrane Fusogenic Liposomes to Produce Functionalized Extracellular Vesicles.

PubMed

Lee, Junsung; Lee, Hyoungjin; Goh, Unbyeol; Kim, Jiyoung; Jeong, Moonkyoung; Lee, Jean; Park, Ji-Ho

2016-03-23

Engineering of extracellular vesicles (EVs) without affecting biological functions remains a challenge, limiting the broad applications of EVs in biomedicine. Here, we report a method to equip EVs with various functional agents, including fluorophores, drugs, lipids, and bio-orthogonal chemicals, in an efficient and controlled manner by engineering parental cells with membrane fusogenic liposomes, while keeping the EVs intact. As a demonstration of how this method can be applied, we prepared EVs containing azide-lipids, and conjugated them with targeting peptides using copper-free click chemistry to enhance targeting efficacy to cancer cells. We believe that this liposome-based cellular engineering method will find utility in studying the biological roles of EVs and delivering therapeutic agents through their innate pathway.

Morning Glory Syndrome with Carotid and Middle Cerebral Artery Vasculopathy.

PubMed

Nezzar, Hachemi; Mbekeani, Joyce N; Dalens, Helen

2015-12-01

To report a case of incidental asymptomatic atypical morning glory syndrome (MGS) with concomitant ipsilateral carotid and middle cerebral dysgenesis. A 6-year-old child was discovered to have incidental findings of MGS, with atypia. All visual functions were normal including vision and stereopsis. Neuroimaging revealed ipsilateral carotid and middle cerebral vascular narrowing without associated collateral vessels or cerebral ischemia commonly seen in Moyamoya disease. Subsequent annual examinations have been stable, without signs of progression. This case demonstrates disparity between structural aberrations and final visual and neurological function and reinforces the association between MGS and intracranial vascular disruption. Full ancillary ophthalmic and neuroimaging studies should be performed in all patients with MGS with interval reassessments, even when the patient is asymptomatic and functionally intact.

Children's use of comparison and function in novel object categorization.

PubMed

Kimura, Katherine; Hunley, Samuel B; Namy, Laura L

2018-06-01

Although young children often rely on salient perceptual cues, such as shape, when categorizing novel objects, children eventually shift towards deeper relational reasoning about category membership. This study investigates what information young children use to classify novel instances of familiar categories. Specifically, we investigated two sources of information that have the potential to facilitate the classification of novel exemplars: (1) comparison of familiar category instances, and (2) attention to function information that might direct children's attention to functionally relevant perceptual features. Across two experiments, we found that comparing two perceptually similar category members-particularly when function information was also highlighted-led children to discover non-obvious relational features that supported their categorization of novel category instances. Together, these findings demonstrate that comparison may aid in novel object categorization by heightening the salience of less obvious, yet functionally relevant, relational structures that support conceptual reasoning. Copyright © 2018. Published by Elsevier Inc.

The Impacts of Social Support and Cognitive Function on Depression among Community-Dwelling Older Japanese Americans.

PubMed

Kim, Bum Jung; Nakaoka, Susan; Underwood, Charna

2017-02-17

Research has demonstrated a relationship between social support, cognitive function, and depression among older adults, yet fewer studies have explored this association with Japanese American elders. This study aims to examine depression and describe its relationship with social support, cognitive function, and socioeconomic condition among Japanese American elders. A cross-sectional study of 205 Japanese American elders was conducted in Honolulu and Los Angeles County. A hierarchical regression model was used with depression as a dependent variable and with independent variables such as social support, cognitive function, and socioeconomic status. The study found that social support and cognitive function were significantly associated with depression for Japanese American elders. Also age and education were significantly associated with depression. Based on the findings, the study indicates the importance of developing preventive strategies to reduce the depression issue using culturally tailored programs to the study population.

Functional Assessment and Intervention by Nursing Assistants in Hospice and Palliative Care Inpatient Care Settings: A Quality Improvement Pilot Study.

PubMed

Mueller, Karen; Hamilton, Gillian; Rodden, Betheny; DeHeer, Hendrick D

2016-03-01

This study assessed the impact of a nursing assistant-led functional intervention in an urban hospice. Thirty-three patients participated. A physical therapist trained 4 nursing assistants to assess 4 basic functional activities at admission and discharge and to provide daily activity training to intervention group participants. Control group participants were assessed at admission and discharge and received the usual standard of care. Both groups improved. The intervention group participants demonstrated significant improvement in the Timed up and Go test as well as their self-reported ability to achieve goals on the Patient-Specific Functional Scale. Control group participants made significant improvements in the ability to move from supine to sit in bed. These findings suggest that nursing assistants can provide activity-based assessment and intervention leading to improved function among patients in hospice. © The Author(s) 2014.

Stuttering on function words in bilingual children who stutter: A preliminary study.

PubMed

Gkalitsiou, Zoi; Byrd, Courtney T; Bedore, Lisa M; Taliancich-Klinger, Casey L

2017-01-01

Evidence suggests young monolingual children who stutter (CWS) are more disfluent on function than content words, particularly when produced in the initial utterance position. The purpose of the present preliminary study was to investigate whether young bilingual CWS present with this same pattern. The narrative and conversational samples of four bilingual Spanish- and English-speaking CWS were analysed. All four bilingual participants produced significantly more stuttering on function words compared to content words, irrespective of their position in the utterance, in their Spanish narrative and conversational speech samples. Three of the four participants also demonstrated more stuttering on function compared to content words in their narrative speech samples in English, but only one participant produced more stuttering on function than content words in her English conversational sample. These preliminary findings are discussed relative to linguistic planning and language proficiency and their potential contribution to stuttered speech.

Conduction aphasia as a function of the dominant posterior perisylvian cortex. Report of two cases.

PubMed

Quigg, Mark; Geldmacher, David S; Elias, W Jeff

2006-05-01

Assessment of eloquent functions during brain mapping usually relies on testing reading, speech, and comprehension to uncover transient deficits during electrical stimulation. These tests stem from findings predicted by the Geschwind-Wernicke hypothesis of receptive and expressive cortices connected by white matter tracts. Later work, however, has emphasized cortical mechanisms of language function. The authors report two cases that demonstrate that conduction aphasia is cortically mediated and can be inadequately assessed if not specifically evaluated during brain mapping. To determine the distribution of language on the dominant cortex, electrical cortical stimulation was performed in two cases by using implanted subdural electrodes during brain mapping before epilepsy surgery. A transient isolated deficit in repetition of language was reported during stimulation of the posterior portion of the dominant superior temporal gyrus in one patient and during stimulation of the supramarginal gyrus in the other patient. These cases demonstrate a localization of language repetition to the posterior perisylvian cortex. Brain mapping of this region should include assessment of verbal repetition to avoid potential deficits resembling conduction aphasia.

Real-time cellular and molecular dynamics of bi-metallic self-therapeutic nanoparticle in cancer cells

NASA Astrophysics Data System (ADS)

Vishwakarma, Sandeep Kumar; Bardia, Avinash; Lakkireddy, Chandrakala; Paspala, Syed Ameer Basha; Habeeb, Md. Aejaz; Khan, Aleem Ahmed

2018-02-01

Since last decades various kinds of nanoparticles have been functionalized to improve their biomedical applications. However, the biological effect of un-modified/non-functionalized bi-metallic magnetic nanoparticles remains under investigated. Herein we demonstrate a multifaceted non-functionalized bi-metallic inorganic Gd-SPIO nanoparticle which passes dual high MRI contrast and can kill the cancer cells through several mechanisms. The results of the present study demonstrate that Gd-SPIO nanoparticles have potential to induce cancer cell death by production of reactive oxygen species and apoptotic events. Furthermore, Gd-SPIO nanoparticles also enhance the expression levels of miRNA-199a and miRNA-181a-7p which results in decreased levels of cancer markers such as C-met, TGF-β and hURP. One very interesting finding of this study reveals side scatter-based real-time analysis of nanoparticle uptake in cancer cells using flow cytometry analysis. In conclusion, this study paves a way for future investigation of un-modified inorganic nanoparticles to purport enhanced therapeutic effect in combination with potential anti-tumor drugs/molecules in cancer cells.

Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

PubMed

Rushaidhi, M; Zhang, H; Liu, P

2013-03-27

Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo.

PubMed

Yamada, Eri; Nakaoka, Shinji; Klein, Lukas; Reith, Elisabeth; Langer, Simon; Hopfensperger, Kristina; Iwami, Shingo; Schreiber, Gideon; Kirchhoff, Frank; Koyanagi, Yoshio; Sauter, Daniel; Sato, Kei

2018-01-10

The HIV-1-encoded accessory protein Vpu exerts several immunomodulatory functions, including counteraction of the host restriction factor tetherin, downmodulation of CD4, and inhibition of NF-κB activity to facilitate HIV-1 infection. However, the relative contribution of individual Vpu functions to HIV-1 infection in vivo remained unclear. Here, we used a humanized mouse model and HIV-1 strains with selective mutations in vpu to demonstrate that the anti-tetherin activity of Vpu is a prerequisite for efficient viral spread during the early phase of infection. Mathematical modeling and gain-of-function mutations in SIVcpz, the simian precursor of pandemic HIV-1, corroborate this finding. Blockage of interferon signaling combined with transcriptome analyses revealed that basal tetherin levels are sufficient to control viral replication. These results establish tetherin as a key effector of the intrinsic immune defense against HIV-1, and they demonstrate that Vpu-mediated tetherin antagonism is critical for efficient viral spread during the initial phase of HIV-1 replication. Copyright © 2017 Elsevier Inc. All rights reserved.

The molecular mechanism of SPOROCYTELESS/NOZZLE in controlling Arabidopsis ovule development

PubMed Central

Wei, Baoye; Zhang, Jinzhe; Pang, Changxu; Yu, Hao; Guo, Dongshu; Jiang, Hao; Ding, Mingxin; Chen, Zhuoyao; Tao, Qing; Gu, Hongya; Qu, Li-Jia; Qin, Genji

2015-01-01

Ovules are essential for plant reproduction and develop into seeds after fertilization. SPOROCYTELESS/NOZZLE (SPL/NZZ) has been known for more than 15 years as an essential factor for ovule development in Arabidopsis, but the biochemical nature of SPL function has remained unsolved. Here, we demonstrate that SPL functions as an adaptor-like transcriptional repressor. We show that SPL recruits TOPLESS/TOPLESS-RELATED (TPL/TPR) co-repressors to inhibit the CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors. We reveal that SPL uses its EAR motif at the C-terminal end to recruit TPL/TPRs and its N-terminal part to bind and inhibit the TCPs. We demonstrate that either disruption of TPL/TPRs or overexpression of TCPs partially phenocopies the defects of megasporogenesis in spl. Moreover, disruption of TCPs causes phenotypes that resemble spl-D gain-of-function mutants. These results define the action mechanism for SPL, which along with TPL/TPRs controls ovule development by repressing the activities of key transcription factors. Our findings suggest that a similar gene repression strategy is employed by both plants and fungi to control sporogenesis. PMID:25378179

Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells

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

Shi, Yongguo, E-mail: 1138303166@qq.com; Lu, Jianwei, E-mail: jianwei2010077@163.com; Zhou, Jing, E-mail: 2310848@163.com

2014-04-04

Highlights: • First, we have shown that upregulated of the Loc554202 in breast cancer tissues. • Second, we demonstrated the function of Loc554202 in breast cancer cell. • Finally, we demonstrated that LOC554202 knockdown could inhibit tumor growth in vivo. - Abstract: Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question,more » we assay the expression level of lncRNAs–Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis.« less

Expression and function of CD8 alpha/beta chains on rat and human mast cells.

PubMed

Kim, Mi-Sun; Kim, Sung-Hoon; Lee, Hye-Jung; Kim, Hyung-Min

2004-03-01

The expression and functional role of CD8 glycoprotein, a marker of cytotoxic/suppressor T lymphocytes and NK cells, were not studied on freshly isolated connective tissue type rat peritoneal mast cells, a rat mucosal type mast cell line (RBL 2H3), or human mast cell line (HMC-1). We used the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, immunohistochemistry and enzyme-linked immunosorbent assay. RT-PCR and Western blot analysis identified the presence of CD8 alpha/beta chains on the mast cells, and immunohistochemistry confirmed CD8alpha expression on rat or human mast cells. Functional studies demonstrated that stimulation of CD8 alpha/beta chains on rat mast cells induced the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), which are regarded as important mediators during infection. However, co-stimulation with stem cell factor had no effect on CD8-induced mediator secretion. Our findings demonstrate novel biological roles of CD8 molecules in mast cells.

Role of the human supplementary eye field in the control of saccadic eye movements

PubMed Central

Parton, Andrew; Nachev, Parashkev; Hodgson, Timothy L.; Mort, Dominic; Thomas, David; Ordidge, Roger; Morgan, Paul S.; Jackson, Stephen; Rees, Geraint; Husain, Masud

2007-01-01

The precise function of the supplementary eye field (SEF) is poorly understood. Although electrophysiological and functional imaging studies are important for demonstrating when SEF neurones are active, lesion studies are critical to establish the functions for which the SEF is essential. Here we report a series of investigations performed on an extremely rare individual with a highly focal lesion of the medial frontal cortex. High-resolution structural imaging demonstrated that his lesion was confined to the region of the left paracentral sulcus, the anatomical locus of the SEF. Behavioural testing revealed that the patient was significantly impaired when required to switch between anti- and pro-saccades, when there were conflicting rules governing stimulus–response mappings for saccades. Similarly, the results of an arbitrary stimulus–response associative learning task demonstrated that he was impaired when required to select the appropriate saccade from conflicting eye movement responses, but not for limb movements on an analogous manual task. When making memory-guided saccadic sequences, the patient demonstrated hypometria, like patients with Parkinson's disease, but had no significant difficulties in reproducing the order of saccades correctly on a task that emphasized accuracy with a wide temporal segregation between responses. These findings are consistent with the hypothesis that the SEF plays a key role in implementing control when there is conflict between several, ongoing competing saccadic responses, but not when eye movements need to be made accurately in sequence. PMID:17069864

The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

PubMed

Mistry, Abinash C; Wynne, Brandi M; Yu, Ling; Tomilin, Viktor; Yue, Qiang; Zhou, Yiqun; Al-Khalili, Otor; Mallick, Rickta; Cai, Hui; Alli, Abdel A; Ko, Benjamin; Mattheyses, Alexa; Bao, Hui-Fang; Pochynyuk, Oleh; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

2016-10-01

The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Evidence for Functional Networks within the Human Brain's White Matter.

PubMed

Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

2017-07-05

Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry. SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders. Copyright © 2017 the authors 0270-6474/17/376394-14$15.00/0.

Is intelligence equivalent to executive functions?

PubMed

Ardila, Alfredo

2018-05-01

Since the mid 19th century, cognitive and behavioral neurosciences have attempted to find the neurological bases of intellectual abilities. During the early 20th century the psychometric concept of "intelligence" was coined; and toward the end of the 20th century the neuropsychological concept of "executive functions" was introduced. Controversies, however, remain about the unity or heterogeneity of so-called executive functions. It is proposed that two major executive functions could be separated: metacognitive -or intelectual- and emotional/motivational. A similar distinction has been suggested by several authors. Standard definitions of intelligence implicitly assume that executive functions represent the fundamental components of intelligence. Research has demonstrated that, if considered as a whole, executive functions only partially correspond to the psychometric concept of intelligence; whereas some specific executive functions clearly correspond to intelligence, some others do not involve intelligence. If using a major distinction between metacognitive -or simply "intellectual"-executive functions, and emotional/ motivational -or simply non-intellectual-executive functions, it becomes evident that general intelligence can be equated with metacognitive executive functions but not with emotional/ motivational executive functions.

Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development

PubMed Central

Chou, Ai Mei; Sem, Kai Ping; Lam, Wei Jun; Ahmed, Sohail; Lim, Chin Yan

2017-01-01

The insulin receptor substrate of 53 kDa, IRSp53, is an adaptor protein that works with activated GTPases, Cdc42 and Rac, to modulate actin dynamics and generate membrane protrusions in response to cell signaling. Adult mice that lack IRSp53 fail to regulate synaptic plasticity and exhibit hippocampus-associated learning deficiencies. Here, we show that 60% of IRSp53 null embryos die at mid to late gestation, indicating a vital IRSp53 function in embryonic development. We find that IRSp53 KO embryos displayed pleiotropic phenotypes such as developmental delay, oligodactyly and subcutaneous edema, and died of severely impaired cardiac and placental development. We further show that double knockout of IRSp53 and its closest family member, IRTKS, resulted in exacerbated placental abnormalities, particularly in spongiotrophoblast differentiation and development, giving rise to complete embryonic lethality. Hence, our findings demonstrate a hitherto under-appreciated IRSp53 function in embryonic development, and further establish an essential genetic interaction between IRSp53 and IRTKS in placental formation. PMID:28067313

Glypican Is a Modulator of Netrin-Mediated Axon Guidance

PubMed Central

Blanchette, Cassandra R.; Perrat, Paola N.; Thackeray, Andrea; Bénard, Claire Y.

2015-01-01

Netrin is a key axon guidance cue that orients axon growth during neural circuit formation. However, the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown. Here we demonstrate that in Caenorhabditis elegans, LON-2/glypican, a heparan sulfate proteoglycan, modulates UNC-6/netrin signaling and may do this through interactions with the UNC-40/DCC receptor. We show that developing axons misorient in the absence of LON-2/glypican when the SLT-1/slit guidance pathway is compromised and that LON-2/glypican functions in both the attractive and repulsive UNC-6/netrin pathways. We find that the core LON-2/glypican protein, lacking its heparan sulfate chains, and secreted forms of LON-2/glypican are functional in axon guidance. We also find that LON-2/glypican functions from the epidermal substrate cells to guide axons, and we provide evidence that LON-2/glypican associates with UNC-40/DCC receptor–expressing cells. We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration. PMID:26148345

Worldsheet instantons and the amplitude for string pair production in an external field as a WKB exact functional integral

NASA Astrophysics Data System (ADS)

Gordon, James; Semenoff, Gordon W.

2018-05-01

We revisit the problem of charged string pair creation in a constant external electric field. The string states are massive and creation of pairs from the vacuum is a tunnelling process, analogous to the Schwinger process where charged particle-anti-particle pairs are created by an electric field. We find the instantons in the worldsheet sigma model which are responsible for the tunnelling events. We evaluate the sigma model partition function in the multi-instanton sector in the WKB approximation which keeps the classical action and integrates the quadratic fluctuations about the solution. We find that the summation of the result over all multi-instanton sectors reproduces the known amplitude. This suggests that corrections to the WKB limit must cancel. To show that they indeed cancel, we identify a fermionic symmetry of the sigma model which occurs in the instanton sectors and which is associated with collective coordinates. We demonstrate that the action is symmetric and that the interaction action is an exact form. These conditions are sufficient for localization of the worldsheet functional integral onto its WKB limit.

Combining Biomarkers Linearly and Nonlinearly for Classification Using the Area Under the ROC Curve

PubMed Central

Fong, Youyi; Yin, Shuxin; Huang, Ying

2016-01-01

In biomedical studies, it is often of interest to classify/predict a subject’s disease status based on a variety of biomarker measurements. A commonly used classification criterion is based on AUC - Area under the Receiver Operating Characteristic Curve. Many methods have been proposed to optimize approximated empirical AUC criteria, but there are two limitations to the existing methods. First, most methods are only designed to find the best linear combination of biomarkers, which may not perform well when there is strong nonlinearity in the data. Second, many existing linear combination methods use gradient-based algorithms to find the best marker combination, which often result in sub-optimal local solutions. In this paper, we address these two problems by proposing a new kernel-based AUC optimization method called Ramp AUC (RAUC). This method approximates the empirical AUC loss function with a ramp function, and finds the best combination by a difference of convex functions algorithm. We show that as a linear combination method, RAUC leads to a consistent and asymptotically normal estimator of the linear marker combination when the data is generated from a semiparametric generalized linear model, just as the Smoothed AUC method (SAUC). Through simulation studies and real data examples, we demonstrate that RAUC out-performs SAUC in finding the best linear marker combinations, and can successfully capture nonlinear pattern in the data to achieve better classification performance. We illustrate our method with a dataset from a recent HIV vaccine trial. PMID:27058981

Assessing Density Functionals Using Many Body Theory for Hybrid Perovskites

NASA Astrophysics Data System (ADS)

Bokdam, Menno; Lahnsteiner, Jonathan; Ramberger, Benjamin; Schäfer, Tobias; Kresse, Georg

2017-10-01

Which density functional is the "best" for structure simulations of a particular material? A concise, first principles, approach to answer this question is presented. The random phase approximation (RPA)—an accurate many body theory—is used to evaluate various density functionals. To demonstrate and verify the method, we apply it to the hybrid perovskite MAPbI3 , a promising new solar cell material. The evaluation is done by first creating finite temperature ensembles for small supercells using RPA molecular dynamics, and then evaluating the variance between the RPA and various approximate density functionals for these ensembles. We find that, contrary to recent suggestions, van der Waals functionals do not improve the description of the material, whereas hybrid functionals and the strongly constrained appropriately normed (SCAN) density functional yield very good agreement with the RPA. Finally, our study shows that in the room temperature tetragonal phase of MAPbI3 , the molecules are preferentially parallel to the shorter lattice vectors but reorientation on ps time scales is still possible.

Can home care services achieve cost savings in long-term care for older people?

PubMed

Greene, V L; Ondrich, J; Laditka, S

1998-07-01

To determine whether efficient allocation of home care services can produce net long-term care cost savings. Hazard function analysis and nonlinear mathematical programming. Optimal allocation of home care services resulted in a 10% net reduction in overall long-term care costs for the frail older population served by the National Long-Term Care (Channeling) Demonstration, in contrast to the 12% net cost increase produced by the demonstration intervention itself. Our findings suggest that the long-sought goal of overall cost-neutrality or even cost-savings through reducing nursing home use sufficiently to more than offset home care costs is technically feasible, but requires tighter targeting of services and a more medically oriented service mix than major home care demonstrations have implemented to date.

The Dual Functions of WLIM1a in Cell Elongation and Secondary Wall Formation in Developing Cotton Fibers[C][W

PubMed Central

Han, Li-Bo; Li, Yuan-Bao; Wang, Hai-Yun; Wu, Xiao-Min; Li, Chun-Li; Luo, Ming; Wu, Shen-Jie; Kong, Zhao-Sheng; Pei, Yan; Jiao, Gai-Li; Xia, Gui-Xian

2013-01-01

LIN-11, Isl1 and MEC-3 (LIM)-domain proteins play pivotal roles in a variety of cellular processes in animals, but plant LIM functions remain largely unexplored. Here, we demonstrate dual roles of the WLIM1a gene in fiber development in upland cotton (Gossypium hirsutum). WLIM1a is preferentially expressed during the elongation and secondary wall synthesis stages in developing fibers. Overexpression of WLIM1a in cotton led to significant changes in fiber length and secondary wall structure. Compared with the wild type, fibers of WLIM1a-overexpressing plants grew longer and formed a thinner and more compact secondary cell wall, which contributed to improved fiber strength and fineness. Functional studies demonstrated that (1) WLIM1a acts as an actin bundler to facilitate elongation of fiber cells and (2) WLIM1a also functions as a transcription factor to activate expression of Phe ammonia lyase–box genes involved in phenylpropanoid biosynthesis to build up the secondary cell wall. WLIM1a localizes in the cytosol and nucleus and moves into the nucleus in response to hydrogen peroxide. Taken together, these results demonstrate that WLIM1a has dual roles in cotton fiber development, elongation, and secondary wall formation. Moreover, our study shows that lignin/lignin-like phenolics may substantially affect cotton fiber quality; this finding may guide cotton breeding for improved fiber traits. PMID:24220634

Platform for combined analysis of functional and biomolecular phenotypes of the same cell

PubMed Central

Kelbauskas, L.; Ashili, S.; Zeng, J.; Rezaie, A.; Lee, K.; Derkach, D.; Ueberroth, B.; Gao, W.; Paulson, T.; Wang, H.; Tian, Y.; Smith, D.; Reid, B.; Meldrum, Deirdre R.

2017-01-01

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression. PMID:28300162

Spectral domain optical coherence tomography findings in acute syphilitic posterior placoid chorioretinitis.

PubMed

Burkholder, Bryn M; Leung, Theresa G; Ostheimer, Trucian A; Butler, Nicholas J; Thorne, Jennifer E; Dunn, James P

2014-01-27

We describe the spectral domain optical coherence tomography (SD-OCT) findings in three patients with acute syphilitic posterior placoid chorioretinitis (ASPPC). The SD-OCT images demonstrate the pathologic changes in ASPPC with a high level of anatomic detail and may provide information about the pathophysiology of the disease. We report a series of three consecutive patients seen at the Wilmer Eye Institute in 2012 and 2013 who presented with clinical and laboratory findings consistent with a diagnosis of unilateral ASPPC. Two of the three patients had HIV co-infection with good immune recovery. SD-OCT images from their initial (pre-treatment) presentation demonstrated thickening and hyperreflective nodularity of the choroid-retinal pigment epithelium (RPE) complex, with focal disruption of the overlying photoreceptor inner segment-outer segment junction in the areas corresponding to the retinal lesions seen on clinical examination. These changes improved with intravenous antibiotic treatment over a 3-month period of follow-up. SD-OCT imaging in ASPPC demonstrates reversible, focal thickening, and nodularity of the RPE with disruption of the overlying photoreceptor inner segment-outer segment junction. We believe that these SD-OCT images support the concept that ASPPC involves an inflammatory process at the level of the choroid-RPE with resultant structural and functional changes in the retinal photoreceptors. Further study with OCT imaging may be helpful in better understanding this disease.

Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

DOE PAGES

Kale, Seyit; Sode, Olaseni; Weare, Jonathan; ...

2014-11-07

Finding transition paths for chemical reactions can be computationally costly owing to the level of quantum-chemical theory needed for accuracy. Here, we show that a multilevel preconditioning scheme that was recently introduced (Tempkin et al. J. Chem. Phys. 2014, 140, 184114) can be used to accelerate quantum-chemical string calculations. We demonstrate the method by finding minimum-energy paths for two well-characterized reactions: tautomerization of malonaldehyde and Claissen rearrangement of chorismate to prephanate. For these reactions, we show that preconditioning density functional theory (DFT) with a semiempirical method reduces the computational cost for reaching a converged path that is an optimum undermore » DFT by several fold. In conclusion, the approach also shows promise for free energy calculations when thermal noise can be controlled.« less

Interferometric direction finding with a metamaterial detector

NASA Astrophysics Data System (ADS)

Venkatesh, Suresh; Shrekenhamer, David; Xu, Wangren; Sonkusale, Sameer; Padilla, Willie; Schurig, David

2013-12-01

We present measurements and analysis demonstrating useful direction finding of sources in the S band (2-4 GHz) using a metamaterial detector. An augmented metamaterial absorber that supports magnitude and phase measurement of the incident electric field, within each unit cell, is described. The metamaterial is implemented in a commercial printed circuit board process with off-board back-end electronics. We also discuss on-board back-end implementation strategies. Direction finding performance is analyzed for the fabricated metamaterial detector using simulated data and the standard algorithm, MUtiple SIgnal Classification. The performance of this complete system is characterized by its angular resolution as a function of radiation density at the detector. Sources with power outputs typical of mobile communication devices can be resolved at kilometer distances with sub-degree resolution and high frame rates.

Diminished Neural Adaptation during Implicit Learning in Autism

PubMed Central

Schipul, Sarah E.; Just, Marcel Adam

2015-01-01

Neuroimaging studies have shown evidence of disrupted neural adaptation during learning in individuals with autism spectrum disorder (ASD) in several types of tasks, potentially stemming from frontal-posterior cortical underconnectivity (Schipul et al., 2012). The aim of the current study was to examine neural adaptations in an implicit learning task that entails participation of frontal and posterior regions. Sixteen high-functioning adults with ASD and sixteen neurotypical control participants were trained on and performed an implicit dot pattern prototype learning task in a functional magnetic resonance imaging (fMRI) session. During the preliminary exposure to the type of implicit prototype learning task later to be used in the scanner, the ASD participants took longer than the neurotypical group to learn the task, demonstrating altered implicit learning in ASD. After equating task structure learning, the two groups’ brain activation differed during their learning of a new prototype in the subsequent scanning session. The main findings indicated that neural adaptations in a distributed task network were reduced in the ASD group, relative to the neurotypical group, and were related to ASD symptom severity. Functional connectivity was reduced and did not change as much during learning for the ASD group, and was related to ASD symptom severity. These findings suggest that individuals with ASD show altered neural adaptations during learning, as seen in both activation and functional connectivity measures. This finding suggests why many real-world implicit learning situations may pose special challenges for ASD. PMID:26484826

Evaluation of child and parent outcomes after a pediatric cardiac camp experience.

PubMed

Bultas, Margaret W; Budhathoki, Chakra; Balakas, Karen

2013-10-01

This study evaluated the effects of a cardiac camp experience on children with heart disease and their parents. A repeated measures design was used with 49 parent-child dyads. Repeated measures evaluated the effects of camp on anxiety, attitude toward illness, and psychosocial functioning of the children. Parental anxiety was also evaluated. Results demonstrated decreases in parent anxiety, decreases in child trait anxiety, and positive psychosocial outcomes in the areas of self-esteem, social, physical, and emotional functioning. Findings can be used to support decisions for those contemplating a camping experience for the child with heart disease. © 2013, Wiley Periodicals, Inc.

Quantifying Individual Brain Connectivity with Functional Principal Component Analysis for Networks.

PubMed

Petersen, Alexander; Zhao, Jianyang; Carmichael, Owen; Müller, Hans-Georg

2016-09-01

In typical functional connectivity studies, connections between voxels or regions in the brain are represented as edges in a network. Networks for different subjects are constructed at a given graph density and are summarized by some network measure such as path length. Examining these summary measures for many density values yields samples of connectivity curves, one for each individual. This has led to the adoption of basic tools of functional data analysis, most commonly to compare control and disease groups through the average curves in each group. Such group differences, however, neglect the variability in the sample of connectivity curves. In this article, the use of functional principal component analysis (FPCA) is demonstrated to enrich functional connectivity studies by providing increased power and flexibility for statistical inference. Specifically, individual connectivity curves are related to individual characteristics such as age and measures of cognitive function, thus providing a tool to relate brain connectivity with these variables at the individual level. This individual level analysis opens a new perspective that goes beyond previous group level comparisons. Using a large data set of resting-state functional magnetic resonance imaging scans, relationships between connectivity and two measures of cognitive function-episodic memory and executive function-were investigated. The group-based approach was implemented by dichotomizing the continuous cognitive variable and testing for group differences, resulting in no statistically significant findings. To demonstrate the new approach, FPCA was implemented, followed by linear regression models with cognitive scores as responses, identifying significant associations of connectivity in the right middle temporal region with both cognitive scores.

PTEN knockdown alters dendritic spine/protrusion morphology, not density

PubMed Central

Haws, Michael E.; Jaramillo, Thomas C.; Espinosa-Becerra, Felipe; Widman, Allie; Stuber, Garret D.; Sparta, Dennis R.; Tye, Kay M.; Russo, Scott J.; Parada, Luis F.; Kaplitt, Michael; Bonci, Antonello; Powell, Craig M.

2014-01-01

Mutations in phosphatase and tensin homolog deleted on chromosome ten (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala neurons on synaptic spine density and morphology using fluorescent dye confocal imaging. Contrary to previous studies in dentate gyrus, we find that knockdown of PTEN in basolateral amygdala leads to a significant decrease in total spine density in distal dendrites. Curiously, this decreased spine density is associated with increased miniature excitatory post-synaptic current frequency and amplitude, suggesting an increase in number and function of mature spines. These seemingly contradictory findings were reconciled by spine morphology analysis demonstrating increased mushroom spine density and size with correspondingly decreased thin protrusion density at more distal segments. The same analysis of PTEN conditional deletion in dentate gyrus demonstrated that loss of PTEN does not significantly alter total density of dendritic protrusions in the dentate gyrus, but does decrease thin protrusion density and increases density of more mature mushroom spines. These findings suggest that, contrary to previous reports, PTEN knockdown may not induce de novo spinogenesis, but instead may increase synaptic activity by inducing morphological and functional maturation of spines. Furthermore, behavioral analysis of basolateral amygdala PTEN knockdown suggests that these changes limited only to the basolateral amygdala complex may not be sufficient to induce increased anxiety-related behaviors. PMID:24264880

Serious Non-AIDS Conditions in HIV: Benefit of Early ART.

PubMed

Lundgren, Jens D; Borges, Alvaro H; Neaton, James D

2018-04-01

Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions. Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections. This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti-cancer effect of early ART shows how the immune system influences important pro-oncogenic processes. In START, there was also some evidence suggesting that early ART initiation preserved kidney function, although the clinical consequence of this remains unclear. Conversely, while no adverse effects were evident, the trials did not demonstrate a clear effect on metabolic-related disease outcomes, pulmonary disease, or neurocognitive function. HIV causes immune impairment soon after acquisition of infection. ART reverses this harm at least partially. The biological nature of the immune impairment needs further elucidation, as well as mechanisms and clinical impact of innate immune activation. Based on the findings from TEMPRANO and START, and because ART lowers the risk of onward transmission, ART initiation should be offered to all persons following their diagnosis of HIV.

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks

PubMed Central

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E.; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A.; Kellis, Manolis

2012-01-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein–protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level. PMID:22456606

Gain-of-Function R225W Mutation in Human AMPKγ3 Causing Increased Glycogen and Decreased Triglyceride in Skeletal Muscle

PubMed Central

Ahituv, Nadav; Chaudhry, Shehla N.; Schackwitz, Wendy S.; Dent, Robert; Pennacchio, Len A.

2007-01-01

Background AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that is evolutionarily conserved from yeast to mammals and functions to maintain cellular and whole body energy homeostasis. Studies in experimental animals demonstrate that activation of AMPK in skeletal muscle protects against insulin resistance, type 2 diabetes and obesity. The regulatory γ3 subunit of AMPK is expressed exclusively in skeletal muscle; however, its importance in controlling overall AMPK activity is unknown. While evidence is emerging that gamma subunit mutations interfere specifically with AMP activation, there remains some controversy regarding the impact of gamma subunit mutations [1]–[3]. Here we report the first gain-of-function mutation in the muscle-specific regulatory γ3 subunit in humans. Methods and Findings We sequenced the exons and splice junctions of the AMPK γ3 gene (PRKAG3) in 761 obese and 759 lean individuals, identifying 87 sequence variants including a novel R225W mutation in subjects from two unrelated families. The γ3 R225W mutation is homologous in location to the γ2R302Q mutation in patients with Wolf-Parkinson-White syndrome and to the γ3R225Q mutation originally linked to an increase in muscle glycogen content in purebred Hampshire Rendement Napole (RN-) pigs. We demonstrate in differentiated muscle satellite cells obtained from the vastus lateralis of R225W carriers that the mutation is associated with an approximate doubling of both basal and AMP-activated AMPK activities. Moreover, subjects bearing the R225W mutation exhibit a ∼90% increase of skeletal muscle glycogen content and a ∼30% decrease in intramuscular triglyceride (IMTG). Conclusions We have identified for the first time a mutation in the skeletal muscle-specific regulatory γ3 subunit of AMPK in humans. The γ3R225W mutation has significant functional effects as demonstrated by increases in basal and AMP-activated AMPK activities, increased muscle glycogen and decreased IMTG. Overall, these findings are consistent with an important regulatory role for AMPK γ3 in human muscle energy metabolism. PMID:17878938

Functional characterization of EZH2β reveals the increased complexity of EZH2 isoforms involved in the regulation of mammalian gene expression

PubMed Central

2013-01-01

Background Histone methyltransferase enhancer of zeste homologue 2 (EZH2) forms an obligate repressive complex with suppressor of zeste 12 and embryonic ectoderm development, which is thought, along with EZH1, to be primarily responsible for mediating Polycomb-dependent gene silencing. Polycomb-mediated repression influences gene expression across the entire gamut of biological processes, including development, differentiation and cellular proliferation. Deregulation of EZH2 expression is implicated in numerous complex human diseases. To date, most EZH2-mediated function has been primarily ascribed to a single protein product of the EZH2 locus. Results We report that the EZH2 locus undergoes alternative splicing to yield at least two structurally and functionally distinct EZH2 methyltransferases. The longest protein encoded by this locus is the conventional enzyme, which we refer to as EZH2α, whereas EZH2β, characterized here, represents a novel isoform. We find that EZH2β localizes to the cell nucleus, complexes with embryonic ectoderm development and suppressor of zeste 12, trimethylates histone 3 at lysine 27, and mediates silencing of target promoters. At the cell biological level, we find that increased EZH2β induces cell proliferation, demonstrating that this protein is functional in the regulation of processes previously attributed to EZH2α. Biochemically, through the use of genome-wide expression profiling, we demonstrate that EZH2β governs a pattern of gene repression that is often ontologically redundant from that of EZH2α, but also divergent for a wide variety of specific target genes. Conclusions Combined, these results demonstrate that an expanded repertoire of EZH2 writers can modulate histone code instruction during histone 3 lysine 27-mediated gene silencing. These data support the notion that the regulation of EZH2-mediated gene silencing is more complex than previously anticipated and should guide the design and interpretation of future studies aimed at understanding the biochemical and biological roles of this important family of epigenomic regulators. PMID:23448518

Staying on Task: Age-Related Changes in the Relationship Between Executive Functioning and Response Time Consistency.

PubMed

Vasquez, Brandon P; Binns, Malcolm A; Anderson, Nicole D

2016-03-01

Little is known about the relationship of executive functioning with age-related increases in response time (RT) distribution indices (intraindividual standard deviation [ISD], and ex-Gaussian parameters mu, sigma, tau). The goals of this study were to (a) replicate findings of age-related changes in response time distribution indices during an engaging touch-screen RT task and (b) investigate age-related changes in the relationship between executive functioning and RT distribution indices. Healthy adults (24 young [aged 18-30], 24 young-old [aged 65-74], and 24 old-old [aged 75-85]) completed a touch-screen attention task and a battery of neuropsychological tests. The relationships between RT performance and executive functions were examined with structural equation modeling (SEM). ISD, mu, and tau, but not sigma, increased with age. SEM revealed tau as the most salient RT index associated with neuropsychological measures of executive functioning. Further analysis demonstrated that correlations between tau and a weighted executive function composite were significant only in the old-old group. Our results replicate findings of greater RT inconsistency in older adults and reveal that executive functioning is related to tau in adults aged 75-85. These results support literature identifying tau as a marker of cognitive control, which deteriorates in old age. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Anisotropy and phonon modes from analysis of the dielectric function tensor and the inverse dielectric function tensor of monoclinic yttrium orthosilicate

NASA Astrophysics Data System (ADS)

Mock, A.; Korlacki, R.; Knight, S.; Schubert, M.

2018-04-01

We determine the frequency dependence of the four independent Cartesian tensor elements of the dielectric function for monoclinic symmetry Y2SiO5 using generalized spectroscopic ellipsometry from 40-1200 cm-1. Three different crystal cuts, each perpendicular to a principle axis, are investigated. We apply our recently described augmentation of lattice anharmonicity onto the eigendielectric displacement vector summation approach [A. Mock et al., Phys. Rev. B 95, 165202 (2017), 10.1103/PhysRevB.95.165202], and we present and demonstrate the application of an eigendielectric displacement loss vector summation approach with anharmonic broadening. We obtain an excellent match between all measured and model-calculated dielectric function tensor elements and all dielectric loss function tensor elements. We obtain 23 Au and 22 Bu symmetry long-wavelength active transverse and longitudinal optical mode parameters including their eigenvector orientation within the monoclinic lattice. We perform density functional theory calculations and obtain 23 Au symmetry and 22 Bu transverse and longitudinal optical mode parameters and their orientation within the monoclinic lattice. We compare our results from ellipsometry and density functional theory and find excellent agreement. We also determine the static and above reststrahlen spectral range dielectric tensor values and find a recently derived generalization of the Lyddane-Sachs-Teller relation for polar phonons in monoclinic symmetry materials satisfied [M. Schubert, Phys Rev. Lett. 117, 215502 (2016), 10.1103/PhysRevLett.117.215502].

Comparison of Combined Endoscopic Ultrasonography and Endoscopic Secretin Testing With the Traditional Secretin Pancreatic Function Test in Patients With Suspected Chronic Pancreatitis: A Prospective Crossover Study.

PubMed

Kothari, Darshan; Ketwaroo, Gyanprakash; Sawhney, Mandeep S; Freedman, Steven D; Sheth, Sunil G

2017-07-01

We aimed to determine the feasibility and accuracy of a combined endoscopic ultrasonography (EUS) with a shortened pancreatic function testing (sEUS) for structural and functional assessment using a single instrument in patients with suspected chronic pancreatitis (CP). We completed a prospective crossover study, enrolling patients with suspected CP. Patients who underwent both traditional 1-hour secretin pancreatic function test (sPFT) and sEUS were included in the analysis. We compared study results for test concordance and for correlation of peak bicarbonate concentrations. Eleven (64.7%) of 17 patients had concordant sPFT and sEUS findings when the cutoff for peak bicarbonate was 80 mEq/L. Six patients had discordant findings with a negative sPFT and positive sEUS. This poor concordance suggests that sEUS is an unreliable functional test. Lowering the sEUS cutoff to 70 mEq/L resulted in improved concordance (64.7% vs 70.6%). Finally, there was no significant correlation between peak bicarbonate concentrations (r = 0.47; 95% confidence interval, -0.02 to 0.79) in these 2 functional tests. We demonstrate poor concordance between sPFT and sEUS suggesting that a combined shortened functional and structural test using a single instrument may not be a feasible test for diagnosis of suspected CP when a cutoff of 80 mEq/L is used.

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility.

PubMed

Berry, Anne S; Shah, Vyoma D; Baker, Suzanne L; Vogel, Jacob W; O'Neil, James P; Janabi, Mustafa; Schwimmer, Henry D; Marks, Shawn M; Jagust, William J

2016-12-14

Aging is accompanied by profound changes in the brain's dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases. Using the PET tracer 6-[ 18 F]fluoro-l-m-tyrosine, we found strong support for upregulated striatal dopamine synthesis capacity in healthy older adult humans free of amyloid pathology, relative to young people. We next used fMRI to define the functional impact of elevated synthesis capacity on cognitive flexibility, a core component of executive function. We found clear evidence in young adults that low levels of synthesis capacity were suboptimal, associated with diminished cognitive flexibility and altered frontoparietal activation relative to young adults with highest synthesis values. Critically, these relationships between dopamine, performance, and activation were transformed in older adults with higher synthesis capacity. Variability in synthesis capacity was related to intrinsic frontoparietal functional connectivity across groups, suggesting that striatal dopamine synthesis influences the tuning of networks underlying cognitive flexibility. Together, these findings define striatal dopamine's association with cognitive flexibility and its neural underpinnings in young adults, and reveal the alteration in dopamine-related neural processes in aging. Few studies have combined measurement of brain dopamine with examination of the neural basis of cognition in youth and aging to delineate the underlying mechanisms of these associations. Combining in vivo PET imaging of dopamine synthesis capacity, fMRI, and a sensitive measure of cognitive flexibility, we reveal three core findings. First, we find evidence supporting older adults' capacity to upregulate dopamine synthesis. Second, we define relationships between dopamine, cognition, and frontoparietal activity in young adults indicating high levels of synthesis capacity are optimal. Third, we demonstrate alteration of these relationships in older adults, suggesting neurochemical modulation of cognitive flexibility changes with age. Copyright © 2016 the authors 0270-6474/16/3612559-11$15.00/0.

Robust, synergistic regulation of human gene expression using TALE activators.

PubMed

Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

2013-03-01

Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

Alterations of CNS structure & function by charged particle radiation & resultant oxidative stress

NASA Astrophysics Data System (ADS)

Nelson, Gregory; Chang, Polly; Favre, Cecile; Fike, John; Komarova, Natalia; Limoli, Charles; Mao, Xiao-Wen; Obenaus, Andre; Raber, Jacob; Spigelman, Igor; Soltesz, Ivan; Song, Sheng-Kwei; Stampanoni, Marco; Vlkolinsky, Roman; Wodarz, Dominik

The NSCOR program project is transitioning from establishing the existence of CNS responses to low doses of charged particles, to an investigation of mechanisms underlying these changes and extending the irradiation paradigm to more space-like exposures. In earlier experiments we examined radiation responses of the mouse brain (hippocampus) following exposure to 250 MeV protons and 600 MeV/n iron ions. Our key findings on structural changes were: 1) Significant dose and time dependent loss of en-dothelial cells and microvessel network remodeling occurs suggesting that vascular insufficiency is produced. 2) Significant dose dependent losses of neural precursor cells were observed in a lineage specific pattern which may be associated with cognitive impairment. 3) Evaluation of DNA damage showed dose and time dependent accumulation of mutations with region-specific mutation structures and gene expression profiling demonstrated activation of neurotrophic and adhesion factors as well as chemokine receptors associated with inflammation. Our key find-ings on functional changes were: 1) Time and dose dependent modifications to neural output expressed as enhanced excitability but reduced synaptic efficacy and plasticity (including long term potentiation). 2) Intrinsic membrane properties of neurons were not significantly modi-fied by radiation exposure but pharmacological treatments demonstrated changes in inhibitory synapses. 3) MRI imaging visualized brain structural changes based on altered water diffu-sion properties and patterns were consistent with demyelination or gliosis. Our key findings on neurodegeneration and fidelity of homeostasis were: 1) APP23 transgenic mice exhibited accelerated APP-type electrophysiological pathology over several months. 2) Microvessel net-work changes following irradiation were suggestive of poor tissue oxygenation. 3) The ability of the brain to respond a controlled septic shock was altered by irradiation; the septic shock reactions were complex and suggested continuous remodeling of the brain for up to 6 months. Thus we demonstrated a suite of CNS structural and functional changes after proton and iron ion exposure in the low dose regime. Based on these findings we will now test whether oxidative stress mediates the reactions of CNS to radiation exposure and what role radiation quality and dose rate play in the responses. We will use cultured neural precursor cells (mouse human) to detect changes in oxidative status and differentiation as functions of charged particle charge and velocity. These results will inform the selection of particles for many in vivo measurements that will compare wild type mice to a transgenic strain that over-expresses a human catalase gene (which inactivates hydrogen peroxide) in the mitochondrial compartment. This will explicitly test the role of reactive oxygen species in mediating the mechanisms underlying the CNS endpoints that we will measure. We will extend the electrophysiological measurements on individual nerves in hippocampal slices to characterize both inhibitory and excitatory synapses. Further, multi-electrode arrays will be used to follow correlated electrical activity in different hippocampal regions in order to understand network-level function as well as synaptic efficacy and plasticity. Controlled oxidative stress on irradiated samples will explore whether response mechanisms are shared. To link alterations in neurogenesis to performance we will explore behavioral changes mediated by the hippocampus simultaneously with measures of expression of the Arc gene in newly-born neurons. This will test whether decrements in performance correlate with loss of new cells and whether behavior properly stimulates functional integration of the new cells; the behavioral paradigm will be contextual fear conditioning. We will develop mathematical frameworks for CNS responses to radiation in order to inform risk estimates. Finally, we will couple a high-fidelity hippocampus network model to modified patterns of neuron activity along simulated charged particle tracks to probe the potential effects on network function.

Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study.

PubMed

Carlson, Christopher S; Matise, Tara C; North, Kari E; Haiman, Christopher A; Fesinmeyer, Megan D; Buyske, Steven; Schumacher, Fredrick R; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D; Duggan, David J; Spencer, Kylee L; Dumitrescu, Logan; Eaton, Charles B; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C; Hindorff, Lucia A; Kooperberg, Charles L

2013-09-01

The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging.

Power Laws from Linear Neuronal Cable Theory: Power Spectral Densities of the Soma Potential, Soma Membrane Current and Single-Neuron Contribution to the EEG

PubMed Central

Pettersen, Klas H.; Lindén, Henrik; Tetzlaff, Tom; Einevoll, Gaute T.

2014-01-01

Power laws, that is, power spectral densities (PSDs) exhibiting behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency power laws with power-law exponents analytically identified as for the soma membrane current, for the current-dipole moment, and for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink () noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how power laws with a wide range of values for the power-law exponent α may arise from a simple, linear partial differential equation. PMID:25393030

Power laws from linear neuronal cable theory: power spectral densities of the soma potential, soma membrane current and single-neuron contribution to the EEG.

PubMed

Pettersen, Klas H; Lindén, Henrik; Tetzlaff, Tom; Einevoll, Gaute T

2014-11-01

Power laws, that is, power spectral densities (PSDs) exhibiting 1/f(α) behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency 1/f(α) power laws with power-law exponents analytically identified as α∞(I) = 1/2 for the soma membrane current, α∞(p) = 3/2 for the current-dipole moment, and α∞(V) = 2 for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink (1/f) noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how 1/f(α) power laws with a wide range of values for the power-law exponent α may arise from a simple, linear partial differential equation.

Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study

PubMed Central

Carlson, Christopher S.; Matise, Tara C.; North, Kari E.; Haiman, Christopher A.; Fesinmeyer, Megan D.; Buyske, Steven; Schumacher, Fredrick R.; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D.; Duggan, David J.; Spencer, Kylee L.; Dumitrescu, Logan; Eaton, Charles B.; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C.; Hindorff, Lucia A.; Kooperberg, Charles L.

2013-01-01

The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging. PMID:24068893

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

PubMed

Pan, Joshua; Meyers, Robin M; Michel, Brittany C; Mashtalir, Nazar; Sizemore, Ann E; Wells, Jonathan N; Cassel, Seth H; Vazquez, Francisca; Weir, Barbara A; Hahn, William C; Marsh, Joseph A; Tsherniak, Aviad; Kadoch, Cigall

2018-05-23

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone, and in combination with large-scale biophysical data, to enhance our understanding of mammalian protein complexes in normal and disease states. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Wisconsin Card Sorting Test performance in children with developmental coordination disorder.

PubMed

Wuang, Yee-Pay; Su, Chwen-Yng; Su, Jui-Hsing

2011-01-01

The primary purpose of this study was to investigate and compare the executive functions measured by the Wisconsin Card Sorting Test (WCST) between children with developmental coordination disorder (DCD) and age-matched normal controls. A second purpose was to examine the relations between executive functions and school functions in DCD children. Seventy-one children with DCD and 70 children without motor problems were recruited from 14 public schools. Executive functions and school functions were assessed using the WCST, and the School Function Assessment--Chinese Version (SFA-C) respectively. Univariate analyses demonstrated significant between-group differences in five WCST measures. The logistic regression analysis showed differences between two groups on eight SFA-C subscales, and significant correlation between items measured on WCST and SFA-C was also found. The result of the study provides further evidence of impaired sub-domains of executive functions (i.e., mental shifting, flexibility) in children with DCD. The finding also adds to recent investigations into the relationship between executive functions and school functions in DCD. Implications for rehabilitation professionals and recommendations for further research are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Frontal lobe neurology and the creative mind

PubMed Central

de Souza, Leonardo C.; Guimarães, Henrique C.; Teixeira, Antônio L.; Caramelli, Paulo; Levy, Richard; Dubois, Bruno; Volle, Emmanuelle

2014-01-01

Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity—as it has been defined and explored by cognitive neuroscience—in artistic creation and may provide leads for future lesion studies. PMID:25101029

Optogenetic fMRI and electrophysiological identification of region-specific connectivity between the cerebellar cortex and forebrain.

PubMed

Choe, Katrina Y; Sanchez, Carlos F; Harris, Neil G; Otis, Thomas S; Mathews, Paul J

2018-06-01

Complex animal behavior is produced by dynamic interactions between discrete regions of the brain. As such, defining functional connections between brain regions is critical in gaining a full understanding of how the brain generates behavior. Evidence suggests that discrete regions of the cerebellar cortex functionally project to the forebrain, mediating long-range communication potentially important in motor and non-motor behaviors. However, the connectivity map remains largely incomplete owing to the challenge of driving both reliable and selective output from the cerebellar cortex, as well as the need for methods to detect region specific activation across the entire forebrain. Here we utilize a paired optogenetic and fMRI (ofMRI) approach to elucidate the downstream forebrain regions modulated by activating a region of the cerebellum that induces stereotypical, ipsilateral forelimb movements. We demonstrate with ofMRI, that activating this forelimb motor region of the cerebellar cortex results in functional activation of a variety of forebrain and midbrain areas of the brain, including the hippocampus and primary motor, retrosplenial and anterior cingulate cortices. We further validate these findings using optogenetic stimulation paired with multi-electrode array recordings and post-hoc staining for molecular markers of activated neurons (i.e. c-Fos). Together, these findings demonstrate that a single discrete region of the cerebellar cortex is capable of influencing motor output and the activity of a number of downstream forebrain as well as midbrain regions thought to be involved in different aspects of behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel functional hepatitis C virus glycoprotein isolates identified using an optimized viral pseudotype entry assay.

PubMed

Urbanowicz, Richard A; McClure, C Patrick; King, Barnabas; Mason, Christopher P; Ball, Jonathan K; Tarr, Alexander W

2016-09-01

Retrovirus pseudotypes are a highly tractable model used to study the entry pathways of enveloped viruses. This model has been extensively applied to the study of the hepatitis C virus (HCV) entry pathway, preclinical screening of antiviral antibodies and for assessing the phenotype of patient-derived viruses using HCV pseudoparticles (HCVpp) possessing the HCV E1 and E2 glycoproteins. However, not all patient-isolated clones produce particles that are infectious in this model. This study investigated factors that might limit phenotyping of patient-isolated HCV glycoproteins. Genetically related HCV glycoproteins from quasispecies in individual patients were discovered to behave very differently in this entry model. Empirical optimization of the ratio of packaging construct and glycoprotein-encoding plasmid was required for successful HCVpp genesis for different clones. The selection of retroviral packaging construct also influenced the function of HCV pseudoparticles. Some glycoprotein constructs tolerated a wide range of assay parameters, while others were much more sensitive to alterations. Furthermore, glycoproteins previously characterized as unable to mediate entry were found to be functional. These findings were validated using chimeric cell-cultured HCV bearing these glycoproteins. Using the same empirical approach we demonstrated that generation of infectious ebolavirus pseudoviruses (EBOVpv) was also sensitive to the amount and ratio of plasmids used, and that protocols for optimal production of these pseudoviruses are dependent on the exact virus glycoprotein construct. These findings demonstrate that it is crucial for studies utilizing pseudoviruses to conduct empirical optimization of pseudotype production for each specific glycoprotein sequence to achieve optimal titres and facilitate accurate phenotyping.

Frontal lobe neurology and the creative mind.

PubMed

de Souza, Leonardo C; Guimarães, Henrique C; Teixeira, Antônio L; Caramelli, Paulo; Levy, Richard; Dubois, Bruno; Volle, Emmanuelle

2014-01-01

Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity-as it has been defined and explored by cognitive neuroscience-in artistic creation and may provide leads for future lesion studies.

RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C. elegans

PubMed Central

Puca, Annibale; Solovieff, Nadia; Kojima, Toshio; Wang, Meng C.; Melista, Efthymia; Meltzer, Micah; Fischer, Sylvia E. J.; Andersen, Stacy; Hartley, Stephen H.; Sedgewick, Amanda; Arai, Yasumichi; Bergman, Aviv; Barzilai, Nir; Terry, Dellara F.; Riva, Alberto; Anselmi, Chiara Viviani; Malovini, Alberto; Kitamoto, Aya; Sawabe, Motoji; Arai, Tomio; Gondo, Yasuyuki; Steinberg, Martin H.; Hirose, Nobuyoshi; Atzmon, Gil; Ruvkun, Gary; Baldwin, Clinton T.; Perls, Thomas T.

2009-01-01

Background The strong familiality of living to extreme ages suggests that human longevity is genetically regulated. The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered. Methodology/Principal Findings Here, we first show that 18 single nucleotide polymorphisms (SNPs) in the RNA editing genes ADARB1 and ADARB2 are associated with extreme old age in a U.S. based study of centenarians, the New England Centenarian Study. We describe replications of these findings in three independently conducted centenarian studies with different genetic backgrounds (Italian, Ashkenazi Jewish and Japanese) that collectively support an association of ADARB1 and ADARB2 with longevity. Some SNPs in ADARB2 replicate consistently in the four populations and suggest a strong effect that is independent of the different genetic backgrounds and environments. To evaluate the functional association of these genes with lifespan, we demonstrate that inactivation of their orthologues adr-1 and adr-2 in C. elegans reduces median survival by 50%. We further demonstrate that inactivation of the argonaute gene, rde-1, a critical regulator of RNA interference, completely restores lifespan to normal levels in the context of adr-1 and adr-2 loss of function. Conclusions/Significance Our results suggest that RNA editors may be an important regulator of aging in humans and that, when evaluated in C. elegans, this pathway may interact with the RNA interference machinery to regulate lifespan. PMID:20011587

Understanding Defect-Stabilized Noncovalent Functionalization of Graphene

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

Zhou, Hua; Uysal, Ahmet; Anjos, Daniela M.

2015-09-01

The noncovalent functionalization of graphene by small molecule aromatic adsorbates, phenanthrenequinone (PQ), is investigated systematically by combining electrochemical characterization, high-resolution interfacial X-ray scattering, and ab initio density functional theory calculations. The findings in this study reveal that while PQ deposited on pristine graphene is unstable to electrochemical cycling, the prior introduction of defects and oxygen functionality (hydroxyl and epoxide groups) to the basal plane by exposure to atomic radicals (i.e., oxygen plasma) effectively stabilizes its noncovalent functionalization by PQ adsorption. The structure of adsorbed PQ molecules resembles the graphene layer stacking and is further stabilized by hydrogen bonding with terminalmore » hydroxyl groups that form at defect sites within the graphene basal plane. The stabilized PQ/graphene interface demonstrates persistent redox activity associated with proton-coupled-electron-transfer reactions. The resultant PQ adsorbed structure is essentially independent of electrochemical potentials. These results highlight a facile approach to enhance functionalities of the otherwise chemically inert graphene using noncovalent interactions.« less

Sexual dimorphism of male face shape, partnership status and the temporal context of relationship sought modulate women's preferences for direct gaze.

PubMed

Conway, Claire A; Jones, Benedict C; DeBruine, Lisa M; Little, Anthony C

2010-02-01

Most previous studies of face preferences have investigated the physical cues that influence face preferences. Far fewer studies have investigated the effects of cues to the direction of others' social interest (i.e. gaze direction) on face preferences. Here we found that unpartnered women demonstrated stronger preferences for direct gaze (indicating social interest) from feminine male faces than from masculine male faces when judging men's attractiveness for long-term relationships, but not when judging men's attractiveness for short-term relationships. Moreover, unpartnered women's preferences for direct gaze from feminine men were stronger for long-term than short-term relationships, but there was no comparable effect for judgements of masculine men. No such effects were evident among women with romantic partners, potentially reflecting different motivations underlying partnered and unpartnered women's judgements of men's attractiveness. Collectively these findings (1) complement previous findings whereby women demonstrated stronger preferences for feminine men as long-term than short-term partners, (2) demonstrate context-sensitivity in the integration of physical and social cues in face preferences, and (3) suggest that gaze preferences may function, at least in part, to facilitate efficient allocation of mating effort.

Experimental demonstration of the influence of alcohol advertising on the activation of alcohol expectancies in memory among fourth- and fifth-grade children.

PubMed

Dunn, M E; Yniguez, R M

1999-11-01

Previous work has demonstrated that children's organization and activation of alcohol expectancies in memory vary as a function of alcohol use, even among children as young as in the 3rd grade. To advance the understanding of influences on the development of alcohol expectancies in children, 551 4th- and 5th-grade children were exposed to 5 beer commercials or 5 soft drink commercials. After viewing the advertisements, all children reported their 1st associate to an alcohol prompt and completed a memory model-based measure of children's alcohol expectancies. Multidimensional scaling was used to map expectancies into hypothetical memory network format, and preference mapping was used to derive possible paths of activation. Children who viewed beer commercials were more likely to activate positive and arousing alcohol expectancies. In view of previous findings demonstrating that this pattern of activation corresponded to higher drinking among 3rd, 6th, 9th, and 12th graders, the present findings suggested that antecedents to drinking like exposure to advertising may promote heavier drinking among children by influencing the activation of expectancies in memory.

Recurrent rewiring and emergence of RNA regulatory networks.

PubMed

Wilinski, Daniel; Buter, Natascha; Klocko, Andrew D; Lapointe, Christopher P; Selker, Eric U; Gasch, Audrey P; Wickens, Marvin

2017-04-04

Alterations in regulatory networks contribute to evolutionary change. Transcriptional networks are reconfigured by changes in the binding specificity of transcription factors and their cognate sites. The evolution of RNA-protein regulatory networks is far less understood. The PUF (Pumilio and FBF) family of RNA regulatory proteins controls the translation, stability, and movements of hundreds of mRNAs in a single species. We probe the evolution of PUF-RNA networks by direct identification of the mRNAs bound to PUF proteins in budding and filamentous fungi and by computational analyses of orthologous RNAs from 62 fungal species. Our findings reveal that PUF proteins gain and lose mRNAs with related and emergent biological functions during evolution. We demonstrate at least two independent rewiring events for PUF3 orthologs, independent but convergent evolution of PUF4/5 binding specificity and the rewiring of the PUF4/5 regulons in different fungal lineages. These findings demonstrate plasticity in RNA regulatory networks and suggest ways in which their rewiring occurs.

RBANS Memory Indices Are Related to Medial Temporal Lobe Volumetrics in Healthy Older Adults and Those with Mild Cognitive Impairment

PubMed Central

England, Heather B.; Gillis, M. Meredith; Hampstead, Benjamin M.

2014-01-01

The current study (i) determined whether NeuroQuant® volumetrics are reflective of differences in medial temporal lobe (MTL) volumes between healthy older adults and those with mild cognitive impairment (MCI) and (ii) examined the relationship between RBANS indices and MTL volumes. Forty-three healthy older adults and 57 MCI patients completed the RBANS and underwent structural MRI. Hippocampal and inferior lateral ventricle (ILV) volumes were obtained using NeuroQuant®. Results revealed significantly smaller hippocampal and larger ILV volumes in MCI patients. MTL volumes were significantly related to the RBANS Immediate and Delayed Memory and Language indices but not the Attention or Visuoconstruction indices; findings that demonstrate anatomical specificity. Following discriminant function analysis, we calculated a cutpoint that may prove clinically useful for integrating MTL volumes into the diagnosis of MCI. These findings demonstrate the potential clinical utility of NeuroQuant® and are the first to document the relationship between RBANS indices and MTL volumes. PMID:24709384

Interfacial Modifiers

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

Martin, Ina; French, Roger H.

Our project objective in the first and only Budget Period was to demonstrate the potential of nm-scale organofunctional silane coatings as a method of extending the lifetime of PV materials and devices. Specifically, the target was to double the lifetime performance of a laminated Cu(In,Ga)Se2 (CIGS) cell under real-world and accelerated aging exposure conditions. Key findings are that modification of aluminum-doped zinc oxide (AZO) films (materials used as transparent conductive oxide (TCO) top contacts) resulted in decreased degradation of optical and electrical properties under damp heat (DH) exposure compared to un-modified AZO. The most significant finding is that modification ofmore » the AZO top contact of full CIGS devices resulted in significantly improved properties under DH exposure compared to un-modified devices, by a factor of 4 after 1000 h. Results of this one-year project have demonstrated that surface functionalization is a viable pathway for extending the lifetime of state-of-the-art CIGS devices.« less

iFORM: Incorporating Find Occurrence of Regulatory Motifs.

PubMed

Ren, Chao; Chen, Hebing; Yang, Bite; Liu, Feng; Ouyang, Zhangyi; Bo, Xiaochen; Shu, Wenjie

2016-01-01

Accurately identifying the binding sites of transcription factors (TFs) is crucial to understanding the mechanisms of transcriptional regulation and human disease. We present incorporating Find Occurrence of Regulatory Motifs (iFORM), an easy-to-use and efficient tool for scanning DNA sequences with TF motifs described as position weight matrices (PWMs). Both performance assessment with a receiver operating characteristic (ROC) curve and a correlation-based approach demonstrated that iFORM achieves higher accuracy and sensitivity by integrating five classical motif discovery programs using Fisher's combined probability test. We have used iFORM to provide accurate results on a variety of data in the ENCODE Project and the NIH Roadmap Epigenomics Project, and the tool has demonstrated its utility in further elucidating individual roles of functional elements. Both the source and binary codes for iFORM can be freely accessed at https://github.com/wenjiegroup/iFORM. The identified TF binding sites across human cell and tissue types using iFORM have been deposited in the Gene Expression Omnibus under the accession ID GSE53962.

A view not to be missed: Salient scene content interferes with cognitive restoration

PubMed Central

Van der Jagt, Alexander P. N.; Craig, Tony; Brewer, Mark J.; Pearson, David G.

2017-01-01

Attention Restoration Theory (ART) states that built scenes place greater load on attentional resources than natural scenes. This is explained in terms of "hard" and "soft" fascination of built and natural scenes. Given a lack of direct empirical evidence for this assumption we propose that perceptual saliency of scene content can function as an empirically derived indicator of fascination. Saliency levels were established by measuring speed of scene category detection using a Go/No-Go detection paradigm. Experiment 1 shows that built scenes are more salient than natural scenes. Experiment 2 replicates these findings using greyscale images, ruling out a colour-based response strategy, and additionally shows that built objects in natural scenes affect saliency to a greater extent than the reverse. Experiment 3 demonstrates that the saliency of scene content is directly linked to cognitive restoration using an established restoration paradigm. Overall, these findings demonstrate an important link between the saliency of scene content and related cognitive restoration. PMID:28723975

A view not to be missed: Salient scene content interferes with cognitive restoration.

PubMed

Van der Jagt, Alexander P N; Craig, Tony; Brewer, Mark J; Pearson, David G

2017-01-01

Attention Restoration Theory (ART) states that built scenes place greater load on attentional resources than natural scenes. This is explained in terms of "hard" and "soft" fascination of built and natural scenes. Given a lack of direct empirical evidence for this assumption we propose that perceptual saliency of scene content can function as an empirically derived indicator of fascination. Saliency levels were established by measuring speed of scene category detection using a Go/No-Go detection paradigm. Experiment 1 shows that built scenes are more salient than natural scenes. Experiment 2 replicates these findings using greyscale images, ruling out a colour-based response strategy, and additionally shows that built objects in natural scenes affect saliency to a greater extent than the reverse. Experiment 3 demonstrates that the saliency of scene content is directly linked to cognitive restoration using an established restoration paradigm. Overall, these findings demonstrate an important link between the saliency of scene content and related cognitive restoration.

Diffusion-Tensor Imaging Findings and Cognitive Function Following Hospitalized Mixed-Mechanism Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

PubMed

Oehr, Lucy; Anderson, Jacqueline

2017-11-01

To undertake a systematic review and meta-analysis of the relationship between microstructural damage and cognitive function after hospitalized mixed-mechanism (HMM) mild traumatic brain injury (mTBI). PsycInfo, EMBASE, and MEDLINE were used to find relevant empirical articles published between January 2002 and January 2016. Studies that examined the specific relationship between diffusion tensor imaging (DTI) and cognitive test performance were included. The final sample comprised previously medically and psychiatrically healthy adults with HMM mTBI. Specific data were extracted including mTBI definitional criteria, descriptive statistics, outcome measures, and specific results of associations between DTI metrics and cognitive test performance. Of the 248 original articles retrieved and reviewed, 8 studies met all inclusion criteria and were included in the meta-analysis. The meta-analysis revealed statistically significant associations between reduced white matter integrity and poor performance on measures of attention (fractional anisotropy [FA]: d=.413, P<.001; mean diffusivity [MD]: d=-.407, P=.001), memory (FA: d=.347, P<.001; MD: d=-.568, P<.001), and executive function (FA: d=.246, P<.05), which persisted beyond 1 month postinjury. The findings from the meta-analysis provide clear support for an association between in vivo markers of underlying neuropathology and cognitive function after mTBI. Furthermore, these results demonstrate clearly for the first time that in vivo markers of structural neuropathology are associated with cognitive dysfunction within the domains of attention, memory, and executive function. These findings provide an avenue for future research to examine the causal relationship between mTBI-related neuropathology and cognitive dysfunction. Furthermore, they have important implications for clinical management of patients with mTBI because they provide a more comprehensive understanding of factors that are associated with cognitive dysfunction after mTBI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Obscurin Targets Ankyrin-B and Protein Phosphatase 2A to the Cardiac M-line*

PubMed Central

Cunha, Shane R.; Mohler, Peter J.

2008-01-01

Ankyrin-B targets ion channels and transporters in excitable cells. Dysfunction in ankyrin-B-based pathways results in defects in cardiac physiology. Despite a wealth of knowledge regarding the role of ankyrin-B for cardiac function, little is known regarding the mechanisms underlying ankyrin-B regulation. Moreover, the pathways underlying ankyrin-B targeting in heart are unclear. We report that alternative splicing regulates ankyrin-B localization and function in cardiomyocytes. Specifically, we identify a novel exon (exon 43′) in the ankyrin-B regulatory domain that mediates interaction with the Rho-GEF obscurin. Ankyrin-B transcripts harboring exon 43′ represent the primary cardiac isoform in human and mouse. We demonstrate that ankyrin-B and obscurin are co-localized at the M-line of myocytes and co-immunoprecipitate from heart. We define the structural requirements for ankyrin-B/obscurin interaction to two motifs in the ankyrin-B regulatory domain and demonstrate that both are critical for obscurin/ankyrin-B interaction. In addition, we demonstrate that interaction with obscurin is required for ankyrin-B M-line targeting. Specifically, both obscurin-binding motifs are required for the M-line targeting of a GFP-ankyrin-B regulatory domain. Moreover, this construct acts as a dominant-negative by competing with endogenous ankyrin-B for obscurin-binding at the M-line, thus providing a powerful new tool to evaluate the function of obscurin/ankyrin-B interactions. With this new tool, we demonstrate that the obscurin/ankyrin-B interaction is critical for recruitment of PP2A to the cardiac M-line. Together, these data provide the first evidence for the molecular basis of ankyrin-B and PP2A targeting and function at the cardiac M-line. Finally, we report that ankyrin-B R1788W is localized adjacent to the ankyrin-B obscurin-binding motif and increases binding activity for obscurin. In summary, our new findings demonstrate that ANK2 is subject to alternative splicing that gives rise to unique polypeptides with diverse roles in cardiac function. PMID:18782775

Psoriasis-associated vascular disease: the role of HDL.

PubMed

Paiva-Lopes, Maria Joao; Delgado Alves, José

2017-09-14

Psoriasis is a chronic inflammatory systemic disease with a prevalence of 2-3%. Overwhelming evidence show an epidemiological association between psoriasis, cardiovascular disease and atherosclerosis. Cardiovascular disease is the most frequent cause of death in patients with severe psoriasis. Several cardiovascular disease classical risk factors are also increased in psoriasis but the psoriasis-associated risk persists after adjusting for other risk factors.Investigation has focused on finding explanations for these epidemiological data. Several studies have demonstrated significant lipid metabolism and HDL composition and function alterations in psoriatic patients. Altered HDL function is clearly one of the mechanisms involved, as these particles are of the utmost importance in atherosclerosis defense. Recent data indicate that biologic therapy can reverse both structural and functional HDL alterations in psoriasis, reinforcing their therapeutic potential.

Intranasal epidermal growth factor treatment rescues neonatal brain injury.

PubMed

Scafidi, Joseph; Hammond, Timothy R; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J; Hyder, Fahmeed; Horvath, Tamas L; Gallo, Vittorio

2014-02-13

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Intranasal epidermal growth factor treatment rescues neonatal brain injury

NASA Astrophysics Data System (ADS)

Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

2014-02-01

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Validation of a prediction model that allows direct comparison of the Oxford Knee Score and American Knee Society clinical rating system.

PubMed

Maempel, J F; Clement, N D; Brenkel, I J; Walmsley, P J

2015-04-01

This study demonstrates a significant correlation between the American Knee Society (AKS) Clinical Rating System and the Oxford Knee Score (OKS) and provides a validated prediction tool to estimate score conversion. A total of 1022 patients were prospectively clinically assessed five years after TKR and completed AKS assessments and an OKS questionnaire. Multivariate regression analysis demonstrated significant correlations between OKS and the AKS knee and function scores but a stronger correlation (r = 0.68, p < 0.001) when using the sum of the AKS knee and function scores. Addition of body mass index and age (other statistically significant predictors of OKS) to the algorithm did not significantly increase the predictive value. The simple regression model was used to predict the OKS in a group of 236 patients who were clinically assessed nine to ten years after TKR using the AKS system. The predicted OKS was compared with actual OKS in the second group. Intra-class correlation demonstrated excellent reliability (r = 0.81, 95% confidence intervals 0.75 to 0.85) for the combined knee and function score when used to predict OKS. Our findings will facilitate comparison of outcome data from studies and registries using either the OKS or the AKS scores and may also be of value for those undertaking meta-analyses and systematic reviews. ©2015 The British Editorial Society of Bone & Joint Surgery.

Stem cell antigen-1 in skeletal muscle function.

PubMed

Bernstein, Harold S; Samad, Tahmina; Cholsiripunlert, Sompob; Khalifian, Saami; Gong, Wenhui; Ritner, Carissa; Aurigui, Julian; Ling, Vivian; Wilschut, Karlijn J; Bennett, Stephen; Hoffman, Julien; Oishi, Peter

2013-08-15

Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca-1 is expressed on muscle-derived stem cells and myogenic precursors recruited to sites of muscle injury. We previously reported that inhibition of Sca-1 expression stimulated myoblast proliferation in vitro and regulated the tempo of muscle repair in vivo. Despite its function in myoblast expansion during muscle repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and hindlimb muscles to elucidate the tissue, contractile, and functional effects of Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber cross-sectional area, and Pax7+ myoblast number showed little differences between ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in KO versus WT mice, with young KO mice achieving results similar to aging WT animals. In addition, KO mice did not improve with practice, while WT animals demonstrated conditioning over time. Surprisingly, myomechanical analysis of isolated muscles showed that KO young muscle generated more force and experienced less fatigue. However, KO muscle also demonstrated incomplete relaxation with fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning with exercise, and that deficient conditioning in Sca-1 KO animals becomes more pronounced with age.

L-Dopa Modulates Functional Connectivity in Striatal Cognitive and Motor Networks: A Double-Blind Placebo-Controlled Study

PubMed Central

Kelly, Clare; de Zubicaray, Greig; Di Martino, Adriana; Copland, David A.; Reiss, Philip T.; Klein, Donald F.; Castellanos, F. Xavier; Milham, Michael P.; McMahon, Katie

2010-01-01

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions-of-interest previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., Cerebral Cortex, 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. While L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions. PMID:19494158

Phenotypes in defined genotypes including siblings with Usher syndrome.

PubMed

Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Andréasson, Sten

2011-06-01

To characterize visual function in defined genotypes including siblings with Usher syndrome. Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

Functional connectivity constrains the category-related organization of human ventral occipitotemporal cortex

PubMed Central

Stevens, W. Dale; Tessler, Michael Henry; Peng, Cynthia S.; Martin, Alex

2015-01-01

One of the most robust and oft-replicated findings in cognitive neuroscience is that several spatially distinct, functionally dissociable ventral occipitotemporal cortex (VOTC) regions respond preferentially to different categories of concrete entities. However, the determinants of this category-related organization remain to be fully determined. One recent proposal is that privileged connectivity of these VOTC regions with other regions that store and/or process category-relevant properties may be a major contributing factor. To test this hypothesis, we used a multi-category functional MRI localizer to individually define category-related brain regions of interest (ROIs) in a large group of subjects (n=33). We then used these ROIs in resting-state functional connectivity MRI analyses to explore spontaneous functional connectivity among these regions. We demonstrate that during rest, distinct category-preferential VOTC regions show differentially stronger functional connectivity with other regions that have congruent category-preference, as defined by the functional localizer. Importantly, a ‘tool’-preferential region in the left medial fusiform gyrus showed differentially stronger functional connectivity with other left lateralized cortical regions associated with perceiving and knowing about common tools – posterior middle temporal gyrus (involved in perception of non-biological motion), lateral parietal cortex (critical for reaching, grasping, manipulating), and ventral premotor cortex (involved in storing/executing motor programs) – relative to other category-related regions in VOTC of both the right and left hemisphere. Our findings support the claim that privileged connectivity with other cortical regions that store and/or process category-relevant properties constrains the category-related organization of VOTC. PMID:25704493

Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: functional connectivity-based parcellation method.

PubMed

Kim, Jae-Hun; Lee, Jong-Min; Jo, Hang Joon; Kim, Sook Hui; Lee, Jung Hee; Kim, Sung Tae; Seo, Sang Won; Cox, Robert W; Na, Duk L; Kim, Sun I; Saad, Ziad S

2010-02-01

Noninvasive parcellation of the human cerebral cortex is an important goal for understanding and examining brain functions. Recently, the patterns of anatomical connections using diffusion tensor imaging (DTI) have been used to parcellate brain regions. Here, we present a noninvasive parcellation approach that uses "functional fingerprints" obtained by correlation measures on resting state functional magnetic resonance imaging (fMRI) data to parcellate brain regions. In other terms, brain regions are parcellated based on the similarity of their connection--as reflected by correlation during resting state--to the whole brain. The proposed method was used to parcellate the medial frontal cortex (MFC) into supplementary motor areas (SMA) and pre-SMA subregions. In agreement with anatomical landmark-based parcellation, we find that functional fingerprint clustering of the MFC results in anterior and posterior clusters. The probabilistic maps from 12 subjects showed that the anterior cluster is mainly located rostral to the vertical commissure anterior (VCA) line, whereas the posterior cluster is mainly located caudal to VCA line, suggesting the homologues of pre-SMA and SMA. The functional connections from the putative pre-SMA cluster were connected to brain regions which are responsible for complex/cognitive motor control, whereas those from the putative SMA cluster were connected to brain regions which are related to the simple motor control. These findings demonstrate the feasibility of the functional connectivity-based parcellation of the human cerebral cortex using resting state fMRI. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Fine Mapping and Functional Analysis Reveal a Role of SLC22A1 in Acylcarnitine Transport.

PubMed

Kim, Hye In; Raffler, Johannes; Lu, Wenyun; Lee, Jung-Jin; Abbey, Deepti; Saleheen, Danish; Rabinowitz, Joshua D; Bennett, Michael J; Hand, Nicholas J; Brown, Christopher; Rader, Daniel J

2017-10-05

Genome-wide association studies have identified a signal at the SLC22A1 locus for serum acylcarnitines, intermediate metabolites of mitochondrial oxidation whose plasma levels associate with metabolic diseases. Here, we refined the association signal, performed conditional analyses, and examined the linkage structure to find coding variants of SLC22A1 that mediate independent association signals at the locus. We also employed allele-specific expression analysis to find potential regulatory variants of SLC22A1 and demonstrated the effect of one variant on the splicing of SLC22A1. SLC22A1 encodes a hepatic plasma membrane transporter whose role in acylcarnitine physiology has not been described. By targeted metabolomics and isotope tracing experiments in loss- and gain-of-function cell and mouse models of Slc22a1, we uncovered a role of SLC22A1 in the efflux of acylcarnitines from the liver to the circulation. We further validated the impacts of human variants on SLC22A1-mediated acylcarnitine efflux in vitro, explaining their association with serum acylcarnitine levels. Our findings provide the detailed molecular mechanisms of the GWAS association for serum acylcarnitines at the SLC22A1 locus by functionally validating the impact of SLC22A1 and its variants on acylcarnitine transport. Copyright © 2017. Published by Elsevier Inc.

Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis

PubMed Central

Lu, Leina; Sun, Kun; Chen, Xiaona; Zhao, Yu; Wang, Lijun; Zhou, Liang; Sun, Hao; Wang, Huating

2013-01-01

Skeletal muscle differentiation is orchestrated by a network of transcription factors, epigenetic regulators, and non-coding RNAs. The transcription factor Yin Yang 1 (YY1) silences multiple target genes in myoblasts (MBs) by recruiting Ezh2 (Enhancer of Zeste Homologue2). To elucidate genome-wide YY1 binding in MBs, we performed chromatin immunoprecipitation (ChIP)-seq and found 1820 specific binding sites in MBs with a large portion residing in intergenic regions. Detailed analysis demonstrated that YY1 acts as an activator for many loci in addition to its known repressor function. No significant co-occupancy was found between YY1 and Ezh2, suggesting an additional Ezh2-independent function for YY1 in MBs. Further analysis of intergenic binding sites showed that YY1 potentially regulates dozens of large intergenic non-coding RNAs (lincRNAs), whose function in myogenesis is underexplored. We characterized a novel muscle-associated lincRNA (Yam-1) that is positively regulated by YY1. Yam-1 is downregulated upon differentiation and acts as an inhibitor of myogenesis. We demonstrated that Yam-1 functions through in cis regulation of miR-715, which in turn targets Wnt7b. Our findings not only provide the first genome-wide picture of YY1 association in muscle cells, but also uncover the functional role of lincRNA Yam-1. PMID:23942234

New platforms for multi-functional ocular lenses: engineering double-sided functionalized nano-coatings.

PubMed

Mehta, Prina; Justo, Lucas; Walsh, Susannah; Arshad, Muhammad S; Wilson, Clive G; O'Sullivan, Ciara K; Moghimi, Seyed M; Vizirianakis, Ioannis S; Avgoustakis, Konstantinos; Fatouros, Dimitris G; Ahmad, Zeeshan

2015-05-01

A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly dissolving polyvinylpyrrolidone (PVP) as the active stabilizing matrix, both sides of ocular lenses were coated using a modified scaled-up masking electrohydrodynamic atomization (EHDA) technique (flow rates variable between 5 and 10 µL/min, applied voltage 4-11 kV). Each side was coated (using a specially designed flip-able well) selectively with a pre-determined morphology and model drug substance. PVP nanoparticles (inner side, to be in contact with the cornea, mean size

Modeling the Radio Foreground for Detection of CMB Spectral Distortions from the Cosmic Dawn and the Epoch of Reionization

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

Sathyanarayana Rao, Mayuri; Subrahmanyan, Ravi; Shankar, N Udaya

Cosmic baryon evolution during the Cosmic Dawn and Reionization results in redshifted 21-cm spectral distortions in the cosmic microwave background (CMB). These encode information about the nature and timing of first sources over redshifts 30–6 and appear at meter wavelengths as a tiny CMB distortion along with the Galactic and extragalactic radio sky, which is orders of magnitude brighter. Therefore, detection requires precise methods to model foregrounds. We present a method of foreground fitting using maximally smooth (MS) functions. We demonstrate the usefulness of MS functions over traditionally used polynomials to separate foregrounds from the Epoch of Reionization (EoR) signal.more » We also examine the level of spectral complexity in plausible foregrounds using GMOSS, a physically motivated model of the radio sky, and find that they are indeed smooth and can be modeled by MS functions to levels sufficient to discern the vanilla model of the EoR signal. We show that MS functions are loss resistant and robustly preserve EoR signal strength and turning points in the residuals. Finally, we demonstrate that in using a well-calibrated spectral radiometer and modeling foregrounds with MS functions, the global EoR signal can be detected with a Bayesian approach with 90% confidence in 10 minutes’ integration.« less

Similar patterns of neural activity predict memory function during encoding and retrieval.

PubMed

Kragel, James E; Ezzyat, Youssef; Sperling, Michael R; Gorniak, Richard; Worrell, Gregory A; Berry, Brent M; Inman, Cory; Lin, Jui-Jui; Davis, Kathryn A; Das, Sandhitsu R; Stein, Joel M; Jobst, Barbara C; Zaghloul, Kareem A; Sheth, Sameer A; Rizzuto, Daniel S; Kahana, Michael J

2017-07-15

Neural networks that span the medial temporal lobe (MTL), prefrontal cortex, and posterior cortical regions are essential to episodic memory function in humans. Encoding and retrieval are supported by the engagement of both distinct neural pathways across the cortex and common structures within the medial temporal lobes. However, the degree to which memory performance can be determined by neural processing that is common to encoding and retrieval remains to be determined. To identify neural signatures of successful memory function, we administered a delayed free-recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We developed multivariate classifiers to identify patterns of spectral power across the brain that independently predicted successful episodic encoding and retrieval. During encoding and retrieval, patterns of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power across the brain predicted successful memory function. Using a cross-decoding approach, we demonstrate the ability to predict memory function across distinct phases of the free-recall task. Furthermore, we demonstrate that classifiers that combine information from both encoding and retrieval states can outperform task-independent models. These findings suggest that the engagement of a core memory network during either encoding or retrieval shapes the ability to remember the past, despite distinct neural interactions that facilitate encoding and retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.

Rotator cuff tear measurement by arthropneumotomography

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

Kilcoyne, R.F.; Matsen, F.A. III

1983-02-01

Five years of experience with a method of shoulder arthrography using upright tomography in cases of suspected or known rotator cuff tears has demonstrated its effectiveness. The value of the procedure lies in its ability to demonstrate the size of the cuff tear and the thickness of the remaining cuff tissue. This information provides the surgeon with a preoperative estimate of the difficulty of the repair and the prognosis for a good functional recovery. In 33 cases, there was good correlation between the upright thin-section tomogram findings and the surgical results. The tomograms provided better information about the size ofmore » the tear and the quality of the remaining cuff than did plain arthrograms.« less

Aurora Kinase B, a novel regulator of TERF1 binding and telomeric integrity

PubMed Central

Chan, Foong Lyn; Vinod, Benjamin; Novy, Karel; Schittenhelm, Ralf B.; Huang, Cheng; Udugama, Maheshi; Nunez-Iglesias, Juan; Lin, Jane I.; Hii, Linda; Chan, Julie; Pickett, Hilda A.; Daly, Roger J.

2017-01-01

Abstract AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation. These findings demonstrate that AURKB is an important regulator of telomere structural integrity. PMID:29040668

Glassy behaviour in simple kinetically constrained models: topological networks, lattice analogues and annihilation-diffusion

NASA Astrophysics Data System (ADS)

Sherrington, David; Davison, Lexie; Buhot, Arnaud; Garrahan, Juan P.

2002-02-01

We report a study of a series of simple model systems with only non-interacting Hamiltonians, and hence simple equilibrium thermodynamics, but with constrained dynamics of a type initially suggested by foams and idealized covalent glasses. We demonstrate that macroscopic dynamical features characteristic of real and more complex model glasses, such as two-time decays in energy and auto-correlation functions, arise from the dynamics and we explain them qualitatively and quantitatively in terms of annihilation-diffusion concepts and theory. The comparison is with strong glasses. We also consider fluctuation-dissipation relations and demonstrate subtleties of interpretation. We find no FDT breakdown when the correct normalization is chosen.

Epigenetic determinants of space radiation-induced cognitive dysfunction

PubMed Central

Acharya, Munjal M.; Baddour, Al Anoud D.; Kawashita, Takumi; Allen, Barrett D.; Syage, Amber R.; Nguyen, Thuan H.; Yoon, Nicole; Giedzinski, Erich; Yu, Liping; Parihar, Vipan K.; Baulch, Janet E.

2017-01-01

Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype. In this study, we have demonstrated a correlation between epigenetic aberrations and adverse effects of space relevant irradiation on cognition. In cognitively impaired irradiated mice we observed increased 5-methylcytosine and 5-hydroxymethylcytosine levels in the hippocampus that coincided with increased levels of the DNA methylating enzymes DNMT3a, TET1 and TET3. By inhibiting methylation using 5-iodotubercidin, we demonstrated amelioration of the epigenetic effects of irradiation. In addition to protecting against those molecular effects of irradiation, 5-iodotubercidin restored behavioral performance to that of unirradiated animals. The findings of this study establish the possibility that neuroepigenetic mechanisms significantly contribute to the functional and structural changes that affect the irradiated brain and cognition. PMID:28220892

Low-dose endotoxemia and human neuropsychological functions.

PubMed

Krabbe, Karen Suárez; Reichenberg, Abraham; Yirmiya, Raz; Smed, Annelise; Pedersen, Bente Klarlund; Bruunsgaard, Helle

2005-09-01

Epidemiological data demonstrate an association between systemic low-grade inflammation defined as 2- to 3-fold increases in circulating inflammatory mediators and age-related decline in cognitive function. However, it is not known whether small elevations of circulating cytokine levels cause direct effects on human neuropsychological functions. We investigated changes in emotional, cognitive, and inflammatory parameters in an experimental in vivo model of low-grade inflammation. In a double-blind crossover study, 12 healthy young males completed neuropsychological tests before as well as 1.5, 6, and 24 h after an intravenous injection of Escherichia coli endotoxin (0.2 ng/kg) or saline in two experimental sessions. Endotoxin administration had no effect on body temperature, cortisol levels, blood pressure or heart rate, but circulating levels of tumor necrosis factor (TNF) and interleukin (IL)-6 increased 2- and 7-fold, respectively, reaching peak values at 3 h, whereas soluble TNF-receptors and IL-1 receptor antagonist peaked at 4.5 h. The neutrophil count increased and the lymphocyte count declined. In this model, low-dose endotoxemia did not affect cognitive performance significantly but declarative memory performance was inversely correlated with cytokine increases. In conclusion, our findings demonstrate a negative association between circulating IL-6 and memory functions during very low-dose endotoxemia independently of physical stress symptoms, and the hypothalamo-pituitary-adrenal axis.

The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+)-dependence of a transient K+ current.

PubMed

Levic, Snezana; Lv, Ping; Yamoah, Ebenezer N

2011-01-01

Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+) current that regulates patterning of action potentials is I(A). This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A) are not normally classified as Ca(2+)-dependent, we demonstrate that throughout the development of chicken hair cells, I(A) is greatly reduced by acute alterations of intracellular Ca(2+). As determinants of spike timing and firing frequency, intracellular Ca(2+) buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A) are tightly regulated by intracellular Ca(2+). Such feedback mechanism between the functional expression of I(A) and intracellular Ca(2+) may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea. © 2011 Levic et al.

Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life

PubMed Central

Weinberg, Marc S.; Michod, Richard E.

2017-01-01

In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3′ end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life. PMID:28989747

Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life

NASA Astrophysics Data System (ADS)

Dhar, Nisha; Weinberg, Marc S.; Michod, Richard E.; Durand, Pierre M.

2017-09-01

In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3' end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life.

Sex-related differences in striatal dopaminergic system after traumatic brain injury.

PubMed

Xu, Xiupeng; Cao, Shengwu; Chao, Honglu; Liu, Yinlong; Ji, Jing

2016-06-01

Several studies have demonstrated alterations in the dopamine (DA) system after traumatic brain injury (TBI). Additionally, the existence of significant sex-related differences in the dopaminergic system has long been recognized. Accordingly, the purpose of the present study was to investigate whether TBI would differentially alter, in female and male mice, the expression and the function of the striatal vesicular monoamine transporter-2 (VMAT-2), an important DA transporter. After controlled cortical impact (CCI) injury, female mice showed significantly lower striatal DA concentrations and K(+)-evoked DA output. By contrast, no significant sex-related differences were observed in the mRNA and protein levels of striatal dopamine transporter (DAT) and VMAT-2 and the methamphetamine (MA)-evoked DA output. These results demonstrated clear sex-related differences in striatal VMAT-2 function in response to TBI and suggested that female mice may be more sensitive to the TBI-induced inhibition of the VMAT-2 function, as indicated by the greater degree of deficits observed when the VMAT-2 DA-storage function was inhibited by TBI. Moreover, the TBI-induced suppression of locomotion was more pronounced than female mice. Such findings highlight the need for sex-specific considerations when examining differences among brain injury conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Using whole-exome sequencing to investigate the genetic bases of lysosomal storage diseases of unknown etiology.

PubMed

Wang, Nan; Zhang, Yeting; Gedvilaite, Erika; Loh, Jui Wan; Lin, Timothy; Liu, Xiuping; Liu, Chang-Gong; Kumar, Dibyendu; Donnelly, Robert; Raymond, Kimiyo; Schuchman, Edward H; Sleat, David E; Lobel, Peter; Xing, Jinchuan

2017-11-01

Lysosomes are membrane-bound, acidic eukaryotic cellular organelles that play important roles in the degradation of macromolecules. Mutations that cause the loss of lysosomal protein function can lead to a group of disorders categorized as the lysosomal storage diseases (LSDs). Suspicion of LSD is frequently based on clinical and pathologic findings, but in some cases, the underlying genetic and biochemical defects remain unknown. Here, we performed whole-exome sequencing (WES) on 14 suspected LSD cases to evaluate the feasibility of using WES for identifying causal mutations. By examining 2,157 candidate genes potentially associated with lysosomal function, we identified eight variants in five genes as candidate disease-causing variants in four individuals. These included both known and novel mutations. Variants were corroborated by targeted sequencing and, when possible, functional assays. In addition, we identified nonsense mutations in two individuals in genes that are not known to have lysosomal function. However, mutations in these genes could have resulted in phenotypes that were diagnosed as LSDs. This study demonstrates that WES can be used to identify causal mutations in suspected LSD cases. We also demonstrate cases where a confounding clinical phenotype may potentially reflect more than one lysosomal protein defect. © 2017 Wiley Periodicals, Inc.

Tumor suppressors Sav/Scrib and oncogene Ras regulate stem cell transformation in adult Drosophila Malpighian Tubules

PubMed Central

Zeng, Xiankun; Singh, Shree Ram; Hou, David; Hou, Steven X.

2012-01-01

An increasing body of evidence suggests that tumors might originate from a few transformed cells that share many properties with normal stem cells. However, it remains unclear how normal stem cells are transformed into cancer stem cells. Here, we demonstrated that mutations causing the loss of tumor suppressor Sav or Scrib or activation of the oncogene Ras transform normal stem cells into cancer stem cells through a multistep process in the adult Drosophila Malpighian Tubules (MTs). In wild-type MTs, each stem cell generates one self-renewing and one differentiating daughter cell. However, in flies with loss-of-function sav or scrib or gain-of-function Ras mutations, both daughter cells grew and behaved like stem cells, leading to the formation of tumors in MTs. Ras functioned downstream of Sav and Scrib in regulating the stem cell transformation. The Ras-transformed stem cells exhibited many of the hallmarks of cancer, such as increased proliferation, reduced cell death, and failure to differentiate. We further demonstrated that several signal transduction pathways (including MEK/MAPK, RhoA, PKA, and TOR) mediate Rasṕ function in the stem cell transformation. Therefore, we have identified a molecular mechanism that regulates stem cell transformation, and this finding may lead to strategies for preventing tumor formation in certain organs. PMID:20432470

New Analytical Solution of the Equilibrium Ampere's Law Using the Walker's Method: a Didactic Example

NASA Astrophysics Data System (ADS)

Sousa, A. N. Laurindo; Ojeda-González, A.; Prestes, A.; Klausner, V.; Caritá, L. A.

2018-02-01

This work aims to demonstrate the analytical solution of the Grad-Shafranov (GS) equation or generalized Ampere's law, which is important in the studies of self-consistent 2.5-D solution for current sheet structures. A detailed mathematical development is presented to obtain the generating function as shown by Walker (RSPSA 91, 410, 1915). Therefore, we study the general solution of the GS equation in terms of the Walker's generating function in details without omitting any step. The Walker's generating function g( ζ) is written in a new way as the tangent of an unspecified function K( ζ). In this trend, the general solution of the GS equation is expressed as exp(- 2Ψ) = 4| K '( ζ)|2/cos2[ K( ζ) - K( ζ ∗)]. In order to investigate whether our proposal would simplify the mathematical effort to find new generating functions, we use Harris's solution as a test, in this case K( ζ) = arctan(exp( i ζ)). In summary, one of the article purposes is to present a review of the Harris's solution. In an attempt to find a simplified solution, we propose a new way to write the GS solution using g( ζ) = tan( K( ζ)). We also present a new analytical solution to the equilibrium Ampere's law using g( ζ) = cosh( b ζ), which includes a generalization of the Harris model and presents isolated magnetic islands.

New Analytical Solution of the Equilibrium Ampere's Law Using the Walker's Method: a Didactic Example

NASA Astrophysics Data System (ADS)

Sousa, A. N. Laurindo; Ojeda-González, A.; Prestes, A.; Klausner, V.; Caritá, L. A.

2017-12-01

This work aims to demonstrate the analytical solution of the Grad-Shafranov (GS) equation or generalized Ampere's law, which is important in the studies of self-consistent 2.5-D solution for current sheet structures. A detailed mathematical development is presented to obtain the generating function as shown by Walker (RSPSA 91, 410, 1915). Therefore, we study the general solution of the GS equation in terms of the Walker's generating function in details without omitting any step. The Walker's generating function g(ζ) is written in a new way as the tangent of an unspecified function K(ζ). In this trend, the general solution of the GS equation is expressed as exp(- 2Ψ) = 4|K '(ζ)|2/cos2[K(ζ) - K(ζ ∗)]. In order to investigate whether our proposal would simplify the mathematical effort to find new generating functions, we use Harris's solution as a test, in this case K(ζ) = arctan(exp(i ζ)). In summary, one of the article purposes is to present a review of the Harris's solution. In an attempt to find a simplified solution, we propose a new way to write the GS solution using g(ζ) = tan(K(ζ)). We also present a new analytical solution to the equilibrium Ampere's law using g(ζ) = cosh(b ζ), which includes a generalization of the Harris model and presents isolated magnetic islands.

Functional connectivity of hippocampal and prefrontal networks during episodic and spatial memory based on real-world environments.

PubMed

Robin, Jessica; Hirshhorn, Marnie; Rosenbaum, R Shayna; Winocur, Gordon; Moscovitch, Morris; Grady, Cheryl L

2015-01-01

Several recent studies have compared episodic and spatial memory in neuroimaging paradigms in order to understand better the contribution of the hippocampus to each of these tasks. In the present study, we build on previous findings showing common neural activation in default network areas during episodic and spatial memory tasks based on familiar, real-world environments (Hirshhorn et al. (2012) Neuropsychologia 50:3094-3106). Following previous demonstrations of the presence of functionally connected sub-networks within the default network, we performed seed-based functional connectivity analyses to determine how, depending on the task, the hippocampus and prefrontal cortex differentially couple with one another and with distinct whole-brain networks. We found evidence for a medial prefrontal-parietal network and a medial temporal lobe network, which were functionally connected to the prefrontal and hippocampal seeds, respectively, regardless of the nature of the memory task. However, these two networks were functionally connected with one another during the episodic memory task, but not during spatial memory tasks. Replicating previous reports of fractionation of the default network into stable sub-networks, this study also shows how these sub-networks may flexibly couple and uncouple with one another based on task demands. These findings support the hypothesis that episodic memory and spatial memory share a common medial temporal lobe-based neural substrate, with episodic memory recruiting additional prefrontal sub-networks. © 2014 Wiley Periodicals, Inc.

Relationship between Structural and Functional Assessment of the Visual System in Mildly Disabled Relapsing-Remitting Multiple Sclerosis Patients

PubMed Central

Huseyinoglu, Nergiz; Ekinci, Metin; Ozben, Serkan; Buyukuysal, Cagatay

2014-01-01

Abstract Studies that explored the anterior visual pathway in the patients with multiple sclerosis (MS) have demonstrated contradictory results about the correlation between structural and functional status of optic nerve and retina. We aimed to investigate the functional and structural findings in our cohort of mildly disabled relapsing-remitting MS patients. A total of 134 eyes (80 eyes of the patients with MS and 54 eyes of the control group) were investigated. Eyes of MS patients were divided into two groups—as eyes with history of optic neuritis (ON group) and without history of optic neuritis (NON group). Ophthalmological investigation including visual evoked potentials, standard automated perimetry, and optical coherence tomography were performed for all participants. Retinal and macular thicknesses were significantly decreased in ON and NON groups compared with controls. Also, visual evoked potential latencies and visual field loss were worse in the both MS groups compared with control group. We did not find any correlation between visual evoked potentials and retinal or macular thickness values but visual field parameters were correlated between retinal and macular layer loss in the NON group. According to our results and some previous studies, although both functional and structural changes were detected in patients with MS, functional status markers do not always show parallelism (or synchrony) with structural changes, especially in eyes with history of optic neuritis. PMID:27928266

Safe Maritime Autonomous Path Planning in a High Sea State

NASA Technical Reports Server (NTRS)

Ono, Masahiro; Quadrelli, Marco; Huntsberger, Terrance L.

2014-01-01

This paper presents a path planning method for sea surface vehicles that prevents capsizing and bow-diving in a high sea-state. A key idea is to use response amplitude operators (RAOs) or, in control terminology, the transfer functions from a sea state to a vessel's motion, in order to find a set of speeds and headings that results in excessive pitch and roll oscillations. This information is translated to arithmetic constraints on the ship's velocity, which are passed to a model predictive control (MPC)-based path planner to find a safe and optimal path that achieves specified goals. An obstacle avoidance capability is also added to the path planner. The proposed method is demonstrated by simulations.

Language lateralization of a bilingual person with epilepsy using a combination of fMRI and neuropsychological assessment findings.

PubMed

O'Grady, Christopher; Omisade, Antonina; Sadler, R Mark

2016-10-01

This report describes the findings of language functional magnetic resonance imaging (fMRI) in a left-handed Urdu and English speaker with right hemisphere-originating epilepsy and unclear language dominance. fMRI is a reliable method for determining hemispheric language dominance in presurgical planning. However, the effects of bilingualism on language activation depend on many factors including age of acquisition and proficiency in the tested language, and morphological properties of the language itself. This case demonstrates that completing fMRI in both spoken languages and interpreting the results within the context of a neuropsychological assessment are essential in arriving at accurate conclusions about language distribution in bilingual patients.

Changes in leadership styles as a function of a four-day leadership training institute for nurse managers: a perspective on continuing education program evaluation.

PubMed

Wolf, M S

1996-01-01

This study measured changes in knowledge acquisition and application of the Hersey and Blanchard model of leadership styles and leadership style adaptability among 144 registered nurses who participated in a four-day management institute. A pre- and post-institute administration of the LEAD-Self instrument was conducted. Although the findings demonstrated a significant change in the participants' leadership styles, the data revealed that outcomes were not as positive as had been assumed based on participants' self-reports. The discussion of findings reveals the complexity and the necessity of measuring learning outcomes for continuing education program improvement.

Tuning thermal conduction via extended defects in graphene

NASA Astrophysics Data System (ADS)

Huang, Huaqing; Xu, Yong; Zou, Xiaolong; Wu, Jian; Duan, Wenhui

2013-05-01

Designing materials for desired thermal conduction can be achieved via extended defects. We theoretically demonstrate the concept by investigating thermal transport in graphene nanoribbons (GNRs) with the extended line defects observed by recent experiments. Our nonequilibrium Green's function study excluding phonon-phonon interactions finds that thermal conductance can be tuned over wide ranges (more than 50% at room temperature), by controlling the orientation and the bond configuration of the embedded extended defect. Further transmission analysis reveals that the thermal-conduction tuning is attributed to two fundamentally different mechanisms, via modifying the phonon dispersion and/or tailoring the strength of defect scattering. The finding, applicable to other materials, provides useful guidance for designing materials with desired thermal conduction.

Channel Capacity Calculation at Large SNR and Small Dispersion within Path-Integral Approach

NASA Astrophysics Data System (ADS)

Reznichenko, A. V.; Terekhov, I. S.

2018-04-01

We consider the optical fiber channel modelled by the nonlinear Shrödinger equation with additive white Gaussian noise. Using Feynman path-integral approach for the model with small dispersion we find the first nonzero corrections to the conditional probability density function and the channel capacity estimations at large signal-to-noise ratio. We demonstrate that the correction to the channel capacity in small dimensionless dispersion parameter is quadratic and positive therefore increasing the earlier calculated capacity for a nondispersive nonlinear optical fiber channel in the intermediate power region. Also for small dispersion case we find the analytical expressions for simple correlators of the output signals in our noisy channel.

How normal is grammatical development in the right hemisphere following hemispherectomy? The root infinitive stage and beyond.

PubMed

Curtiss, Susan; de Bode, Stella

2003-08-01

We examined the morphosyntax of eight left hemispherectomized children at two different stages and compared it to MLU-matched normals. We found that the language of the hemispherectomies paralleled that of their MLU matches with respect to the specific morphosyntactic characteristics of each stage. Our findings provide strong evidence for the presence of functional categories in all early grammars and demonstrate that grammatical development, regardless of its neural substrate, is highly constrained by UG and follows a narrowly determined course. We discuss our findings within a neurobiological framework in which etiology defines the integrity of the remaining hemisphere, which in turn, determines its potential for linguistic reorganization and/or acquisition.

Diffusivity anomaly in modified Stillinger-Weber liquids

NASA Astrophysics Data System (ADS)

Sengupta, Shiladitya; Vasisht, Vishwas V.; Sastry, Srikanth

2014-01-01

By modifying the tetrahedrality (the strength of the three body interactions) in the well-known Stillinger-Weber model for silicon, we study the diffusivity of a series of model liquids as a function of tetrahedrality and temperature at fixed pressure. Previous work has shown that at constant temperature, the diffusivity exhibits a maximum as a function of tetrahedrality, which we refer to as the diffusivity anomaly, in analogy with the well-known anomaly in water upon variation of pressure at constant temperature. We explore to what extent the structural and thermodynamic changes accompanying changes in the interaction potential can help rationalize the diffusivity anomaly, by employing the Rosenfeld relation between diffusivity and the excess entropy (over the ideal gas reference value), and the pair correlation entropy, which provides an approximation to the excess entropy in terms of the pair correlation function. We find that in the modified Stillinger-Weber liquids, the Rosenfeld relation works well above the melting temperatures but exhibits deviations below, with the deviations becoming smaller for smaller tetrahedrality. Further we find that both the excess entropy and the pair correlation entropy at constant temperature go through maxima as a function of the tetrahedrality, thus demonstrating the close relationship between structural, thermodynamic, and dynamical anomalies in the modified Stillinger-Weber liquids.

Effects of Cognitive Training on Resting-State Functional Connectivity of Default Mode, Salience, and Central Executive Networks.

PubMed

Cao, Weifang; Cao, Xinyi; Hou, Changyue; Li, Ting; Cheng, Yan; Jiang, Lijuan; Luo, Cheng; Li, Chunbo; Yao, Dezhong

2016-01-01

Neuroimaging studies have documented that aging can disrupt certain higher cognitive systems such as the default mode network (DMN), the salience network and the central executive network (CEN). The effect of cognitive training on higher cognitive systems remains unclear. This study used a 1-year longitudinal design to explore the cognitive training effect on three higher cognitive networks in healthy older adults. The community-living healthy older adults were divided into two groups: the multi-domain cognitive training group (24 sessions of cognitive training over a 3-months period) and the wait-list control group. All subjects underwent cognitive measurements and resting-state functional magnetic resonance imaging scanning at baseline and at 1 year after the training ended. We examined training-related changes in functional connectivity (FC) within and between three networks. Compared with the baseline, we observed maintained or increased FC within all three networks after training. The scans after training also showed maintained anti-correlation of FC between the DMN and CEN compared to the baseline. These findings demonstrated that cognitive training maintained or improved the functional integration within networks and the coupling between the DMN and CEN in older adults. Our findings suggested that multi-domain cognitive training can mitigate the aging-related dysfunction of higher cognitive networks.

Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity

PubMed Central

Song, Mi-Ryoung; Sun, Yunfu; Bryson, Ami; Gill, Gordon N.; Evans, Sylvia M.; Pfaff, Samuel L.

2009-01-01

Summary LIM transcription factors bind to nuclear LIM interactor (Ldb/NLI/Clim) in specific ratios to form higher-order complexes that regulate gene expression. Here we examined how the dosage of LIM homeodomain proteins Isl1 and Isl2 and LIM-only protein Lmo4 influences the assembly and function of complexes involved in the generation of spinal motor neurons (MNs) and V2a interneurons (INs). Reducing the levels of Islet proteins using a graded series of mutations favored V2a IN differentiation at the expense of MN formation. Although LIM-only proteins (LMOs) are predicted to antagonize the function of Islet proteins, we found that the presence or absence of Lmo4 had little influence on MN or V2a IN specification. We did find, however, that the loss of MNs resulting from reduced Islet levels was rescued by eliminating Lmo4, unmasking a functional interaction between these proteins. Our findings demonstrate that MN and V2a IN fates are specified by distinct complexes that are sensitive to the relative stoichiometries of the constituent factors and we present a model to explain how LIM domain proteins modulate these complexes and, thereby, this binary-cell-fate decision. PMID:19666821

Effects of Cognitive Training on Resting-State Functional Connectivity of Default Mode, Salience, and Central Executive Networks

PubMed Central

Cao, Weifang; Cao, Xinyi; Hou, Changyue; Li, Ting; Cheng, Yan; Jiang, Lijuan; Luo, Cheng; Li, Chunbo; Yao, Dezhong

2016-01-01

Neuroimaging studies have documented that aging can disrupt certain higher cognitive systems such as the default mode network (DMN), the salience network and the central executive network (CEN). The effect of cognitive training on higher cognitive systems remains unclear. This study used a 1-year longitudinal design to explore the cognitive training effect on three higher cognitive networks in healthy older adults. The community-living healthy older adults were divided into two groups: the multi-domain cognitive training group (24 sessions of cognitive training over a 3-months period) and the wait-list control group. All subjects underwent cognitive measurements and resting-state functional magnetic resonance imaging scanning at baseline and at 1 year after the training ended. We examined training-related changes in functional connectivity (FC) within and between three networks. Compared with the baseline, we observed maintained or increased FC within all three networks after training. The scans after training also showed maintained anti-correlation of FC between the DMN and CEN compared to the baseline. These findings demonstrated that cognitive training maintained or improved the functional integration within networks and the coupling between the DMN and CEN in older adults. Our findings suggested that multi-domain cognitive training can mitigate the aging-related dysfunction of higher cognitive networks. PMID:27148042

Altruistic functions for selfish DNA.

PubMed

Faulkner, Geoffrey J; Carninci, Piero

2009-09-15

Mammalian genomes are comprised of 30-50% transposed elements (TEs). The vast majority of these TEs are truncated and mutated fragments of retrotransposons that are no longer capable of transposition. Although initially regarded as important factors in the evolution of gene regulatory networks, TEs are now commonly perceived as neutrally evolving and non-functional genomic elements. In a major development, recent works have strongly contradicted this "selfish DNA" or "junk DNA" dogma by demonstrating that TEs use a host of novel promoters to generate RNA on a massive scale across most eukaryotic cells. This transcription frequently functions to control the expression of protein-coding genes via alternative promoters, cis regulatory non protein-coding RNAs and the formation of double stranded short RNAs. If considered in sum, these findings challenge the designation of TEs as selfish and neutrally evolving genomic elements. Here, we will expand upon these themes and discuss challenges in establishing novel TE functions in vivo.

Flat Engineered Multichannel Reflectors

NASA Astrophysics Data System (ADS)

Asadchy, V. S.; Díaz-Rubio, A.; Tcvetkova, S. N.; Kwon, D.-H.; Elsakka, A.; Albooyeh, M.; Tretyakov, S. A.

2017-07-01

Recent advances in engineered gradient metasurfaces have enabled unprecedented opportunities for light manipulation using optically thin sheets, such as anomalous refraction, reflection, or focusing of an incident beam. Here, we introduce a concept of multichannel functional metasurfaces, which are able to control incoming and outgoing waves in a number of propagation directions simultaneously. In particular, we reveal a possibility to engineer multichannel reflectors. Under the assumption of reciprocity and energy conservation, we find that there exist three basic functionalities of such reflectors: specular, anomalous, and retroreflections. Multichannel response of a general flat reflector can be described by a combination of these functionalities. To demonstrate the potential of the introduced concept, we design and experimentally test three different multichannel reflectors: three- and five-channel retroreflectors and a three-channel power splitter. Furthermore, by extending the concept to reflectors supporting higher-order Floquet harmonics, we forecast the emergence of other multichannel flat devices, such as isolating mirrors, complex splitters, and multi-functional gratings.

Magnetic exchange couplings from noncollinear perturbation theory: dinuclear CuII complexes.

PubMed

Phillips, Jordan J; Peralta, Juan E

2014-08-07

To benchmark the performance of a new method based on noncollinear coupled-perturbed density functional theory [J. Chem. Phys. 138, 174115 (2013)], we calculate the magnetic exchange couplings in a series of triply bridged ferromagnetic dinuclear Cu(II) complexes that have been recently synthesized [Phys. Chem. Chem. Phys. 15, 1966 (2013)]. We find that for any basis-set the couplings from our noncollinear coupled-perturbed methodology are practically identical to those of spin-projected energy-differences when a hybrid density functional approximation is employed. This demonstrates that our methodology properly recovers a Heisenberg description for these systems, and is robust in its predictive power of magnetic couplings. Furthermore, this indicates that the failure of density functional theory to capture the subtle variation of the exchange couplings in these complexes is not simply an artifact of broken-symmetry methods, but rather a fundamental weakness of current approximate density functionals for the description of magnetic couplings.

Kondo effect and enhanced magnetic properties in gadolinium functionalized carbon nanotube supramolecular complex.

PubMed

Ncube, S; Coleman, C; Strydom, A; Flahaut, E; de Sousa, A; Bhattacharyya, S

2018-05-23

We report on the enhancement of magnetic properties of multiwalled carbon nanotubes (MWNTs) functionalized with a gadolinium based supramolecular complex. By employing a newly developed synthesis technique we find that the functionalization method of the nanocomposite enhances the strength of magnetic interaction leading to a large effective moment of 15.79 µ B and non-superparamagnetic behaviour unlike what has been previously reported. Saturating resistance at low temperatures is fitted with the numerical renormalization group formula verifying the Kondo effect for magnetic impurities on a metallic electron system. Magnetoresistance shows devices fabricated from aligned gadolinium functionalized MWNTs (Gd-Fctn-MWNTs) exhibit spin-valve switching behaviour of up to 8%. This study highlights the possibility of enhancing magnetic interactions in carbon systems through chemical modification, moreover we demonstrate the rich physics that might be useful for developing spin based quantum computing elements based on one-dimensional (1D) channels.

Analysis of mammalian gene function through broad based phenotypic screens across a consortium of mouse clinics

PubMed Central

Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl MJ; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie

2015-01-01

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse ES cell knockout resource provides a basis for characterisation of relationships between gene and phenotype. The EUMODIC consortium developed and validated robust methodologies for broad-based phenotyping of knockouts through a pipeline comprising 20 disease-orientated platforms. We developed novel statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no prior functional annotation. We captured data from over 27,000 mice finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. Novel phenotypes were uncovered for many genes with unknown function providing a powerful basis for hypothesis generation and further investigation in diverse systems. PMID:26214591

Dynamic Amygdala Influences on the Fronto-Striatal Brain Mechanisms Involved in Self-Control of Impulsive Desires.

PubMed

Krämer, Bernd; Gruber, Oliver

2015-01-01

Human decisions are guided by a variety of motivational factors, such as immediate rewards, long-term goals, and emotions. We used functional magnetic resonance imaging to investigate the dynamic functional interactions between the amygdala, the nucleus accumbens, and the prefrontal cortex that underlie the influences of emotions, desires, and rationality on human decisions. We found that increased functional connectivity between the amygdala and the nucleus accumbens facilitated the approach of an immediate reward in the presence of emotional information. Further, increased functional interactions of the anteroventral prefrontal cortex with the amygdala and the nucleus accumbens were associated with rational decisions in dilemma situations. These findings support previous animal studies by demonstrating that emotional signals from the amygdala and goal-oriented information from prefrontal cortices interface in the nucleus accumbens to guide human decisions and reward-directed actions. © 2015 S. Karger AG, Basel.

Comparison of Visuospatial and Verbal Abilities in First Psychotic Episode of Schizophrenia Spectrum Disorder: Impact on Global Functioning and Quality of Life

PubMed Central

Rodriguez, Mabel; Spaniel, Filip; Konradova, Lucie; Sedlakova, Katerina; Dvorska, Karolina; Prajsova, Jitka; Kratochvilova, Zuzana; Levcik, David; Vlcek, Kamil; Fajnerova, Iveta

2015-01-01

Objectives: Deficit in visuospatial functions can influence both simple and complex daily life activities. Despite the fact that visuospatial deficit was reported in schizophrenia, research on visuospatial functions as an independent entity is limited. Our study aims to elucidate the impact of visuospatial deficit in comparison with verbal deficit on global functioning and quality of life in the first psychotic episode of schizophrenia spectrum disorder (FES). The significance of clinical symptoms and antipsychotic medication was also studied. Methods: Thirty-six FES patients and a matched group of healthy controls (HC group) were assessed with a neuropsychological battery focused on visuospatial (VIS) and verbal (VERB) functions. Using multiple regression analysis, we evaluated the cumulative effect of VERB and VIS functions, psychiatric symptoms (PANSS) and antipsychotic medication on global functioning (GAF) and quality of life (WHOQOL-BREF) in the FES group. Results: The FES group demonstrated significant impairment both in VIS and VERB cognitive abilities compared to the HC group. Antipsychotic medication did not significantly affect either VIS or VERB functioning. PANSS was not related to cognitive functioning, apart from the Trail Making Test B. In the FES group, the GAF score was significantly affected by the severity of positive symptoms and VERB functioning, explaining together 60% of GAF variability. The severity of negative and positive symptoms affected only the Physical health domain of WHOQOL-BREF. The degree of VERB deficit was associated with both Physical and Psychological health. Although we did not find any relation between VIS functioning, GAF, and WHOQOL-BREF, a paradoxical finding emerged in the Environment quality domain, where a worse quality of the environment was associated with better VIS functioning. Conclusions: Our results suggest that the deficit in VIS functions is an integral part of cognitive deficit in schizophrenia spectrum disorders, rather than a side effect of symptomatology or antipsychotic medication. Moreover, VERB functioning was a better predictor of GAF and WHOQOL-BREF than VIS functioning. Given the findings of negative or missing effect of VIS deficit on WHOQOL-BREF and GAF, the accuracy of these measures in evaluating the impact of global cognitive deficit on everyday life in schizophrenia could be questioned. PMID:26733828

Targeted capture and resequencing of 1040 genes reveal environmentally driven functional variation in grey wolves.

PubMed

Schweizer, Rena M; Robinson, Jacqueline; Harrigan, Ryan; Silva, Pedro; Galverni, Marco; Musiani, Marco; Green, Richard E; Novembre, John; Wayne, Robert K

2016-01-01

In an era of ever-increasing amounts of whole-genome sequence data for individuals and populations, the utility of traditional single nucleotide polymorphisms (SNPs) array-based genome scans is uncertain. We previously performed a SNP array-based genome scan to identify candidate genes under selection in six distinct grey wolf (Canis lupus) ecotypes. Using this information, we designed a targeted capture array for 1040 genes, including all exons and flanking regions, as well as 5000 1-kb nongenic neutral regions, and resequenced these regions in 107 wolves. Selection tests revealed striking patterns of variation within candidate genes relative to noncandidate regions and identified potentially functional variants related to local adaptation. We found 27% and 47% of candidate genes from the previous SNP array study had functional changes that were outliers in sweed and bayenv analyses, respectively. This result verifies the use of genomewide SNP surveys to tag genes that contain functional variants between populations. We highlight nonsynonymous variants in APOB, LIPG and USH2A that occur in functional domains of these proteins, and that demonstrate high correlation with precipitation seasonality and vegetation. We find Arctic and High Arctic wolf ecotypes have higher numbers of genes under selection, which highlight their conservation value and heightened threat due to climate change. This study demonstrates that combining genomewide genotyping arrays with large-scale resequencing and environmental data provides a powerful approach to discern candidate functional variants in natural populations. © 2015 John Wiley & Sons Ltd.

Electrochemical impedance spectroscopy of supercapacitors: A novel analysis approach using evolutionary programming

NASA Astrophysics Data System (ADS)

Oz, Alon; Hershkovitz, Shany; Tsur, Yoed

2014-11-01

In this contribution we present a novel approach to analyze impedance spectroscopy measurements of supercapacitors. Transforming the impedance data into frequency-dependent capacitance allows us to use Impedance Spectroscopy Genetic Programming (ISGP) in order to find the distribution function of relaxation times (DFRT) of the processes taking place in the tested device. Synthetic data was generated in order to demonstrate this technique and a model for supercapacitor ageing process has been obtained.

Longitudinal Associations Between Relationship Quality and Coparenting Across the Transition to Parenthood: A Dyadic Perspective

PubMed Central

Le, Yunying; McDaniel, Brandon T.; Leavitt, Chelom E.; Feinberg, Mark E.

2016-01-01

The couple and coparenting relationship are theorized to influence one another in a reciprocal manner over time. Empirical evidence demonstrates cross-sectional associations between the two as well as prospective predictions of coparenting by relationship quality and vice versa. However, less is known about the longitudinal reciprocity between the couple relationship and coparenting from the perspective of both parents. The current study sought to examine longitudinal associations between relationship quality and coparenting support/undermining across the transition to parenthood from a dyadic perspective. Participants were 164 cohabitating heterosexual couples expecting their first child assessed during pregnancy and at 6 and 36 months after birth. Actor Partner Interdependence Modeling (APIM) was used to examine, for both men and women, (1) stability over time in relationship quality and coparenting; (2) reciprocal associations between relationship quality and coparenting support/undermining; as well as (3) the gender differences in those associations. Moderate rank-order stability in relationship quality and coparenting support/undermining across the first three years of parenthood was demonstrated. For women, but not men, findings suggested longitudinal reciprocal associations between relationship quality and coparenting support/undermining. Specifically, our findings suggested that prenatal relationship quality sets the stage for coparenting functioning after birth for both men and women but that coparenting functioning is then connected to subsequent feelings about the romantic relationship only for women. PMID:27183188

The C. elegans Hox gene egl-5 is required for correct development of the hermaphrodite hindgut and for the response to rectal infection by Microbacterium nematophilum.

PubMed

Nicholas, Hannah R; Hodgkin, Jonathan

2009-05-01

Members of the Hox gene family encode transcription factors that specify positional identity along the anterior-posterior axis of nearly all metazoans. One among the Caenorhabditis elegans Hox genes is egl-5. A deletion allele of egl-5 was isolated in a screen for animals which fail to develop swollen tails when exposed to the bacterial pathogen Microbacterium nematophilum. We show that compromised rectal development, which occurs as a result of loss of egl-5 function, results in a failure of rectal epithelial cells to express the ERK MAP kinase mpk-1, which was previously shown to mediate tail-swelling in response to bacterial infection. Tissue-specific rescue experiments demonstrated that egl-5 and mpk-1 act autonomously in rectal cells in the morphological response. The weak egl-5 allele (n1439), which does not compromise rectal development, fails to affect tail-swelling. We find that this allele carries an inserted repeat element approximately 13.8 kb upstream of the egl-5 open reading frame, which specifically disrupts the cell-specific expression of this gene in HSN egg-laying neurons. Together these findings extend the complexity of regulation and function of Hox genes in C. elegans and demonstrate the importance of their tissue-specific expression for correct development and response to infection.

Mood, body image, fear of kidney failure, life satisfaction, and decisional stability following living kidney donation: Findings from the KDOC study.

PubMed

Rodrigue, J R; Schold, J D; Morrissey, P; Whiting, J; Vella, J; Kayler, L K; Katz, D; Jones, J; Kaplan, B; Fleishman, A; Pavlakis, M; Mandelbrot, D A

2018-06-01

Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Identification of multi-loci hubs from 4C-seq demonstrates the functional importance of simultaneous interactions.

PubMed

Jiang, Tingting; Raviram, Ramya; Snetkova, Valentina; Rocha, Pedro P; Proudhon, Charlotte; Badri, Sana; Bonneau, Richard; Skok, Jane A; Kluger, Yuval

2016-10-14

Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiEκ, 3'Eκ and Edκ, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Identification of multi-loci hubs from 4C-seq demonstrates the functional importance of simultaneous interactions

PubMed Central

Jiang, Tingting; Raviram, Ramya; Snetkova, Valentina; Rocha, Pedro P.; Proudhon, Charlotte; Badri, Sana; Bonneau, Richard; Skok, Jane A.; Kluger, Yuval

2016-01-01

Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiEκ, 3′Eκ and Edκ, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings. PMID:27439714

Distributed patterns of activity in sensory cortex reflect the precision of multiple items maintained in visual short-term memory.

PubMed

Emrich, Stephen M; Riggall, Adam C; Larocque, Joshua J; Postle, Bradley R

2013-04-10

Traditionally, load sensitivity of sustained, elevated activity has been taken as an index of storage for a limited number of items in visual short-term memory (VSTM). Recently, studies have demonstrated that the contents of a single item held in VSTM can be decoded from early visual cortex, despite the fact that these areas do not exhibit elevated, sustained activity. It is unknown, however, whether the patterns of neural activity decoded from sensory cortex change as a function of load, as one would expect from a region storing multiple representations. Here, we use multivoxel pattern analysis to examine the neural representations of VSTM in humans across multiple memory loads. In an important extension of previous findings, our results demonstrate that the contents of VSTM can be decoded from areas that exhibit a transient response to visual stimuli, but not from regions that exhibit elevated, sustained load-sensitive delay-period activity. Moreover, the neural information present in these transiently activated areas decreases significantly with increasing load, indicating load sensitivity of the patterns of activity that support VSTM maintenance. Importantly, the decrease in classification performance as a function of load is correlated with within-subject changes in mnemonic resolution. These findings indicate that distributed patterns of neural activity in putatively sensory visual cortex support the representation and precision of information in VSTM.

Hypothalamic PGC-1α Protects Against High Fat Diet Exposure by Regulating ERα

PubMed Central

Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P.; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F.; Tschöp, Matthias H.; Clegg, Deborah J.

2014-01-01

Summary High fat diets (HFD) lead to obesity and inflammation in the central nervous system. Estrogens and Estrogen Receptor alpha (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity related disease. Here we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of males when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male but not female mice following chronic HFD exposure. Our findings show for the first time that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way. PMID:25373903

Neurocognition in College-Aged Daily Marijuana Users

PubMed Central

Becker, Mary P.; Collins, Paul F.; Luciana, Monica

2014-01-01

Background Marijuana is the most commonly used illicit substance in the United States. Use, particularly when it occurs early, has been associated with cognitive impairments in executive functioning, learning, and memory. Methods This study comprehensively measured cognitive ability as well as comorbid psychopathology and substance use history to determine the neurocognitive profile associated with young adult marijuana use. College-aged marijuana users who initiated use prior to age 17 (n=35) were compared to demographically-matched controls (n=35). Results Marijuana users were high functioning, demonstrating comparable IQs to controls and relatively better processing speed. Marijuana users demonstrated relative cognitive impairments in verbal memory, spatial working memory, spatial planning, and motivated decision-making. Comorbid use of alcohol, which was heavier in marijuana users, was unexpectedly found to be associated with better performance in some of these areas. Conclusions This study provides additional evidence of neurocognitive impairment in the context of adolescent and young adult marijuana use. Findings are discussed in relation to marijuana’s effects on intrinsic motivation and discrete aspects of cognition. PMID:24620756

Asymmetric intramolecular α-cyclopropanation of aldehydes using a donor/acceptor carbene mimetic

PubMed Central

Luo, Chaosheng; Wang, Zhen; Huang, Yong

2015-01-01

Enantioselective α-alkylation of carbonyl is considered as one of the most important processes for asymmetric synthesis. Common alkylation agents, that is, alkyl halides, are notorious substrates for both Lewis acids and organocatalysts. Recently, olefins emerged as a benign alkylating species via photo/radical mechanisms. However, examples of enantioselective alkylation of aldehydes/ketones are scarce and direct asymmetric dialkylation remains elusive. Here we report an intramolecular α-cyclopropanation reaction of olefinic aldehydes to form chiral cyclopropane aldehydes. We demonstrate that an α-iodo aldehyde can function as a donor/acceptor carbene equivalent, which engages in a formal [2+1] annulation with a tethered double bond. Privileged bicyclo[3.1.0]hexane-type scaffolds are prepared in good optical purity using a chiral amine. The synthetic utility of the products is demonstrated by versatile transformations of the bridgehead formyl functionality. We expect the concept of using α-iodo iminium as a donor/acceptor carbene surrogate will find wide applications in chemical reaction development. PMID:26644194

Musical training, bilingualism, and executive function: a closer look at task switching and dual-task performance.

PubMed

Moradzadeh, Linda; Blumenthal, Galit; Wiseheart, Melody

2015-07-01

This study investigated whether musical training and bilingualism are associated with enhancements in specific components of executive function, namely, task switching and dual-task performance. Participants (n = 153) belonging to one of four groups (monolingual musician, bilingual musician, bilingual non-musician, or monolingual non-musician) were matched on age and socioeconomic status and administered task switching and dual-task paradigms. Results demonstrated reduced global and local switch costs in musicians compared with non-musicians, suggesting that musical training can contribute to increased efficiency in the ability to shift flexibly between mental sets. On dual-task performance, musicians also outperformed non-musicians. There was neither a cognitive advantage for bilinguals relative to monolinguals, nor an interaction between music and language to suggest additive effects of both types of experience. These findings demonstrate that long-term musical training is associated with improvements in task switching and dual-task performance. Copyright © 2014 Cognitive Science Society, Inc.

In vivo imaging of kidney glomeruli transplanted into the anterior chamber of the mouse eye

PubMed Central

Kistler, Andreas D.; Caicedo, Alejandro; Abdulreda, Midhat H.; Faul, Christian; Kerjaschki, Dontscho; Berggren, Per-Olof; Reiser, Jochen; Fornoni, Alessia

2014-01-01

Multiphoton microscopy enables live imaging of the renal glomerulus. However, repeated in vivo imaging of the same glomerulus over extended periods of time and the study of glomerular function independent of parietal epithelial and proximal tubular cell effects has not been possible so far. Here, we report a novel approach for non-invasive imaging of acapsular glomeruli transplanted into the anterior chamber of the mouse eye. After microinjection, glomeruli were capable of engrafting on the highly vascularized iris. Glomerular structure was preserved, as demonstrated by podocyte specific expression of cyan fluorescent protein and by electron microscopy. Injection of fluorescence-labeled dextrans of various molecular weights allowed visualization of glomerular filtration and revealed leakage of 70 kDa dextran in an inducible model of proteinuria. Our findings demonstrate functionality and long-term survival of glomeruli devoid of Bowman's capsule and provide a novel approach for non-invasive longitudinal in vivo study of glomerular physiology and pathophysiology. PMID:24464028

Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes

PubMed Central

Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

2016-01-01

Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment. PMID:27272504

mir-125a-5p-mediated Regulation of Lfng is Essential for the Avian Segmentation Clock

PubMed Central

Riley, Maurisa F.; Bochter, Matthew S.; Wahi, Kanu; Nuovo, Gerard J.; Cole, Susan E.

2013-01-01

Summary Somites are embryonic precursors of the axial skeleton and skeletal muscles, and establish the segmental vertebrate body plan. Somitogenesis is controlled in part by a segmentation clock that requires oscillatory expression of genes including Lunatic fringe (Lfng). Oscillatory genes must be tightly regulated both at the transcriptional and post-transcriptional levels for proper clock function. Here we demonstrate that microRNA-mediated regulation of Lfng is essential for proper segmentation during chick somitogenesis. We find that mir-125a-5p targets evolutionarily conserved sequences in the Lfng 3′UTR, and that preventing interactions between mir-125a-5p and Lfng transcripts in vivo causes abnormal segmentation and perturbs clock activity. This provides strong evidence that miRNAs function in the post-transcriptional regulation of oscillatory genes in the segmentation clock. Further, this demonstrates that the relatively subtle effects of miRNAs on target genes can have broad effects in developmental situations that have critical requirements for tight post-transcriptional regulation. PMID:23484856

Investigating paranormal phenomena: Functional brain imaging of telepathy

PubMed Central

Venkatasubramanian, Ganesan; Jayakumar, Peruvumba N; Nagendra, Hongasandra R; Nagaraja, Dindagur; Deeptha, R; Gangadhar, Bangalore N

2008-01-01

Aim: “Telepathy” is defined as “the communication of impressions of any kind from one mind to another, independently of the recognized channels of sense”. Meta-analyses of “ganzfield” studies as well as “card-guessing task” studies provide compelling evidence for the existence of telepathic phenomena. The aim of this study was to elucidate the neural basis of telepathy by examining an individual with this special ability. Materials and Methods: Using functional MRI, we examined a famous “mentalist” while he was performing a telepathic task in a 1.5 T scanner. A matched control subject without this special ability was also examined under similar conditions. Results: The mentalist demonstrated significant activation of the right parahippocampal gyrus after successful performance of a telepathic task. The comparison subject, who did not show any telepathic ability, demonstrated significant activation of the left inferior frontal gyrus. Conclusions: The findings of this study are suggestive of a limbic basis for telepathy and warrant further systematic research. PMID:21829287

No functional role of attention-based rehearsal in maintenance of spatial working memory representations.

PubMed

Belopolsky, Artem V; Theeuwes, Jan

2009-10-01

The present study systematically examined the role of attention in maintenance of spatial representations in working memory as proposed by the attention-based rehearsal hypothesis [Awh, E., Jonides, J., & Reuter-Lorenz, P. A. (1998). Rehearsal in spatial working memory. Journal of Experimental Psychology--Human Perception and Performance, 24(3), 780-790]. Three main issues were examined. First, Experiments 1-3 demonstrated that inhibition and not facilitation of visual processing is often observed at the memorized location during the retention interval. This inhibition was caused by keeping a location in memory and not by the exogenous nature of the memory cue. Second, Experiment 4 showed that inhibition of the memorized location does not lead to any significant impairment in memory accuracy. Finally, Experiment 5 connected current results to the previous findings and demonstrated facilitation of processing at the memorized location. Importantly, facilitation of processing did not lead to more accurate memory performance. The present results challenge the functional role of attention in maintenance of spatial working memory representations.

Pickpocket1 Is an Ionotropic Molecular Sensory Transducer*

PubMed Central

Boiko, Nina; Kucher, Volodymyr; Stockand, James D.; Eaton, Benjamin A.

2012-01-01

The molecular transformation of an external stimulus into changes in sensory neuron activity is incompletely described. Although a number of molecules have been identified that can respond to stimuli, evidence that these molecules can transduce stimulation into useful neural activity is lacking. Here we demonstrate that pickpocket1 (ppk1), a Drosophila homolog of mammalian Degenerin/epithelial sodium channels, encodes an acid-sensing sodium channel that conducts a transient depolarizing current in multidendritic sensory neurons of Drosophila melanogaster. Stimulation of Ppk1 is sufficient to bring these sensory neurons to threshold, eliciting a burst of action potentials. The transient nature of the neural activity produced by Ppk1 activation is the result of Ppk1 channel gating properties. This model is supported by the observation of enhanced bursting activity in neurons expressing a gain of function ppk1 mutant harboring the degenerin mutation. These findings demonstrate that Ppk1 can function as an ionotropic molecular sensory transducer capable of transforming the perception of a stimulus into phasic neuronal activity in sensory neurons. PMID:23033486

Taiman acts as a coactivator of Yorkie in the Hippo pathway to promote tissue growth and intestinal regeneration.

PubMed

Wang, Chao; Yin, Meng-Xin; Wu, Wei; Dong, Liang; Wang, Shimin; Lu, Yi; Xu, Jinjin; Wu, Wenqing; Li, Sheng; Zhao, Yun; Zhang, Lei

2016-01-01

The Hippo signaling pathway regulates tissue growth and organ size through controlling cell growth, proliferation and apoptosis. During these processes, the coactivator Yorkie partners with the transcription factor Scalloped to mediate Hippo pathway-regulated cellular functions. Here, we demonstrate that Taiman facilitates the activity of Yorkie. First, Taiman overexpression upregulates Hippo pathway-responsive genes and induces tissue overgrowth. Second, the loss of tai downregulates the expression of Hippo pathway target genes and reduces organ size as well as tissue overgrowth caused by Yorkie overexpression. Furthermore, we provide evidence that Taiman binds to Yorkie and facilitates the activity of Yorkie-Scalloped to activate the transcription of several Hippo pathway target genes. Moreover, we found that the C-terminus of Taiman is indispensable for the function of Taiman in Hippo signaling. Finally, we demonstrate that Taiman is also required in intestinal stem cell proliferation. Our findings suggest Taiman is an essential coactivator of Yorkie.

Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes.

PubMed

Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

2016-06-07

Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment.

Mimicking Neurotransmitter Release in Chemical Synapses via Hysteresis Engineering in MoS2 Transistors.

PubMed

Arnold, Andrew J; Razavieh, Ali; Nasr, Joseph R; Schulman, Daniel S; Eichfeld, Chad M; Das, Saptarshi

2017-03-28

Neurotransmitter release in chemical synapses is fundamental to diverse brain functions such as motor action, learning, cognition, emotion, perception, and consciousness. Moreover, improper functioning or abnormal release of neurotransmitter is associated with numerous neurological disorders such as epilepsy, sclerosis, schizophrenia, Alzheimer's disease, and Parkinson's disease. We have utilized hysteresis engineering in a back-gated MoS 2 field effect transistor (FET) in order to mimic such neurotransmitter release dynamics in chemical synapses. All three essential features, i.e., quantal, stochastic, and excitatory or inhibitory nature of neurotransmitter release, were accurately captured in our experimental demonstration. We also mimicked an important phenomenon called long-term potentiation (LTP), which forms the basis of human memory. Finally, we demonstrated how to engineer the LTP time by operating the MoS 2 FET in different regimes. Our findings could provide a critical component toward the design of next-generation smart and intelligent human-like machines and human-machine interfaces.

A robust molecular probe for Ångstrom-scale analytics in liquids

PubMed Central

Nirmalraj, Peter; Thompson, Damien; Dimitrakopoulos, Christos; Gotsmann, Bernd; Dumcenco, Dumitru; Kis, Andras; Riel, Heike

2016-01-01

Traditionally, nanomaterial profiling using a single-molecule-terminated scanning probe is performed at the vacuum–solid interface often at a few Kelvin, but is not a notion immediately associated with liquid–solid interface at room temperature. Here, using a scanning tunnelling probe functionalized with a single C60 molecule stabilized in a high-density liquid, we resolve low-dimensional surface defects, atomic interfaces and capture Ångstrom-level bond-length variations in single-layer graphene and MoS2. Atom-by-atom controllable imaging contrast is demonstrated at room temperature and the electronic structure of the C60–metal probe complex within the encompassing liquid molecules is clarified using density functional theory. Our findings demonstrates that operating a robust single-molecular probe is not restricted to ultra-high vacuum and cryogenic settings. Hence the scope of high-precision analytics can be extended towards resolving sub-molecular features of organic elements and gauging ambient compatibility of emerging layered materials with atomic-scale sensitivity under experimentally less stringent conditions. PMID:27516157

Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα.

PubMed

Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P; Li, Dan L; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F; Tschöp, Matthias H; Clegg, Deborah J

2014-10-23

High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor α (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis

PubMed Central

Stein, Sokrates; Lohmann, Christine; Schäfer, Nicola; Hofmann, Janin; Rohrer, Lucia; Besler, Christian; Rothgiesser, Karin M.; Becher, Burkhard; Hottiger, Michael O.; Borén, Jan; McBurney, Michael W.; Landmesser, Ulf; Lüscher, Thomas F.; Matter, Christian M.

2010-01-01

Aims Endothelial activation, macrophage infiltration, and foam cell formation are pivotal steps in atherogenesis. Our aim in this study was to analyse the role of SIRT1, a class III deacetylase with important metabolic functions, in plaque macrophages and atherogenesis. Methods and results Using partial SIRT1 deletion in atherosclerotic mice, we demonstrate that SIRT1 protects against atherosclerosis by reducing macrophage foam cell formation. Peritoneal macrophages from heterozygous SIRT1 mice accumulate more oxidized low-density lipoprotein (oxLDL), thereby promoting foam cell formation. Bone marrow-restricted SIRT1 deletion confirmed that SIRT1 function in macrophages is sufficient to decrease atherogenesis. Moreover, we show that SIRT1 reduces the uptake of oxLDL by diminishing the expression of lectin-like oxLDL receptor-1 (Lox-1) via suppression of the NF-κB signalling pathway. Conclusion Our findings demonstrate protective effects of SIRT1 in atherogenesis and suggest pharmacological SIRT1 activation as a novel anti-atherosclerotic strategy by reducing macrophage foam cell formation. PMID:20418343

Suppression of autophagy impedes glioblastoma development and induces senescence.

PubMed

Gammoh, Noor; Fraser, Jane; Puente, Cindy; Syred, Heather M; Kang, Helen; Ozawa, Tatsuya; Lam, Du; Acosta, Juan Carlos; Finch, Andrew J; Holland, Eric; Jiang, Xuejun

2016-09-01

The function of macroautophagy/autophagy during tumor initiation or in established tumors can be highly distinct and context-dependent. To investigate the role of autophagy in gliomagenesis, we utilized a KRAS-driven glioblastoma mouse model in which autophagy is specifically disrupted via RNAi against Atg7, Atg13 or Ulk1. Inhibition of autophagy strongly reduced glioblastoma development, demonstrating its critical role in promoting tumor formation. Further supporting this finding is the observation that tumors originating from Atg7-shRNA injections escaped the knockdown effect and thereby still underwent functional autophagy. In vitro, autophagy inhibition suppressed the capacity of KRAS-expressing glial cells to form oncogenic colonies or to survive low serum conditions. Molecular analyses revealed that autophagy-inhibited glial cells were unable to maintain active growth signaling under growth-restrictive conditions and were prone to undergo senescence. Overall, these results demonstrate that autophagy is crucial for glioma initiation and growth, and is a promising therapeutic target for glioblastoma treatment.

Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation.

PubMed

Kanda, Keitaro; Sakamoto, Jiro; Matsumoto, Yoshihide; Ikuta, Kozo; Goto, Norihiro; Morita, Yusuke; Ohno, Mikiko; Nishi, Kiyoto; Eto, Koji; Kimura, Yuto; Nakanishi, Yuki; Ikegami, Kanako; Yoshikawa, Takaaki; Fukuda, Akihisa; Kawada, Kenji; Sakai, Yoshiharu; Ito, Akihiro; Yoshida, Minoru; Kimura, Takeshi; Chiba, Tsutomu; Nishi, Eiichiro; Seno, Hiroshi

2018-04-19

Colon cancer is a complex disease affected by a combination of genetic and epigenetic factors. Here we demonstrate that nardilysin (N-arginine dibasic convertase; NRDC), a metalloendopeptidase of the M16 family, regulates intestinal tumorigenesis via its nuclear functions. NRDC is highly expressed in human colorectal cancers. Deletion of the Nrdc gene in ApcMin mice crucially suppressed intestinal tumor development. In ApcMin mice, epithelial cell-specific deletion of Nrdc recapitulated the tumor suppression observed in Nrdc-null mice. Moreover, epithelial cell-specific overexpression of Nrdc significantly enhanced tumor formation in ApcMin mice. Notably, epithelial NRDC controlled cell apoptosis in a gene dosage-dependent manner. In human colon cancer cells, nuclear NRDC directly associated with HDAC1, and controlled both acetylation and stabilization of p53, with alterations of p53 target apoptotic factors. These findings demonstrate that NRDC is critically involved in intestinal tumorigenesis through its epigenetic regulatory function, and targeting NRDC may lead to a novel prevention or therapeutic strategy against colon cancer.

The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus.

PubMed

Martin, E Anne; Muralidhar, Shruti; Wang, Zhirong; Cervantes, Diégo Cordero; Basu, Raunak; Taylor, Matthew R; Hunter, Jennifer; Cutforth, Tyler; Wilke, Scott A; Ghosh, Anirvan; Williams, Megan E

2015-11-17

Synaptic target specificity, whereby neurons make distinct types of synapses with different target cells, is critical for brain function, yet the mechanisms driving it are poorly understood. In this study, we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber (MF) synapses, which connect dentate granule (DG) neurons to both CA3 and GABAergic neurons. Here, we show Kirrel3 is required for formation of MF filopodia; the structures that give rise to DG-GABA synapses and that regulate feed-forward inhibition of CA3 neurons. Consequently, loss of Kirrel3 robustly increases CA3 neuron activity in developing mice. Alterations in the Kirrel3 gene are repeatedly associated with intellectual disabilities, but the role of Kirrel3 at synapses remained largely unknown. Our findings demonstrate that subtle synaptic changes during development impact circuit function and provide the first insight toward understanding the cellular basis of Kirrel3-dependent neurodevelopmental disorders.

HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2.

PubMed

Metzler, M; Legendre-Guillemin, V; Gan, L; Chopra, V; Kwok, A; McPherson, P S; Hayden, M R

2001-10-19

Polyglutamine expansion in huntingtin is the underlying mutation leading to neurodegeneration in Huntington disease. This mutation influences the interaction of huntingtin with different proteins, including huntingtin-interacting protein 1 (HIP1), in which affinity to bind to mutant huntingtin is profoundly reduced. Here we demonstrate that HIP1 colocalizes with markers of clathrin-mediated endocytosis in neuronal cells and is highly enriched on clathrin-coated vesicles (CCVs) purified from brain homogenates. HIP1 binds to the clathrin adaptor protein 2 (AP2) and the terminal domain of the clathrin heavy chain, predominantly through a small fragment encompassing amino acids 276-335. This region, which contains consensus clathrin- and AP2-binding sites, functions in conjunction with the coiled-coil domain to target HIP1 to CCVs. Expression of various HIP1 fragments leads to a potent block of clathrin-mediated endocytosis. Our findings demonstrate that HIP1 is a novel component of the endocytic machinery.

Residual Neurocognitive Features of Long-Term Ecstasy Users With Minimal Exposure to Other Drugs

PubMed Central

Halpern, John H.; Sherwood, Andrea R.; Hudson, James I.; Gruber, Staci; Kozin, David; Pope, Harrison G.

2010-01-01

Aims In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias. Design We compared illicit ecstasy users and non-users while 1) excluding individuals with significant lifetime exposure to other illicit drugs or alcohol; 2) requiring that all participants be members of the “rave” subculture; and 3) testing all participants with breath, urine, and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables, and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons. Setting Field study. Participants Fifty-two illicit ecstasy users and 59 non-users, age 18-45. Measurements Battery of 15 neuropsychological tests tapping a range of cognitive functions. Findings We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity. However this finding might have reflected a premorbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings—including our own—and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users. PMID:21205042

The ABCs of flower development: mutational analysis of AP1/FUL-like genes in rice provides evidence for a homeotic (A)-function in grasses.

PubMed

Wu, Feng; Shi, Xiaowei; Lin, Xuelei; Liu, Yuan; Chong, Kang; Theißen, Günter; Meng, Zheng

2017-01-01

The well-known ABC model describes the combinatorial interaction of homeotic genes in specifying floral organ identities. While the B- and C-functions are highly conserved throughout flowering plants and even in gymnosperms, the A-function, which specifies the identity of perianth organs (sepals and petals in eudicots), remains controversial. One reason for this is that in most plants that have been investigated thus far, with Arabidopsis being a remarkable exception, one does not find recessive mutants in which the identity of both types of perianth organs is affected. Here we report a comprehensive mutational analysis of all four members of the AP1/FUL-like subfamily of MADS-box genes in rice (Oryza sativa). We demonstrate that OsMADS14 and OsMADS15, in addition to their function of specifying meristem identity, are also required to specify palea and lodicule identities. Because these two grass-specific organs are very likely homologous to sepals and petals of eudicots, respectively, we conclude that there is a floral homeotic (A)-function in rice as defined previously. Together with other recent findings, our data suggest that AP1/FUL-like genes were independently recruited to fulfil the (A)-function in grasses and some eudicots, even though other scenarios cannot be excluded and are discussed. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures

PubMed Central

Bohlen, Christopher J.; Bennett, F. Chris; Tucker, Andrew F.; Collins, Hannah Y.; Mulinyawe, Sara B.; Barres, Ben A.

2017-01-01

Summary Microglia, the resident macrophages of the central nervous system (CNS), engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol. Using microglial cultures that have never been exposed to serum, we demonstrate a dramatic and lasting change in phagocytic capacity after serum exposure. Finally, we find that mature microglia rapidly lose signature gene expression after isolation, and that this loss can be reversed by engrafting cells back into an intact CNS environment. These data indicate that the specialized gene expression profile of mature microglia requires continuous instructive signaling from the intact CNS. PMID:28521131

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

Ichikawa, Akie; Matsuoka, Yoshiki, E-mail: ichikawa@cosmos.phys.sci.ehime-u.ac.jp

We present a new analysis of the stellar mass function and morphology of recently quenched galaxies (RQGs), whose star formation has been recently quenched for some reason. The COSMOS2015 catalog was exploited to select those galaxies at 0.2 < z < 4.8, over 1.5 deg{sup 2} of the Cosmic Evolution Survey (COSMOS) UltraVISTA field. This is the first time that RQGs are consistently selected and studied in such a wide range of redshift. We find increasing number density of RQGs with time in a broad mass range at z > 1, while low-mass RQGs start to grow very rapidly atmore » z < 1. We also demonstrate that the migration of RQGs may largely drive the evolution of the stellar mass function of passive galaxies. Moreover, we find that the morphological type distribution of RQGs are intermediate between those of star-forming and passive galaxies. These results indicate that RQGs represent a major transitional phase of galaxy evolution, in which star-forming galaxies turn into passive galaxies, accompanied by the build up of spheroidal component.« less

Disk storage management for LHCb based on Data Popularity estimator

NASA Astrophysics Data System (ADS)

Hushchyn, Mikhail; Charpentier, Philippe; Ustyuzhanin, Andrey

2015-12-01

This paper presents an algorithm providing recommendations for optimizing the LHCb data storage. The LHCb data storage system is a hybrid system. All datasets are kept as archives on magnetic tapes. The most popular datasets are kept on disks. The algorithm takes the dataset usage history and metadata (size, type, configuration etc.) to generate a recommendation report. This article presents how we use machine learning algorithms to predict future data popularity. Using these predictions it is possible to estimate which datasets should be removed from disk. We use regression algorithms and time series analysis to find the optimal number of replicas for datasets that are kept on disk. Based on the data popularity and the number of replicas optimization, the algorithm minimizes a loss function to find the optimal data distribution. The loss function represents all requirements for data distribution in the data storage system. We demonstrate how our algorithm helps to save disk space and to reduce waiting times for jobs using this data.

Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures.

PubMed

Bohlen, Christopher J; Bennett, F Chris; Tucker, Andrew F; Collins, Hannah Y; Mulinyawe, Sara B; Barres, Ben A

2017-05-17

Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol. Using microglial cultures that have never been exposed to serum, we demonstrate a dramatic and lasting change in phagocytic capacity after serum exposure. Finally, we find that mature microglia rapidly lose signature gene expression after isolation, and that this loss can be reversed by engrafting cells back into an intact CNS environment. These data indicate that the specialized gene expression profile of mature microglia requires continuous instructive signaling from the intact CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical Forces Program the Orientation of Cell Division during Airway Tube Morphogenesis.

PubMed

Tang, Zan; Hu, Yucheng; Wang, Zheng; Jiang, Kewu; Zhan, Cheng; Marshall, Wallace F; Tang, Nan

2018-02-05

Oriented cell division plays a key role in controlling organogenesis. The mechanisms for regulating division orientation at the whole-organ level are only starting to become understood. By combining 3D time-lapse imaging, mouse genetics, and mathematical modeling, we find that global orientation of cell division is the result of a combination of two types of spindles with distinct spindle dynamic behaviors in the developing airway epithelium. Fixed spindles follow the classic long-axis rule and establish their division orientation before metaphase. In contrast, rotating spindles do not strictly follow the long-axis rule and determine their division orientation during metaphase. By using both a cell-based mechanical model and stretching-lung-explant experiments, we showed that mechanical force can function as a regulatory signal in maintaining the stable ratio between fixed spindles and rotating spindles. Our findings demonstrate that mechanical forces, cell geometry, and oriented cell division function together in a highly coordinated manner to ensure normal airway tube morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Beauty at the ballot box: disease threats predict preferences for physically attractive leaders.

PubMed

White, Andrew Edward; Kenrick, Douglas T; Neuberg, Steven L

2013-12-01

Why does beauty win out at the ballot box? Some researchers have posited that it occurs because people ascribe generally positive characteristics to physically attractive candidates. We propose an alternative explanation-that leadership preferences are related to functional disease-avoidance mechanisms. Because physical attractiveness is a cue to health, people concerned with disease should especially prefer physically attractive leaders. Using real-world voting data and laboratory-based experiments, we found support for this relationship. In congressional districts with elevated disease threats, physically attractive candidates are more likely to be elected (Study 1). Experimentally activating disease concerns leads people to especially value physical attractiveness in leaders (Study 2) and prefer more physically attractive political candidates (Study 3). In a final study, we demonstrated that these findings are related to leadership preferences, specifically, rather than preferences for physically attractive group members more generally (Study 4). Together, these findings highlight the nuanced and functional nature of leadership preferences.

Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking

PubMed Central

Voelzmann, Andre; Okenve-Ramos, Pilar; Qu, Yue; Chojnowska-Monga, Monika; del Caño-Espinel, Manuela; Prokop, Andreas; Sanchez-Soriano, Natalia

2016-01-01

The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease. DOI: http://dx.doi.org/10.7554/eLife.14694.001 PMID:27501441

Industrial ammonia gassing

PubMed Central

Walton, M.

1973-01-01

Walton, M. (1972).British Journal of Industrial Medicine,30, 78-86. Industrial ammonia gassing. Seven cases of ammonia gassing are described with follow-up for five years of the six survivors and the post-mortem findings of the fatal case. All the survivors attributed continuing symptoms to the gassing. The study failed to demonstrate permanent ill effects in the one case of mild exposure. Of the more serious cases one has stopped smoking and taken up physical training teaching. He now has above average lung function. Two serious cases who continued to smoke have the lung function abnormalities expected from their smoking. In the other two seriously exposed cases, who also continued to smoke, there is a persistent reduction in ventilation and gas transfer which seems to be due to the ammonia gassing. The post-mortem findings in the fatal case showed acute congestion and oedema of the mucosa of the respiratory tract, the bronchial walls being stripped of their lining epithelium and the alveoli stuffed with red blood cells and oedema fluid. Images PMID:4685304

The dissociation of video head impulse test (vHIT) and bithermal caloric test results provide topological localization of vestibular system impairment in patients with "definite" Ménière's disease.

PubMed

McCaslin, Devin L; Rivas, Alejandro; Jacobson, Gary P; Bennett, Marc L

2015-03-01

We report 3 patients with Ménière's disease and describe how the combination of audiometry, video head impulse testing, and caloric results may prove helpful in the diagnosis of Ménière's disease. Three patients with "definite" Ménière's disease were evaluated in a tertiary care medical center. Each patient underwent videonystagmography, horizontal canal video head impulse testing, and audiometry. All 3 patients demonstrated moderate, flat, sensorineural hearing losses; significant caloric asymmetries; and bilaterally normal video head impulse testing. This pattern of findings suggests differential preservation of high-frequency function (video head impulse testing) with impairment of low-frequency function (unilaterally abnormal caloric test results) in these patients. Ipsilesional abnormal caloric testing in the presence of normal video head impulse testing is a pattern of findings observed in a cohort of patients who have "definite" Ménière's disease.

The Ldb1 and Ldb2 Transcriptional Cofactors Interact with the Ste20-like Kinase SLK and Regulate Cell Migration

PubMed Central

Storbeck, Chris J.; Wagner, Simona; O'Reilly, Paul; McKay, Marlene; Parks, Robin J.; Westphal, Heiner

2009-01-01

Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses, and tissue repair. Here, we show that the microtubule-associated Ste20 kinase SLK, required for cell migration, interacts with the LIM domain binding transcriptional cofactor proteins Ldb1/CLIM2 and Ldb2/CLIM1/NLI. We demonstrate that Ldb1 and 2 bind directly to the SLK carboxy-terminal AT1-46 homology domain in vitro and in vivo. We find that Ldb1 and -2 colocalize with SLK in migrating cells and that both knockdown and overexpression of either factor results in increased motility. Supporting this, knockdown of Ldb1 increases focal adhesion turnover and enhances migration in fibroblasts. We propose that Ldb1/2 function to maintain SLK in an inactive state before its activation. These findings highlight a novel function for Ldb1 and -2 and expand their role to include the control of cell migration. PMID:19675209

Incorporating Religiosity into a Developmental Model of Positive Family Functioning across Generations

PubMed Central

Spilman, Sarah K.; Neppl, Tricia K.; Donnellan, M. Brent; Schofield, Thomas J.; Conger, Rand D.

2012-01-01

This study evaluated a developmental model of intergenerational continuity in religiosity and its association with observed competency in romantic and parent-child relationships across two generations. Using multi-informant data from the Family Transitions Project, a 20-year longitudinal study of families that began during early adolescence (N = 451), we found that parental religiosity assessed during the youth’s adolescence was positively related to the youth’s own religiosity during adolescence which, in turn, predicted their religiosity after the transition to adulthood. The findings also supported the theoretical model guiding the study, which proposes that religiosity acts as a personal resource that will be uniquely and positively associated with the quality of family relationships. Especially important, the findings demonstrate support for the role of religiosity in a developmental process that promotes positive family functioning after addressing earlier methodological limitations in this area of study, such as cross-sectional research designs, single informant measurement, retrospective reports, and the failure to control for other individual differences. PMID:22545832

Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium

PubMed Central

Barron, Melissa L; Rybchyn, Mark S; Ramesh, Sutharshani; Mason, Rebecca S; Fiona Bonar, S; Stalley, Paul; Khosla, Sundeep; Hudson, Bernie; Arthur, Christopher; Kim, Edward; Clifton-Bligh, Roderick J; Clifton-Bligh, Phillip B

2017-01-01

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient’s osteoblasts in culture. When normal osteoblasts were cultured with the patient’s serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function. PMID:28326223

Cortical depth dependent population receptive field attraction by spatial attention in human V1.

PubMed

Klein, Barrie P; Fracasso, Alessio; van Dijk, Jelle A; Paffen, Chris L E; Te Pas, Susan F; Dumoulin, Serge O

2018-04-27

Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions. Copyright © 2018. Published by Elsevier Inc.

SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy.

PubMed

Goldstein, Jeffery A; Kelly, Sean M; LoPresti, Peter P; Heydemann, Ahlke; Earley, Judy U; Ferguson, Edwin L; Wolf, Matthew J; McNally, Elizabeth M

2011-03-01

Loss-of-function mutations in the genes encoding dystrophin and the associated membrane proteins, the sarcoglycans, produce muscular dystrophy and cardiomyopathy. The dystrophin complex provides stability to the plasma membrane of striated muscle during muscle contraction. Increased SMAD signaling due to activation of the transforming growth factor-β (TGFβ) pathway has been described in muscular dystrophy; however, it is not known whether this canonical TGFβ signaling is pathogenic in the muscle itself. Drosophila deleted for the γ/δ-sarcoglycan gene (Sgcd) develop progressive muscle and heart dysfunction and serve as a model for the human disorder. We used dad-lacZ flies to demonstrate the signature of TGFβ activation in response to exercise-induced injury in Sgcd null flies, finding that those muscle nuclei immediately adjacent to muscle injury demonstrate high-level TGFβ signaling. To determine the pathogenic nature of this signaling, we found that partial reduction of the co-SMAD Medea, homologous to SMAD4, or the r-SMAD, Smox, corrected both heart and muscle dysfunction in Sgcd mutants. Reduction in the r-SMAD, MAD, restored muscle function but interestingly not heart function in Sgcd mutants, consistent with a role for activin but not bone morphogenic protein signaling in cardiac dysfunction. Mammalian sarcoglycan null muscle was also found to exhibit exercise-induced SMAD signaling. These data demonstrate that hyperactivation of SMAD signaling occurs in response to repetitive injury in muscle and heart. Reduction of this pathway is sufficient to restore cardiac and muscle function and is therefore a target for therapeutic reduction.

SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy

PubMed Central

Goldstein, Jeffery A.; Kelly, Sean M.; LoPresti, Peter P.; Heydemann, Ahlke; Earley, Judy U.; Ferguson, Edwin L.; Wolf, Matthew J.; McNally, Elizabeth M.

2011-01-01

Loss-of-function mutations in the genes encoding dystrophin and the associated membrane proteins, the sarcoglycans, produce muscular dystrophy and cardiomyopathy. The dystrophin complex provides stability to the plasma membrane of striated muscle during muscle contraction. Increased SMAD signaling due to activation of the transforming growth factor-β (TGFβ) pathway has been described in muscular dystrophy; however, it is not known whether this canonical TGFβ signaling is pathogenic in the muscle itself. Drosophila deleted for the γ/δ-sarcoglycan gene (Sgcd) develop progressive muscle and heart dysfunction and serve as a model for the human disorder. We used dad-lacZ flies to demonstrate the signature of TGFβ activation in response to exercise-induced injury in Sgcd null flies, finding that those muscle nuclei immediately adjacent to muscle injury demonstrate high-level TGFβ signaling. To determine the pathogenic nature of this signaling, we found that partial reduction of the co-SMAD Medea, homologous to SMAD4, or the r-SMAD, Smox, corrected both heart and muscle dysfunction in Sgcd mutants. Reduction in the r-SMAD, MAD, restored muscle function but interestingly not heart function in Sgcd mutants, consistent with a role for activin but not bone morphogenic protein signaling in cardiac dysfunction. Mammalian sarcoglycan null muscle was also found to exhibit exercise-induced SMAD signaling. These data demonstrate that hyperactivation of SMAD signaling occurs in response to repetitive injury in muscle and heart. Reduction of this pathway is sufficient to restore cardiac and muscle function and is therefore a target for therapeutic reduction. PMID:21138941

Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram

PubMed Central

Neigh, Gretchen N.; Nemeth, Christina L; Kelly, Sean D.; Hardy, Emily E.; Bourke, Chase; Stowe, Zachary N.; Owens, Michael J.

2016-01-01

Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function. PMID:27422674

The Transcription Factor p53 Influences Microglial Activation Phenotype

PubMed Central

Jayadev, Suman; Nesser, Nicole K.; Hopkins, Stephanie; Myers, Scott J.; Case, Amanda; Lee, Rona J.; Seaburg, Luke A.; Uo, Takuma; Murphy, Sean P.; Morrison, Richard S.; Garden, Gwenn A.

2011-01-01

Several neurodegenerative diseases are influenced by the innate immune response in the central nervous system (CNS). Microglia, have pro-inflammatory and subsequently neurotoxic actions as well as anti-inflammatory functions that promote recovery and repair. Very little is known about the transcriptional control of these specific microglial behaviors. We have previously shown that in HIV associated neurocognitive disorders (HAND), the transcription factor p53 accumulates in microglia and that microglial p53 expression is required for the in vitro neurotoxicity of the HIV coat glycoprotein gp120. These findings suggested a novel function for p53 in regulating microglial activation. Here we report that in the absence of p53, microglia demonstrate a blunted response to interferon-γ, failing to increase expression of genes associated with classical macrophage activation or secrete pro-inflammatory cytokines. Microarray analysis of global gene expression profiles revealed increased expression of genes associated with anti-inflammatory functions, phagocytosis and tissue repair in p53 knockout (p53−/−) microglia compared with those cultured from strain matched p53 expressing (p53+/+) mice. We further observed that p53−/− microglia demonstrate increased phagocytic activity in vitro and expression of markers for alternative macrophage activation both in vitro and in vivo. In HAND brain tissue, the alternative activation marker CD163 was expressed in a separate subset of microglia than those demonstrating p53 accumulation. These data suggest that p53 influences microglial behavior, supporting the adoption of a pro-inflammatory phenotype, while p53 deficiency promotes phagocytosis and gene expression associated with alternative activation and anti-inflammatory functions. PMID:21598312

Fife, a Drosophila Piccolo-RIM Homolog, Promotes Active Zone Organization and Neurotransmitter Release

PubMed Central

Bruckner, Joseph J.; Gratz, Scott J.; Slind, Jessica K.; Geske, Richard R.; Cummings, Alexander M.; Galindo, Samantha E.; Donohue, Laura K.; O'Connor-Giles, Kate M.

2012-01-01

Neuronal communication depends on the precisely orchestrated release of neurotransmitter at specialized sites called active zones (AZs). A small number of scaffolding and cytoskeletal proteins comprising the cytomatrix of the active zone (CAZ) are thought to organize the architecture and functional properties of AZs. The majority of CAZ proteins are evolutionarily conserved, underscoring the fundamental similarities in neurotransmission at all synapses. However, core CAZ proteins Piccolo and Bassoon have long been believed exclusive to vertebrates, raising intriguing questions about the conservation of the molecular mechanisms that regulate presynaptic properties. Here, we present the identification of a piccolo-rim-related gene in invertebrates, together with molecular phylogenetic analyses that indicate the encoded proteins may represent Piccolo orthologs. In accordance, we find that the Drosophila homolog, Fife, is neuronal and localizes to presynaptic AZs. To investigate the in vivo function of Fife, we generated a deletion of the fife locus. We find that evoked neurotransmitter release is substantially decreased in fife mutants and loss of fife results in motor deficits. Through morphological analysis of fife synapses, we identify underlying AZ abnormalities including pervasive presynaptic membrane detachments and reduced synaptic vesicle clustering. Our data demonstrate the conservation of a Piccolo-related protein in invertebrates and identify critical roles for Fife in regulating AZ structure and function. These findings suggest the CAZ is more conserved than previously thought, and open the door to a more complete understanding of how CAZ proteins regulate presynaptic structure and function through genetic studies in simpler model systems. PMID:23197698

Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents.

PubMed

Saleem, A; Datta, R; Yuan, Z M; Kharbanda, S; Kufe, D

1995-12-01

The cellular response to 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of Jun/AP-1, induction of c-jun transcription, and programmed cell death. The stress-activated protein (SAP) kinases stimulate the transactivation function of c-jun by amino terminal phosphorylation. The present work demonstrates that ara-C activates p54 SAP kinase. The finding that SAP kinase is also activated by alkylating agents (mitomycin C and cisplatinum) and the topoisomerase I inhibitor 9-amino-camptothecin supports DNA damage as an initial signal in this cascade. The results demonstrate that ara-C also induces binding of SAP kinase to the SH2/SH3-containing adapter protein Grb2. SAP kinase binds to the SH3 domains of Grb2, while interaction of the p85 alpha-subunit of phosphatidylinositol 3-kinase complex. The results also demonstrate that ara-C treatment is associated with inhibition of lipid and serine kinase activities of PI 3-kinase. The potential significance of the ara-C-induced interaction between SAP kinase and PI 3-kinase is further supported by the demonstration that Wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. The finding that Wortmannin treatment is also associated with internucleosomal DNA fragmentation may support a potential link between PI 3-kinase and regulation of both SAP kinase and programmed cell death.

Altered Functional Connectivity of Insular Subregions in Alzheimer’s Disease

PubMed Central

Liu, Xingyun; Chen, Xiaodan; Zheng, Weimin; Xia, Mingrui; Han, Ying; Song, Haiqing; Li, Kuncheng; He, Yong; Wang, Zhiqun

2018-01-01

Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer’s disease (AD). However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI) data including 32 AD patients and 38 healthy controls (HCs). By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC) and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1) an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN); (2) a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN); (3) a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN). In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN) regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN), suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients. PMID:29695961

Altered Functional Connectivity of Insular Subregions in Alzheimer's Disease.

PubMed

Liu, Xingyun; Chen, Xiaodan; Zheng, Weimin; Xia, Mingrui; Han, Ying; Song, Haiqing; Li, Kuncheng; He, Yong; Wang, Zhiqun

2018-01-01

Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer's disease (AD). However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI) data including 32 AD patients and 38 healthy controls (HCs). By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC) and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1) an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN); (2) a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN); (3) a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN). In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN) regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN), suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients.

Rat Bone Marrow-Derived Schwann-Like Cells Differentiated by the Optimal Inducers Combination on Microfluidic Chip and Their Functional Performance

PubMed Central

Lv, Decheng

2012-01-01

Numerous researches demonstrated the possibility of derivation of Schwann-like (SC-like) cells in vitro from bone marrow stromal cells (BMSCs). However, the concentration of the induce factors were different in those studies, especially for the critical factors forskolin (FSK) and β-heregulin (HRG). Here, we used a new and useful method to build an integrated microfluidic chip for rapid analyses of the optimal combination between the induce factors FSK and HRG. The microfluidic device was mainly composed of an upstream concentration gradient generator (CGG) and a downstream cell culture module. Rat BMSCs were cultured in the cell chambers for 11 days at the different concentrations of induce factors generated by CGG. The result of immunofluorescence staining on-chip showed that the group of 4.00 µM FSK and 250.00 ng/ml HRG presented an optimal effect to promote the derivation of SC-like cells. Moreover, the optimal SC-like cells obtained on-chip were further tested using DRG co-culture and ELISA to detect their functional performance. Our findings demonstrate that SC-like cells could be obtained with high efficiency and functional performance in the optimal inducers combination. PMID:22880114

Rat bone marrow-derived Schwann-like cells differentiated by the optimal inducers combination on microfluidic chip and their functional performance.

PubMed

Tian, Xiliang; Wang, Shouyu; Zhang, Zhen; Lv, Decheng

2012-01-01

Numerous researches demonstrated the possibility of derivation of Schwann-like (SC-like) cells in vitro from bone marrow stromal cells (BMSCs). However, the concentration of the induce factors were different in those studies, especially for the critical factors forskolin (FSK) and β-heregulin (HRG). Here, we used a new and useful method to build an integrated microfluidic chip for rapid analyses of the optimal combination between the induce factors FSK and HRG. The microfluidic device was mainly composed of an upstream concentration gradient generator (CGG) and a downstream cell culture module. Rat BMSCs were cultured in the cell chambers for 11 days at the different concentrations of induce factors generated by CGG. The result of immunofluorescence staining on-chip showed that the group of 4.00 µM FSK and 250.00 ng/ml HRG presented an optimal effect to promote the derivation of SC-like cells. Moreover, the optimal SC-like cells obtained on-chip were further tested using DRG co-culture and ELISA to detect their functional performance. Our findings demonstrate that SC-like cells could be obtained with high efficiency and functional performance in the optimal inducers combination.

Iconic hand gestures and the predictability of words in context in spontaneous speech.

PubMed

Beattie, G; Shovelton, H

2000-11-01

This study presents a series of empirical investigations to test a theory of speech production proposed by Butterworth and Hadar (1989; revised in Hadar & Butterworth, 1997) that iconic gestures have a functional role in lexical retrieval in spontaneous speech. Analysis 1 demonstrated that words which were totally unpredictable (as measured by the Shannon guessing technique) were more likely to occur after pauses than after fluent speech, in line with earlier findings. Analysis 2 demonstrated that iconic gestures were associated with words of lower transitional probability than words not associated with gesture, even when grammatical category was controlled. This therefore provided new supporting evidence for Butterworth and Hadar's claims that gestures' lexical affiliates are indeed unpredictable lexical items. However, Analysis 3 found that iconic gestures were not occasioned by lexical accessing difficulties because although gestures tended to occur with words of significantly lower transitional probability, these lower transitional probability words tended to be uttered quite fluently. Overall, therefore, this study provided little evidence for Butterworth and Hadar's theoretical claim that the main function of the iconic hand gestures that accompany spontaneous speech is to assist in the process of lexical access. Instead, such gestures are reconceptualized in terms of communicative function.

Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

PubMed

Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

Anti-Correlated Cortical Networks of Intrinsic Connectivity in the Rat Brain

PubMed Central

Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

Abstract In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline “DMN-like” network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans. PMID:23919836

Skin tissue generation by laser cell printing.

PubMed

Koch, Lothar; Deiwick, Andrea; Schlie, Sabrina; Michael, Stefanie; Gruene, Martin; Coger, Vincent; Zychlinski, Daniela; Schambach, Axel; Reimers, Kerstin; Vogt, Peter M; Chichkov, Boris

2012-07-01

For the aim of ex vivo engineering of functional tissue substitutes, Laser-assisted BioPrinting (LaBP) is under investigation for the arrangement of living cells in predefined patterns. So far three-dimensional (3D) arrangements of single or two-dimensional (2D) patterning of different cell types have been presented. It has been shown that cells are not harmed by the printing procedure. We now demonstrate for the first time the 3D arrangement of vital cells by LaBP as multicellular grafts analogous to native archetype and the formation of tissue by these cells. For this purpose, fibroblasts and keratinocytes embedded in collagen were printed in 3D as a simple example for skin tissue. To study cell functions and tissue formation process in 3D, different characteristics, such as cell localisation and proliferation were investigated. We further analysed the formation of adhering and gap junctions, which are fundamental for tissue morphogenesis and cohesion. In this study, it was demonstrated that LaBP is an outstanding tool for the generation of multicellular 3D constructs mimicking tissue functions. These findings are promising for the realisation of 3D in vitro models and tissue substitutes for many applications in tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions.

PubMed

Phillips, Jack O; Butt, Louise E; Henderson, Charlotte A; Devonshire, Martin; Healy, Jess; Conway, Stuart J; Locker, Nicolas; Pickford, Andrew R; Vincent, Helen A; Callaghan, Anastasia J

2018-05-28

We are just beginning to unravel the myriad of interactions in which non-coding RNAs participate. The intricate RNA interactome is the foundation of many biological processes, including bacterial virulence and human disease, and represents unexploited resources for the development of potential therapeutic interventions. However, identifying specific associations of a given RNA from the multitude of possible binding partners within the cell requires robust high-throughput systems for their rapid screening. Here, we present the first demonstration of functional-RNA arrays as a novel platform technology designed for the study of such interactions using immobilized, active RNAs. We have generated high-density RNA arrays by an innovative method involving surface-capture of in vitro transcribed RNAs. This approach has significant advantages over existing technologies, particularly in its versatility in regards to binding partner character. Indeed, proof-of-principle application of RNA arrays to both RNA-small molecule and RNA-RNA pairings is demonstrated, highlighting their potential as a platform technology for mapping RNA-based networks and for pharmaceutical screening. Furthermore, the simplicity of the method supports greater user-accessibility over currently available technologies. We anticipate that functional-RNA arrays will find broad utility in the expanding field of RNA characterization.

Opposing Amygdala and Ventral Striatum Connectivity During Emotion Identification

PubMed Central

Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

2011-01-01

Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed a well-characterized emotion identification task. As expected, the amygdala responded to THREAT (angry or fearful) faces more than NON-THREAT (sad or happy) faces. A functional connectivity analysis of the time series from an anatomically defined amygdala seed revealed a strong anti-correlation between the amygdala and the ventral striatum /ventral pallidum, consistent with an opposing role for these regions in during emotion identification. A second functional connectivity analysis (psychophysiological interaction) investigating relative connectivity on THREAT vs. NON-THREAT trials demonstrated that the amygdala had increased connectivity with the orbitofrontal cortex during THREAT trials, whereas the ventral striatum demonstrated increased connectivity with the posterior hippocampus on NON-THREAT trials. These results indicate that activity in the amygdala and ventral striatum may be inversely related, and that both regions may provide opposing affective bias signals during emotion identification. PMID:21600684

Estimating sales and sales market share from sales rank data for consumer appliances

NASA Astrophysics Data System (ADS)

Touzani, Samir; Van Buskirk, Robert

2016-06-01

Our motivation in this work is to find an adequate probability distribution to fit sales volumes of different appliances. This distribution allows for the translation of sales rank into sales volume. This paper shows that the log-normal distribution and specifically the truncated version are well suited for this purpose. We demonstrate that using sales proxies derived from a calibrated truncated log-normal distribution function can be used to produce realistic estimates of market average product prices, and product attributes. We show that the market averages calculated with the sales proxies derived from the calibrated, truncated log-normal distribution provide better market average estimates than sales proxies estimated with simpler distribution functions.